A tool to assess risk of bias in non-randomized follow-up studies of exposure effects (ROBINS-E).

BACKGROUND: Observational epidemiologic studies provide critical data for the evaluation of the potential effects of environmental, occupational and behavioural exposures on human health. Systematic reviews of these studies play a key role in informing policy and practice. Systematic reviews should incorporate assessments of the risk of bias in results of the included studies. OBJECTIVE: To develop a new tool, Risk Of Bias In Non-randomized Studies - of Exposures (ROBINS-E) to assess risk of bias in estimates from cohort studies of the causal effect of an exposure on an outcome. METHODS AND RESULTS: ROBINS-E was developed by a large group of researchers from diverse research and public health disciplines through a series of working groups, in-person meetings and pilot testing phases. The tool aims to assess the risk of bias in a specific result (exposure effect estimate) from an individual observational study that examines the effect of an exposure on an outcome. A series of preliminary considerations informs the core ROBINS-E assessment, including details of the result being assessed and the causal effect being estimated. The assessment addresses bias within seven domains, through a series of 'signalling questions'. Domain-level judgements about risk of bias are derived from the answers to these questions, then combined to produce an overall risk of bias judgement for the result, together with judgements about the direction of bias. CONCLUSION: ROBINS-E provides a standardized framework for examining potential biases in results from cohort studies. Future work will produce variants of the tool for other epidemiologic study designs (e.g. case-control studies). We believe that ROBINS-E represents an important development in the integration of exposure assessment, evidence synthesis and causal inference.

Personal Care Product Use during Puberty and Incident Breast Cancer among Black, Hispanic/Latina, and White Women in a Prospective US-Wide Cohort.

BACKGROUND: Some personal care products (PCPs) contain endocrine-disrupting chemicals that may affect breast cancer (BC) risk. Patterns of use vary by race and ethnicity. Use often starts in adolescence, when rapidly developing breast tissue may be more susceptible to environmental carcinogens. Few studies have examined associations of BC with PCP use during this susceptible window. OBJECTIVES: We characterized race and ethnicity-specific patterns of PCP use at 10-13 years of age and estimated associations of use with incident BC. METHODS: At enrollment (2003-2009), Sister Study participants (n=4,049 Black, 2,104 Latina, and 39,312 White women) 35-74 years of age reported use of 37 "everyday" PCPs during the ages of 10-13 y (did not use, sometimes, or frequently used). We conducted race and ethnicity-specific latent class analyses to separately identify groups of women with similar patterns of beauty, hair, and skincare/hygiene product use. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for associations of identified PCP classes and single products with incident BC using Cox proportional hazards regression. RESULTS: During a mean follow-up time of 10.8 y, 280 Black, 128 Latina, and 3,137 White women were diagnosed with BC. Classes of adolescent PCP use were not clearly associated with BC diagnosis among Black, Latina, or White women. HRs were elevated but imprecise for frequent nail product and perfume use in Black women (HR=1.34; 95% CI: 0.85, 2.12) and greater hair product use in Black (HR=1.28; 95% CI: 0.91, 1.80) and Latina (HR=1.42; 95% CI: 0.81, 2.48) women compared with lighter use. In single-product models, we observed higher BC incidence associated with frequent use of lipstick, nail products, pomade, perfume, makeup remover, and acne/blemish products in at least one group. DISCUSSION: This work provides some support for the hypothesis that PCP use during puberty is associated with BC risk. More research is needed to confirm these novel findings. https://doi.org/10.1289/EHP13882.

I-REFF diagrams: enhancing transparency in systematic review through interactive reference flow diagrams.

