Table 1.
Representative Examples of EDC Exposures, Body Burdens, and Neurobehavioral and Disease Associations in Humansa
| EDCs | Population Characteristics | Sample Size | Medium in Which EDCs Were Measured | Concentrations Detected | Neurobehavioral Outcome | Other Outcome | Observations | Reference |
|---|---|---|---|---|---|---|---|---|
| Atrazine | Prospective population-based cohort in Brittany (France): PELAGIE cohort from 2002–2006. | 579 urine samples were selected from women whose babies had major congenital or male genital anomalies, including FGR and small head circumference | Urine (single sample) collected before wk 19 of pregnancy | Median [atrazine] = 0.12 μg/L; other metabolites of atrazine and other herbicides were also measured | Adverse pregnancy outcomes (FGR, SHC) were associated with atrazine and its metabolites; for FGR, OR = 1.5 (95% CI = 1.0–2.2), and for SHC, OR = 1.7 (95% CI = 1.0–2.7); congenital abnormalities were not associated with exposure | Study was conducted after atrazine was banned so data interpretation should be conducted in this context | (51) | |
| BPA | Mothers during prenancy; children at 5 y of age | n = 292 mother-child pairs | Urine | Geometric mean [maternal BPA] (unadjusted or specific gravity adjusted) = 1.1, 1.3 μg/L; [child BPA] (unadjusted or specific gravity-adjusted) = 2.5, 3.7 μg/L | In boys, higher maternal BPA was associated with increased internalizing problems at age 7. Specifically, internalizing scores were increased by 1.8 points (95% CI = 0.3–3.3) by mothers' reports and 2.5 points (95% CI = 0.7–4.4) by teachers' reports; no association with inattention or hyperactivity was found in boys or girls or any behaviors in girls | (52) | ||
| BPA | Mothers and their 3-y-old children in the Cincinnati, OH, area | n = 244 mother-child pairs | Urine | Median maternal urine [BPA] = 2.0 μg/L), child urine [BPA] = 4.1 μg/L | Higher gestational [BPA] was associated with increased anxious and depressive behaviors on BASC-2 and poorer emotional control and inhibition on BRIEF-P; effects were more pronounced in girls | BPA was detected in 97% gestational and childhood urine samples | (49) | |
| BPA, phthalate metabolites, PCBs, organochlorine pesticides, brominated flame retardants, perfluoroalkyl substances | Mothers and their children (4–5 y old) in the HOME Study, Cincinnati, Ohio | n = 175 mother-child pairs | Urine, blood from pregnant women | Table 1 of this paper presents concentrations of urinary or serum EDCs in this study | Autistic behaviors were assessed by the mother completing the SRS; PBDE-28 was associated with more autistic behaviors [β = 4.1, 95% CI = 0.8–7.3]; fewer autistic behaviors were observed between women with detectable vs nondetectable PCB-178 [β = −3.0, 95% CI = −6.3, 0.2], β-hexachlorocyclohexane [β = −3.3; 95% CI = −6.1, −0.5], or PBDE-85 [β = −3.2, 95% CI = −5.9, −0.5] | Most EDCs were associated with negligible changes in SRS scores; only PBDE-28 had a positive association with autistic behaviors; other EDCs had a negative association; women in this study had from 21–52 (median 44) detectable EDCs in serum or urine during pregnancy | (134) | |
| BPA | Children from 2009–2010 NHANES | n = 710 children | Urine | Mean [BPA] = 1.889 (male) and 1.934 (female) ng/mL | The albumin-to-creatinine ratio was associated with urinary BPA (highest ratio in the highest quartile) consistent with modest albuminuria | (54) | ||
| BPA, tOP | Participants 6 y and older in the 2003–2004 NHANES | n = 2517 | Urine | Geometric mean [BPA] in the entire population was 2.6 μg/L, range 0.4–149 μg/L; tOP range = 0.2–20.6 μg/L | BPA was found in 93% and tOP in 57% of people; concentrations varied by sex, race/ethnicity, age, and household income | (48) | ||
