Phthalate and BPA exposure in women and newborns through

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Phthalate and BPA exposure in women and newborns through personal care product use and food packaging. Mandy Fisher, Tye Arbuckle, Susan MacPherson, Joseph M. Braun, Mark Feeley, and Éric Gaudreau Environ. Sci. Technol., Just Accepted Manuscript • DOI: 10.1021/acs.est.9b02372 • Publication Date (Web): 19 Aug 2019 Downloaded from pubs.acs.org on August 21, 2019

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Environmental Science & Technology

Phthalate and BPA exposure in women and newborns through personal care product use and food packaging. Mandy Fisher1*, Tye E. Arbuckle1, Susan MacPherson1, Joseph M. Braun2, Mark Feeley3, Éric Gaudreau4

1. Population Studies Division, Environmental Health Science and Research Bureau, Health Canada. Ottawa, ON. Canada 2. Department of Epidemiology, Brown University, Providence, RI. U.S.A. 3. Foods Directorate, Health Canada. Ottawa. ON. Canada 4. Centre de Toxicologie du Québec (CTQ), Institut National de Santé Publique du Québec (INSPQ), QC. Canda

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*corresponding author

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Health Canada, Population Studies Division 269 Laurier Avenue W Ottawa, Ontario K1A 0K9 Canada Mail Stop 4908, Room 8-128 Phone: 613-946-7496 Email: [email protected]

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Targeted Journal: Environmental Science and Technology

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Abstract

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Phthalates and bisphenol A (BPA) are used in some personal care products (PCPs) and

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containers for food processing and packaging. The Plastics and Personal-Care Product use in

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Pregnancy (P4) Study (2009-10) explored the association between PCP use during pregnancy

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and the postpartum period among 80 pregnant women and 55 infants and BPA and phthalate

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concentrations in multiple maternal and infant urine specimens collected throughout the study

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(n=1260 samples). The type, frequency and timing of PCP and food packaging use 24 h before

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and during the urine collection period was collected at 5 time points for the mother using

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prospective diaries. Infant urine was collected up to 2 times before 3 months of age and mothers

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answered questions about infant feeding and PCP use on their baby. In mothers, monoethyl

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phthalate (MEP) metabolite concentrations were significantly higher when women reported

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using makeup or body lotion in the last 24h. MEP concentrations were consistently higher when

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the usage occurred within 0-6 h before the urine sample collection for almost all of the PCP

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categories. Infant lotion or baby powder application in the previous 24h was associated with

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higher phthalate metabolite concentrations in infants.

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were lower in exclusively breastfed infants compared to those who were exclusively formula-fed

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or breastfed with supplementation. Given that PCPs tend to undergo frequent formulation

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changes, which could impact the relative importance of a certain product type as a source of

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exposure, continued research of this type is warranted.

Total BPA metabolite concentrations

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Environmental Science & Technology

Introduction Both phthalates and bisphenol A (BPA) are chemicals used in some cosmetics, personal 1,2.

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care products (PCPs), food packaging materials and medications

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have been measured in urine, blood, cord blood, human milk, amniotic fluid, follicular fluid,

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meconium, saliva, sweat, dust and air 3-17.

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They are ubiquitous and

Phthalates and BPA are both suspected endocrine disrupting chemicals

18-20.

Phthalates

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have shown associations with abnormal sperm quality, preterm birth, growth restriction, and

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gestational hypertension

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development (anogenital distance), allergies, asthma and behaviour 24-27.

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utero, infancy) to BPA and phthalates may increase the risk of neurodevelopmental disorders in

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children by disrupting hormone-mediated processes during critical windows of development 28,29.

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1,21-23.

In children, associations have been seen with sexual

Studies of pregnant women

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Early life exposure (in

show increased concentrations of urinary phthalates 30-32,34,36,

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mainly among users of leave-on PCPs including: makeup or cosmetics

hair spray or

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hair products 31,36, lotion 30,36,37 or sunscreen 31,33, deodorant 30,36,37, nail polish 30,36 and perfume

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30-32,35-37.

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in the last 24 h has shown associations with phthalates

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between PCP use and BPA, however, consuming foods in metal cans has been associated with

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increased urinary levels of BPA39.

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Much of the previous research on pregnant women has evaluated exposure by measuring

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between 1 to 3 spot urine samples and examining the association with recalled PCP use over the

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past 24 30,36 to 48 31,32,35,37 hours, past 7 days 33 or estimated frequency of use in a week or month

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at specified time periods

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studies in women show moderate to high reproducibility of these chemicals across a day 43,44, but

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higher variability across the entire pregnancy

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multiple spot urine samples in a 24 h period, for non-pregnant women, and showed both positive

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and negative associations of urinary phthalates with both leave-on and wash-off PCPs.

In infants, mothers’ reported use of infant lotion and powder as well as baby shampoo

33,34.

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Few studies have shown association

These chemicals have very short half-lives (6 to 24 h) with phthalate or total BPA concentrations,

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suggesting that food packaging may not be an important source of phthalate and BPA exposure

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in this population, or that we did not have enough statistical power to detect such associations. It

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has been suggested that the elimination half-life of dietary exposure to some phthalates can be as

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short as 3 h 42 and less than 6 h for BPA40-42.

