Phthalate and Organophosphate Plasticizers in Nail Polish: Evaluation of Labels and IngredientsClick to copy article linkArticle link copied!
- Anna S. Young*Anna S. Young*Phone: (617) 432-1270; e-mail: [email protected] (A.S.Y.).Department of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, United StatesMore by Anna S. Young
- Joseph G. AllenJoseph G. AllenDepartment of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, United StatesMore by Joseph G. Allen
- Un-Jung KimUn-Jung KimWadsworth Center, New York State Department of Health, Albany, New York 12201, United StatesMore by Un-Jung Kim
- Stephanie SellerStephanie SellerBoston Public Health Commission, Boston, Massachusetts 02118, United StatesMore by Stephanie Seller
- Thomas F. WebsterThomas F. WebsterDepartment of Environmental Health, Boston University School of Public Health, Boston, Massachusetts 02118, United StatesMore by Thomas F. Webster
- Kurunthachalam KannanKurunthachalam KannanWadsworth Center, New York State Department of Health, Albany, New York 12201, United StatesMore by Kurunthachalam Kannan
- Diana M. CeballosDiana M. CeballosDepartment of Environmental Health, Harvard T. H. Chan School of Public Health, Boston, Massachusetts 02115, United StatesMore by Diana M. Ceballos
Abstract
In the 2000s, nail polish manufacturers started promoting “3-Free” products, phasing out three widely publicized toxic chemicals: toluene, formaldehyde, and dibutyl phthalate (DnBP). However, DnBP was sometimes replaced by another endocrine-disrupting plasticizer, triphenyl phosphate (TPHP). Many new “n-Free” labels have since appeared, without any standardization on which n chemicals are excluded. This study aimed to compare measured plasticizer content against nail polish labels. First, we summarized definitions of labels. Then, we measured 12 phthalate and 10 organophosphate plasticizers in 40 nail polishes from 12 brands selected for popularity and label variety. We found labels ranging from 3- to 13-Free; 10-Free was the most inconsistently defined (six definitions). Our samples contained TPHP and bis(2-ethylhexyl) phthalate (DEHP) at up to 7940 and 331 μg/g, respectively. The 5- to 13-Free samples had lower TPHP levels than unlabeled or 3-Free samples (median <0.002 vs 3730 μg/g, p < 0.001). The samples that did not contain TPHP had higher DEHP levels (median 68.5 vs 1.51 μg/g, p < 0.05). We measured plasticizers above 100 μg/g in five brands that did not disclose them and in two that excluded them in labels. This study highlights inconsistencies in nail polish labels and identifies TPHP and DEHP as ingredient substitutes for DnBP.
Introduction
Methods
Nail Polish Labels
Plasticizer Ingredient Levels
Statistical Analyses
Results
Nail Polish Labels
Plasticizer Ingredient Levels
Limits of detection (LODs) for OP plasticizers were 10, 5.0, 0.2, and 2.0 ng/g (in order of appearance).
LODs for phthalate plasticizers were 2.0, 2.0, 1.0, 1.0, 1.0, 0.5, 0.5, 0.5, and 0.5 ng/g (in order of appearance).
Newer labels after 5-Free are described in categories in order to preserve brand anonymity.
Product description reported the exclusion of the toxic trio chemicals without a specific ″3-Free” label.
Semipermanent UV-cured nail polish (but not a full gel polish).
Safety Data Sheet was not acquired.
Note: Plasticizers not detected in any of the samples were TEP, TPP, TCEP, TCIPP, TDCIPP, TBPhP, DCHP, DEHtP, and DiNP.
plasticizer | n (%) detected | median [range] | |
---|---|---|---|
OPsb | |||
EHDPP | 9 (22.5) | <0.01 [<0.01, 49.4] | |
PBDPP | 30 (75) | 0.387 [<0.005, 115] | |
TMPP | 12 (30) | <0.0002 [<0.0002, 0.379] | |
TPHP | 24 (60) | 2.73 [<0.002, 7940] | |
phthalatesc | |||
BBP | 40 (100) | 1.00 [0.415, 2.13] | |
DEHA | 35 (87.5) | 0.107 [<0.002, 0.467] | |
DEHP | 39 (97.5) | 1.65 [<0.001, 331] | |
DEP | 25 (62.5) | 0.0140 [<0.001, 1.56] | |
DiBP | 40 (100) | 0.114 [0.00300, 0.778] | |
DMP | 2 (5) | <0.0005 [<0.0005, 1.57] | |
DnBP | 36 (90) | 0.021 [<0.0005, 0.138] | |
DnHP | 3 (7.5) | <0.0005 [<0.0005, 0.918] | |
DnOP | 8 (20) | <0.0005 [<0.0005, 11.5] |
Note: < means the calculated value for the median or range fell below the limit of detection.
OP plasticizers not detected in any of the samples were TEP, TPP, TCEP, TCIPP, TDCIPP, and TBPhP.
Phthalate plasticizers not detected in any of the samples were DCHP, DEHtP, and DiNP.
median [range] | |||||
---|---|---|---|---|---|
plasticizer | type | old generation label (n = 12) | new generation label (n = 28) | detected TPHP (n = 24) | no detected TPHP (n = 16) |
DEHP | phthalate | 1.61 [0.703, 2.23] | 1.67 [<0.001, 331] | 1.51 [<0.001, 2.50] | 68.5 [0.684, 331]b |
PBDPP | OP | 0.287 [<0.005, 0.62] | 0.522 [<0.005, 115] | 0.531 [<0.005, 2.27] | 0.151 [<0.005, 115] |
TPHP | OP | 3730 [<0.002, 7940] | <0.002 [<0.002, 5330]c |
Note: Old generation, unlabeled or 3-Free; New generation, 5- to 13-Free; < , calculated value fell below the limit of detection.
Samples with detected TPHP significantly different from samples without detected TPHP at p < 0.05 (Wilcoxon rank sum test).
New generation samples significantly different from old generation samples at p < 0.001 (Wilcoxon rank sum test).
Discussion
Nail Polish Labels
Plasticizer Ingredient Levels
OPs | phthalates | ||||||||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|
country | sample selection | n | TPHP | BBP | DCHP | DEHA | DEHP | DEP | DiBP | DMP | DnBP | DnOP | reference |
U.S.A. | |||||||||||||
popularity & labels | 40 | 7900 | 2.1 | ND | 0.47 | 330 | 1.6 | 0.78 | 1.6 | 0.14 | 12 | this study | |
convenience & TPHP | 10 | 17 000 | Mendelsohnet al (2016) | ||||||||||
convenience & popularity | 8 | 2.2 | ND | 140 | 9.2 | 59 | 0.22 | 27000 | ND | Guo & Kannan (2013) | |||
convenience | 4 | ND | ND | ND | 1–100 | ND | 1–100 | ND | ND | Dodson et al (2012) | |||
convenience & 3-Free | 25 | 25 000 | 88 000 | CalEPA (2012) | |||||||||
convenience | 24 | ND | ND | ND | ND | 63 000 | Hubinger (2010) | ||||||
convenience | 6 | 110 | ND | 1100 | 15 000 | 60 000 | Hubinger & Havery (2006) | ||||||
otherb | |||||||||||||
Canada | convenience | 20 | ND | ND | 1000 | ND | 0.4 | ND | 24 000 | ND | Koniecki et al (2011) | ||
China | convenience | 10 | ND | 140 | 80 | 2 | 79 | ND | 5.7 | 5 | Bao et al (2015) | ||
Korea | convenience | 21 | ND | 25 | 31 | 3900 | Koo & Lee (2004) |
Note: ND, not detected. Nearly all minimum concentrations in the studies were below the limit of detection (LOD) or not reported. Maximums were selected as metrics due to their reporting across studies.
Only literature in English was searched.
Strengths and Limitations
Implications
Supporting Information
The Supporting Information is available free of charge on the ACS Publications website at DOI: 10.1021/acs.est.8b04495.
Detailed summary of methods for laboratory analysis (PDF)
Terms & Conditions
Most electronic Supporting Information files are available without a subscription to ACS Web Editions. Such files may be downloaded by article for research use (if there is a public use license linked to the relevant article, that license may permit other uses). Permission may be obtained from ACS for other uses through requests via the RightsLink permission system: http://pubs.acs.org/page/copyright/permissions.html.
Acknowledgments
We would like to acknowledge the Massachusetts Healthy Cosmetology Committee, Nan Pham, Lorri Ducharme, and local nail salons for their help with recruitment and worker interviews, and nail polish manufacturers for some donated samples. We would also like to thank Jose Vallarino, Jaime Hart, Francine Laden, Aaron Specht, and Chensheng Lu for their help. This investigation was made possible by Grant No. T42 OH008416 from the National Institute for Occupational Safety and Health (NIOSH). Its contents are solely the responsibility of the authors and do not necessarily represent the official views of the NIOSH. This research was also supported by NIH P30ES000002, NIH/NIEHS 2R25ES023635-04, and the Harvard Hoffman Program on Chemicals and Health. D.M.C. is a JPB Environmental Health Fellow at the Harvard Chan School. T.F.W. is supported in part by R01 ES016099 and R01 ES028800.
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- 23Mendelsohn, E.; Hagopian, A.; Hoffman, K.; Butt, C. M.; Lorenzo, A.; Congleton, J.; Webster, T. F.; Stapleton, H. M. Nail Polish as a Source of Exposure to Triphenyl Phosphate. Environ. Int. 2016, 86, 45– 51, DOI: 10.1016/j.envint.2015.10.005Google Scholar23https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslWisr7E&md5=a390d01ba0c50afece646a084b844f2eNail polish as a source of exposure to triphenyl phosphateMendelsohn, Emma; Hagopian, Audrey; Hoffman, Kate; Butt, Craig M.; Lorenzo, Amelia; Congleton, Johanna; Webster, Thomas F.; Stapleton, Heather M.Environment International (2016), 86 (), 45-51CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)Tri-Ph phosphate (TPHP) is primarily used as either a flame retardant or plasticizer, and is listed as an ingredient in nail polishes. However, the concn. of TPHP in nail polish and the extent of human exposure following applications have not been previously studied. We measured TPHP in ten different nail polish samples purchased from department stores and pharmacies in 2013-2014. Concns. up to 1.68% TPHP by wt. were detected in eight samples, including two that did not list TPHP as an ingredient. Two cohorts (n = 26 participants) were recruited to assess fingernail painting as a pathway of TPHP exposure. Participants provided urine samples before and after applying one brand of polish contg. 0.97% TPHP by wt. Di-Ph phosphate (DPHP), a TPHP metabolite, was then measured in urine samples (n = 411) and found to increase nearly seven-fold 10-14 h after fingernail painting (p < 0.001). To det. relative contributions of inhalation and dermal exposure, ten participants also painted their nails and painted synthetic nails adhered to gloves on two sep. occasions, and collected urine for 24 h following applications. Urinary DPHP was significantly diminished when wearing gloves, suggesting that the primary exposure route is dermal. Our results indicate that nail polish may be a significant source of short-term TPHP exposure and a source of chronic exposure for frequent users or those occupationally exposed.
- 24Carignan, C. C.; Mínguez-Alarcón, L.; Butt, C. M.; Williams, P. L.; Meeker, J. D.; Stapleton, H. M.; Toth, T. L.; Ford, J. B.; Hauser, R. Urinary Concentrations of Organophosphate Flame Retardant Metabolites and Pregnancy Outcomes among Women Undergoing in Vitro Fertilization for the EARTH Study Team. Environ. Health Perspect. 2017, 125 (8), 8, DOI: 10.1289/EHP1021Google ScholarThere is no corresponding record for this reference.
- 25Liu, C.; Wang, Q.; Liang, K.; Liu, J.; Zhou, B.; Zhang, X.; Liu, H.; Giesy, J. P.; Yu, H. Effects of tris(1,3-Dichloro-2-Propyl) Phosphate and Triphenyl Phosphate on Receptor-Associated mRNA Expression in Zebrafish Embryos/larvae. Aquat. Toxicol. 2013, 128–129, 147– 157, DOI: 10.1016/j.aquatox.2012.12.010Google Scholar25https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1CjsLk%253D&md5=33025295f1a38a4c45cd602605c29ee4Effects of tris(1,3-dichloro-2-propyl) phosphate and triphenyl phosphate on receptor-associated mRNA expression in zebrafish embryos/larvaeLiu, Chunsheng; Wang, Qiangwei; Liang, Kang; Liu, Jingfu; Zhou, Bingsheng; Zhang, Xiaowei; Liu, Hongling; Giesy, John P.; Yu, HongxiaAquatic Toxicology (2013), 128-129 (), 147-157CODEN: AQTODG; ISSN:0166-445X. (Elsevier B.V.)Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tri-Ph phosphate (TPP) are frequently detected in biota, including fish. However, knowledge of the toxicol. and mol. effects of these currently used flame retardants is limited. In the present study, an in vivo screening approach was developed to evaluate effects of TDCPP and TPP on developmental endpoints and receptor-assocd. expression of mRNA in zebrafish embryos/larvae. Exposure to TDCPP or TPP resulted in significantly smaller rates of hatching and survival, in dose- and time-dependent manners. The median lethal concn. (LC50) was 7.0 mg/L for TDCPP and 29.6 mg/L for TPP at 120 h post-fertilization (hpf). Real-time PCR revealed alterations in expression of mRNAs involved in aryl hydrocarbon receptors (AhRs)-, peroxisome proliferator-activated receptor alpha (PPARα)-, estrogenic receptors (ERs)-, thyroid hormone receptor alpha (TRα)-, glucocorticoid receptor (GR)-, and mineralocorticoid receptor (MR)-centered gene networks. Exposure to pos. control chems. significantly altered abundances of mRNA in corresponding receptor-centered gene networks, a result that suggests that it is feasible to use zebrafish embryos/larvae to evaluate effects of chems. on mRNA expression in these gene networks. Exposure to TDCPP altered transcriptional profiles in all six receptor-centered gene networks, thus exerting multiple toxic effects. TPP was easily metabolized and its potency to change expression of mRNA involved in receptor-centered gene networks was weaker than that of TDCPP. The PPARα- and TRα-centered gene networks might be the primary pathways affected by TPP. Taken together, these results demonstrated that TDCPP and TPP could alter mRNA expression of genes involved in the six receptor-centered gene networks in zebrafish embryos/larvae, and TDCPP seemed to have higher potency in changing the mRNA expression of these genes.
