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Phthalates – Targeted Search for Epidemiological Studies

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468 References Were Found:

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Mediation analysis for the relationship between urinary phthalate metabolites and type 2 diabetes via oxidative stress in a population in Jeddah, Saudi Arabia

Authors: Li, AJ; Martinez-Moral, MP; Al-Malki, AL; Al-Ghamdi, MA; Al-Bazi, MM; Kumosani, TA; Kannan, K (2019) Environment International 126:153-161. HERO ID: 5043620

[Less] Human exposure to phthalates is ubiquitous and has received considerable attention due to their association . . . [More] Human exposure to phthalates is ubiquitous and has received considerable attention due to their association with adverse health outcomes, including type 2 diabetes mellitus (T2DM). Nevertheless, earlier studies that link phthalate exposure to T2DM yielded ambiguous results. Furthermore, studies that associate phthalate exposure with oxidative stress and then with T2DM are scant. In this diabetic case-control study, urine samples collected from 101 individuals aged 28-68 years from Jeddah, Saudi Arabia, were analyzed to determine 20 phthalate metabolites (PhMs) and seven oxidative stress biomarkers (OSBs). Unconditional logistic regression was used to estimate odds ratios for the association between diabetes and urinary PhMs and OSBs in participants, stratified by age, gender, nationality, smoking status, occupation, and urinary creatinine. Twelve PhMs and five OSBs were found at detection rates above 50%, with geometric mean concentrations of 0.61-100 and 0.35-10.7 ng/mL (1.04-171 and 0.61-18.6 μg/g creatinine), respectively. Almost all exposures were significantly higher in diabetic cases than in controls. The 12 PhMs were positively associated with higher urinary concentrations of 8-hydroxy-2'-deoxyguanosine (8-OHdG) and 8-iso-prostaglandin F2α (8-PGF2α). Individuals in the 3rd and/or 4th quartile(s) for urinary concentrations of PhMs and OSBs showed 3.7- and 7.3-fold increase, respectively, in the odds of having diabetes compared with those in the 1st quartile. The rank order of association of PhMs/OSBs with diabetes followed the order of: mEP ≈ mBP > mEHP > mCPP > mECPP ≈ mEOHP ≈ mEHHP ≈ mIBP ≈ mMP > mCMHP ≈ mBzP and 8-OHdG > 8-PGF2α ≈ 15-PGF2α. The relationship between phthalate exposure and risk of developing T2DM was mediated in part by phthalate-induced oxidative stress, especially 8-OHdG. Our study suggests that human exposure to phthalates is associated with increased oxidative stress which mediates the development of T2DM.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Exposure to phthalate-containing prescription drugs and the risk of colorectal adenocarcinoma: A Danish nationwide case-control study

Authors: Ennis, ZN; Pottegård, A; Ahern, TP; Hallas, J; Damkier, P (2019) Pharmacoepidemiology and Drug Safety 28:528-535. HERO ID: 5432848

[Less] PURPOSE: Some drug products contain phthalates as excipients, and in vitro studies . . . [More] PURPOSE: Some drug products contain phthalates as excipients, and in vitro studies have demonstrated that phthalates interfere with cellular mechanisms involved in colorectal cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and risk of colorectal adenocarcinomas.

METHODS: We used the Danish Cancer Registry to identify all patients with incident colorectal adenocarcinoma from 2008 to 2015 (n = 25 814). Each cancer case was matched to ten population controls. Linking information from Danish registers, we quantified cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP) and dibutyl phthalate (DBP) as well as enteric phthalate polymers from orally administered drugs. The association between cumulative phthalate exposure and colorectal cancer was estimated using conditional logistic regression.

RESULTS: Cumulative exposure to ortho-phthalates exceeding 500 mg was associated with lower odds of colorectal cancer diagnosis (ORadj  = 0.89; 95% CI, 0.81-0.96). Similar associations were observed for all DEP exposure exceeding 500 mg. Subgroup analysis excluding NSAID users, demonstrated that ortho-phthalate exposure was positively associated with colorectal cancer (ORadj  = 1.26; 95% CI, 1.05-1.51).

