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3 Potential Health Effects of PFAS
Pages 57-101

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From page 57...
... MeFOSAA Methylperfluorooctane sulfonamidoacetic acid 2355-31-9 PFHxS Perfluorohexanesulfonic acid 355-46-4 perfluorohexane sulfonic acid n-PFOA (linear isomer) , Sb-PFOA Perfluorooctanoic acid 335-67-1*
From page 58...
... As detailed in Appendix D, the committee focused on the findings from the following organizations, presented in chronological order by year the literature search was completed:  C-8 Science Panel reports (last report published 2012)  European Food Safety Authority (EFSA)
From page 59...
... Review of Systematic Reviews As detailed in Appendix D, the committee's review of systematic reviews consisted of the following steps: a literature search, screening of abstracts, a full-text review of studies identified in the abstract screening, and evaluation of a final set of relevant studies. The literature search identified 639 potentially relevant articles, of which 26 systematic reviews met the committee's inclusion criteria and were evaluated using AMSTAR-2 (A MeaSurement Tool to Assess systematic Reviews)
From page 60...
... Evidence Synthesis To assess the strength of evidence regarding the potential for PFAS to cause a particular health effect, the committee integrated the evidence reviewed in ATSDR's Toxicological Profile for Perfluoroalkyls with the evidence from its review of the original epidemiologic studies. A framework based on the Hill considerations, which help determine whether associations are causal, guided the synthesis of available evidence (Fedak et al., 2015; Hill, 1965; NASEM, 2018a)
From page 61...
... FIGURE 3-1 Evidence map describing the number of studies found, by PFAS, for each health outcome category. NOTES: MeFOSAA = methylperfluorooctane sulfonamidoacetic acid; PFDA = perfluorodecanoic acid; PFHxS = perfluorohexanesulfonic acid; PFNA = perfluorononanoic acid; PFOA = perfluorooctanoic acid; PFOS = perfluorooctanesulfonic acid; PFUnDA = perfluoroundecanoic acid; sumPFAS = the additive sum of PFAS.
From page 62...
... COMMITTEE'S CONCLUSIONS Annex Table 3-1 at the end of the chapter summarizes the health outcomes considered by the committee, the relevant conclusions from authoritative reviews, and the committee's overall conclusions for endpoints relevant to each outcome. The committee's conclusions reflect its integration of evidence reviewed in ATSDR's Toxicological Profile for Perfluoroalkyls and other authoritative reviews with the evidence garnered from the review of recent epidemiologic studies.
From page 63...
... With one exception (decreased infant and fetal growth) , the committee provided forest plots for all outcomes with sufficient evidence of an association to display effect estimates from the studies with low or probably low risk of bias.
From page 64...
... Taken together, these three recent studies add support for the conclusion of sufficient evidence of an association between PFAS exposure and decreased antibody response. The committee reviewed four papers focused on specific infectious diseases (chicken pox, common cold, otitis media, pneumonia, and respiratory tract infection)
From page 65...
... The committee reviewed several studies evaluating the impact of PFAS exposure on allergic symptoms and disease, all with a probably low risk of bias. The specific outcomes studied included allergies to food and inhaled substances, atopic dermatitis, dermatitis, changes in serum immunoglobulin E (IgE)
From page 66...
... 66 Guidance on PFAS Exposure, Testing, and Clinical Follow-Up FIGURE 3-5 Regression coefficients for percent change in hand, foot, and mouth disease antibody response per doubling of natural logarithm (ln) -nanograms per milliliter (ng /mL)
From page 67...
... As noted in authoritative reviews by the EPA and OECD, the C-8 Science Panel identified an association between PFAS and ulcerative colitis, a rare autoimmune condition of the gastrointestinal (GI) tract.
From page 68...
... The committee concluded that the evidence is insufficient for other findings related to cardiovascular risk factors and nonpregnancy clinical cardiovascular diseases. This conclusion is consistent with those of the authoritative reviews, which concluded that there was mixed to limited evidence supporting associations between PFAS and cardiovascular risk factors and diseases other than the four discussed above because of inconsistencies in measurement, differences in study designs and populations, and differences in adjustment for potential confounding factors.
From page 69...