- 26Meeker, J. D.; Stapleton, H. M. House Dust Concentrations of Organophosphate Flame Retardants in Relation to Hormone Levels and Semen Quality Parameters. Environ. Health Perspect. 2010, 118 (3), 318– 323, DOI: 10.1289/ehp.0901332Google Scholar26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXksVyltrk%253D&md5=e2b4fce9dd40b375ff120863b3a2a4d8House dust concentrations of organophosphate flame retardants in relation to hormone levels and semen quality parametersMeeker, John D.; Stapleton, Heather M.Environmental Health Perspectives (2010), 118 (3), 318-323CODEN: EVHPAZ; ISSN:0091-6765. (U. S. Department of Health and Human Services, Public Health Services)Background: Organophosphate (OP) compds., such as tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tri-Ph phosphate (TPP), are commonly used as additive flame retardants and plasticizers in a wide range of materials. Although widespread human exposure to OP flame retardants is likely, there is a lack of human and animal data on potential health effects. Objective: We explored relationships of TDCPP and TPP concns. in house dust with hormone levels and semen quality parameters. Methods: We analyzed house dust from 50 men recruited through a U.S. infertility clinic for TDCPP and TPP. Relationships with reproductive and thyroid hormone levels, as well as semen quality parameters, were assessed using crude and multivariable linear regression. Results: TDCPP and TPP were detected in 96% and 98% of samples, resp., with widely varying concns. up to 1.8 mg/g. In models adjusted for age and body mass index, an interquartile range (IQR) increase in TDCPP was assocd. with a 3% [95% confidence interval (CI), -5% to -1%) decline in free thyroxine and a 17% (95% CI, 4-32%) increase in prolactin. There was a suggestive inverse assocn. between TDCPP and free androgen index that became less evident in adjusted models. In the adjusted models, an IQR increase in TPP was assocd. with a 10% (95% CI, 2-19%) increase in prolactin and a 19% (95% CI, -30% to -5%) decrease in sperm concn. Conclusion: OP flame retardants may be assocd. with altered hormone levels and decreased semen quality in men. More research on sources and levels of human exposure to OP flame retardants and assocd. health outcomes are needed.
- 27Meeker, J. D.; Cooper, E. M.; Stapleton, H. M.; Hauser, R. Exploratory Analysis of Urinary Metabolites of Phosphorus-Containing Flame Retardants in Relation to Markers of Male Reproductive Health. Endocr. Disruptors 2013, 1 (1), e26306, DOI: 10.4161/endo.26306Google ScholarThere is no corresponding record for this reference.
- 28Preston, E. V.; McClean, M. D.; Claus Henn, B.; Stapleton, H. M.; Braverman, L. E.; Pearce, E. N.; Makey, C. M.; Webster, T. F. Associations between Urinary Diphenyl Phosphate and Thyroid Function. Environ. Int. 2017, 101, 158– 164, DOI: 10.1016/j.envint.2017.01.020Google Scholar28https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitlKltr0%253D&md5=c0aeb1a55cbc13aec7c5e4be4694e724Associations between urinary diphenyl phosphate and thyroid functionPreston, Emma V.; McClean, Michael D.; Claus Henn, Birgit; Stapleton, Heather M.; Braverman, Lewis E.; Pearce, Elizabeth N.; Makey, Colleen M.; Webster, Thomas F.Environment International (2017), 101 (), 158-164CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)Tri-Ph phosphate (TPHP) is a commonly used organophosphate flame retardant and plasticizer with widespread human exposure. Data on health effects of TPHP are limited. Recent toxicol. studies suggest TPHP may alter thyroid function. We used repeated measures to assess the temporal variability in urinary concns. of the TPHP metabolite, di-Ph phosphate (DPHP), and to examine relationships between DPHP concns. and thyroid hormones. We sampled 51 adults at months 1, 6, and 12 from 2010 to 2011. Urine samples were analyzed for DPHP. Serum samples were analyzed for free and total thyroxine (fT4, TT4), total triiodothyronine (TT3), and TSH (TSH). We assessed variability in DPHP using intraclass correlation coeffs. (ICCs) and kappa statistics. We used linear mixed-effects models to examine assocns. between DPHP and thyroid hormones. DPHP was detected in 95% of urine samples. Mean DPHP concns. were 43% higher in women than men. DPHP showed high within-subject variability (ICC range, 0.13-0.39; kappa range, 0.16-0.39). High vs. low (≥ 2.65 vs. < 2.65 ng/mL) DPHP in all participants was assocd. with a 0.43 μg/dL (95% confidence interval: 0.15, 0.72) increase in mean TT4 levels. In sex-stratified analyses, high vs. low DPHP was assocd. with a 0.91 μg/dL (95% CI: 0.47, 1.36) increase in mean TT4 in women. The assocn. was attenuated in men (βeta = 0.19; 95% CI: - 0.15, 0.52). We found no significant assocns. between DPHP and fT4, TT3, or TSH. We found evidence that TPHP exposure may be assocd. with increased TT4 levels, esp. in women.
- 29Scherer, L. D.; Maynard, A.; Dolinoy, D. C.; Fagerlin, A.; Zikmund-Fisher, B. J. The Psychology of “Regrettable Substitutions”: Examining Consumer Judgements of Bisphenol A and Its Alternatives. Health. Risk Soc. 2014, 16 (7–8), 649– 666, DOI: 10.1080/13698575.2014.969687Google Scholar29https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1MvlvF2mtA%253D%253D&md5=06643cf2b9777361ffa8fb34dc4e7564The psychology of 'regrettable substitutions': Examining consumer judgements of Bisphenol A and its alternativesScherer Laura D; Maynard Andrew; Zikmund-Fisher Brian J; Maynard Andrew; Dolinoy Dana C; Fagerlin Angela; Fagerlin Angela; Zikmund-Fisher Brian J; Fagerlin Angela; Zikmund-Fisher Brian J; Fagerlin Angela; Zikmund-Fisher Brian JHealth, risk & society (2014), 16 (7-8), 649-666 ISSN:1369-8575.Bisphenol A is a chemical used to make certain types of plastics and is found in numerous consumer products. Because scientific studies have raised concerns about Bisphenol A's potential impact on human health, it has been removed from some (but not all) products. What many consumers do not know, however, is that Bisphenol A is often replaced with other, less-studied chemicals whose health implications are virtually unknown. This type of situation is known as a potential 'regrettable substitution', because the substitute material might actually be worse than the material that it replaces. Regrettable substitutions are a common concern among policymakers, and they are a real-world manifestation of the tension that can exist between the desire to avoid risk (known possible consequences that might or might not occur) and ambiguity (second-order uncertainty), which is itself aversive. In this article we examine how people make such trade-offs using the example of Bisphenol A. Using data from Study 1, we show that people have inconsistent preferences toward these alternatives and that choice is largely determined by irrelevant contextual factors such as the order in which the alternatives are evaluated. Using data from Study 2 we further demonstrate that when people are informed of the presence of substitute chemicals, labeling the alternative product as 'free' of Bisphenol A causes them to be significantly more likely to choose the alternative despite its ambiguity. We discuss the relevance of these findings for extant psychological theories as well as their implications for risk, policy and health communication.
- 30Zimmerman, J. B.; Anastas, P. T. Toward Substitution with No Regrets. Science 2015, 347 (6227), 1198– 1199, DOI: 10.1126/science.aaa0812Google Scholar30https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXls1Squ7Y%253D&md5=4539fc1fe159ead2954d6dadcdab4078Toward substitution with no regretsZimmerman, Julie B.; Anastas, Paul T.Science (Washington, DC, United States) (2015), 347 (6227), 1198-1199CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)There is no expanded citation for this reference.
- 31FDA (Food and Drug Administration). Cosmetics: FDA authority over cosmetics: how cosmetics are not FDA-approved, but are FDA-regulated https://www.fda.gov/Cosmetics/GuidanceRegulation/LawsRegulations/ucm074162.htm (accessed Feb 25, 2018).Google ScholarThere is no corresponding record for this reference.
- 32FDA. Cosmetics: prohibited & restricted ingredients https://www.fda.gov/Cosmetics/GuidanceRegulation/LawsRegulations/ucm127406.htm (accessed Feb 25, 2018).Google ScholarThere is no corresponding record for this reference.
- 33FDA. About FDA: Part II: 1938, Food, Drug, Cosmetic Act https://www.fda.gov/AboutFDA/WhatWeDo/History/FOrgsHistory/EvolvingPowers/ucm054826.htm (accessed Feb 25, 2018).Google ScholarThere is no corresponding record for this reference.
- 34FTC (Federal Trade Commission). Rule 16 CFR Part 260: Guides for the use of environmental marketing claims https://www.ecfr.gov/cgi-bin/text-idx?SID=ddcda39ef66f41f82d4b3910f7d5082a&mc=true&node=pt16.1.260&rgn=div5 (accessed Sep 17, 2018).Google ScholarThere is no corresponding record for this reference.
- 35FDA. Cosmetics: fragrances in cosmetics https://www.fda.gov/Cosmetics/ProductsIngredients/Ingredients/ucm388821.htm (accessed Feb 25, 2018).Google ScholarThere is no corresponding record for this reference.
- 36FDA. Cosmetics: phthalates https://www.fda.gov/Cosmetics/ProductsIngredients/Ingredients/ucm128250.htm (accessed Feb 25, 2018).Google ScholarThere is no corresponding record for this reference.
- 37FDA. Cosmetic Labeling Guide https://www.fda.gov/cosmetics/labeling/regulations/ucm126444.htm#clgl (accessed Sep 17, 2018).Google ScholarThere is no corresponding record for this reference.
- 38OSHA (Occupational Safety and Health Administration). Hazard communication standard: Safety Data Sheets https://www.osha.gov/Publications/OSHA3514.html (accessed Feb 25, 2018).Google ScholarThere is no corresponding record for this reference.
- 39EPA. Exposure Factors Handbook ; 2011.Google ScholarThere is no corresponding record for this reference.
- 40Mintel. Nail Color and Care: US, January 2016 ; 2016.Google ScholarThere is no corresponding record for this reference.
- 412017 Big Book Statistics. NAILS Magazine . 2018.Google ScholarThere is no corresponding record for this reference.
- 42Buckley, J. P.; Palmieri, R. T.; Matuszewski, J. M.; Herring, A. H.; Baird, D. D.; Hartmann, K. E.; Hoppin, J. A. Consumer Product Exposures Associated with Urinary Phthalate Levels in Pregnant Women. J. Exposure Sci. Environ. Epidemiol. 2012, 22 (5), 468– 475, DOI: 10.1038/jes.2012.33Google Scholar42https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1GjtrjN&md5=9fefccf71d12fcd2d5318b9cc2365fb6Consumer product exposures associated with urinary phthalate levels in pregnant womenBuckley, Jessie P.; Palmieri, Rachel T.; Matuszewski, Jeanine M.; Herring, Amy H.; Baird, Donna D.; Hartmann, Katherine E.; Hoppin, Jane A.Journal of Exposure Science & Environmental Epidemiology (2012), 22 (5), 468-475CODEN: JESEBS; ISSN:1559-0631. (Nature Publishing Group)Human phthalate exposure is ubiquitous, but little is known regarding predictors of urinary phthalate levels. To explore this, 50 pregnant women aged 18-38 years completed two questionnaires on potential phthalate exposures and provided a first morning void. Urine samples were analyzed for 12 phthalate metabolites. Assocns. with questionnaire items were evaluated via Wilcoxon tests and t-tests, and r-squared values were calcd. in multiple linear regression models. Few measured factors were statistically significantly assocd. with phthalate levels. Individuals who used nail polish had higher levels of mono-Bu phthalate (P=0.048) than non-users. Mono-benzyl phthalate levels were higher among women who used eye makeup (P=0.034) or used makeup on a regular basis (P=0.004). Women who used cologne or perfume had higher levels of di-(2-ethylhexyl) phthalate metabolites. Household products, home flooring or paneling, and other personal care products were also assocd. with urinary phthalates. The proportion of variance in metabolite concns. explained by questionnaire items ranged between 0.31 for mono-Et phthalate and 0.42 for mono-n-Me phthalate. Although personal care product use may be an important predictor of urinary phthalate levels, most of the variability in phthalate exposure was not captured by our relatively comprehensive set of questionnaire items. Journal of Exposure Science and Environmental Epidemiol. (2012) 22, 468-475; doi:10.1038/jes.2012.33; published online 4 July 2012.
- 43Hines, E. P.; Calafat, A. M.; Silva, M. J.; Mendola, P.; Fenton, S. E. Concentrations of Phthalate Metabolites in Milk, Urine, Saliva, and Serum of Lactating North Carolina Women. Environ. Health Perspect. 2009, 117 (1), 86– 92, DOI: 10.1289/ehp.11610Google Scholar43https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhvV2nt7k%253D&md5=8ff89074500ababe804c2fff2f6ac779Concentrations of phthalate metabolites in milk, urine, saliva, and serum of lactating North Carolina womenHines, Erin P.; Calafat, Antonia M.; Silva, Manori J.; Mendola, Pauline; Fenton, Suzanne E.Environmental Health Perspectives (2009), 117 (1), 86-92CODEN: EVHPAZ; ISSN:0091-6765. (U. S. Department of Health and Human Services, Public Health Services)Phthalates are ubiquitous in the environment, but concns. in multiple media from breast-feeding U.S. women have not been evaluated. The objective of this study was to accurately measure and compare the concns. of oxidative monoester phthalate metabolites in milk and surrogate fluids (serum, saliva, and urine) of 33 lactating North Carolina women. We analyzed serum, saliva, urine, and milk for the oxidative phthalate metabolites mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate using isotope-diln. high-performance liq. chromatog. tandem mass spectroscopy. Because only urine lacks esterases, we analyzed it for the hydrolytic phthalate monoesters. We detected phthalate metabolites in few milk (< 10%) and saliva samples. MECPP was detected in > 80% of serum samples, but other metabolites were less common (3-22%). Seven of the 10 urinary metabolites were detectable in ≥ 85% of samples. Monoethyl phthalate had the highest mean concn. in urine. Metabolite concns. differed by body fluid (urine > serum > milk and saliva). Questionnaire data suggest that frequent nail polish use, IgA, and fasting serum glucose and triglyceride levels were increased among women with higher concns. of urinary and/or serum phthalate metabolites; motor vehicle age was inversely correlated with certain urinary phthalate concns. Our data suggest that phthalate metabolites are most frequently detected in urine of lactating women and are less often detected in serum, milk, or saliva. Urinary phthalate concns. reflect maternal exposure and do not represent the concns. of oxidative metabolites in other body fluids, esp. milk.