CONCLUSION: We found an apparent overall protective effect of cumulative phthalate exposure from drug excipients for colorectal adenocarcinoma. Omitting NSAID users reversed the signal and suggested a slightly increased risk associated with high cumulative ortho-phthalate exposure.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Use of phthalate-containing prescription drugs and the risk of gastric cancer: a Danish nationwide case-control study

Authors: Nymand Ennis, Z; Arnspang Pedersen, S; Rix Hansen, M; Pottegård, A; Patrick Ahern, T; Hallas, J; Damkier, P (2019) Acta Oncologica 58:1-7. HERO ID: 5053638

[Less] BACKGROUND: Phthalates are used as excipients in some drug products, and up to a 50-fold . . . [More] BACKGROUND: Phthalates are used as excipients in some drug products, and up to a 50-fold increased urinary excretion of phthalate metabolites compared to non-users has been demonstrated in users of such products. In vitro studies have demonstrated that phthalates stimulate mechanisms involved in gastric cancer development. We therefore examined the association between cumulative phthalate exposure from drug products and the risk of gastric adenocarcinomas.

METHODS: Using the Danish Cancer Registry, we identified all patients with incident gastric adenocarcinoma from 2008 to 2015 (n = 1525). Cancer cases were matched to 10 controls. Linking information retrieved from nationwide Danish registries, we determined individual cumulative phthalate exposure to the ortho-phthalates diethyl phthalate (DEP), dibutyl phthalate (DBP) and enteric phthalate polymers from prescription drugs. The association between cumulative phthalate exposure and gastric adenocarcinoma was estimated using conditional logistic regression, adjusting for socioeconomical status and drugs or comorbidities known or suspected to modify the risk of gastric adenocarcinoma.

RESULTS: No association was seen for the risk of gastric adenocarcinomas among individuals with high cumulative exposure to ortho-phthalates (exceeding 500 mg) (ORadj 1.22, 95% CI: 0.84-1.77). Likewise, no associations were observed individually for DEP (ORadj 1.06 95% CI: 0.63-1.76) or DBP (ORadj 1.32 95% CI: 0.78-2.23). Cumulative exposure to enteric phthalate polymers exceeding 10,000 mg, did not reveal an association with gastric adenocarcinoma (ORadj 0.79, 95% CI: 0.54-1.16) and no association was seen for individual compounds. Additionally, no dose-response pattern was observed across exposure strata (p = .39, test for trend).

CONCLUSION: We did not find an increased risk of gastric adenocarcinoma among Danish users of phthalate-containing drug products. Our study is limited by a low number of cases exposed to high cumulative doses of phthalates.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Identifying periods of susceptibility to the impact of phthalates on children's cognitive abilities

Authors: Li, N; Papandonatos, GD; Calafat, AM; Yolton, K; Lanphear, BP; Chen, A; Braun, JM (2019) Environmental Research 172:604-614. HERO ID: 5053633

[Less] BACKGROUND: Early-life phthalate exposures may adversely affect children's neurodevelopment by disrupting . . . [More] BACKGROUND:
Early-life phthalate exposures may adversely affect children's neurodevelopment by disrupting thyroid function, reducing gonadal hormone levels, or altering fatty acid concentrations in the brain. This study aimed to identify periods of heightened susceptibility during gestation, infancy, and childhood to the impact of phthalates on children's cognitive abilities.

METHODS:
We used data from 253 mother-child pairs in the Health Outcomes and Measures of the Environment (HOME) Study (Cincinnati, Ohio), a longitudinal pregnancy and birth cohort. We quantified urinary concentrations of 11 phthalate metabolites in samples collected twice during gestation and 6 times during study visits when children were aged 1-8 years using a modified method of on-line solid phase extraction coupled with isotope dilution-high performance liquid chromatography-tandem mass spectrometry. We assessed children's intelligence (IQ) at ages 5 and 8 years using the Wechsler Preschool and Primary Scale of Intelligence-III and Wechsler Intelligence Scale for Children-IV, respectively. We estimated covariate-adjusted associations between a 1-standard deviation increase in log10-transformed urinary phthalate metabolite concentrations at each visit and children's IQ, adjusting for demographic, perinatal, and child factors; we tested for differences in these associations across visits using multiple informant models.