... Overall, the committee concluded that there is sufficient evidence of an association between PFAS and dyslipidemia, as the recent epidemiologic literature provides additional confidence in the conclusions of authoritative reviews regarding this association. FIGURE 3-6 Regression coefficients for changes in total cholesterol in adults.
From page 70...
... The committee identified four studies rated as having probably low or definitely low risk of bias that evaluated the impact of PFAS exposure on hypertension, blood pressure, systolic blood pressure, and diastolic blood pressure (Donat-Vargas et al., 2019b; Lin et al., 2020b; Mitro et al., 2020a)
From page 71...
... for PFOA, but not for PFOS and PFHxS. The study in Shanghai, China, was a prospective birth cohort study that measured 10 PFAS in cord blood plasma and assessed child adiposity measures at 5 years of age.
From page 72...
... conducted a cohort study with probably low risk of bias and reported inconsistent findings regarding PFAS and anogenital distance. Although the authors observed an association between PFOA (measured in first-trimester maternal plasma)
From page 73...
... Autism spectrum disorder The committee identified four studies with low or probably low risk of bias evaluating the impacts of PFAS exposure on autism spectrum disorder (Long et al., 2019; Lyall et al., 2018; Oh et al., 2021; Shin et al., 2020)
From page 74...
... The committee concluded that there is limited or suggestive evidence for cancers of the testis and breast. The conclusion on testicular cancer is consistent with the authoritative reviews, and the finding on breast cancer is based on the more recent epidemiological studies considered by the committee.
From page 75...
... FIGURE 3-9 Testicular cancer adjusted rate ratios and 95% confidence intervals by study and PFOA exposure category. DATA SOURCES: Barry et al., 2013; Vieira et al., 2013.
From page 76...
... The committee found that this body of literature constitutes limited or suggestive evidence of an association of PFAS exposure with breast cancer. Reproductive Outcomes In its review of reproductive outcomes, the committee considered evidence on hypertensive disorders of pregnancy, female reproductive effects, reproductive hormone levels, infertility and subfecundity, and gestational diabetes.
From page 77...
... FIGURE 3-10 Breast cancer adjusted rate ratios and 95% confidence intervals by study and PFOS exposure category. NOTE: ER = estrogen receptor; PR = progesterone receptor.
From page 78...
... Fertility and Fecundity A conclusion in ATSDR's Toxicological Profile for Perfluoroalkyls is that "epidemiological studies provided mixed evidence of impaired fertility (increased risks of longer time to pregnancy and infertility) for PFOA, PFOS, PFHxS PFNA, PFHpA, and PFBS: the results are not consistent across studies or were only based on a single study.
From page 79...
... Potential Health Effects of PFAS 79 FIGURE 3-12 Adjusted risk estimates for preeclampsia, gestational hypertension (hypertension without preeclampsia) , and hypertensive disorders of pregnancy and 95% confidence intervals by study and PFOA exposure category.
From page 80...
... conducted a small cohort study in a fertility clinic in Zhejiang, China, that evaluated the association between PFAS exposure and fertility measures (numbers of retrieved oocytes, mature oocytes, two-pronuclei (2 PN) zygotes, goodquality embryos, and semen parameters)
From page 81...
... FIGURE 3-14 Adjusted risk estimates for preeclampsia, gestational hypertension (hypertension without preeclampsia) , and hypertensive disorders of pregnancy and 95% confidence intervals by study and PFHxS exposure category.
From page 82...
... , and hypertensive disorders of pregnancy and 95% confidence intervals by study and PFNA exposure category. NOTE: All studies present odds ratios except Birukov et al., 2021, which presents a hazard ratio.
From page 83...
... , and the committee identified no new studies of these effects. In its Toxicological Profile for Perfluoroalkyls, ATSDR concludes that there is some suggestive evidence of an association between serum PFAS levels and an increased risk of early menopause; however, this finding may be due to reverse causation since an earlier onset of menopause would result in a decrease in the removal of perfluoroalkyls in menstrual blood.
From page 84...