- 44Hines, C. J.; Nilsen Hopf, N. B.; Deddens, J. A.; Calafat, A. M.; Silva, M. J.; Grote, A. A.; Sammons, D. L. Urinary Phthalate Metabolite Concentrations among Workers in Selected Industries: A Pilot Biomonitoring Study. Ann. Occup. Hyg. 2009, 53 (1), 1– 17, DOI: 10.1093/annhyg/men066Google Scholar44https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtVegtrw%253D&md5=fa504e65beacfc575e4e3b41b8751a5bUrinary Phthalate Metabolite Concentrations among Workers in Selected Industries: A Pilot Biomonitoring StudyHines, Cynthia J.; Nilsen Hopf, Nancy B.; Deddens, James A.; Calafat, Antonia M.; Silva, Manori J.; Grote, Ardith A.; Sammons, Deborah L.Annals of Occupational Hygiene (2009), 53 (1), 1-17CODEN: AOHYA3; ISSN:0003-4878. (Oxford University Press)Phthalates are used as plasticizers and solvents in industrial, medical and consumer products; however, occupational exposure information is limited. We sought to obtain preliminary information on occupational exposures to di-Et phthalate (DEP), di-Bu phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) by analyzing for their metabolites in urine samples collected from workers in a cross-section of industries. We also obtained data on metabolites of di-Me phthalate (DMP), benzylbutyl phthalate (BzBP), di-iso-Bu phthalate and di-isononyl phthalate. We recruited 156 workers in 2003-2005 from eight industry sectors. We assessed occupational contribution by comparing end-shift metabolite concns. to the US general population. Evidence of occupational exposure to DEHP was strongest in polyvinyl chloride (PVC) film manufg., PVC compounding and rubber boot manufg. where geometric mean (GM) end-shift concns. of DEHP metabolites exceeded general population levels by 8-, 6- and 3-fold, resp. Occupational exposure to DBP was most evident in rubber gasket, phthalate (raw material) and rubber hose manufg., with DBP metabolite concns. exceeding general population levels by 26-, 25- and 10-fold, resp., whereas DBP exposure in nail-only salons (manicurists) was only 2-fold higher than in the general population. Concns. of DEP and DMP metabolites in phthalate manufg. exceeded general population levels by 4- and >1000-fold, resp. We also found instances where GM end-shift concns. of some metabolites exceeded general population concns. even when no workplace use was reported, e.g. BzBP in rubber hose and rubber boot manufg. In summary, using urinary metabolites, we successfully identified workplaces with likely occupational phthalate exposure. Addnl. work is needed to distinguish occupational from non-occupational sources in low-exposure workplaces.
- 45John, E. M.; Savitz, D. A.; Shy, C. M. Spontaneous Abortions among Cosmetologists. Epidemiology 1994, 5 (2), 147– 155, DOI: 10.1097/00001648-199403000-00004Google ScholarThere is no corresponding record for this reference.
- 46Quach, T.; Von Behren, J.; Goldberg, D.; Layefsky, M.; Reynolds, P. Adverse Birth Outcomes and Maternal Complications in Licensed Cosmetologists and Manicurists in California. Int. Arch. Occup. Environ. Health 2015, 88 (7), 823– 833, DOI: 10.1007/s00420-014-1011-0Google ScholarThere is no corresponding record for this reference.
- 47Tran, T. M.; Kannan, K. Occurrence of Phthalate Diesters in Particulate and Vapor Phases in Indoor Air and Implications for Human Exposure in Albany, New York, USA. Arch. Environ. Contam. Toxicol. 2015, 68 (3), 489– 499, DOI: 10.1007/s00244-015-0140-0Google Scholar47https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXjt1aktb0%253D&md5=7ddbce90b29899e79783cc823fb4ec48Occurrence of Phthalate Diesters in Particulate and Vapor Phases in Indoor Air and Implications for Human Exposure in Albany, New York, USATran, Tri Manh; Kannan, KurunthachalamArchives of Environmental Contamination and Toxicology (2015), 68 (3), 489-499CODEN: AECTCV; ISSN:0090-4341. (Springer)Phthalate diesters are used as plasticizers in a wide range of consumer products. Because phthalates have been shown in lab. animal studies to be toxic, human exposure to these chems. is a matter of concern. Nevertheless, little is known about inhalation exposure to phthalates in the United States. In this study, occurrence of nine phthalates was detd. in 60 indoor air samples collected in 2014 in Albany, New York, USA. Airborne particulate and vapor phase samples were collected from various sampling locations by use of a low-vol. air sampler. The median concns. of nine phthalates in air samples collected from homes, offices, labs., schools, salons (hair and nail salons), and public places were 732, 143, 170, 371, 2600, and 354 ng/m3, resp. Di-Et phthalate (DEP) was found at the highest concns., which ranged from 4.83 to 2250 ng/m3 (median 152) followed by di-Bu phthalate, which ranged from 4.05 to 1170 ng/m3 (median 63.3). The median inhalation exposure dose to phthalates was estd. at 0.845, 0.423, 0.203, 0.089, and 0.070 μg/kg-bw/d for infants, toddlers, children, teenagers, and adults, resp. Inhalation is an important pathway of human exposure to DEP.
- 48Weschler, C. J.; Bekö, G.; Koch, H. M.; Salthammer, T.; Schripp, T.; Toftum, J.; Clausen, G. Transdermal Uptake of Diethyl Phthalate and Di(n-Butyl) Phthalate Directly from Air: Experimental Verification. Environ. Health Perspect. 2015, 123 (10), 928– 934, DOI: 10.1289/ehp.1409151Google Scholar48https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXls1Smsr0%253D&md5=9fd358f98c03275e58bf98976fdbdf16Transdermal uptake of diethyl phthalate and di(n-butyl) phthalate directly from air: experimental verificationWeschler, Charles J.; Beko, Gabriel; Koch, Holger M.; Salthammer, Tunga; Schripp, Tobias; Toftum, Joern; Clausen, GeoEnvironmental Health Perspectives (2015), 123 (10), 928-934CODEN: EVHPAZ; ISSN:1552-9924. (U. S. Department of Health and Human Services, National Institutes of Health)Background: Fundamental considerations indicate that, for certain phthalate esters, dermal absorption from air is an uptake pathway that is comparable to or greater than inhalation. Yet this pathway has not been exptl. evaluated and has been largely overlooked when assessing uptake of phthalate esters. OBjectives: This study investigated transdermal uptake, directly from air, of di-Et phthalate (DEP) and di(n-butyl) phthalate (DnBP) in humans. Methods: In a series of expts., six human participants were exposed for 6 h in a chamber contg. deliberately elevated air concns. of DEP and DnBP. The participants either wore a hood and breathed air with phthalate concns. substantially below those in the chamber or did not wear a hood and breathed chamber air. All urinations were collected from initiation of exposure until 54 h later. Metabolites of DEP and DnBP were measured in these samples and extrapolated to parent phthalate intakes, cor. for background and hood air exposures. Results: For DEP, the median dermal uptake directly from air was 4.0 μg/(μg/m3 in air) compared with an inhalation intake of 3.8 μg/(μg/m3 in air). For DnBP, the median dermal uptake from air was 3.1 μg/(μg/m3 in air) compared with an inhalation intake of 3.9 μg/(μg/m3 in air). Conclusions: This study shows that dermal uptake directly from air can be a meaningful exposure pathway for DEP and DnBP. For other semivolatile org. compds. (SVOCs) whose mol. wt. and lipid/air partition coeff. are in the appropriate range, direct absorption from air is also anticipated to be significant.
- 49Weschler, C. J.; Nazaroff, W. W. Semivolatile Organic Compounds in Indoor Environments. Atmos. Environ. 2008, 42 (40), 9018– 9040, DOI: 10.1016/j.atmosenv.2008.09.052Google Scholar49https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhsVSqtrnE&md5=13951f3772d946437b6bc08e9773c36eSemivolatile organic compounds in indoor environmentsWeschler, Charles J.; Nazaroff, William W.Atmospheric Environment (2008), 42 (40), 9018-9040CODEN: AENVEQ; ISSN:1352-2310. (Elsevier Ltd.)Semivolatile org. compds. (SVOCs) are ubiquitous in indoor environments, redistributing from their original sources to all indoor surfaces. Exposures resulting from their indoor presence contribute to detectable body burdens of diverse SVOCs, including pesticides, plasticizers, and flame retardants. This paper critically examines equil. partitioning of SVOCs among indoor compartments. It proceeds to evaluate kinetic constraints on sorptive partitioning to org. matter on fixed surfaces and airborne particles. Analyses indicate that equil. partitioning is achieved faster for particles than for typical indoor surfaces; indeed, for a strongly sorbing SVOC and a thick sorptive reservoir, equil. partitioning is never achieved. Mass-balance considerations are used to develop phys.-science-based models that connect source- and sink-rates to airborne concns. for commonly encountered situations, such as the application of a pesticide or the emission of a plasticizer or flame retardant from its host material. Calcns. suggest that many SVOCs have long indoor persistence, even after the primary source is removed. If the only removal mechanism is ventilation, moderately sorbing compds. (K oa > 1010) may persist indoors for hundreds to thousands of hours, while strongly sorbing compds. (K oa > 1012) may persist for years. The paper concludes by applying the newly developed framework to explore exposure pathways of building occupants to indoor SVOCs. Accumulation of SVOCs as a consequence of direct air-to-human transport is shown to be potentially large, with a max. indoor-air processing rate of 10-20 m3/h for SVOC uptake by human skin, hair and clothing. Levels on human skin calcd. with a simple model of direct air-to-skin transfer agree remarkably well with levels measured in dermal hand wipes for SVOCs possessing a wide range of octanol-air partition coeffs.
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- 55Jefferson, J.; Rich, P. Update on Nail Cosmetics. Dermatol. Ther. 2012, 25 (6), 481– 490, DOI: 10.1111/j.1529-8019.2012.01543.xGoogle Scholar55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3s7ptVKktw%253D%253D&md5=fef0f0611ce9da009cbb5e3599df28b1Update on nail cosmeticsJefferson Julie; Rich PhoebeDermatologic therapy (2012), 25 (6), 481-90 ISSN:.Nail cosmetics are used by millions of people worldwide who desire smooth, lustrous nails. The nail cosmetic industry continues to expand to meet increasing consumer demand. In 2011 alone, consumers spent $6.6 billion on nail salon services. Although nail cosmetics are relatively safe, poor application techniques can promote disease, deformity, and allergic and irritant contact dermatitis. The foundation for managing nail cosmetic problems is prevention through education. Familiarity with the procedures and materials used in the nail cosmetic industry is necessary in order to recommend safe nail care strategies.
- 56OSHA. Appendix A to §1910.1200 - health hazard criteria (mandatory) https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=10100 (accessed Mar 1, 2018).Google ScholarThere is no corresponding record for this reference.
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- 64Fong, J. P.; Lee, F. J.; Lu, I. S.; Uang, S. N.; Lee, C. C. Estimating the contribution of inhalation exposure to di-2-ethylhexyl phthalate (DEHP) for PVC production workers, using personal air sampling and urinary metabolite monitoring. Int. J. Hyg. Environ. Health 2014, 217 (1), 102– 109, DOI: 10.1016/j.ijheh.2013.04.002Google ScholarThere is no corresponding record for this reference.
- 65Kurahashi, N.; Kondo, T.; Omura, M.; Umemura, T.; Ma, M.; Kishi, R. The effects of subacute inhalation of di (2-ethylhexyl) phthalate (DEHP) on the testes of prepubertal Wistar rats. J. Occup. Health 2005, 47 (5), 437– 444, DOI: 10.1539/joh.47.437Google Scholar65https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtFyqtLzJ&md5=fa004cd6b4cdcae4ddcaafb23bcea62eThe effects of subacute inhalation of Di (2-ethylhexyl) phthalate (DEHP) on the testes of prepubertal Wistar ratsKurahashi, Norie; Kondo, Tomoko; Omura, Minoru; Umemura, Tomohiro; Ma, Mingyue; Kishi, ReikoJournal of Occupational Health (2005), 47 (5), 437-444CODEN: JOCHFV; ISSN:1341-9145. (Japan Society for Occupational Health)In animal studies using oral dosing for short periods, di (2-ethylhexyl) phthalate (DEHP) is well known for its reproductive toxicity, esp. for its testicular toxicity. However, extending the period of DEHP exposure in prepubertal rats resulted in significant increases in testosterone. This suggests that the reproductive effect of DEHP might be assocd. with the timing and the term of exposure. Moreover, the route of exposure may induce differences in its effect because tissue levels of metabolites of DEHP after inhalation are thought to be different from those after oral administration. We researched the effects of inhalation of DEHP on testes of prepubertal rats. These results showed that inhalation of DEHP by 4-wk-old male Wistar rats at doses of 5 or 25 mg/m3, 6 h per day, for 4 and 8 wk significantly increased the concn. of plasma testosterone and wt. of seminal vesicles. However, the concn. of LH, follicular stimulating hormone (FSH) and the expression of mRNAs of androgen biosynthesis enzyme, cytochrome P 450 cholesterol side-chain-cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), cytochrome P 450 17α-hydroxylase/17, 20 lyase (CYP17) and aromatase (CYP19) did not change. Rats with precocious testes did not increase in any of the DEHP groups. We also found that the estd. ED in this study was less than those reported in previous studies which used oral dosing. Our study showed that inhaled DEHP increased plasma testosterone concns. in prepubertal rats and suggested that their effects were more sensitive to inhalation of DEHP than oral dosing.
- 66Rasmussen, L. M.; Sen, N.; Vera, J. C.; Liu, X.; Craig, Z. R. Effects of in Vitro Exposure to Dibutyl Phthalate, Mono-Butyl Phthalate, and Acetyl Tributyl Citrate on Ovarian Antral Follicle Growth and Viability. Biol. Reprod. 2017, 96 (5), 1105– 1117, DOI: 10.1095/biolreprod.116.144691Google Scholar66https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1crlsFWrsg%253D%253D&md5=5a976d3870376017fb50a5797d3b8813Effects of in vitro exposure to dibutyl phthalate, mono-butyl phthalate, and acetyl tributyl citrate on ovarian antral follicle growth and viabilityRasmussen Lindsay M; Sen Nivedita; Vera Jahaira C; Liu Xiaosong; Craig Zelieann RBiology of reproduction (2017), 96 (5), 1105-1117 ISSN:.Dibutyl phthalate (DBP) is present in consumer products and the coating of some oral medications. Acetyl tributyl citrate (ATBC) has been proposed as an alternative to DBP because DBP causes endocrine disruption in animal models. Following ingestion, DBP is converted to its main metabolite mono-butyl phthalate (MBP) which has been detected in >90% of human follicular fluid samples. Previous studies show that DBP reduces the number of antral follicles present in the ovaries of mice. Thus, this study was designed to evaluate the effects of DBP, MBP, and ATBC on in vitro growth and viability of mouse ovarian antral follicles. Antral follicles were isolated from CD-1 females (PND32-37) and treated with vehicle, DBP, MBP, or ATBC (starting at 0.001 and up to 1000 μg/ml for DBP; 24-72 h). Follicle diameter, ATP production, qPCR, and TUNEL were used to measure follicle growth, viability, cell cycle and apoptosis gene expression, and cell death-associated DNA fragmentation, respectively. While MBP did not cause toxicity, DBP exposure at ≥10 μg/ml resulted in growth inhibition followed by cytoxicity at ≥500 μg/ml. ATBC increased the number of nongrowing follicles at 0.01 μg/ml and did not affect ATP production, but increased TUNEL positive area in treated follicles. Gene expression results suggest that cytotoxicity in DBP-treated follicles occurs via activation of cell cycle arrest prior to follicular death. These findings suggest that concentrations of DBP ≥10 μg/ml are detrimental to antral follicles and that ATBC should be examined further as it may disrupt antral follicle function at low concentrations.