RESULTS:
Associations between some phthalate metabolites and IQ varied by visit (phthalate x visit interaction p-values<0.20). The sum of di(2-ethylhexyl) phthalate metabolites (ΣDEHP), mono(3-carboxypropyl) phthalate, and monoethyl phthalate at age 3 years, and monobenzyl phthalate at 16 weeks gestation and child ages 3, 5, and 8 years were inversely associated with children's full-scale IQ. For example, each 1-standard deviation increase in ΣDEHP at age 3 was associated with a 1.9-point decrease in full-scale IQ (95% confidence interval: -3.7, -0.2). Mono-n-butyl phthalate and mono-isobutyl phthalate at age 4 years were positively associated with children's full-scale IQ.

CONCLUSION:
Urinary concentrations of several phthalate metabolites at age 3 years, compared to other time periods, were more strongly associated with decreased cognitive abilities in these children.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

In utero effects of maternal phthalate exposure on male genital development

Authors: Wineland, RJ; Bloom, MS; Cruze, L; Butts, CD; Wenzel, AG; Unal, ER; Kohno, S; Willan, KB; Brock, JW; Newman, RB (2019) HERO ID: 5043474

[Less] BACKGROUND: Phthalates are used extensively in commercial and personal care products . . . [More] BACKGROUND: Phthalates are used extensively in commercial and personal care products and maternal exposure is ubiquitous. Phthalates are anti-androgenic, but the potential effects of phthalates on male penile development have not been assessed in utero.

OBJECTIVE: The study aims to investigate the association between early pregnancy phthalate exposure and fetal penile development, overall and by race.

METHODS: Prospective cohort study of women with singleton pregnancies presenting for prenatal ultrasound between 18 and 22 weeks' gestation. Maternal urine samples were assayed for eight phthalate monoester metabolites. We used maternal phthalate levels at 18 to 22 weeks' gestation as predictors of fetal size using multiple linear regression models, adjusted for fetal gestational age, maternal age, race, smoking, and education. We incorporated a phthalate by race interaction into a second set of regression models.

RESULTS: We detected statistically significant race interactions for continuous phthalates with penile width. Race interactions were also suggested for penile length and volume using tertiles of phthalates with point estimates generally positive for whites and negative for African Americans.

CONCLUSION: Penile development is significantly influenced by race, and the impact of maternal phthalates on penile measurements also varies by race. Maternal phthalate exposure can adversely affect in utero penile growth and development, especially among African Americans.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Methodological approaches to analyzing IVF data with multiple cycles

Authors: Yland, J; Messerlian, C; Mínguez-Alarcón, L; Ford, JB; Hauser, R; Williams, SPL; EARTH Study Team (2019) Human Reproduction 34:549-557. HERO ID: 5043574

[Less] STUDY QUESTION: Which methodological approaches are most appropriate for analyzing . . . [More] STUDY QUESTION: Which methodological approaches are most appropriate for analyzing IVF data with multiple cycles in the context of a binary outcome?

SUMMARY ANSWER: Both mixed effect models and generalized estimating equation (GEE) modeling approaches can account for multiple IVF cycles and may reduce bias over first-cycle only approaches, but CIs were narrowest with cluster-weighted generalized estimating equation models (CWGEE).

WHAT IS KNOWN ALREADY: There is a lack of consensus among investigators regarding how to best incorporate data from multiple cycles and whether to present odds or risks in the analysis of IVF data. Failure to account for correlated outcomes within individuals and informative cluster size may lead to invalid CIs and biased estimates.

STUDY DESIGN, SIZE, DURATION: The Environment and Reproductive Health (EARTH) Study is an ongoing prospective cohort study of subfertile couples conducted at an academic medical center. This cohort was established in 2004 and follows couples seeking treatment for infertility throughout the course of their treatment and pregnancy.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Women aged 18-46 years enrolled in the EARTH Study from 2004 to 2017 who initiated at least one IVF cycle were eligible. Cycle initiation was defined as beginning ovulation induction with the intent to progress through an IVF or ICSI cycle. This analysis included 442 women undergoing 642 cycles who met the study inclusion criteria. We compared the results and interpretations of log-binomial and logistic models restricting to the first cycle, as well as mixed effects models, unweighted GEE models, and CWGEE models including all cycles. This analysis was conducted for two distinct exposures: maternal age at cycle initiation, and maternal preconception urinary concentrations of di(2-ethylhexyl) phthalate (DEHP) metabolites (previously reported to be associated with a decreased probability of live birth).