Systematic review methods are recognized for their rigor and transparency and are widely adapted to frameworks that cover review types such as systematic reviews, scoping reviews, and systematic evidence maps. Reporting guidelines help promote better systematic review practices and detailed documentation of the review process for different types of health research (e.g., PRISMA-Preferred Reporting Items for Systematic Reviews and Meta-Analyses; CONSORT-Consolidated Standards of Reporting Trials; and STROBE-Strengthening the Reporting of Observational Studies in Epidemiology). Transparency in the systematic review process and reporting of results is one of the key advantages of the methods and particularly important for hazard and risk assessments due to the high level of scrutiny these reviews face from scientific, political, and public communities. Data visualizations are important to clearly convey information from a review by helping readers perceive, understand, and assess the displayed information easily and quickly. The study flow diagram is a required element of a systematic review and maps out the number of included and excluded records identified, and the reasons for exclusion. Static literature flow diagrams help viewers readily understand the general review methodology and summarize the number of records included or excluded at each stage of the review. However, such diagrams can be time-consuming to develop and maintain during a systematic review or scoping review, and they provide limited summary-level information. We explored how the use of online systematic review tools such as DistillerSR coupled with visualization software such as Tableau can efficiently generate an Interactive REFerence Flow (I-REFF) diagram that is linked to the literature screening data, thus requiring minimal preparation, and resulting in a simplified process for updating the diagram. Furthermore, I-REFF diagrams enhance transparency and traceability by not only summarizing the records in the review but also allowing viewers to follow specific records throughout the review process. We present an example I-REFF diagram and discuss recommendations for key interactive elements to include in these diagrams and how this workflow can improve efficiency and result in an accessible and transparent interactive literature flow diagram without advanced programming.

Use of personal care product mixtures and incident hormone-sensitive cancers in the Sister Study: A U.S.-wide prospective cohort.

BACKGROUND: Personal care products (PCPs), a source of endocrine-disrupting chemical exposure, may be associated with the risk of hormone-sensitive cancers. Few studies have investigated associations for PCP use with the incidence of hormone-sensitive cancers or considered the joint effect of multiple correlated PCPs. We examined associations between frequently used, or "everyday", PCPs and incident cancers of the breast, ovary, and uterus with a fucus on the joint effect of multiple product exposure. METHODS: Sister Study participants (n=49 899) self-reported frequency of use in the year before enrollment (2003-2009) for 41 PCPs. Using five-level frequency categories based on questionnaire options, hazard ratios (HRs) and 95% confidence intervals (CIs) were estimated for the associations between multiple PCP use and incident breast, ovarian, and uterine cancer using quantile-based g-computation with Cox proportional hazards regression as the underlying model. Multiple PCP use was examined using groupings (beauty, hygiene, and skincare products) determined by both a priori knowledge and Spearman correlation coefficients for co-occurring product use. Associations between individual PCPs and the three cancers were also examined using Cox proportional hazards models coupling with Benjamini-Hochberg procedure for multiple comparisons. RESULTS: Over an average of 11.6 years, 4 226 breast, 277 ovarian, and 403 uterine cancer cases were identified. Positive associations were observed between the hygiene mixture and ovarian cancer (HR=1.35, 95%CI=1.00, 1.83) and the beauty mixture with postmenopausal breast cancer (HR=1.08, 95%CI=1.01, 1.16). Additionally, we observed an inverse association between the skincare mixture and breast cancer (HR=0.91, 95%CI=0.83, 0.99). No significant associations were observed for individual products after corrected for multiple comparison. CONCLUSIONS: Findings from this multi-product, joint-effect approach contribute to the growing body of evidence for associations between PCPs and breast cancer and provides novel information on ovarian and uterine cancer.

Systematic evidence mapping informs a class-based approach to assessing personal care products and pubertal timing.

BACKGROUND: Personal care products (PCPs) contain many different compounds and are a source of exposure to endocrine disrupting chemicals (EDCs), including phthalates and phenols. Early-life exposure to EDCs commonly found in PCPs has been linked to earlier onset of puberty. OBJECTIVE: To characterize the human and animal evidence on the association between puberty-related outcomes and exposure to PCPs and their chemical constituents and, if there is sufficient evidence, identify groups of chemicals and outcomes to support a systematic review for a class-based hazard or risk assessment. METHODS: We followed the OHAT systematic review framework to characterize the human and animal evidence on the association between puberty-related health outcomes and exposure to PCPs and their chemical constituents. RESULTS: Ninety-eight human and 299 animal studies that evaluated a total of 96 different chemicals were identified and mapped by key concepts including chemical class, data stream, and puberty-related health outcome. Among these studies, phthalates and phenols were the most well-studied chemical classes. Most of the phthalate and phenol studies examined secondary sex characteristics and changes in estradiol and testosterone levels. Studies evaluating PCP use and other chemical classes (e.g., parabens) had less data. CONCLUSIONS: This systematic evidence map identified and mapped the published research evaluating the association between exposure to PCPs and their chemical constituents and puberty-related health outcomes. The resulting interactive visualization allows researchers to make evidence-based decisions on the available research by enabling them to search, sort, and filter the literature base of puberty-related studies by key concepts. This map can be used by researchers and regulators to prioritize and target future research and funding to reduce uncertainties and address data gaps. It also provides information to inform a class-based hazard or risk assessment on the association between phthalate and phenol exposures and puberty-related health outcomes.