- 67Rasmussen, L. M.; Sen, N.; Liu, X.; Craig, Z. R. Effects of Oral Exposure to the Phthalate Substitute Acetyl Tributyl Citrate on Female Reproduction in Mice. J. Appl. Toxicol. 2017, 37 (6), 668– 675, DOI: 10.1002/jat.3413Google Scholar67https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvVymt7vK&md5=a59ef5ba3325f3abff3b9b419b179a1aEffects of oral exposure to the phthalate substitute acetyl tributyl citrate on female reproduction in miceRasmussen, Lindsay M.; Sen, Nivedita; Liu, Xiaosong; Craig, Zelieann R.Journal of Applied Toxicology (2017), 37 (6), 668-675CODEN: JJATDK; ISSN:0260-437X. (John Wiley & Sons Ltd.)Acetyl tri-Bu citrate (ATBC), is a phthalate substitute used in food and medical plastics, cosmetics and toys. Although systemically safe up to 1000 mg kg-1 day-1, its ability to cause reproductive toxicity in females at levels below 50 mg kg-1 day-1 has not been examd. This study evaluated the effects of lower ATBC exposures on female reprodn. using mice. Adult CD-1 females (n = 7-8 per treatment) were dosed orally with tocopherol-stripped corn oil (vehicle), 5 or 10 mg kg-1 day-1 ATBC daily for 15 days, and then bred with a proven breeder male. ATBC exposure did not alter body wts., estrous cyclicity, and gestational and litter parameters. Relative spleen wt. was slightly increased in the 5 mg kg-1 day-1 group. ATBC at 10 mg kg-1 day-1 targeted ovarian follicles and decreased the no. of primordial, primary and secondary follicles present in the ovary. These findings suggest that low levels of ATBC may be detrimental to ovarian function, thus, more information is needed to understand better the impact of ATBC on female reprodn.
- 68Strajhar, P.; Tonoli, D.; Jeanneret, F.; Imhof, R. M.; Malagnino, V.; Patt, M.; Kratschmar, D. V.; Boccard, J.; Rudaz, S.; Odermatt, A. Steroid Profiling in H295R Cells to Identify Chemicals Potentially Disrupting the Production of Adrenal Steroids. Toxicology 2017, 381, 51– 63, DOI: 10.1016/j.tox.2017.02.010Google Scholar68https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXjsl2lsb8%253D&md5=2e9cb701d5814d8597fa3b0c51d8dc38Steroid profiling in H295R cells to identify chemicals potentially disrupting the production of adrenal steroidsStrajhar, Petra; Tonoli, David; Jeanneret, Fabienne; Imhof, Raphaella M.; Malagnino, Vanessa; Patt, Melanie; Kratschmar, Denise V.; Boccard, Julien; Rudaz, Serge; Odermatt, AlexToxicology (2017), 381 (), 51-63CODEN: TXCYAC; ISSN:0300-483X. (Elsevier Ltd.)The validated OECD test guideline 456 based on human adrenal H295R cells promotes measurement of testosterone and estradiol prodn. as read-out to identify potential endocrine disrupting chems. This study aimed to establish optimal conditions for using H295R cells to detect chems. interfering with the prodn. of key adrenal steroids. H295R cells' supernatants were characterized by liq. chromatog.-mass spectrometry (LC-MS)-based steroid profiling, and the influence of exptl. conditions including time and serum content was assessed. Steroid profiles were detd. before and after incubation with ref. compds. and chems. to be tested for potential disruption of adrenal steroidogenesis. The H295R cells cultivated according to the OECD test guideline produced progestins, glucocorticoids, mineralocorticoids and adrenal androgens but only very low amts. of testosterone. However, testosterone contained in Nu-serum was metabolized during the 48 h incubation. Thus, inclusion of pos. and neg. controls and a steroid profile of the complete medium prior to the expt. (t = 0 h) was necessary to characterize H295R cells' steroid prodn. and indicate alterations caused by exposure to chems. Among the tested chems., octyl methoxycinnamate and acetyl tributylcitrate resembled the corticosteroid induction pattern of the pos. control torcetrapib. Gene expression anal. revealed that octyl methoxycinnamate and acetyl tributylcitrate enhanced CYP11B2 expression, although less pronounced than torcetrapib. Further expts. need to assess the toxicol. relevance of octyl methoxycinnamate- and acetyl tributylcitrate-induced corticosteroid prodn. In conclusion, the extended profiling and appropriate controls allow detecting chems. that act on steroidogenesis and provide initial mechanistic evidence for prioritizing chems. for further investigations.
- 69Takeshita, A.; Igarashi-Migitaka, J.; Nishiyama, K.; Takahashi, H.; Takeuchi, Y.; Koibuchi, N. Acetyl Tributyl Citrate, the Most Widely Used Phthalate Substitute Plasticizer, Induces Cytochrome p450 3a through Steroid and Xenobiotic Receptor. Toxicol. Sci. 2011, 123 (2), 460– 470, DOI: 10.1093/toxsci/kfr178Google Scholar69https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1eiu7jN&md5=8e776e514982e1fb73fbb0c8dc3874cdAcetyl Tributyl Citrate, the Most Widely Used Phthalate Substitute Plasticizer, Induces through Steroid and Xenobiotic ReceptorTakeshita, Akira; Igarashi-Migitaka, Junko; Nishiyama, Kazusa; Takahashi, Hideyo; Takeuchi, Yasuhiro; Koibuchi, NoriyukiToxicological Sciences (2011), 123 (2), 460-470CODEN: TOSCF2; ISSN:1096-0929. (Oxford University Press)Steroid and xenobiotic receptor (SXR) is activated by endogenous and exogenous chems. including steroids, bile acids, and prescription drugs. SXR is highly expressed in the liver and intestine, where it regulates cytochrome P 450 3A4 (CYP3A4), which in turn controls xenobiotic and endogenous steroid hormone metab. However, it is unclear whether Food and Drug Administration (FDA)-approved plasticizers exert such activity. In the present study, the authors evaluated the effects of FDA-approved plasticizers on SXR-mediated transcription in vitro by luciferase reporter, SXR-coactivator interaction, quant. real-time PCR anal. of CYP3A4 expression, CYP3A4 enzyme activity assays, and SXR knockdown. Rats, treated with gavage and i.p. injection of compds., were examd. for CYP3A1 expression in vivo. The authors found that 4 of 8 FDA-approved plasticizers increased SXR-mediated transcription. In particular, acetyl tri-Bu citrate (ATBC), an industrial plasticizer widely used in products such as food wrap, vinyl toys, and pharmaceutical excipients, strongly activated human and rat SXR. ATBC increased CYP3A4 mRNA levels and enzyme activity in the human intestinal cells but not in human liver cells. Similarly, CYP3A1 mRNA levels were increased in the intestine but not the liver of ATBC-treated rats. These in vitro and in vivo results suggest that ATBC specifically induces CYP3A in the intestine by activating SXR. We suggest that ATBC-contg. products be used cautiously because they may alter metab. of endogenous steroid hormones and prescription drugs.
- 70Baran, R. Nail Cosmetics: Allergies and Irritations. Am. J. Clin. Dermatol. 2002, 3 (8), 547– 555, DOI: 10.2165/00128071-200203080-00005Google Scholar70https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD38vpslCguw%253D%253D&md5=5a487679f1251f0f4caaafbaca41501aNail cosmetics: allergies and irritationsBaran RobertAmerican journal of clinical dermatology (2002), 3 (8), 547-55 ISSN:1175-0561.Recent precise figures are not available for the number of adverse reactions related to the use of nail care products. Reactions to nail cosmetic procedures may be divided into reactions at the site of application to the nail itself and ectopic reactions, when the hand transfers a small amount of nail cosmetic to other areas of the skin. Fingernail coatings encompass two types: coatings that harden upon evaporation (nail enamel, base coat, top coat); and coatings that polymerize (sculptured nails, light-curing gels, preformed artificial nails, nail mending and nail wrapping). The test battery enables us to distinguish allergic reactions from irritant reactions. Interestingly, some reactions, such as distant allergic contact dermatitis, are more frequent with nail enamel than with coatings that polymerize. On the other hand, the latter are greater offenders in the nail area. Nail hardeners may just be modified nail enamels containing nylon fibers, acrylate resin and hydrolyzed proteins. Others may contain up to 5% formaldehyde tissue fixative (which can have adverse effects on the nail), but are designed in the US to be applied only to the free edge of the nail while the skin is shielded. Caution is necessary in interpreting formaldehyde patch testing reactions.
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- 5Foster, P. M. D.; Thomas, L. V.; Cook, M. W.; Gangolli, S. D. Study of the Testicular Effects and Changes in Zinc Excretion Produced by Some N-Alkyl Phthalates in the Rat. Toxicol. Appl. Pharmacol. 1980, 54 (3), 392– 398, DOI: 10.1016/0041-008X(80)90165-95https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaL3cXlt1Kmtbc%253D&md5=8658b52ad4b7f1c3c5eacde370a72bd4Study of the testicular effects and changes in zinc excretion produced by some n-alkyl phthalates in the ratFoster, Paul M. D.; Thomas, Lucy V.; Cook, Melvyn W.; Gangolli, Sharat D.Toxicology and Applied Pharmacology (1980), 54 (3), 392-8CODEN: TXAPA9; ISSN:0041-008X.A study was made of the comparative effects of treatment with phthalates [I, R = Me, Et, Pr, (CH2)4Me, (CH2)6Me, or (CH2)7Me] on testicular tissue and Zn excretion in the rat. I were given orally, at 7.2 mmol/kg/day, equiv. to 2 g/kg/day of I (R = Bu) (II) for 4 days to young male rats. I [R = (CH2)4Me and (CH2)5Me] produced testicular atrophy similar to II. In addn., the 2 agents also induced an increase in urinary Zn excretion together with a lowering of testicular Zn content. The other I investigated did not damage the testes and had no effect on the Zn urinary excretion or testicular Zn content.
- 6Heindel, J. J.; Powell, C. J. Phthalate Ester Effects on Rat Sertoli Cell Function in Vitro: Effects of Phthalate Side Chain and Age of Animal. Toxicol. Appl. Pharmacol. 1992, 115 (1), 116– 123, DOI: 10.1016/0041-008X(92)90374-26https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADyaK38XlvVKitL8%253D&md5=ab5e5534d9d5645b40fd5ad93159494dPhthalate ester effects on rat Sertoli cell function in vitro: effects of phthalate side chain and age of animalHeindel, Jerrold J.; Powell, Cassandra J.Toxicology and Applied Pharmacology (1992), 115 (1), 116-23CODEN: TXAPA9; ISSN:0041-008X.The effect of animal age and phthalate monoester on the Sertoli cell FSH-stimulated cAMP accumulation, lactate secretion, and ATP levels were examd. to det. if these effects are part of the mechanism of action of phthalate esters in vivo. Mono(2-ethylhexyl) phthalate (MEHP), monobutyl and monopentyl phthalates but not the monoethyl, monomethyl, or monopropyl phthalates inhibited FSH-stimulated cAMP accumulation, a segregation which matches the in vivo toxicity potential of these agents. MEHP and monopentyl, but not monobutyl phthalates, also stimulated Sertoli cell lactate secretion. The effect of the active phthalates on FSH-stimulated cAMP accumulation and lactate secretion is not dependent on the age of the animal over a range of 13-80 days, suggesting that the age-related toxicity in vivo may be related to differences in metab. and disposition rather than tissue sensitivity. Since the ED50 of MEHP inhibition of cAMP accumulation and lactate secretion is similar, these two effects may be related to a common initial effect of the active phthalates. Inhibition of intracellular ATP levels is specific for MEHP and is lost with age (>28 days of age) and thus is not likely to be an essential part of the in vivo mechanism of action of phthalate diesters.
- 7Shiota, K.; Chou, M. J.; Nishimura, H. Embryotoxic Effects of Di-2-Ethylhexyl Phthalate (DEHP) and Di-N-Butyl Phthalate (DBP) in Mice. Environ. Res. 1980, 22 (1), 245– 253, DOI: 10.1016/0013-9351(80)90136-XThere is no corresponding record for this reference.
- 8Blount, B. C.; Silva, M. J.; Caudill, S. P.; Needham, L. L.; Pirkle, J. L.; Sampson, E. J.; Lucier, G. W.; Jackson, R. J.; Brock, J. W. Levels of Seven Urinary Phthalate Metabolites in a Human Reference Population. Environ. Health Perspect. 2000, 108 (10), 979– 982, DOI: 10.1289/ehp.001089798https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD3cXotVWrur4%253D&md5=2adfffcb7645d6b657b2146596db9b99Levels of seven urinary phthalate metabolites in a human reference populationBlount, Benjamin C.; Silva, Manori J.; Caudill, Samuel P.; Needham, Larry L.; Pirkle, Jim L.; Sampson, Eric J.; Lucier, George W.; Jackson, Richard J.; Brock, John W.Environmental Health Perspectives (2000), 108 (10), 979-982CODEN: EVHPAZ; ISSN:0091-6765. (National Institute of Environmental Health Sciences)Using a novel and highly selective technique, we measured monoester metabolites of seven commonly used phthalates in urine samples from a ref. population of 289 adult humans. This anal. approach allowed us to directly measure the individual phthalate metabolites responsible for the animal reproductive and developmental toxicity while avoiding contamination from the ubiquitous parent compds. The monoesters with the highest urinary levels found were monoethyl phthalate (95th percentile, 3750 ppb, 2610 μg/g creatinine), monobutyl phthalate (95th percentile, 294 ppb, 162 μg/g creatinine), and monobenzyl phthalate (95th percentile, 137 ppb, 92 μg/g creatinine), reflecting exposure to di-Et phthalate, di-Bu phthalate, and benzyl Bu phthalate. Women of reproductive age (20-40 yr) were found to have significantly higher levels of monobutyl phthalate, a reproductive and developmental toxicant in rodents, than other age/gender groups (p < 0.005). Current scientific and regulatory attention on phthalates has focused almost exclusively on health risks from exposure to only two phthalates, di-(2-ethylhexyl) phthalate and di-isononyl phthalate. These findings strongly suggest that health-risk assessments for phthalate exposure in humans should include di-Et, di-Bu, and benzyl Bu phthalates.