MAIN RESULTS AND THE ROLE OF CHANCE: In general, the CIs were widest for mixed effects models and narrowest for CWGEE models. Further, in models evaluating the sum of urinary concentrations of DEHP metabolites (∑DEHP, available for 91% of women), the point estimates were surprisingly different between the first-cycle and multiple-cycle models. We observed significant associations between maternal age and live birth in all models. However, we observed no associations between ∑DEHP and live birth.

LIMITATIONS, REASONS FOR CAUTION: This analysis was limited to an example dataset in which the true effect of any exposure is unknown. While this allows us to observe model performance in the context of real data, future analyses should be conducted within simulated datasets under various assumptions to further evaluate the appropriateness of each approach. In addition, we did not address differential loss to follow-up in our statistical approaches.

WIDER IMPLICATIONS OF THE FINDINGS: The use of CWGEE models should be more widely considered in the analysis of IVF data with multiple cycles per woman. The CWGEE approach is computationally simple, addresses non-ignorable (informative) cluster size, and is robust against mis-specification of the underlying covariance structure. Among the methods compared in this analysis, CWGEE models generally yielded the narrowest CIs, possibly indicating the most precise estimates. We also stress the importance of estimating risks rather than odds in the analysis of IVF data.

STUDY FUNDING/COMPETING INTEREST(S): The project was funded by Grants (R01ES022955, R01ES009718, and P30ES000002) from the National Institutes of Health. None of the authors has any conflicts of interest to declare.

Journal Article
Journal Article

Early-life exposome and lung function in children in Europe: an analysis of data from the longitudinal, population-based HELIX cohort

Authors: Agier, L; Basagaña, X; Maitre, L; Granum, B; Bird, PK; Casas, M; Oftedal, B; Wright, J; Andrusaityte, S; de Castro, M; Cequier, E; Chatzi, L; Donaire-Gonzalez, D; Grazuleviciene, R; Haug, LS; Sakhi, AK; Leventakou, V; Mceachan, R; Nieuwenhuijsen, M; Petraviciene, I; Robinson, O; Roumeliotaki, T; Sunyer, J; Tamayo-Uria, I; Thomsen, C; Urquiza, J; Valentin, A; Slama, R; Vrijheid, M; Siroux, V (2019) The Lancet Planetary Health 3:e81-e92. HERO ID: 5043613

[Less] BACKGROUND: Several single-exposure studies have documented possible effects of environmental . . . [More] BACKGROUND: Several single-exposure studies have documented possible effects of environmental factors on lung function, but none has relied on an exposome approach. We aimed to evaluate the association between a broad range of prenatal and postnatal lifestyle and environmental exposures and lung function in children.

METHODS: In this analysis, we used data from 1033 mother-child pairs from the European Human Early-Life Exposome (HELIX) cohort (consisting of six existing longitudinal birth cohorts in France, Greece, Lithuania, Norway, Spain, and the UK of children born between 2003 and 2009) for whom a valid spirometry test was recorded for the child. 85 prenatal and 125 postnatal exposures relating to outdoor, indoor, chemical, and lifestyle factors were assessed, and lung function was measured by spirometry in children at age 6-12 years. Two agnostic linear regression methods, a deletion-substitution-addition (DSA) algorithm considering all exposures simultaneously, and an exposome-wide association study (ExWAS) considering exposures independently, were applied to test the association with forced expiratory volume in 1 s percent predicted values (FEV1%). We tested for two-way interaction between exposures and corrected for confounding by co-exposures.

FINDINGS: In the 1033 children (median age 8·1 years, IQR 6·5-9·0), mean FEV1% was 98·8% (SD 13·2). In the ExWAS, prenatal perfluorononanoate (p=0·034) and perfluorooctanoate (p=0·030) exposures were associated with lower FEV1%, and inverse distance to nearest road during pregnancy (p=0·030) was associated with higher FEV1%. Nine postnatal exposures were associated with lower FEV1%: copper (p=0·041), ethyl-paraben (p=0·029), five phthalate metabolites (mono-2-ethyl 5-carboxypentyl phthalate [p=0·016], mono-2-ethyl-5-hydroxyhexyl phthalate [p=0·023], mono-2-ethyl-5-oxohexyl phthalate [p=0·0085], mono-4-methyl-7-oxooctyl phthalate [p=0·040], and the sum of di-ethylhexyl phthalate metabolites [p=0·014]), house crowding (p=0·015), and facility density around schools (p=0·027). However, no exposure passed the significance threshold when corrected for multiple testing in ExWAS, and none was selected with the DSA algorithm, including when testing for exposure interactions.