Correlates of non-persistent endocrine disrupting chemical mixtures among reproductive-aged Black women in Detroit, Michigan.

Some studies indicate that Black women have higher exposure to multiple non-persistent endocrine disrupting chemicals (EDCs) than white women, but little is known about correlates of exposure to EDC mixtures. Using baseline data from a prospective cohort study of reproductive-aged Black women (N = 751), we characterized profiles of EDC mixtures and identified correlates of exposure. At baseline, we quantified biomarkers of 16 phthalates, 7 phenols, 4 parabens, and triclocarban in urine and collected covariate data through self-administered questionnaires and interviews. We used principal component (PC) analysis and k-means clustering to describe EDC mixture profiles. Associations between correlates and PCs were estimated as the mean difference (ß) in PC scores, while associations between correlates and cluster membership were estimated as the odds ratio (OR) of cluster membership. Personal care product use was consistently associated with profiles of higher biomarker concentrations of non-persistent EDCs. Use of nail polish, menstrual and vaginal products (e.g., vaginal powder, vaginal deodorant), and sunscreen was associated with a mixture of phthalate and some phenol biomarkers using both methods. Current vaginal ring use, a form of hormonal contraception placed inside the vagina, was strongly associated with higher concentrations of high molecular weight phthalate biomarkers (k-means clustering: OR = 2.42, 95% CI = 1.28, 4.59; PCA: ß = -0.32, 95% CI = -0.71, 0.07). Several dietary, reproductive, and demographic correlates were also associated with mixtures of EDC biomarkers. These findings suggest that personal care product use, diet, and contraceptive use may be sources of exposure to multiple non-persistent EDCs among reproductive-aged Black women. Targeted interventions to reduce exposure to multiple EDCs among Black women are warranted.

An approach to quantifying the potential importance of residual confounding in systematic reviews of observational studies: A GRADE concept paper.

Small relative effect sizes are common in observational studies of exposure in environmental and public health. However, such effects can still have considerable policy importance when the baseline rate of the health outcome is high, and many persons are exposed. Assessing the certainty of the evidence based on these effect sizes is challenging because they can be prone to residual confounding due to the non-randomized nature of the evidence. When applying GRADE, a precise relative risk >2.0 increases the certainty in an existing effect because residual confounding is unlikely to explain the association. GRADE also suggests rating up when opposing plausible residual confounding exists for other effect sizes. In this concept paper, we propose using the E-value, defined as the smallest effect size of a confounder that still can reduce an observed RR to the null value, and a reference confounder to assess the likelihood of residual confounding. We propose a 4-step approach. 1. Assess the association of interest for relevant exposure levels. 2. Calculate the E-value for this observed association. 3. Choose a reference confounder with sufficient strength and information and assess its effect on the observed association using the E-value. 4. Assess how likely it is that residual confounding will still bias the observed RR. We present three case studies and discuss the feasibility of the approach.

Integrating Personal Air Sensor and GPS to Determine Microenvironment-Specific Exposures to Volatile Organic Compounds.

Personal exposure to volatile organic compounds (VOCs) from indoor sources including consumer products is an understudied public health concern. To develop and evaluate methods for monitoring personal VOC exposures, we performed a pilot study and examined time-resolved sensor-based measurements of geocoded total VOC (TVOC) exposures across individuals and microenvironments (MEs). We integrated continuous (1 min) data from a personal TVOC sensor and a global positioning system (GPS) logger, with a GPS-based ME classification model, to determine TVOC exposures in four MEs, including indoors at home (Home-In), indoors at other buildings (Other-In), inside vehicles (In-Vehicle), and outdoors (Out), across 45 participant-days for five participants. To help identify places with large emission sources, we identified high-exposure events (HEEs; TVOC > 500 ppb) using geocoded TVOC time-course data overlaid on Google Earth maps. Across the 45 participant-days, the MEs ranked from highest to lowest median TVOC were: Home-In (165 ppb), Other-In (86 ppb), In-Vehicle (52 ppb), and Out (46 ppb). For the two participants living in single-family houses with attached garages, the median exposures for Home-In were substantially higher (209, 416 ppb) than the three participant homes without attached garages: one living in a single-family house (129 ppb), and two living in apartments (38, 60 ppb). The daily average Home-In exposures exceeded the estimated Leadership in Energy and Environmental Design (LEED) building guideline of 108 ppb for 60% of the participant-days. We identified 94 HEEs across all participant-days, and 67% of the corresponding peak levels exceeded 1000 ppb. The MEs ranked from the highest to the lowest number of HEEs were: Home-In (60), Other-In (13), In-Vehicle (12), and Out (9). For Other-In and Out, most HEEs occurred indoors at fast food restaurants and retail stores, and outdoors in parking lots, respectively. For Home-In HEEs, the median TVOC emission and removal rates were 5.4 g h-1 and 1.1 h-1, respectively. Our study demonstrates the ability to determine individual sensor-based time-resolved TVOC exposures in different MEs, in support of identifying potential sources and exposure factors that can inform exposure mitigation strategies.