- 9Kohn, M. C.; Parham, F.; Masten, S. A.; Portier, C. J.; Shelby, M. D.; Brock, J. W.; Needham, L. L. Human Exposure Estimates for Phthalates. Environ. Health Perspect. 2000, 108 (10), A440– 2, DOI: 10.1289/ehp.108-a440bThere is no corresponding record for this reference.
- 10EU (European Union). Regulation (EC) No 1223/2009 of the European Parliament and of the Council of 30 November 2009 on Cosmetic Products ; 2016.There is no corresponding record for this reference.
- 11Breskey, J. D. California Again Leading the Way: Cosmetics Safety and Worker Health. Calif. J. Heal. Promot. 2013, 11 (1), vi– viiiThere is no corresponding record for this reference.
- 12Cal EPA (California Environmental Protection Agency). Summary of Data and Findings from Testing of a Limited Number of Nail Products ; 2012.There is no corresponding record for this reference.
- 13EPA (Environmental Protection Agency). Toluene Hazard Summary ; 2012.There is no corresponding record for this reference.
- 14IARC. IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: List of Classifications, Volumes 1–121; 2018.There is no corresponding record for this reference.
- 15Nir, S. M. Perfect Nails, Poisoned Workers. New York Times ; 2015.There is no corresponding record for this reference.
- 16Casals-Casas, C.; Desvergne, B. Endocrine Disruptors: From Endocrine to Metabolic Disruption. Annu. Rev. Physiol. 2011, 73, 135– 162, DOI: 10.1146/annurev-physiol-012110-14220016https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXktVKjtb8%253D&md5=3cbdf6eb334add87c80f2c53fccfeb2dEndocrine disruptors: from endocrine to metabolic disruptionCasals-Casas, Cristina; Desvergne, BeatriceAnnual Review of Physiology (2011), 73 (), 135-162CODEN: ARPHAD; ISSN:0066-4278. (Annual Reviews Inc.)A review. Synthetic chems. currently used in a variety of industrial and agricultural applications are leading to widespread contamination of the environment. Even though the intended uses of pesticides, plasticizers, antimicrobials, and flame retardants are beneficial, effects on human health are a global concern. These so-called endocrine-disrupting chems. (EDCs) can disrupt hormonal balance and result in developmental and reproductive abnormalities. New in vitro, in vivo, and epidemiol. studies link human EDC exposure with obesity, metabolic syndrome, and type 2 diabetes. Here we review the main chem. compds. that may contribute to metabolic disruption. We then present their demonstrated or suggested mechanisms of action with respect to nuclear receptor signaling. Finally, we discuss the difficulties of fairly assessing the risks linked to EDC exposure, including developmental exposure, problems of high- and low-dose exposure, and the complexity of current chem. environments.
- 17Ferguson, K. K.; McElrath, T. F.; Meeker, J. D. Environmental Phthalate Exposure and Preterm Birth. JAMA Pediatr. 2014, 168 (1), 61– 67, DOI: 10.1001/jamapediatrics.2013.369917https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC2c7otFSqsQ%253D%253D&md5=39f19c2df37fcc4042b2d7150f905216Environmental phthalate exposure and preterm birthFerguson Kelly K; Meeker John D; McElrath Thomas FJAMA pediatrics (2014), 168 (1), 61-67 ISSN:.IMPORTANCE: Preterm birth is a leading cause of neonatal mortality, with a variety of contributing causes and risk factors. Environmental exposures represent a group of understudied, but potentially important, factors. Phthalate diesters are used extensively in a variety of consumer products worldwide. Consequently, exposure in pregnant women is highly prevalent. OBJECTIVE: To assess the relationship between phthalate exposure during pregnancy and preterm birth. DESIGN, SETTING, AND PARTICIPANTS: This nested case-control study was conducted at Brigham and Women's Hospital, Boston, Massachusetts. Women were recruited for a prospective observational cohort study from 2006-2008. Each provided demographic data, biological samples, and information about birth outcomes. From within this group, we selected 130 cases of preterm birth and 352 randomly assigned control participants, and we analyzed urine samples from up to 3 time points during pregnancy for levels of phthalate metabolites. EXPOSURE: Phthalate exposure during pregnancy. MAIN OUTCOMES AND MEASURES: We examined associations between average levels of phthalate exposure during pregnancy and preterm birth, defined as fewer than 37 weeks of completed gestation, as well as spontaneous preterm birth, defined as preterm preceded by spontaneous preterm labor or preterm premature rupture of the membranes (n = 57). RESULTS: Geometric means of the di-2-ethylhexyl phthalate (DEHP) metabolites mono-(2-ethyl)-hexyl phthalate (MEHP) and mono-(2-ethyl-5-carboxypentyl) phthalate (MECPP), as well as mono-n-butyl phthalate (MBP), were significantly higher in cases compared with control participants. In adjusted models, MEHP, MECPP, and Σ DEHP metabolites were associated with significantly increased odds of preterm birth. When spontaneous preterm births were examined alone, MEHP, mono-(2-ethyl-5-oxohexyl) phthalate, MECPP, Σ DEHP, MBP, and mono-(3-carboxypropyl) phthalate metabolite levels were all associated with significantly elevated odds of prematurity. CONCLUSIONS AND RELEVANCE: Women exposed to phthalates during pregnancy have significantly increased odds of delivering preterm. Steps should be taken to decrease maternal exposure to phthalates during pregnancy.
- 18Hauser, R.; Meeker, J. D.; Duty, S.; Silva, M. J.; Calafat, A. M. Altered Semen Quality in Relation to Urinary Concentrations of Phthalate Monoester and Oxidative Metabolites. Epidemiology 2006, 17 (6), 682– 691, DOI: 10.1097/01.ede.0000235996.89953.d7There is no corresponding record for this reference.
- 19Huang, P.; Kuo, P.; Guo, Y.; Liao, P.; Lee, C. Associations between Urinary Phthalate Monoesters and Thyroid Hormones in Pregnant Women. Hum. Reprod. 2007, 22 (10), 2715– 2722, DOI: 10.1093/humrep/dem20519https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2sXhtlekt77O&md5=944437691f53b7d157f5b566e292b558Associations between urinary phthalate monoesters and thyroid hormones in pregnant womenHuang, Po-Chin; Kuo, Pao-Lin; Guo, Yue-Liang; Liao, Pao-Chi; Lee, Ching-ChangHuman Reproduction (2007), 22 (10), 2715-2722CODEN: HUREEE; ISSN:0268-1161. (Oxford University Press)Background: Maternal hypothyroidism during pregnancy can cause adverse effects in the fetus. Scientific evidence has shown that probable thyroid-like function of some phthalates in vitro and in vivo, and phthalates exposure, can begin in utero. This study investigated the assocn. between phthalate exposure and thyroid hormones in pregnant women. Methods: Serum and spot urine samples were collected from 76 Taiwanese pregnant women at second trimester. Thyroid hormones, including TSH (TSH), triiodothyronine (T3), thyroxine (T4) and free T4 (FT4) were analyzed in serum samples, and five urinary phthalate monoesters, including mono Bu phthalate (MBP), monoethyl phthalate (MEP) and mono ethylhexyl phthalate (MEHP), were measured. Results: Urinary MBP, MEP and MEHP, the median levels of which were 81.8, 27.7 and 20.6 ng/mL, resp., were the predominant substances in the urinary phthalate monoesters. Significant mild neg. correlations were found between T4 and urinary MBP (R = -0.248, P < 0.05), and between FT4 and urinary MBP (R = -0.368, P < 0.05). After adjusting for age, BMI and gestation, urinary MBP levels showed neg. assocns. with FT4 and T4 (FT4: β = -0.110, P < 0.001; T4: β = -0.112, P = 0.003). Conclusions: Exposure to di-Bu phthalate (DBP) may affect thyroid activity in pregnant women, but how DBP affects thyroid function is unclear. Further studies are needed to elucidate the mechanism of action and to investigate whether any other factors related to DBP exposure alter the thyroid function.
- 20Schug, T. T.; Janesick, A.; Blumberg, B.; Heindel, J. J. Endocrine Disrupting Chemicals and Disease Susceptibility. J. Steroid Biochem. Mol. Biol. 2011, 127, 204– 215, DOI: 10.1016/j.jsbmb.2011.08.00720https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXhsFSksrnE&md5=4c95fa724875f3e63ebcd3ff3442d678Endocrine disrupting chemicals and disease susceptibilitySchug, Thaddeus T.; Janesick, Amanda; Blumberg, Bruce; Heindel, Jerrold J.Journal of Steroid Biochemistry and Molecular Biology (2011), 127 (3-5), 204-215CODEN: JSBBEZ; ISSN:0960-0760. (Elsevier Ltd.)A review. Environmental chems. have significant impacts on biol. systems. Chem. exposures during early stages of development can disrupt normal patterns of development and thus dramatically alter disease susceptibility later in life. Endocrine disrupting chems. (EDCs) interfere with the body's endocrine system and produce adverse developmental, reproductive, neurol., cardiovascular, metabolic and immune effects in humans. A wide range of substances, both natural and man-made, are thought to cause endocrine disruption, including pharmaceuticals, dioxin and dioxin-like compds., polychlorinated biphenyls, DDT and other pesticides, and components of plastics such as bisphenol A (BPA) and phthalates. EDCs are found in many everyday products - including plastic bottles, metal food cans, detergents, flame retardants, food additives, toys, cosmetics, and pesticides. EDCs interfere with the synthesis, secretion, transport, activity, or elimination of natural hormones. This interference can block or mimic hormone action, causing a wide range of effects. This review focuses on the mechanisms and modes of action by which EDCs alter hormone signaling. It also includes brief overviews of select disease endpoints assocd. with endocrine disruption.
- 21Swan, S. H.; Main, K. M.; Liu, F.; Stewart, S. L.; Kruse, R. L.; Calafat, A. M.; Mao, C. S.; Redmon, J. B.; Ternand, C. L.; Sullivan, S.; Teague, J. L. the Study for Future Families Research Team. Decrease in Anogenital Distance among Male Infants with Prenatal Phthalate Exposure. Environ. Health Perspect. 2005, 113 (8), 1056– 1061, DOI: 10.1289/ehp.8100There is no corresponding record for this reference.
- 22EWG (Environmental Working Group). Skin Deep Cosmetic Database http://www.ewg.org/skindeep (accessed Feb 5, 2018).There is no corresponding record for this reference.
- 23Mendelsohn, E.; Hagopian, A.; Hoffman, K.; Butt, C. M.; Lorenzo, A.; Congleton, J.; Webster, T. F.; Stapleton, H. M. Nail Polish as a Source of Exposure to Triphenyl Phosphate. Environ. Int. 2016, 86, 45– 51, DOI: 10.1016/j.envint.2015.10.00523https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXhslWisr7E&md5=a390d01ba0c50afece646a084b844f2eNail polish as a source of exposure to triphenyl phosphateMendelsohn, Emma; Hagopian, Audrey; Hoffman, Kate; Butt, Craig M.; Lorenzo, Amelia; Congleton, Johanna; Webster, Thomas F.; Stapleton, Heather M.Environment International (2016), 86 (), 45-51CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)Tri-Ph phosphate (TPHP) is primarily used as either a flame retardant or plasticizer, and is listed as an ingredient in nail polishes. However, the concn. of TPHP in nail polish and the extent of human exposure following applications have not been previously studied. We measured TPHP in ten different nail polish samples purchased from department stores and pharmacies in 2013-2014. Concns. up to 1.68% TPHP by wt. were detected in eight samples, including two that did not list TPHP as an ingredient. Two cohorts (n = 26 participants) were recruited to assess fingernail painting as a pathway of TPHP exposure. Participants provided urine samples before and after applying one brand of polish contg. 0.97% TPHP by wt. Di-Ph phosphate (DPHP), a TPHP metabolite, was then measured in urine samples (n = 411) and found to increase nearly seven-fold 10-14 h after fingernail painting (p < 0.001). To det. relative contributions of inhalation and dermal exposure, ten participants also painted their nails and painted synthetic nails adhered to gloves on two sep. occasions, and collected urine for 24 h following applications. Urinary DPHP was significantly diminished when wearing gloves, suggesting that the primary exposure route is dermal. Our results indicate that nail polish may be a significant source of short-term TPHP exposure and a source of chronic exposure for frequent users or those occupationally exposed.
- 24Carignan, C. C.; Mínguez-Alarcón, L.; Butt, C. M.; Williams, P. L.; Meeker, J. D.; Stapleton, H. M.; Toth, T. L.; Ford, J. B.; Hauser, R. Urinary Concentrations of Organophosphate Flame Retardant Metabolites and Pregnancy Outcomes among Women Undergoing in Vitro Fertilization for the EARTH Study Team. Environ. Health Perspect. 2017, 125 (8), 8, DOI: 10.1289/EHP1021There is no corresponding record for this reference.