INTERPRETATION: Our systematic exposome approach identified several environmental exposures, mainly chemicals, that might be associated with lung function. Reducing exposure to these ubiquitous chemicals could help to prevent the development of chronic respiratory disease.

FUNDING: European Community's Seventh Framework Programme (HELIX project).

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Urinary Phthalate Biomarker Concentrations and Postmenopausal Breast Cancer Risk

Authors: Reeves, KW; Santana, MD; Manson, JE; Hankinson, SE; Zoeller, RT; Bigelow, C; Sturgeon, SR; Spiegelman, D; Tinker, L; Luo, J; Chen, B; Meliker, J; Bonner, MR; Cote, ML; Cheng, TD; Calafat, AM (2019) Journal of the National Cancer Institute. HERO ID: 5043615

[Less] Background: Growing laboratory and animal model evidence supports the potentially carcinogenic . . . [More] Background: Growing laboratory and animal model evidence supports the potentially carcinogenic effects of some phthalates, chemicals used as plasticizers in a wide variety of consumer products, including cosmetics, medications, and vinyl flooring. However, prospective data on whether phthalates are associated with human breast cancer risk are lacking.

Methods: We conducted a nested case-control study within the Women's Health Initiative (WHI) prospective cohort (N = 419 invasive cases and 838 controls). Controls were matched 2:1 to cases on age, enrollment date, follow-up time, and WHI study group. We quantified thirteen phthalate metabolites and creatinine in two or three urine samples per participant over one to three years. Multivariable conditional logistic regression analysis was used to estimate odds ratios and 95% confidence intervals (OR, 95% CI) for breast cancer risk associated with each phthalate biomarker over up to 19 years of follow-up.

Results: Overall, we did not observe statistically significant positive associations between phthalate biomarkers and breast cancer risk in multivariable analyses (e.g. 4th vs 1st quartile of diethylhexyl phthalate OR 1.03, 95% CI 0.91 - 1.17). Results were generally similar in analyses restricted to disease subtypes, to non-users of postmenopausal hormone therapy, stratified by body mass index, or to cases diagnosed within three, five, or ten years.

Conclusions: In the first prospective analysis of phthalates and postmenopausal breast cancer, phthalate biomarker concentrations did not result in an increased risk of developing invasive breast cancer.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Prenatal Exposure to Select Phthalates and Phenols and Associations with Fetal and Placental Weight among Male Births in the EDEN Cohort (France)

Authors: Philippat, C; Heude, B; Botton, J; Alfaidy, N; Calafat, AM; Slama, R; EDEN Mother–Child Cohort Study Group (2019) Environmental Health Perspectives 127:17002. HERO ID: 5041225

[Less] BACKGROUND: The placenta performs crucial physiological functions to ensure normal . . . [More] BACKGROUND: The placenta performs crucial physiological functions to ensure normal fetal development. Few epidemiological studies investigated placental weight sensitivity to phthalates and phenols.

OBJECTIVE: Our goal was to explore whether maternal exposure to select phthalates and phenols is associated with changes in placental weight at birth and in placental–to–birth weight ratio (PFR).

METHODS: Placental weight and birth weight were available for 473 mother–son pairs in the EDEN (Etude des Déterminants pré et postnatals du développement et de la santé de l'Enfant) cohort for whom 9 phenols (4 parabens, 2 dichlorophenols, triclosan, benzophenone-3, bisphenol A) and 11 phthalate metabolites were measured in spot urine samples collected between weeks 23 and 29 of gestation. We used adjusted Elastic Net penalized regression models (ENET) to select biomarkers associated with placental weight, birth weight and PFR. Unpenalized effect estimates were then obtained by fitting linear regression models simultaneously adjusted for the ENET-selected biomarkers and a priori chosen confounders.

RESULTS: The multipollutant ENET model for placental weight retained four biomarkers: triclosan and monocarboxy-isononyl phthalate (MCNP), which were negatively associated with placental weight, and benzophenone-3 and the sum of parabens, which were positively associated with this outcome. The ENET model for PFR retained two phthalate metabolites [MCNP and monocarboxy-isooctyl phthalate (MCOP)], which were negatively associated with this outcome.