Correlates of urinary concentrations of phthalate and phthalate alternative metabolites among reproductive-aged Black women from Detroit, Michigan.

BACKGROUND: Phthalates are endocrine-disrupting chemicals that are widely present in consumer products. In the United States, Black women are more highly exposed to phthalates than other racial/ethnic groups, yet information on predictors of phthalate exposure among Black women is limited. OBJECTIVE: We evaluated the association of demographics, lifestyle, reproductive history, and personal care product use with urinary concentrations of phthalate and phthalate alternative metabolites, using cross-sectional data from a study of 754 Black women from Detroit, Michigan (2010-2012). METHODS: Women completed questionnaires and provided urine specimens which were analyzed for 16 phthalate and phthalate alternative metabolites. We used linear regression models to estimate mean percentage differences and 95% confidence intervals (CIs) in concentrations across levels of correlates. RESULTS: Monoethyl phthalate (MEP) and MBP concentrations were positively associated with personal care product use, particularly nail products. Educational attainment was positively associated with high molecular weight phthalate concentrations but inversely associated with monobenzyl phthalate (MBzP) concentrations. Parity was positively associated with MBzP concentrations and inversely associated with concentrations of MEP and high molecular weight phthalates. SIGNIFICANCE: We found that sociodemographics, reproductive characteristics, and use of certain personal care products were associated with urinary phthalate concentrations among Black women. Our results emphasize the importance of examining exposure determinants among multiply marginalized populations.

Challenges and recommendations on the conduct of systematic reviews of observational epidemiologic studies in environmental and occupational health.

Systematic reviews are powerful tools for drawing causal inference for evidence-based decision-making. Published systematic reviews and meta-analyses of environmental and occupational epidemiology studies have increased dramatically in recent years; however, the quality and utility of published reviews are variable. Most methodologies were adapted from clinical epidemiology and have not been adequately modified to evaluate and integrate evidence from observational epidemiology studies assessing environmental and occupational hazards, especially in evaluating the quality of exposure assessments. Although many reviews conduct a systematic and transparent assessment for the potential for bias, they are often deficient in subsequently integrating across a body of evidence. A cohesive review considers the impact of the direction and magnitude of potential biases on the results, systematically evaluates important scientific issues such as study sensitivity and effect modifiers, identifies how different studies complement each other, and assesses other potential sources of heterogeneity. Given these challenges of conducting informative systematic reviews of observational studies, we provide a series of specific recommendations based on practical examples for cohesive evidence integration to reach an overall conclusion on a body of evidence to better support policy making in public health.

Adolescent use of hair dyes, straighteners and perms in relation to breast cancer risk.

Hair products can contain hormonally active and carcinogenic compounds. Adolescence may be a period of enhanced susceptibility of the breast tissue to exposure to chemicals. We therefore evaluated associations between adolescent hair product use and breast cancer risk. Sister Study participants (ages 35-74 years) who had completed enrollment questionnaires (2003-2009) on use of hair dyes, straighteners/relaxers and perms at ages 10 to 13 years (N = 47 522) were included. Cox proportional hazards regression was used to estimate adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for associations between hair products and incident breast cancer (invasive cancer or ductal carcinoma in situ), with consideration of heterogeneity by menopausal status and race/ethnicity. Over an average of 10 years of follow-up, 3380 cases were diagnosed. Frequent use of straighteners and perms was associated with a higher risk of premenopausal (HR = 2.11, 95% CI: 1.26-3.55 and HR = 1.55, 95% CI: 0.96-2.53, respectively) but not postmenopausal breast cancer (HR = 0.99, 95% CI: 0.76-1.30 and HR = 1.09, 95% CI: 0.89-1.35, respectively). Permanent hair dye use during adolescence was uncommon (<3%) and not associated with breast cancer overall (HR = 0.97, 95% CI: 0.78-1.20), though any permanent dye use was associated with a higher risk among black women (HR = 1.77, 95% CI: 1.01-3.11). Although frequency of use of perms (37% non-Hispanic white vs 9% black) and straighteners (3% non-Hispanic white vs 75% black) varied by race/ethnicity, associations with breast cancer did not. Use of hair products, specifically perms and straighteners, during adolescence may be associated with a higher risk of premenopausal breast cancer.