- 25Liu, C.; Wang, Q.; Liang, K.; Liu, J.; Zhou, B.; Zhang, X.; Liu, H.; Giesy, J. P.; Yu, H. Effects of tris(1,3-Dichloro-2-Propyl) Phosphate and Triphenyl Phosphate on Receptor-Associated mRNA Expression in Zebrafish Embryos/larvae. Aquat. Toxicol. 2013, 128–129, 147– 157, DOI: 10.1016/j.aquatox.2012.12.01025https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3sXhs1CjsLk%253D&md5=33025295f1a38a4c45cd602605c29ee4Effects of tris(1,3-dichloro-2-propyl) phosphate and triphenyl phosphate on receptor-associated mRNA expression in zebrafish embryos/larvaeLiu, Chunsheng; Wang, Qiangwei; Liang, Kang; Liu, Jingfu; Zhou, Bingsheng; Zhang, Xiaowei; Liu, Hongling; Giesy, John P.; Yu, HongxiaAquatic Toxicology (2013), 128-129 (), 147-157CODEN: AQTODG; ISSN:0166-445X. (Elsevier B.V.)Tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tri-Ph phosphate (TPP) are frequently detected in biota, including fish. However, knowledge of the toxicol. and mol. effects of these currently used flame retardants is limited. In the present study, an in vivo screening approach was developed to evaluate effects of TDCPP and TPP on developmental endpoints and receptor-assocd. expression of mRNA in zebrafish embryos/larvae. Exposure to TDCPP or TPP resulted in significantly smaller rates of hatching and survival, in dose- and time-dependent manners. The median lethal concn. (LC50) was 7.0 mg/L for TDCPP and 29.6 mg/L for TPP at 120 h post-fertilization (hpf). Real-time PCR revealed alterations in expression of mRNAs involved in aryl hydrocarbon receptors (AhRs)-, peroxisome proliferator-activated receptor alpha (PPARα)-, estrogenic receptors (ERs)-, thyroid hormone receptor alpha (TRα)-, glucocorticoid receptor (GR)-, and mineralocorticoid receptor (MR)-centered gene networks. Exposure to pos. control chems. significantly altered abundances of mRNA in corresponding receptor-centered gene networks, a result that suggests that it is feasible to use zebrafish embryos/larvae to evaluate effects of chems. on mRNA expression in these gene networks. Exposure to TDCPP altered transcriptional profiles in all six receptor-centered gene networks, thus exerting multiple toxic effects. TPP was easily metabolized and its potency to change expression of mRNA involved in receptor-centered gene networks was weaker than that of TDCPP. The PPARα- and TRα-centered gene networks might be the primary pathways affected by TPP. Taken together, these results demonstrated that TDCPP and TPP could alter mRNA expression of genes involved in the six receptor-centered gene networks in zebrafish embryos/larvae, and TDCPP seemed to have higher potency in changing the mRNA expression of these genes.
- 26Meeker, J. D.; Stapleton, H. M. House Dust Concentrations of Organophosphate Flame Retardants in Relation to Hormone Levels and Semen Quality Parameters. Environ. Health Perspect. 2010, 118 (3), 318– 323, DOI: 10.1289/ehp.090133226https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3cXksVyltrk%253D&md5=e2b4fce9dd40b375ff120863b3a2a4d8House dust concentrations of organophosphate flame retardants in relation to hormone levels and semen quality parametersMeeker, John D.; Stapleton, Heather M.Environmental Health Perspectives (2010), 118 (3), 318-323CODEN: EVHPAZ; ISSN:0091-6765. (U. S. Department of Health and Human Services, Public Health Services)Background: Organophosphate (OP) compds., such as tris(1,3-dichloro-2-propyl) phosphate (TDCPP) and tri-Ph phosphate (TPP), are commonly used as additive flame retardants and plasticizers in a wide range of materials. Although widespread human exposure to OP flame retardants is likely, there is a lack of human and animal data on potential health effects. Objective: We explored relationships of TDCPP and TPP concns. in house dust with hormone levels and semen quality parameters. Methods: We analyzed house dust from 50 men recruited through a U.S. infertility clinic for TDCPP and TPP. Relationships with reproductive and thyroid hormone levels, as well as semen quality parameters, were assessed using crude and multivariable linear regression. Results: TDCPP and TPP were detected in 96% and 98% of samples, resp., with widely varying concns. up to 1.8 mg/g. In models adjusted for age and body mass index, an interquartile range (IQR) increase in TDCPP was assocd. with a 3% [95% confidence interval (CI), -5% to -1%) decline in free thyroxine and a 17% (95% CI, 4-32%) increase in prolactin. There was a suggestive inverse assocn. between TDCPP and free androgen index that became less evident in adjusted models. In the adjusted models, an IQR increase in TPP was assocd. with a 10% (95% CI, 2-19%) increase in prolactin and a 19% (95% CI, -30% to -5%) decrease in sperm concn. Conclusion: OP flame retardants may be assocd. with altered hormone levels and decreased semen quality in men. More research on sources and levels of human exposure to OP flame retardants and assocd. health outcomes are needed.
- 27Meeker, J. D.; Cooper, E. M.; Stapleton, H. M.; Hauser, R. Exploratory Analysis of Urinary Metabolites of Phosphorus-Containing Flame Retardants in Relation to Markers of Male Reproductive Health. Endocr. Disruptors 2013, 1 (1), e26306, DOI: 10.4161/endo.26306There is no corresponding record for this reference.
- 28Preston, E. V.; McClean, M. D.; Claus Henn, B.; Stapleton, H. M.; Braverman, L. E.; Pearce, E. N.; Makey, C. M.; Webster, T. F. Associations between Urinary Diphenyl Phosphate and Thyroid Function. Environ. Int. 2017, 101, 158– 164, DOI: 10.1016/j.envint.2017.01.02028https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXitlKltr0%253D&md5=c0aeb1a55cbc13aec7c5e4be4694e724Associations between urinary diphenyl phosphate and thyroid functionPreston, Emma V.; McClean, Michael D.; Claus Henn, Birgit; Stapleton, Heather M.; Braverman, Lewis E.; Pearce, Elizabeth N.; Makey, Colleen M.; Webster, Thomas F.Environment International (2017), 101 (), 158-164CODEN: ENVIDV; ISSN:0160-4120. (Elsevier Ltd.)Tri-Ph phosphate (TPHP) is a commonly used organophosphate flame retardant and plasticizer with widespread human exposure. Data on health effects of TPHP are limited. Recent toxicol. studies suggest TPHP may alter thyroid function. We used repeated measures to assess the temporal variability in urinary concns. of the TPHP metabolite, di-Ph phosphate (DPHP), and to examine relationships between DPHP concns. and thyroid hormones. We sampled 51 adults at months 1, 6, and 12 from 2010 to 2011. Urine samples were analyzed for DPHP. Serum samples were analyzed for free and total thyroxine (fT4, TT4), total triiodothyronine (TT3), and TSH (TSH). We assessed variability in DPHP using intraclass correlation coeffs. (ICCs) and kappa statistics. We used linear mixed-effects models to examine assocns. between DPHP and thyroid hormones. DPHP was detected in 95% of urine samples. Mean DPHP concns. were 43% higher in women than men. DPHP showed high within-subject variability (ICC range, 0.13-0.39; kappa range, 0.16-0.39). High vs. low (≥ 2.65 vs. < 2.65 ng/mL) DPHP in all participants was assocd. with a 0.43 μg/dL (95% confidence interval: 0.15, 0.72) increase in mean TT4 levels. In sex-stratified analyses, high vs. low DPHP was assocd. with a 0.91 μg/dL (95% CI: 0.47, 1.36) increase in mean TT4 in women. The assocn. was attenuated in men (βeta = 0.19; 95% CI: - 0.15, 0.52). We found no significant assocns. between DPHP and fT4, TT3, or TSH. We found evidence that TPHP exposure may be assocd. with increased TT4 levels, esp. in women.
- 29Scherer, L. D.; Maynard, A.; Dolinoy, D. C.; Fagerlin, A.; Zikmund-Fisher, B. J. The Psychology of “Regrettable Substitutions”: Examining Consumer Judgements of Bisphenol A and Its Alternatives. Health. Risk Soc. 2014, 16 (7–8), 649– 666, DOI: 10.1080/13698575.2014.96968729https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1MvlvF2mtA%253D%253D&md5=06643cf2b9777361ffa8fb34dc4e7564The psychology of 'regrettable substitutions': Examining consumer judgements of Bisphenol A and its alternativesScherer Laura D; Maynard Andrew; Zikmund-Fisher Brian J; Maynard Andrew; Dolinoy Dana C; Fagerlin Angela; Fagerlin Angela; Zikmund-Fisher Brian J; Fagerlin Angela; Zikmund-Fisher Brian J; Fagerlin Angela; Zikmund-Fisher Brian JHealth, risk & society (2014), 16 (7-8), 649-666 ISSN:1369-8575.Bisphenol A is a chemical used to make certain types of plastics and is found in numerous consumer products. Because scientific studies have raised concerns about Bisphenol A's potential impact on human health, it has been removed from some (but not all) products. What many consumers do not know, however, is that Bisphenol A is often replaced with other, less-studied chemicals whose health implications are virtually unknown. This type of situation is known as a potential 'regrettable substitution', because the substitute material might actually be worse than the material that it replaces. Regrettable substitutions are a common concern among policymakers, and they are a real-world manifestation of the tension that can exist between the desire to avoid risk (known possible consequences that might or might not occur) and ambiguity (second-order uncertainty), which is itself aversive. In this article we examine how people make such trade-offs using the example of Bisphenol A. Using data from Study 1, we show that people have inconsistent preferences toward these alternatives and that choice is largely determined by irrelevant contextual factors such as the order in which the alternatives are evaluated. Using data from Study 2 we further demonstrate that when people are informed of the presence of substitute chemicals, labeling the alternative product as 'free' of Bisphenol A causes them to be significantly more likely to choose the alternative despite its ambiguity. We discuss the relevance of these findings for extant psychological theories as well as their implications for risk, policy and health communication.
- 30Zimmerman, J. B.; Anastas, P. T. Toward Substitution with No Regrets. Science 2015, 347 (6227), 1198– 1199, DOI: 10.1126/science.aaa081230https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXls1Squ7Y%253D&md5=4539fc1fe159ead2954d6dadcdab4078Toward substitution with no regretsZimmerman, Julie B.; Anastas, Paul T.Science (Washington, DC, United States) (2015), 347 (6227), 1198-1199CODEN: SCIEAS; ISSN:0036-8075. (American Association for the Advancement of Science)There is no expanded citation for this reference.
- 31FDA (Food and Drug Administration). Cosmetics: FDA authority over cosmetics: how cosmetics are not FDA-approved, but are FDA-regulated https://www.fda.gov/Cosmetics/GuidanceRegulation/LawsRegulations/ucm074162.htm (accessed Feb 25, 2018).There is no corresponding record for this reference.
- 32FDA. Cosmetics: prohibited & restricted ingredients https://www.fda.gov/Cosmetics/GuidanceRegulation/LawsRegulations/ucm127406.htm (accessed Feb 25, 2018).There is no corresponding record for this reference.
- 33FDA. About FDA: Part II: 1938, Food, Drug, Cosmetic Act https://www.fda.gov/AboutFDA/WhatWeDo/History/FOrgsHistory/EvolvingPowers/ucm054826.htm (accessed Feb 25, 2018).There is no corresponding record for this reference.
- 34FTC (Federal Trade Commission). Rule 16 CFR Part 260: Guides for the use of environmental marketing claims https://www.ecfr.gov/cgi-bin/text-idx?SID=ddcda39ef66f41f82d4b3910f7d5082a&mc=true&node=pt16.1.260&rgn=div5 (accessed Sep 17, 2018).There is no corresponding record for this reference.
- 35FDA. Cosmetics: fragrances in cosmetics https://www.fda.gov/Cosmetics/ProductsIngredients/Ingredients/ucm388821.htm (accessed Feb 25, 2018).There is no corresponding record for this reference.
- 36FDA. Cosmetics: phthalates https://www.fda.gov/Cosmetics/ProductsIngredients/Ingredients/ucm128250.htm (accessed Feb 25, 2018).There is no corresponding record for this reference.
- 37FDA. Cosmetic Labeling Guide https://www.fda.gov/cosmetics/labeling/regulations/ucm126444.htm#clgl (accessed Sep 17, 2018).There is no corresponding record for this reference.
- 38OSHA (Occupational Safety and Health Administration). Hazard communication standard: Safety Data Sheets https://www.osha.gov/Publications/OSHA3514.html (accessed Feb 25, 2018).There is no corresponding record for this reference.
- 39EPA. Exposure Factors Handbook ; 2011.There is no corresponding record for this reference.
- 40Mintel. Nail Color and Care: US, January 2016 ; 2016.There is no corresponding record for this reference.
- 412017 Big Book Statistics. NAILS Magazine . 2018.There is no corresponding record for this reference.
- 42Buckley, J. P.; Palmieri, R. T.; Matuszewski, J. M.; Herring, A. H.; Baird, D. D.; Hartmann, K. E.; Hoppin, J. A. Consumer Product Exposures Associated with Urinary Phthalate Levels in Pregnant Women. J. Exposure Sci. Environ. Epidemiol. 2012, 22 (5), 468– 475, DOI: 10.1038/jes.2012.3342https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC38Xht1GjtrjN&md5=9fefccf71d12fcd2d5318b9cc2365fb6Consumer product exposures associated with urinary phthalate levels in pregnant womenBuckley, Jessie P.; Palmieri, Rachel T.; Matuszewski, Jeanine M.; Herring, Amy H.; Baird, Donna D.; Hartmann, Katherine E.; Hoppin, Jane A.Journal of Exposure Science & Environmental Epidemiology (2012), 22 (5), 468-475CODEN: JESEBS; ISSN:1559-0631. (Nature Publishing Group)Human phthalate exposure is ubiquitous, but little is known regarding predictors of urinary phthalate levels. To explore this, 50 pregnant women aged 18-38 years completed two questionnaires on potential phthalate exposures and provided a first morning void. Urine samples were analyzed for 12 phthalate metabolites. Assocns. with questionnaire items were evaluated via Wilcoxon tests and t-tests, and r-squared values were calcd. in multiple linear regression models. Few measured factors were statistically significantly assocd. with phthalate levels. Individuals who used nail polish had higher levels of mono-Bu phthalate (P=0.048) than non-users. Mono-benzyl phthalate levels were higher among women who used eye makeup (P=0.034) or used makeup on a regular basis (P=0.004). Women who used cologne or perfume had higher levels of di-(2-ethylhexyl) phthalate metabolites. Household products, home flooring or paneling, and other personal care products were also assocd. with urinary phthalates. The proportion of variance in metabolite concns. explained by questionnaire items ranged between 0.31 for mono-Et phthalate and 0.42 for mono-n-Me phthalate. Although personal care product use may be an important predictor of urinary phthalate levels, most of the variability in phthalate exposure was not captured by our relatively comprehensive set of questionnaire items. Journal of Exposure Science and Environmental Epidemiol. (2012) 22, 468-475; doi:10.1038/jes.2012.33; published online 4 July 2012.