DISCUSSION: The positive association between the sum of parabens and placental weight was consistent with results of a previous study among 49 male births. Our results provide preliminary evidence of possible associations between other compounds such as triclosan, benzophenone-3, MCNP, and MCOP and both placental weight and PFR. These associations were not reported in previous studies and should be seen as hypothesis generating. Studies relying on repeated assessments of exposure in prospective mother–child cohorts are needed to substantiate the plausibility of the hypotheses generated by our results. https://doi.org/10.1289/EHP3523.

The "refereed" or "peer review" status of a journal comes from the Ulrichsweb Global Serials Directory (http://ulrichsweb.serialssolutions.com/), as supplied by the publisher. The term refers to the system of critical evaluation of manuscripts/articles by professional colleagues or peers. The content of refereed publications is sanctioned, vetted, or otherwise approved by a peer-review or editorial board. The peer-review and evaluation system is utilized to protect, maintain, and raise the quality of scholarly material published in serials. Publications subject to the referee process are assumed, then, to contain higher quality content than those that are not.
Peer Reviewed Journal Article

Association of phthalates, parabens and phenols found in personal care products with pubertal timing in girls and boys

Authors: Harley, KG; Berger, KP; Kogut, K; Parra, K; Lustig, RH; Greenspan, LC; Calafat, AM; Ye, X; Eskenazi, B (2019) Human Reproduction 34:109-117. HERO ID: 5043449

[Less] STUDY QUESTION: Are in-utero or peripubertal exposures to phthalates, parabens and . . . [More] STUDY QUESTION: Are in-utero or peripubertal exposures to phthalates, parabens and other phenols found in personal care products associated with timing of pubertal onset in boys and girls?

SUMMARY ANSWER: We found some associations of altered pubertal timing in girls, but little evidence in boys.

WHAT IS KNOWN ALREADY: Certain chemicals in personal care and consumer products, including low molecular weight phthalates, parabens and phenols, or their precursors, are associated with altered pubertal timing in animal studies.

STUDY DESIGN, SIZE, DURATION: Data were from the Center for the Health Assessment of Mothers and Children of Salinas (CHAMACOS) longitudinal cohort study which followed 338 children in the Salinas Valley, California, from before birth to adolescence.

PARTICIPANTS/MATERIALS, SETTING, METHODS: Pregnant women were enrolled in 1999-2000. Mothers were mostly Latina, living below the federal poverty threshold and without a high school diploma. We measured concentrations of three phthalate metabolites (monoethyl phthalate [MEP], mono-n-butyl phthalate and mono-isobutyl phthalate), methyl and propyl paraben and four other phenols (triclosan, benzophenone-3 and 2,4- and 2,5-dichlorophenol) in urine collected from mothers during pregnancy and from children at age 9. Pubertal timing was assessed among 179 girls and 159 boys every 9 months between ages 9 and 13 using clinical Tanner staging. Accelerated failure time models were used to obtain mean shifts of pubertal timing associated with concentrations of prenatal and peripubertal biomarkers.

MAIN RESULTS AND THE ROLE OF CHANCE: In girls, we observed earlier onset of pubic hair development with prenatal urinary MEP concentrations and earlier menarche with prenatal triclosan and 2,4-dichlorophenol concentrations. Regarding peripubertal biomarkers, we observed: earlier breast development, pubic hair development and menarche with methyl paraben; earlier menarche with propyl paraben; and later pubic hair development with 2,5-dichlorophenol. In boys, we observed no associations with prenatal urinary biomarker concentrations and only one association with peripubertal concentrations: earlier genital development with propyl paraben.

LIMITATIONS, REASONS FOR CAUTION: These chemicals are quickly metabolized and one to two urinary measurements per developmental point may not accurately reflect usual exposure. Associations of peripubertal measurements with parabens may reflect reverse causality: children going through puberty early may be more likely to use personal care products. The study population was limited to Latino children of low socioeconomic status living in a farmworker community and may not be widely generalizable.

WIDER IMPLICATIONS OF THE FINDINGS: This study contributes to a growing literature that suggests that exposure to certain endocrine disrupting chemicals may impact timing of puberty in children.

STUDY FUNDING/COMPETING INTEREST(S): This study was funded by the National Institute of Environmental Health Sciences and the US Environmental Protection Agency. The authors declare no conflicts of interest.

TRIAL REGISTRATION NUMBER: N/A.