| BPA | Participants from 6–19 y of age in the 2003–2008 NHANES | n = 2838 | Urine | Mean urinary [BPA] = 2.8 ng/mL | Children in the lowest quartile of BPA had lower prevalence of obesity (10%, 95% CI = 7.6%–12.5%); the second, third, and fourth quartiles had OR (95% CIs) of 2.22 (1.53–3.23), 2.09 (1.48–2.95), and 2.53 (1.72–3.74), respectively | (53) | ||
| BPA and metabolites | Second-trimester pregnancies (13–24 wk) in northern and central California | n = 85 participants from 2010–2012 | Cord blood | Geometric mean [BPA] = 0.16, [BPA-glucuronide] = 0.14, [BPA-sulfate] = 0.32 ng/mL | BPA and/or its metabolites BPA-glucuronide and BPA-sulfate was found in 100% of cord blood samples assayed by LC-MS/MS | (56) | ||
| PBDEs | Second-trimester pregnancies in California from 2008–2009 | n = 25 (pilot study) | Serum | 37 PBDE analytes were measured, along with TSH, free T4, and total T4 | Median [PBDEs] and [OH-PBDEs] are the highest reported in pregnant women; some association with transthyretin and TSH was found, but not with T4 | (47) | ||
| PCBs | Children recruited as newborns from 1980–1981, born to women known to have eaten Lake Michigan fish contaminated with PCBs | n = 212 children | Maternal serum, milk, and umbilical cord serum | Mean [PCBs] = 3 ng/mL (cord serum), 6 ng/mL (maternal serum), 841 ng/g fat (milk), and 1–2 ng/mL in the childrens' serum at 4 and 11 y | Prenatal PCB exposure was associated with lower verbal IQ, memory, and attention | DDT, lead, and mercury were also measured | (128) | |
| PCBs | Mother-infant pairs | n = 207 mother-infant pairs; 105 were breastfed, 102 bottle-fed | Maternal plasma in last month of pregnancy; levels in breast milk and duration of breastfeeding | Mean [PCBs] = 2.2 ng/g plasma; 419 ng/g milk fat | Higher prenatal PCBs (from maternal plasma) were associated with lower psychomotor scores on the Bayley test at 3 mo; postnatal PCB-dioxins were associated with poorer performance at 7 mo | Breastfed babies performed better than bottle-fed babies | (132) | |
| PCBs, dioxin | Dutch children at 42 mo of age, born from women recruited in 1990–1992 | n = 395 (cognitive abilities), a subgroup (n = 193) used for verbal comprehension | Plasma from 42-mo-old children and from maternal plasma | Median [PCB] in plasma (μg/L) was 2.04 (maternal), 0.38 (cord), and 0.35 (children at 42 mo); breast milk levels were about 200× higher | Maternal PCBs were associated with lower scores on aspects of the Kaufman Assessment Battery for Children, with the highest-exposed group having the poorest performance; lactational and the children's own PCB levels were not related to cognitive performance | Breast milk PCBs in the Netherlands at the time of the study were among the highest in the world | (129) | |
| PCBs, dioxin | Dutch Duisburg cohort recruited 2000–2002; children tested at 6–8 y of age. | n = 232 pregnant women, of which 121 fulfilled eligibility criteria | Maternal blood collected wk 28–43 or gestation; maternal milk during the first 3 wk after parturition | Mean concentrations of PCDD/F and PCBs in maternal blood were 14.5 and 6.9 pg/g blood lipid, respectively; mean levels in milk were 11.6 and 9.0 pg/g milk lipid, respectively | Sexually dimorphic behaviors in children were assessed by the PSAI scores for 3 categories (preferred toys, preferred activities, behavioral characteristics); significant interactions of sex and exposure were found, especially femininity scores, which showed positive correlations in boys with PCBs in milk and negative associations in girls | Exposure levels were relatively low compared with other studies | (279) | |
| PCBs | Milk samples from women aged 19–46 from 5 regions of Canada in 1992 | n = 497 milk samples | Breast milk | See Table 1 of this paper; medians ranged from 0–308 ng/g lipid; Most abundant PCBs were PCBs 138, 153, 118, 137, 170, 187, 49, 156, 180, 74 | 12 PCB congeners were detectable in 90% of samples, another 12 in 40%–90%; many of the major congeners were intercorrelated | (58) | ||