A national toxicology program systematic review of the evidence for long-term effects after acute exposure to sarin nerve agent.

Sarin is a highly toxic nerve agent that was developed for chemical warfare during World War II and is used in present conflicts. Immediate effects of acute sarin exposure are established; however, whether effects persist after initial signs have subsided is debated. The National Toxicology Program (NTP) conducted a systematic review to evaluate the evidence for long-term neurological effects following acute (<24 hour) exposure to sarin. The literature search and screening process identified 32 data sets within the 34 human studies and 47 data sets within the 51 animal studies (from 6837 potentially relevant references) that met the objective and the inclusion criteria. Four main health effect categories of neurological response were identified as having sufficient data to reach hazard conclusions: (1) cholinesterase levels; (2) visual and ocular effects; (3) effects on learning, memory, and intelligence; and (4) morphology and histopathology in nervous system tissues. NTP concluded that acute sarin exposure is known to be a neurological hazard to humans in the period following exposure up to 7 days and suspected to be a hazard week to years after exposure, given a lower level of evidence in later time periods. Effects included reduced cholinesterase, visual and ocular effects, impaired learning and memory, and altered nervous system morphology. Further mechanistic, targeted animal studies, translational research, and rapid research responses after human exposures may reduce uncertainties on long-term consequences of sarin.

Chemical/straightening and other hair product usage during childhood, adolescence, and adulthood among African-American women: potential implications for health.

Few studies have characterized life course hair product usage beyond ever/never. We investigated hair product use from childhood to adulthood, usage patterns in adulthood, and socioeconomic status (SES) correlates among African-American (AA) women. Using self-reported data from 1555 AA women enrolled in the Study of Environment, Lifestyle, and Fibroids (2010-2018), we estimated the usage frequency of chemical relaxer/straightener (≥twice/year, once/year, and rarely/never) and leave-in/leave-on conditioner (≥once/week, 1-3 times/month, and rarely/never) during childhood, adolescence, and adulthood. Latent class analysis was used to identify patterns of adulthood usage of multiple hair products. SES was compared across latent classes. With a mean age of 33 ± 3.4 years, most women reported ever using chemical relaxers/straighteners (89%), and use ≥twice/year increased from childhood (9%) to adolescence (73%) but decreased in adulthood (29%). Leave-in/leave-on conditioner use followed the same pattern. Each of three identified latent classes reported frequent styling product use and infrequent relaxer/straightener use. Class One was unlikely to use any other products, Class Two moderately used shampoo and conditioner, and Class Three frequently used multiple product types (e.g., moisturizers and conditioners). Participants in the latter two classes reported higher SES. Ever/never characterization may miss important and distinctive patterns of hair product use, which may vary by SES.

Longitudinal association of biomarkers of pesticide exposure with cardiovascular disease risk factors in youth with diabetes.