... Thyroid Hormones and Disease The authoritative review of the C-8 Science Panel and subsequent authoritative reviews completed by ATSDR, EPA, and OECD found associations between PFAS exposure and thyroid hormones and disease. Among the more recent cohort studies with probably low or low risk of bias, the majority observed weak to no association with thyroid hormone levels or subclinical hypothyroidism in children and adults (Blake et al., 2018; Itoh et al., 2019; Jansen et al., 2020; Kim et al., 2020; Lebeaux et al., 2020; Liang et al., 2020; Preston et al., 2020b; Reardon et al., 2019; Xiao et al., 2020)
From page 85...
... Taken together, the committee concludes that the available studies provide limited or suggestive evidence of an association between PFAS exposure and liver enzyme levels. Respiratory Outcomes Authoritative reviews, including those of ATSDR, EFSA, and EPA, have not yet drawn conclusions about PFAS exposure and respiratory effects.
From page 86...
... Neurological Outcomes The authoritative reviews do not draw conclusions about the impact of PFAS on neurological outcomes, such as changes in motor function; behavioral changes; mood disorders; sensory disorders; cognitive disorders; and changes in neurochemistry, neurophysiology, or neuropathology. One recent case-control study nested within the diabetes prevention trial mentioned above found no association between any PFAS measured in serum and neuropathy in either the diabetes cases or the controls (Cardenas et al., 2019)
From page 87...
... It is critical to recognize that an assessment of inadequate or insufficient evidence does not mean there is no significant and important association between PFAS exposure and the outcome under consideration. It is quite possible that further research into the association of PFAS exposure with these outcomes would provide the evidence necessary to change the assessment to the category of either limited or suggestive or sufficient evidence.
From page 88...
... 2019. Association between prenatal exposure to perfluoroalkyl substances and asthma in 5-year-old children in the Odense Child Cohort.
From page 89...
... 2018. Prenatal exposure to perfluoroalkyl and polyfluoroalkyl substances and childhood atopic dermatitis: A prospective birth cohort study.
From page 90...
... 2019. Exposure to perfluoroalkyl substances during fetal life and pubertal development in boys and girls from the Danish National Birth Cohort.
From page 91...
... 2020. Association between prenatal exposure to perfluoroalkyl substances and respiratory tract infections in preschool children.
From page 92...
... 2020. Prenatal exposure to 11 perfluoroalkyl substances and fetal growth: A large scale, prospective birth cohort study.
From page 93...
... 2019. Prenatal exposure to perfluoroalkyl substances, immune-related outcomes, and lung function in children from a Spanish birth cohort study.
From page 94...
... 2018. Maternal plasma concentrations of per- and polyfluoroalkyl substances and breastfeeding duration in the Norwegian mother and child cohort.
From page 95...
... 2018. Prenatal exposure to perfluoroalkyl substances: Infant birth weight and early life growth.
From page 96...
... 2020. Maternal serum levels of perfluoroalkyl substances in early pregnancy and offspring birth weight.
From page 97...
... 2018. Association of perfluoroalkyl and polyfluoroalkyl substances with premature ovarian insufficiency in Chinese Women.
From page 98...
... A large epidemiological study of 69,000 persons conducted by the C-8 Science Panel found probable links between elevated PFOA blood levels and ulcerative colitis.
From page 99...
... Inadequate or insufficient: EFSA: Epidemiological studies provide clear evidence of an association between exposure to other outcomes PFOS, PFOA, and PFNA and increased serum levels of cholesterol. There is insufficient evidence of associations with diabetes, obesity, and metabolic syndrome.
From page 100...
... , 8:2 FTOH, and PFOA show endocrine effects in different in fecundity, infertility, male vitro and in vivo tests. The C-8 Science Panel's epidemiological study of 69,000 persons reproductive effects, found probable links between elevated PFOA blood levels and preeclampsia and elevated female reproductive effects, blood pressure during pregnancy.
From page 101...
... Respiratory Respiratory symptoms, None Insufficient pulmonary function, respiratory diseases Hematological Blood disorders or impacts on None Insufficient blood-forming organs Musculoskeletal Loss of muscle tone or None Insufficient strength, muscular rigidity, muscular atrophy, arthritis, altered bone density, arthralgia (joint pain) Renal Kidney disease and None Insufficient biomarkers of renal function Neurological Parkinson's disease, memory None Insufficient loss, neuropsychological function NOTE: ATSDR = Agency for Toxic Substances and Disease Registry; EFSA = European Food Safety Authority; EPA = U.S.


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