| PCBs | Infants at 6 and 12 mo from the Oswego Newborn and Infant Development Project, focusing on maternal consumption of Lake Ontario fish contaminated with chemicals | n = 230 (6 mo) and 219 (12 mo) | Cord blood, breast milk 1–3 mo after delivery | Cord blood median [total PCBs] = 0.52 ng/g wet; breast milk median [total PCBs] = 153 ng/g lipid | Small but significant associations between total PCBs and declining FTII performance at 6 and 12 mo of age; no association between breast milk total PCBs and FTII performance at either age | (130) | ||
| PCBs | Field study of children born in 1978–1985 whose mothers were poisoned by PCBs from 1978–1979 in the Yucheng incident in Taiwan (PCB-contaminated cooking oil); comparisons were made with nonpoisoned age-matched subjects | n = 118 | PCBs were not measured here, but participants' mothers had known exposure to PCB-contaminated cooking oil | Not applicable | Performance on the MDI and PDI (0.5–2 y of age) was slightly but significantly poorer in the Yucheng children; Stanford-Binet IQs were also significantly lower, especially at 4 and 5 y of age; in older children, performance continued to be poorer in the Yucheng group, although there appeared to be some catch-up as children developed | (131) | ||
| PCBs, pesticides, PBDE | Couples in Michigan or Texas in the Longitudinal Investigation of Fertility and the Environment (LIFE) study, discontinuing contraception to become pregnant | n = 501 couples | Serum from men and women collected at initial (prepregnancy) interview | See Table 2 of this paper for geometric means (GM, ng/g serum) of compounds associated with reduced fecundability OR; for those compounds with strongest association with reduced fecundability, PCB 167 in women: GM = 0.003 (achieved pregnancy) and 0.004 (no pregnancy); PCB 138 in men: 0.038 (achieved pregnancy) and 0.044 (no pregnancy) | A reduction in fecundability was associated with increases in PCBs 118, 167, and 209 and perfluorooctane sulfonamide in females (strongest for PCB 167 [OR = 0.79; 95% CI = 0.64–0.97)]; and p,p′-DDE and PCBs 138, 156, 157, 167, 170, 172, and 209 in males [strongest for PCB 138 [OR = 0.71; 95% CI = 0.52–0.98)] | (59) | ||
| Persistent organochlorines (PCBs, DDE, dieldrin, hexachlorobenzene) | CPP, which enrolled pregnant women in 1959–1965, and their children until 7 y of age | n = 1915 children (for BMI) and corresponding serum from mothers during pregnancy | Third-trimester blood from pregnant women | See Table 2 of this paper for median concentrations across selected percentiles (μg/L); for dieldrin, the 25th percentile was 0.60 μg/L and the 95th was 1.81 μg/L; levels in this CPP study were higher than those detected in NHANES | The only association found was for dieldrin; compared with the lowest quintile, the obesity OR was 3.6 (95% CI = 1.3–10.5) and 2.3 (95% CI = 0.8–7.1) for the fourth and highest quintile, respectively | 8.6% of children were considered overweight and 3.5% were obese; chemicals were found in nearly 100% of samples | (60) | |
| PFCs | Girls and mothers in the Avon Longitudinal Study of Parents and Children | n = 448 girls from singleton births | Serum | Median [PFOS] = 19.6 ng/mL; median [PFOA] = 3.7 ng/mL | Girls born to mothers whose PFCs were in the highest tertile weighed 140 g less than those in the lowest tertile (95% CI = −238-−42) at birth but weighed 580 g more at 20 mo (95% CI = 301–858) | 100% of samples had PFCs | (61) | |
| Phthalates | Mother-infant pairs studied from 2006–2009 in 3 cities (Seoul, Cheonan, Ulsan) in Korea | n = 460 mother-infant pairs | Urine (1 sample collected during third trimester of pregnancy) | Median [MEHHP] = 10.1 μg/L, [MEOHP] = 7.9 μg/L, [MBP] = 16.6 μg/L | There were inverse associations between prenatal MEHHP, MEOHP, and MBP in a third-trimester urine sample and MDI and PDI in male infants at 6 mo; no associations were found in females | (62) | ||