BACKGROUND: Cardiovascular disease (CVD) is the leading cause of death among individuals with diabetes, but little is known about the role of exposures to environmental chemicals such as pesticides in the early development of CVD risk in this population. OBJECTIVES: To describe changes over time in concentrations of pesticide biomarkers among youth with diabetes in the United States and to estimate the longitudinal association between these concentrations and established risk factors for CVD. METHODS: Pesticide biomarkers were quantified in urine and serum samples from 87 youth with diabetes participating in the multi-center SEARCH cohort study. Samples were obtained around the time of diagnosis (baseline visit, between 2006 and 2010) and, on average, 5.4 years later (follow-up visit, between 2012 and 2015). We calculated geometric mean (95% CI) pesticide biomarker concentrations. Eight CVD risk factors were measured at these two time points: body mass index (BMI) z-score, HbA1c, insulin sensitivity, fasting C-peptide (FCP), LDL cholesterol, HDL cholesterol, total cholesterol, and triglycerides. Linear regression models were used to estimate the associations between each pesticide biomarker at baseline and each CVD risk factor at follow-up, adjusting for baseline health outcome, elapsed time between baseline and follow up, sex, age, race/ethnicity, and diabetes type. RESULTS: Participants were, on average, 14.2 years old at their baseline visit, and most were diagnosed with type 1 diabetes (57.5%). 4-nitrophenol, 3-phenoxybenzoic acid, 2,4-dichlorophenoxyacetic acid (2,4-D), 3,5,6-trichloro-2-pyridinol, 2,2-bis(4-chlorophenyl)-1,1-dichloroethene, and hexachlorobenzene were detected in a majority of participants at both time points. Participants in the highest quartile of 2,4-D and 4-nitrophenol at baseline had HbA1c levels at follow-up that were 1.05 percentage points (95% CI: -0.40, 2.51) and 1.27 percentage points (0.22, 2.75) higher, respectively, than participants in the lowest quartile of these pesticide biomarkers at baseline. These participants also had lower log FCP levels (indicating reduced beta-cell function) compared to participants in the lowest quartile at baseline: beta (95% CI) for log FCP of -0.64 (-1.17, -0.11) for 2,4-D and -0.39 (-0.96, 0.18) for 4-nitrophenol. In other words, participants in the highest quartile of 2,4-D had a 47.3% lower FCP level compared to participants in the lowest quartile, and those in the highest quartile of 4-nitrophenol had a 32.3% lower FCP level than those in the lowest quartile. Participants with trans-nonachlor concentrations in the highest quartile at baseline had HbA1c levels that were 1.45 percentage points (-0.11, 3.01) higher and log FCP levels that were -0.28 (-0.84, 0.28) lower than participants in the lowest quartile at baseline, that is to say, participants in the highest quartile of trans-nonachlor had a 24.4% lower FCP level than those in the lowest quartile. While not all of these results were statistically significant, potentially due to the small same size, clinically, there appears to be quantitative differences. No associations were observed between any pesticide biomarker at baseline with BMI z-score or insulin sensitivity at follow-up. CONCLUSIONS: Exposure to select pesticides may be associated with impaired beta-cell function and poorer glycemic control among youth with diabetes.

Hair dye and chemical straightener use and breast cancer risk in a large US population of black and white women.

Many hair products contain endocrine-disrupting compounds and carcinogens potentially relevant to breast cancer. Products used predominately by black women may contain more hormonally-active compounds. In a national prospective cohort study, we examined the association between hair dye and chemical relaxer/straightener use and breast cancer risk by ethnicity. Sister Study participants (n = 46,709), women ages 35-74, were enrolled between 2003 and 2009, and had a sister with breast cancer but were breast cancer-free themselves. Enrollment questionnaires included past 12-month hair product use. Cox proportional hazards models estimated adjusted hazard ratios (HRs) and 95% confidence intervals (95% CIs) for the association between hair products and breast cancer; effect measure modification by ethnicity was evaluated. During follow-up (mean = 8.3 years), 2,794 breast cancers were identified. Fifty-five percent of participants reported using permanent dye at enrollment. Permanent dye use was associated with 45% higher breast cancer risk in black women (HR = 1.45, 95% CI: 1.10-1.90), and 7% higher risk in white women (HR = 1.07, 95% CI: 0.99-1.16; heterogeneity p = 0.04). Among all participants, personal straightener use was associated with breast cancer risk (HR = 1.18, 95% CI 0.99-1.41); with higher risk associated with increased frequency (p for trend = 0.02). Nonprofessional application of semipermanent dye (HR = 1.28, 95% CI 1.05-1.56) and straighteners (HR = 1.27, 95% CI 0.99-1.62) to others was associated with breast cancer risk. We observed a higher breast cancer risk associated with any straightener use and personal use of permanent dye, especially among black women. These results suggest that chemicals in hair products may play a role in breast carcinogenesis.

Associations between Personal Care Product Use Patterns and Breast Cancer Risk among White and Black Women in the Sister Study.