- 43Hines, E. P.; Calafat, A. M.; Silva, M. J.; Mendola, P.; Fenton, S. E. Concentrations of Phthalate Metabolites in Milk, Urine, Saliva, and Serum of Lactating North Carolina Women. Environ. Health Perspect. 2009, 117 (1), 86– 92, DOI: 10.1289/ehp.1161043https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhvV2nt7k%253D&md5=8ff89074500ababe804c2fff2f6ac779Concentrations of phthalate metabolites in milk, urine, saliva, and serum of lactating North Carolina womenHines, Erin P.; Calafat, Antonia M.; Silva, Manori J.; Mendola, Pauline; Fenton, Suzanne E.Environmental Health Perspectives (2009), 117 (1), 86-92CODEN: EVHPAZ; ISSN:0091-6765. (U. S. Department of Health and Human Services, Public Health Services)Phthalates are ubiquitous in the environment, but concns. in multiple media from breast-feeding U.S. women have not been evaluated. The objective of this study was to accurately measure and compare the concns. of oxidative monoester phthalate metabolites in milk and surrogate fluids (serum, saliva, and urine) of 33 lactating North Carolina women. We analyzed serum, saliva, urine, and milk for the oxidative phthalate metabolites mono(3-carboxypropyl) phthalate, mono(2-ethyl-5-carboxypentyl) phthalate (MECPP), mono(2-ethyl-5-hydroxyhexyl) phthalate, and mono(2-ethyl-5-oxohexyl) phthalate using isotope-diln. high-performance liq. chromatog. tandem mass spectroscopy. Because only urine lacks esterases, we analyzed it for the hydrolytic phthalate monoesters. We detected phthalate metabolites in few milk (< 10%) and saliva samples. MECPP was detected in > 80% of serum samples, but other metabolites were less common (3-22%). Seven of the 10 urinary metabolites were detectable in ≥ 85% of samples. Monoethyl phthalate had the highest mean concn. in urine. Metabolite concns. differed by body fluid (urine > serum > milk and saliva). Questionnaire data suggest that frequent nail polish use, IgA, and fasting serum glucose and triglyceride levels were increased among women with higher concns. of urinary and/or serum phthalate metabolites; motor vehicle age was inversely correlated with certain urinary phthalate concns. Our data suggest that phthalate metabolites are most frequently detected in urine of lactating women and are less often detected in serum, milk, or saliva. Urinary phthalate concns. reflect maternal exposure and do not represent the concns. of oxidative metabolites in other body fluids, esp. milk.
- 44Hines, C. J.; Nilsen Hopf, N. B.; Deddens, J. A.; Calafat, A. M.; Silva, M. J.; Grote, A. A.; Sammons, D. L. Urinary Phthalate Metabolite Concentrations among Workers in Selected Industries: A Pilot Biomonitoring Study. Ann. Occup. Hyg. 2009, 53 (1), 1– 17, DOI: 10.1093/annhyg/men06644https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1MXhtVegtrw%253D&md5=fa504e65beacfc575e4e3b41b8751a5bUrinary Phthalate Metabolite Concentrations among Workers in Selected Industries: A Pilot Biomonitoring StudyHines, Cynthia J.; Nilsen Hopf, Nancy B.; Deddens, James A.; Calafat, Antonia M.; Silva, Manori J.; Grote, Ardith A.; Sammons, Deborah L.Annals of Occupational Hygiene (2009), 53 (1), 1-17CODEN: AOHYA3; ISSN:0003-4878. (Oxford University Press)Phthalates are used as plasticizers and solvents in industrial, medical and consumer products; however, occupational exposure information is limited. We sought to obtain preliminary information on occupational exposures to di-Et phthalate (DEP), di-Bu phthalate (DBP) and di(2-ethylhexyl) phthalate (DEHP) by analyzing for their metabolites in urine samples collected from workers in a cross-section of industries. We also obtained data on metabolites of di-Me phthalate (DMP), benzylbutyl phthalate (BzBP), di-iso-Bu phthalate and di-isononyl phthalate. We recruited 156 workers in 2003-2005 from eight industry sectors. We assessed occupational contribution by comparing end-shift metabolite concns. to the US general population. Evidence of occupational exposure to DEHP was strongest in polyvinyl chloride (PVC) film manufg., PVC compounding and rubber boot manufg. where geometric mean (GM) end-shift concns. of DEHP metabolites exceeded general population levels by 8-, 6- and 3-fold, resp. Occupational exposure to DBP was most evident in rubber gasket, phthalate (raw material) and rubber hose manufg., with DBP metabolite concns. exceeding general population levels by 26-, 25- and 10-fold, resp., whereas DBP exposure in nail-only salons (manicurists) was only 2-fold higher than in the general population. Concns. of DEP and DMP metabolites in phthalate manufg. exceeded general population levels by 4- and >1000-fold, resp. We also found instances where GM end-shift concns. of some metabolites exceeded general population concns. even when no workplace use was reported, e.g. BzBP in rubber hose and rubber boot manufg. In summary, using urinary metabolites, we successfully identified workplaces with likely occupational phthalate exposure. Addnl. work is needed to distinguish occupational from non-occupational sources in low-exposure workplaces.
- 45John, E. M.; Savitz, D. A.; Shy, C. M. Spontaneous Abortions among Cosmetologists. Epidemiology 1994, 5 (2), 147– 155, DOI: 10.1097/00001648-199403000-00004There is no corresponding record for this reference.
- 46Quach, T.; Von Behren, J.; Goldberg, D.; Layefsky, M.; Reynolds, P. Adverse Birth Outcomes and Maternal Complications in Licensed Cosmetologists and Manicurists in California. Int. Arch. Occup. Environ. Health 2015, 88 (7), 823– 833, DOI: 10.1007/s00420-014-1011-0There is no corresponding record for this reference.
- 47Tran, T. M.; Kannan, K. Occurrence of Phthalate Diesters in Particulate and Vapor Phases in Indoor Air and Implications for Human Exposure in Albany, New York, USA. Arch. Environ. Contam. Toxicol. 2015, 68 (3), 489– 499, DOI: 10.1007/s00244-015-0140-047https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2MXjt1aktb0%253D&md5=7ddbce90b29899e79783cc823fb4ec48Occurrence of Phthalate Diesters in Particulate and Vapor Phases in Indoor Air and Implications for Human Exposure in Albany, New York, USATran, Tri Manh; Kannan, KurunthachalamArchives of Environmental Contamination and Toxicology (2015), 68 (3), 489-499CODEN: AECTCV; ISSN:0090-4341. (Springer)Phthalate diesters are used as plasticizers in a wide range of consumer products. Because phthalates have been shown in lab. animal studies to be toxic, human exposure to these chems. is a matter of concern. Nevertheless, little is known about inhalation exposure to phthalates in the United States. In this study, occurrence of nine phthalates was detd. in 60 indoor air samples collected in 2014 in Albany, New York, USA. Airborne particulate and vapor phase samples were collected from various sampling locations by use of a low-vol. air sampler. The median concns. of nine phthalates in air samples collected from homes, offices, labs., schools, salons (hair and nail salons), and public places were 732, 143, 170, 371, 2600, and 354 ng/m3, resp. Di-Et phthalate (DEP) was found at the highest concns., which ranged from 4.83 to 2250 ng/m3 (median 152) followed by di-Bu phthalate, which ranged from 4.05 to 1170 ng/m3 (median 63.3). The median inhalation exposure dose to phthalates was estd. at 0.845, 0.423, 0.203, 0.089, and 0.070 μg/kg-bw/d for infants, toddlers, children, teenagers, and adults, resp. Inhalation is an important pathway of human exposure to DEP.
- 48Weschler, C. J.; Bekö, G.; Koch, H. M.; Salthammer, T.; Schripp, T.; Toftum, J.; Clausen, G. Transdermal Uptake of Diethyl Phthalate and Di(n-Butyl) Phthalate Directly from Air: Experimental Verification. Environ. Health Perspect. 2015, 123 (10), 928– 934, DOI: 10.1289/ehp.140915148https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC1cXls1Smsr0%253D&md5=9fd358f98c03275e58bf98976fdbdf16Transdermal uptake of diethyl phthalate and di(n-butyl) phthalate directly from air: experimental verificationWeschler, Charles J.; Beko, Gabriel; Koch, Holger M.; Salthammer, Tunga; Schripp, Tobias; Toftum, Joern; Clausen, GeoEnvironmental Health Perspectives (2015), 123 (10), 928-934CODEN: EVHPAZ; ISSN:1552-9924. (U. S. Department of Health and Human Services, National Institutes of Health)Background: Fundamental considerations indicate that, for certain phthalate esters, dermal absorption from air is an uptake pathway that is comparable to or greater than inhalation. Yet this pathway has not been exptl. evaluated and has been largely overlooked when assessing uptake of phthalate esters. OBjectives: This study investigated transdermal uptake, directly from air, of di-Et phthalate (DEP) and di(n-butyl) phthalate (DnBP) in humans. Methods: In a series of expts., six human participants were exposed for 6 h in a chamber contg. deliberately elevated air concns. of DEP and DnBP. The participants either wore a hood and breathed air with phthalate concns. substantially below those in the chamber or did not wear a hood and breathed chamber air. All urinations were collected from initiation of exposure until 54 h later. Metabolites of DEP and DnBP were measured in these samples and extrapolated to parent phthalate intakes, cor. for background and hood air exposures. Results: For DEP, the median dermal uptake directly from air was 4.0 μg/(μg/m3 in air) compared with an inhalation intake of 3.8 μg/(μg/m3 in air). For DnBP, the median dermal uptake from air was 3.1 μg/(μg/m3 in air) compared with an inhalation intake of 3.9 μg/(μg/m3 in air). Conclusions: This study shows that dermal uptake directly from air can be a meaningful exposure pathway for DEP and DnBP. For other semivolatile org. compds. (SVOCs) whose mol. wt. and lipid/air partition coeff. are in the appropriate range, direct absorption from air is also anticipated to be significant.
- 49Weschler, C. J.; Nazaroff, W. W. Semivolatile Organic Compounds in Indoor Environments. Atmos. Environ. 2008, 42 (40), 9018– 9040, DOI: 10.1016/j.atmosenv.2008.09.05249https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD1cXhsVSqtrnE&md5=13951f3772d946437b6bc08e9773c36eSemivolatile organic compounds in indoor environmentsWeschler, Charles J.; Nazaroff, William W.Atmospheric Environment (2008), 42 (40), 9018-9040CODEN: AENVEQ; ISSN:1352-2310. (Elsevier Ltd.)Semivolatile org. compds. (SVOCs) are ubiquitous in indoor environments, redistributing from their original sources to all indoor surfaces. Exposures resulting from their indoor presence contribute to detectable body burdens of diverse SVOCs, including pesticides, plasticizers, and flame retardants. This paper critically examines equil. partitioning of SVOCs among indoor compartments. It proceeds to evaluate kinetic constraints on sorptive partitioning to org. matter on fixed surfaces and airborne particles. Analyses indicate that equil. partitioning is achieved faster for particles than for typical indoor surfaces; indeed, for a strongly sorbing SVOC and a thick sorptive reservoir, equil. partitioning is never achieved. Mass-balance considerations are used to develop phys.-science-based models that connect source- and sink-rates to airborne concns. for commonly encountered situations, such as the application of a pesticide or the emission of a plasticizer or flame retardant from its host material. Calcns. suggest that many SVOCs have long indoor persistence, even after the primary source is removed. If the only removal mechanism is ventilation, moderately sorbing compds. (K oa > 1010) may persist indoors for hundreds to thousands of hours, while strongly sorbing compds. (K oa > 1012) may persist for years. The paper concludes by applying the newly developed framework to explore exposure pathways of building occupants to indoor SVOCs. Accumulation of SVOCs as a consequence of direct air-to-human transport is shown to be potentially large, with a max. indoor-air processing rate of 10-20 m3/h for SVOC uptake by human skin, hair and clothing. Levels on human skin calcd. with a simple model of direct air-to-skin transfer agree remarkably well with levels measured in dermal hand wipes for SVOCs possessing a wide range of octanol-air partition coeffs.
- 50Bui, H. S.; Li, C.; Fairneny, S.; Ortega, L.; Kanji, M.; Hariharan, R. Nitrocellulose-Free Nail Polish Compositions. 9713588, 2011.There is no corresponding record for this reference.
- 51Crescimanno, S. Low Haze Film Formers for Top Coat Nail Polish. 9603786, 2016.There is no corresponding record for this reference.
- 52Homma, M.; Homma, V. Nail Polish Composition. 9050272, 2014.There is no corresponding record for this reference.
- 53McFadden, D.; Steffier, L. Nail Polish Composition and Method of Making a Nail Polish. 9248091, 2014.There is no corresponding record for this reference.
- 54Ortega, L.; Bui, H. S.; Hariharan, R.; Kanji, M. Nitrocellulose-Free Nail Polish Compositions. 9517360, 2010.There is no corresponding record for this reference.
- 55Jefferson, J.; Rich, P. Update on Nail Cosmetics. Dermatol. Ther. 2012, 25 (6), 481– 490, DOI: 10.1111/j.1529-8019.2012.01543.x55https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC3s7ptVKktw%253D%253D&md5=fef0f0611ce9da009cbb5e3599df28b1Update on nail cosmeticsJefferson Julie; Rich PhoebeDermatologic therapy (2012), 25 (6), 481-90 ISSN:.Nail cosmetics are used by millions of people worldwide who desire smooth, lustrous nails. The nail cosmetic industry continues to expand to meet increasing consumer demand. In 2011 alone, consumers spent $6.6 billion on nail salon services. Although nail cosmetics are relatively safe, poor application techniques can promote disease, deformity, and allergic and irritant contact dermatitis. The foundation for managing nail cosmetic problems is prevention through education. Familiarity with the procedures and materials used in the nail cosmetic industry is necessary in order to recommend safe nail care strategies.
- 56OSHA. Appendix A to §1910.1200 - health hazard criteria (mandatory) https://www.osha.gov/pls/oshaweb/owadisp.show_document?p_table=STANDARDS&p_id=10100 (accessed Mar 1, 2018).There is no corresponding record for this reference.
- 57BPHC (Boston Public Health Commission). Choose Green & Clean for your next mani-pedi http://www.bphc.org/onlinenewsroom/Blog/Lists/Posts/Post.aspx?List=24ee0d58-2a85-4a4a-855b-f5af9d781627&ID=969&Web=03126e14-4972-4333-b8a3-800cbc1cafce (accessed May 7, 2018).There is no corresponding record for this reference.
- 58Cal EPA. Healthy Nail Salon Recognition Program Guidelines ; 2018.There is no corresponding record for this reference.
- 59California Healthy Nail Salon Collaborative. What is a healthy nail salon? https://cahealthynailsalons.org/what-is-a-healthy-salon-1/ (accessed May 7, 2018).There is no corresponding record for this reference.