| Phthalates | Women from the Study for Future Families pregnancy cohort study at Los Angeles, CA; Minneapolis, MN; and Columbia, MS; from 1999–2002 | n = 85 boys 2–36 mo of age | Urine collected during pregnancy | Mean (median) concentrations of the 4 phthalates associated with shorter AGI are shown in Table 5, and range from: MBP 13.1 (11.5) to 38.7 (24.5); MBzP 10.6 (6.6) to 25.8 (16.1); MEP 124 (47.1) to 1076 (225); and MiBP 2.3 (1.5) to 7.7 (4.8) ng/mL; ranges are reported for quartiles with the longest AGI (lowest levels) to the shortest AGI (highest levels) | 4 phthalate metabolites (MEP, MBP, MBzP, MiBP) were inversely related to AGI (anogenital distance divided by weight); compared with lowest quartile, shorter AGI was found for MBP (OR = 10.2; 95% CI = 2.5–42.2) | (63) | ||
| Phthalates (DEHP) | Participants from 12–19 y of age in the 2003–2008 NHANES study | n = 766 | Urine | Low-molecular-weight phthalate metabolites were 0.508 and 0.729 μM in boys and girls, respectively; high-molecular-weight phthalates were 0.313 and 0.380 μM (boys and girls); DEHP was 0.224 and 0.273 μM in boys and girls | Prevalence of insulin resistance as measured by HOMA-IR was greater in groups with higher DEHP metabolites. | (55) | ||
| Pesticides | Cohort of urban minority women | n = 314 African American and Dominican women in northern Manhattan and the South Bronx | Ambient air monitoring | Ranges: diazinon, 2–6010 ng/m3; chlorpyrifos, 0.7–193 ng/m3; propoxur, 3.8–1380 ng/m3 | 85% of women reported that pest control was used in the house during pregnancy; 100% had detectable levels of diazinon, chlorpyrifos, and propoxur | (64) | ||
| Pesticides | CHARGE study; California residents living in proximity (within 1.5 km) to agricultural pesticide use during pregnancy; children were aged 2–5 y | Children (970) were recruited from those with ASD or DD; age-matched referents were recruited from the general population | Chemical body burdens were not measured but estimated based on geographical proximity to use of organophosphate, carbamate, pyrethroid, or organochlorine classes | Most common pesticides were organophosphates, especially chlorpyrifos, then acephate and diazinon; the next-frequent pesticide class was pyrethroids | Children with ASD were 60% more likely to have organophosphates applied near the home during pregnancy, and those with DD were 150% more likely to have carbamate pesticides applied near the home; For ASD, second- and third-trimester exposures had the strongest positive associations | (135) |
Abbreviations: AGI, anogenital index; BASC-2, Behavior Assessment System for Children-2; BMI, body mass index; BRIEF-P, Behavior Rating Inventory of Executive Function-Preschool; CHARGE, Childhood Autism Risks from Genetics and Environment; CCP, U.S. Collaborative Perinatal Project; DD, developmental delay; DDE, dichlorodiphenyldichloroethylene; DDT, dichlorodiphenyltrichloroethane; DEHP, di-2-ethylhexylphthalate; FGR, fetal growth restriction; FTII (Fagan Test of Infant Intelligence); GluR1, glutamate receptor R1; HOMA-IR, homeostatic model assessment of insulin resistance; LC-MS/MS, liquid chromatography tandem mass spectrometry; MBP, mono-n-butyl phthalate; MBZP, monobenzyl phthalate; MEHHP, mono(2-ethyl-5-hydroxyhexyl) phthalate; MEOHP, mono(2-ethyl-5-oxohexyl) phthalate; MEP, monoethyl phthlate; MiBP, monoisobutyl phthalate; NHANES, National Health and Nutrition Examination Survey; NRI, N-methyl-d-aspartate receptor subunit 1; PBDE, polybrominated diphenyl ether; PCDD/F, polychlorinated dibenzo-p-dioxins and dibenzofurans; PFC, perfluorinated compound; PFOA, perfluorooctane; PFOS, perfluorooctane sulfonate; PSAI, preschool activities index; SHC, small head circumference; SRS, Social Responsiveness Scale; tOP, 4-tertiary-octylphenol.
a
Studies were selected based on their focus on prenatal/early postnatal/childhood exposure, and/or pregnancy outcomes.