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Medication Form

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We examined the association between medication form (tablet, or capsule) and the

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percent changes in total BPA urine concentrations and phthalate molar sums but we did not

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observe consistent results (See Supplementary Table S5). Consuming medication in capsule form

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in the past 24 h was associated with a 27% (95% CI: -4%, 69%), 75% (95% CI: -2%, 212%),

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68% (95% CI:-18%, 247%) and 22% (95% CI: -3%, 55%) percent increase in concentrations of

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MEP, ∑DiBP, ∑DiNP and total BPA respectively.

Various phthalates, including DEP, DBP, 13

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DMP, and dioctylphthalate are used as non-medicinal ingredients in numerous types of enteric-

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coated and delayed-release capsules, as well as controlled-released transdermal films

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contrast, consuming tablet form medication in the past 24 h was associated with a significant

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decrease in urinary ΣBBzP (-45%; 95% CI:-61%,-22%) and MEP (-31%; 95% CI: -49%, -5%)

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concentrations. We have no explanation for this finding, unless the medication type might have

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increased excretion of contaminants from the body, or it is a chance finding. Due to our very

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limited sample size, we were not able to investigate further into the medication types. We did

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not find any significant associations between medication form and phthalates or total BPA

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concentrations in maternal urine, but consuming medication in capsule form in the previous 24 h

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was associated with non-significant increases in MEP (27%, p=0.09) and ΣDiBP (86%, p=0.07)

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concentrations.

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In

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Exposure to medication with phthalates as non-medicinal ingredients has been previously

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reported. In a case study, Hauser et al. 68 described a man who took a medication for ulcerative

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colitis (Asacol) with DBP urinary concentrations (16,868 µg/L) that were more than 2 orders of

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magnitude higher than the 95th percentile in NHANES (1999-2000). DBP is still used in the

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enteric coating of some, but not all medications containing mesalamine, the active ingredient in

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commonly prescribed medications for inflammatory bowel diseases

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over/cross-back study of men taking mesalamine, with and without DBP used in the enteric

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coating, it was found that the combination of mesalamine and DBP disrupted serum levels of

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pituitary and gonadal hormones. This effect was reversed after removal of the DBP exposure

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among men who did not have long-term exposure to medication with high concentrations of

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DBP69. Alterations were also seen for thyroid hormones 70 and semen parameters 71 in this same

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study. Messerlian et al.72 showed an increase in DEHP metabolites following dermal application

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of ultrasound gel during routine obstetrical scans at 20 weeks. Using results from NHANES

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(from 1999-2000 through 2013-2014) Romano et al.73 found an association between regular use

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of multivitamin/multimineral supplements and increased concentrations of MEP (11% higher),

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compared to non-users; however, no association was seen with MBP. Given that medications

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and supplements can be an important source of long-term exposure, the proportional contribution

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to a person’s total phthalate exposure, relative to other sources, should be further explored.

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In a recent cross-

Infants & PCPs

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Infants who used lotion in the past 24 h (applied by caregiver) had significantly higher

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geometric mean phthalate metabolite concentrations of MBzP, MCPP, and MBP (See Figure 4).

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The percent change in molar sum concentrations for infants who had lotion applied in the past 24

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h was 163% (95% CI: 11%, 522%), 200% (95% CI: 41%, 539%), and 96% (95% CI: 17%,

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227%) for these phthalates, respectively, compared to infants without application. Although

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only 4 infants had baby powder applied to them in the last 24 h, we showed high, however

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imprecise, associations with MBzP (324%; 95% CI: -2%, 1740%); , MBP (200%; 95% CI: 27%,

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610%) and total BPA (466%; 95% CI: -40%, 5216% ) concentrations, compared to those infants

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who did not have baby powder applied.

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explored this further and found that the percent change was still near 200% when we removed

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one infant whose total BPA concentrations were near the 95th percentile. However, if we

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assume that the mothers of these babies applied the baby powder, we did not see high total BPA

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concentrations in the mothers urine (median 1.18 µg/L (range 0.87-2.4) compared to 1.21 µg/L

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in the full study).

Given the low number of users of baby powder, we

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When we compared the geometric mean infant urine concentrations of low (≤2), medium

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(3) and high (≥4) product users, we observed increased geometric mean concentrations for total

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BPA (145%; 95% CI:-43%, 948%), MCPP (62%, 95% CI:-28%, 264), MBP (71%; 95% CI:2%,

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187%), and MBzP (78%, 95% CI:-26, 332) among high product users compared to low product

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users; however they were not statistically significant (See Supplementary Figure S2).

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change in total BPA and phthalate urinary concentrations were association with the amount of

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time per day that the child spends using soft plastic toys, teething rings, or a pacifier (See SI

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Table S6 and S7). The use of a pacifier during sleep within the past 24 h was associated with a

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non-significant increase (154%; 95% CI:-63%, 1626) in urinary total BPA concentrations.

No

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Very few studies have examined the relationship between infant exposures to phthalates

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and total BPA and product use. In the Study for Future Families, in the U.S. (1999-2002), infant

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(n=154) urinary phthalate concentrations were associated with mothers’ reported use of infant

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lotion (MEP, MMP), infant powder (MiBP) and baby shampoo (MMP) in the last 24 h 38. This

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association was strongest for infants who were