- 60King County Healthy Nail Salon Recognition Program. Healthy nail salon recognition program: application form 4–5 stars http://www.hazwastehelp.org/health/nail-salons-recog.aspx (accessed May 4, 2018).There is no corresponding record for this reference.
- 61Oregon OSHA. Nail salons http://osha.oregon.gov/OSHAPubs/4783e.pdf (accessed May 4, 2018).There is no corresponding record for this reference.
- 62OSHA. Health hazards in nail salons https://www.osha.gov/SLTC/nailsalons/chemicalhazards.html (accessed Mar 1, 2018).There is no corresponding record for this reference.
- 63ATSDR (Agency for Toxic Substances and Disease Registry). Toxicological profile for di(e-ethylhexyl)phthalate; 2012.There is no corresponding record for this reference.
- 64Fong, J. P.; Lee, F. J.; Lu, I. S.; Uang, S. N.; Lee, C. C. Estimating the contribution of inhalation exposure to di-2-ethylhexyl phthalate (DEHP) for PVC production workers, using personal air sampling and urinary metabolite monitoring. Int. J. Hyg. Environ. Health 2014, 217 (1), 102– 109, DOI: 10.1016/j.ijheh.2013.04.002There is no corresponding record for this reference.
- 65Kurahashi, N.; Kondo, T.; Omura, M.; Umemura, T.; Ma, M.; Kishi, R. The effects of subacute inhalation of di (2-ethylhexyl) phthalate (DEHP) on the testes of prepubertal Wistar rats. J. Occup. Health 2005, 47 (5), 437– 444, DOI: 10.1539/joh.47.43765https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BD2MXhtFyqtLzJ&md5=fa004cd6b4cdcae4ddcaafb23bcea62eThe effects of subacute inhalation of Di (2-ethylhexyl) phthalate (DEHP) on the testes of prepubertal Wistar ratsKurahashi, Norie; Kondo, Tomoko; Omura, Minoru; Umemura, Tomohiro; Ma, Mingyue; Kishi, ReikoJournal of Occupational Health (2005), 47 (5), 437-444CODEN: JOCHFV; ISSN:1341-9145. (Japan Society for Occupational Health)In animal studies using oral dosing for short periods, di (2-ethylhexyl) phthalate (DEHP) is well known for its reproductive toxicity, esp. for its testicular toxicity. However, extending the period of DEHP exposure in prepubertal rats resulted in significant increases in testosterone. This suggests that the reproductive effect of DEHP might be assocd. with the timing and the term of exposure. Moreover, the route of exposure may induce differences in its effect because tissue levels of metabolites of DEHP after inhalation are thought to be different from those after oral administration. We researched the effects of inhalation of DEHP on testes of prepubertal rats. These results showed that inhalation of DEHP by 4-wk-old male Wistar rats at doses of 5 or 25 mg/m3, 6 h per day, for 4 and 8 wk significantly increased the concn. of plasma testosterone and wt. of seminal vesicles. However, the concn. of LH, follicular stimulating hormone (FSH) and the expression of mRNAs of androgen biosynthesis enzyme, cytochrome P 450 cholesterol side-chain-cleavage enzyme (P450scc), 3β-hydroxysteroid dehydrogenase (3β-HSD), cytochrome P 450 17α-hydroxylase/17, 20 lyase (CYP17) and aromatase (CYP19) did not change. Rats with precocious testes did not increase in any of the DEHP groups. We also found that the estd. ED in this study was less than those reported in previous studies which used oral dosing. Our study showed that inhaled DEHP increased plasma testosterone concns. in prepubertal rats and suggested that their effects were more sensitive to inhalation of DEHP than oral dosing.
- 66Rasmussen, L. M.; Sen, N.; Vera, J. C.; Liu, X.; Craig, Z. R. Effects of in Vitro Exposure to Dibutyl Phthalate, Mono-Butyl Phthalate, and Acetyl Tributyl Citrate on Ovarian Antral Follicle Growth and Viability. Biol. Reprod. 2017, 96 (5), 1105– 1117, DOI: 10.1095/biolreprod.116.14469166https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BC1crlsFWrsg%253D%253D&md5=5a976d3870376017fb50a5797d3b8813Effects of in vitro exposure to dibutyl phthalate, mono-butyl phthalate, and acetyl tributyl citrate on ovarian antral follicle growth and viabilityRasmussen Lindsay M; Sen Nivedita; Vera Jahaira C; Liu Xiaosong; Craig Zelieann RBiology of reproduction (2017), 96 (5), 1105-1117 ISSN:.Dibutyl phthalate (DBP) is present in consumer products and the coating of some oral medications. Acetyl tributyl citrate (ATBC) has been proposed as an alternative to DBP because DBP causes endocrine disruption in animal models. Following ingestion, DBP is converted to its main metabolite mono-butyl phthalate (MBP) which has been detected in >90% of human follicular fluid samples. Previous studies show that DBP reduces the number of antral follicles present in the ovaries of mice. Thus, this study was designed to evaluate the effects of DBP, MBP, and ATBC on in vitro growth and viability of mouse ovarian antral follicles. Antral follicles were isolated from CD-1 females (PND32-37) and treated with vehicle, DBP, MBP, or ATBC (starting at 0.001 and up to 1000 μg/ml for DBP; 24-72 h). Follicle diameter, ATP production, qPCR, and TUNEL were used to measure follicle growth, viability, cell cycle and apoptosis gene expression, and cell death-associated DNA fragmentation, respectively. While MBP did not cause toxicity, DBP exposure at ≥10 μg/ml resulted in growth inhibition followed by cytoxicity at ≥500 μg/ml. ATBC increased the number of nongrowing follicles at 0.01 μg/ml and did not affect ATP production, but increased TUNEL positive area in treated follicles. Gene expression results suggest that cytotoxicity in DBP-treated follicles occurs via activation of cell cycle arrest prior to follicular death. These findings suggest that concentrations of DBP ≥10 μg/ml are detrimental to antral follicles and that ATBC should be examined further as it may disrupt antral follicle function at low concentrations.
- 67Rasmussen, L. M.; Sen, N.; Liu, X.; Craig, Z. R. Effects of Oral Exposure to the Phthalate Substitute Acetyl Tributyl Citrate on Female Reproduction in Mice. J. Appl. Toxicol. 2017, 37 (6), 668– 675, DOI: 10.1002/jat.341367https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC28XhvVymt7vK&md5=a59ef5ba3325f3abff3b9b419b179a1aEffects of oral exposure to the phthalate substitute acetyl tributyl citrate on female reproduction in miceRasmussen, Lindsay M.; Sen, Nivedita; Liu, Xiaosong; Craig, Zelieann R.Journal of Applied Toxicology (2017), 37 (6), 668-675CODEN: JJATDK; ISSN:0260-437X. (John Wiley & Sons Ltd.)Acetyl tri-Bu citrate (ATBC), is a phthalate substitute used in food and medical plastics, cosmetics and toys. Although systemically safe up to 1000 mg kg-1 day-1, its ability to cause reproductive toxicity in females at levels below 50 mg kg-1 day-1 has not been examd. This study evaluated the effects of lower ATBC exposures on female reprodn. using mice. Adult CD-1 females (n = 7-8 per treatment) were dosed orally with tocopherol-stripped corn oil (vehicle), 5 or 10 mg kg-1 day-1 ATBC daily for 15 days, and then bred with a proven breeder male. ATBC exposure did not alter body wts., estrous cyclicity, and gestational and litter parameters. Relative spleen wt. was slightly increased in the 5 mg kg-1 day-1 group. ATBC at 10 mg kg-1 day-1 targeted ovarian follicles and decreased the no. of primordial, primary and secondary follicles present in the ovary. These findings suggest that low levels of ATBC may be detrimental to ovarian function, thus, more information is needed to understand better the impact of ATBC on female reprodn.
- 68Strajhar, P.; Tonoli, D.; Jeanneret, F.; Imhof, R. M.; Malagnino, V.; Patt, M.; Kratschmar, D. V.; Boccard, J.; Rudaz, S.; Odermatt, A. Steroid Profiling in H295R Cells to Identify Chemicals Potentially Disrupting the Production of Adrenal Steroids. Toxicology 2017, 381, 51– 63, DOI: 10.1016/j.tox.2017.02.01068https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC2sXjsl2lsb8%253D&md5=2e9cb701d5814d8597fa3b0c51d8dc38Steroid profiling in H295R cells to identify chemicals potentially disrupting the production of adrenal steroidsStrajhar, Petra; Tonoli, David; Jeanneret, Fabienne; Imhof, Raphaella M.; Malagnino, Vanessa; Patt, Melanie; Kratschmar, Denise V.; Boccard, Julien; Rudaz, Serge; Odermatt, AlexToxicology (2017), 381 (), 51-63CODEN: TXCYAC; ISSN:0300-483X. (Elsevier Ltd.)The validated OECD test guideline 456 based on human adrenal H295R cells promotes measurement of testosterone and estradiol prodn. as read-out to identify potential endocrine disrupting chems. This study aimed to establish optimal conditions for using H295R cells to detect chems. interfering with the prodn. of key adrenal steroids. H295R cells' supernatants were characterized by liq. chromatog.-mass spectrometry (LC-MS)-based steroid profiling, and the influence of exptl. conditions including time and serum content was assessed. Steroid profiles were detd. before and after incubation with ref. compds. and chems. to be tested for potential disruption of adrenal steroidogenesis. The H295R cells cultivated according to the OECD test guideline produced progestins, glucocorticoids, mineralocorticoids and adrenal androgens but only very low amts. of testosterone. However, testosterone contained in Nu-serum was metabolized during the 48 h incubation. Thus, inclusion of pos. and neg. controls and a steroid profile of the complete medium prior to the expt. (t = 0 h) was necessary to characterize H295R cells' steroid prodn. and indicate alterations caused by exposure to chems. Among the tested chems., octyl methoxycinnamate and acetyl tributylcitrate resembled the corticosteroid induction pattern of the pos. control torcetrapib. Gene expression anal. revealed that octyl methoxycinnamate and acetyl tributylcitrate enhanced CYP11B2 expression, although less pronounced than torcetrapib. Further expts. need to assess the toxicol. relevance of octyl methoxycinnamate- and acetyl tributylcitrate-induced corticosteroid prodn. In conclusion, the extended profiling and appropriate controls allow detecting chems. that act on steroidogenesis and provide initial mechanistic evidence for prioritizing chems. for further investigations.
- 69Takeshita, A.; Igarashi-Migitaka, J.; Nishiyama, K.; Takahashi, H.; Takeuchi, Y.; Koibuchi, N. Acetyl Tributyl Citrate, the Most Widely Used Phthalate Substitute Plasticizer, Induces Cytochrome p450 3a through Steroid and Xenobiotic Receptor. Toxicol. Sci. 2011, 123 (2), 460– 470, DOI: 10.1093/toxsci/kfr17869https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A528%3ADC%252BC3MXht1eiu7jN&md5=8e776e514982e1fb73fbb0c8dc3874cdAcetyl Tributyl Citrate, the Most Widely Used Phthalate Substitute Plasticizer, Induces through Steroid and Xenobiotic ReceptorTakeshita, Akira; Igarashi-Migitaka, Junko; Nishiyama, Kazusa; Takahashi, Hideyo; Takeuchi, Yasuhiro; Koibuchi, NoriyukiToxicological Sciences (2011), 123 (2), 460-470CODEN: TOSCF2; ISSN:1096-0929. (Oxford University Press)Steroid and xenobiotic receptor (SXR) is activated by endogenous and exogenous chems. including steroids, bile acids, and prescription drugs. SXR is highly expressed in the liver and intestine, where it regulates cytochrome P 450 3A4 (CYP3A4), which in turn controls xenobiotic and endogenous steroid hormone metab. However, it is unclear whether Food and Drug Administration (FDA)-approved plasticizers exert such activity. In the present study, the authors evaluated the effects of FDA-approved plasticizers on SXR-mediated transcription in vitro by luciferase reporter, SXR-coactivator interaction, quant. real-time PCR anal. of CYP3A4 expression, CYP3A4 enzyme activity assays, and SXR knockdown. Rats, treated with gavage and i.p. injection of compds., were examd. for CYP3A1 expression in vivo. The authors found that 4 of 8 FDA-approved plasticizers increased SXR-mediated transcription. In particular, acetyl tri-Bu citrate (ATBC), an industrial plasticizer widely used in products such as food wrap, vinyl toys, and pharmaceutical excipients, strongly activated human and rat SXR. ATBC increased CYP3A4 mRNA levels and enzyme activity in the human intestinal cells but not in human liver cells. Similarly, CYP3A1 mRNA levels were increased in the intestine but not the liver of ATBC-treated rats. These in vitro and in vivo results suggest that ATBC specifically induces CYP3A in the intestine by activating SXR. We suggest that ATBC-contg. products be used cautiously because they may alter metab. of endogenous steroid hormones and prescription drugs.
- 70Baran, R. Nail Cosmetics: Allergies and Irritations. Am. J. Clin. Dermatol. 2002, 3 (8), 547– 555, DOI: 10.2165/00128071-200203080-0000570https://chemport.cas.org/services/resolver?origin=ACS&resolution=options&coi=1%3ACAS%3A280%3ADC%252BD38vpslCguw%253D%253D&md5=5a487679f1251f0f4caaafbaca41501aNail cosmetics: allergies and irritationsBaran RobertAmerican journal of clinical dermatology (2002), 3 (8), 547-55 ISSN:1175-0561.Recent precise figures are not available for the number of adverse reactions related to the use of nail care products. Reactions to nail cosmetic procedures may be divided into reactions at the site of application to the nail itself and ectopic reactions, when the hand transfers a small amount of nail cosmetic to other areas of the skin. Fingernail coatings encompass two types: coatings that harden upon evaporation (nail enamel, base coat, top coat); and coatings that polymerize (sculptured nails, light-curing gels, preformed artificial nails, nail mending and nail wrapping). The test battery enables us to distinguish allergic reactions from irritant reactions. Interestingly, some reactions, such as distant allergic contact dermatitis, are more frequent with nail enamel than with coatings that polymerize. On the other hand, the latter are greater offenders in the nail area. Nail hardeners may just be modified nail enamels containing nylon fibers, acrylate resin and hydrolyzed proteins. Others may contain up to 5% formaldehyde tissue fixative (which can have adverse effects on the nail), but are designed in the US to be applied only to the free edge of the nail while the skin is shielded. Caution is necessary in interpreting formaldehyde patch testing reactions.
- 71EPA. Design for the Environment Program Alternatives Assessment Criteria for Hazard Evaluation ; 2011.There is no corresponding record for this reference.
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