BACKGROUND: Many personal care products include chemicals that might act as endocrine disruptors and thus increase the risk of breast cancer. OBJECTIVE: We examined the association between usage patterns of beauty, hair, and skin-related personal care products and breast cancer incidence in the Sister Study, a national prospective cohort study (enrollment 2003-2009). METHODS: Non-Hispanic black (4,452) and white women (n=42,453) were examined separately using latent class analysis (LCA) to identify groups of individuals with similar patterns of self-reported product use in three categories (beauty, skin, hair). Multivariable Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for associations between product use and breast cancer incidence. RESULTS: A total of 2,326 women developed breast cancer during follow-up (average follow-up=5.4y). Among black women, none of the latent class hazard ratios was elevated, but there were <100 cases in any category, limiting power. Among white women, those classified as "moderate" and "frequent" users of beauty products had increased risk of breast cancer relative to "infrequent" users [HR=1.13 (95% CI: 1.00, 1.27) and HR=1.15 (95% CI: 1.02, 1.30), respectively]. Frequent users of skincare products also had increased risk of breast cancer relative to infrequent users [HR=1.13 (95% CI: 1.00, 1.29)]. None of the hair product classes was associated with increased breast cancer risk. The associations with beauty and skin products were stronger in postmenopausal women than in premenopausal women, but not significantly so. CONCLUSIONS: This work generates novel hypotheses about personal care product use and breast cancer risk. Whether these results are due to specific chemicals or to other correlated behaviors needs to be evaluated. https://doi.org/10.1289/EHP1480.

Associations among personal care product use patterns and exogenous hormone use in the NIEHS Sister Study.

It is hypothesized that certain chemicals in personal care products may alter the risk of adverse health outcomes. The primary aim of this study was to use a data-centered approach to classify complex patterns of exposure to personal care products and to understand how these patterns vary according to use of exogenous hormone exposures, oral contraceptives (OCs) and post-menopausal hormone therapy (HT). The NIEHS Sister Study is a prospective cohort study of 50,884 US women. Limiting the sample to non-Hispanic blacks and whites (N=47,019), latent class analysis (LCA) was used to identify groups of individuals with similar patterns of personal care product use based on responses to 48 survey questions. Personal care products were categorized into three product types (beauty, hair, and skincare products) and separate latent classes were constructed for each type. Adjusted prevalence differences (PD) were calculated to estimate the association between exogenous hormone use, as measured by ever/never OC or HT use, and patterns of personal care product use. LCA reduced data dimensionality by grouping of individuals with similar patterns of personal care product use into mutually exclusive latent classes (three latent classes for beauty product use, three for hair, and four for skin care. There were strong differences in personal care usage by race, particularly for haircare products. For both blacks and whites, exogenous hormone exposures were associated with higher levels of product use, especially beauty and skincare products. Relative to individual product use questions, latent class variables capture complex patterns of personal care product usage. These patterns differed by race and were associated with ever OC and HT use. Future studies should consider personal care product exposures with other exogenous exposures when modeling health risks.

Exposure to multiple chemicals in a cohort of reproductive-aged Danish women.

BACKGROUND: Current exposure assessment research does not sufficiently address multi-pollutant exposure and their correlations in human media. Understanding the extent of chemical exposure in reproductive-aged women is of particular concern due to the potential for in utero exposure and fetal susceptibility. OBJECTIVES: The objectives of this study were to characterize concentrations of chemical biomarkers during preconception and examine correlations between and within chemical classes. METHODS: We examined concentrations of 135 biomarkers from 16 chemical classes in blood and urine from 73 women aged 18-40 enrolled in Snart Foraeldre/Milieu, a prospective cohort study of pregnancy planners in Denmark (2011-2014). We compared biomarker concentrations with United States similarly-aged, non-pregnant women who participated in the National Health and Nutrition Environmental Survey (NHANES) and with other international biomonitoring studies. We performed principal component analysis to examine biomarker correlations. RESULTS: The mean number of biomarkers detected in the population was 92 (range: 60-108). The most commonly detected chemical classes were phthalates, metals, phytoestrogens and polycyclic aromatic hydrocarbons. Except blood mercury, urinary barium and enterolactone, geometric means were higher in women from NHANES. Chemical classes measured in urine generally did not load on a single component, suggesting high between-class correlation among urinary biomarkers, while there is high within-class correlation for biomarkers measured in serum and blood. CONCLUSIONS: We identified ubiquitous exposure to multiple chemical classes in reproductive-aged Danish women, supporting the need for more research on chemical mixtures during preconception and early pregnancy. Inter- and intra-class correlation between measured biomarkers may reflect common exposure sources, specific lifestyle factors or shared metabolism pathways.