Serum levels of environmental pollutants is a risk factor for breast cancer in Inuit: a case control study. Environmental Health16,1 (2017): 56. doi:10.1186/s12940-017-0269-6. the contents by NLM or the National Institutes of Health. Association of osteoarthritis with perfluorooctanoate and perfluorooctane sulfonate in NHANES 20032008. Additionally, hypomethylation affects mostly repeated sequences in the genome and can contribute to carcinogenesis by triggering transcription of oncogenes and inducing genetic instability [68]. Environmental chemicals and breast cancer: an updated review of epidemiological literature informed by biological mechanisms. [37] Das, Kaberi P et al. and transmitted securely. Perfluorinated alkylated substances serum concentration and breast cancer risk: Evidence from a nested case-control study in the French E3N cohort. International Journal of Cancer146, 4 (2020): 917-928. doi:10.1002/ijc.32357. [41] Shi, Zhimin et al. RT @pfoaprojectny1: Overall, our study provides a better overview of the mechanisms associated with PFASs-induced breast cancer development and progression results showed breast cancer cell migration and invasion were promoted by PFOA. PFAS stands for per- and polyfluoroalkyl substances, breast cancer and an increased likelihood of miscarriage and developing high blood pressure and preeclampsia Int J Environ Res Public Health. Girardi P., Merler E. A mortality study on male subjects exposed to polyfluoroalkyl acids with high internal dose of perfluorooctanoic acid. Disclaimer. [6], immortalized cells are not subject to the Hayflick limit for the number of successive cell growth-and-division cycles, which is controlled in senescent, non-immortalized cells due to DNA damage or shortened telomeres resulting in cell death. [65] Fei, Chunyuan et al. Exposure to per- and polyfluoroalkyl substances leads to immunotoxicity: Epidemiological and toxicological evidence. As summer starts, its crucial for parents and caregivers to make their kids sun safety a priority. In addition, PFOA levels were associated with total serum IgE in this cohort [127]. Would you like email updates of new search results? Wang X., Kong B., He B., Wei L., Zhu J., Jin Y., Shan Y., Wang W., Pan C., Fu Z. In differentiating neurological cells, treatment with PFOA, PFOS, PFOSA and PFBS at micromolar concentrations increased oxidative stress via increased MDA production [102]. #PFAS. That represents a small percentage - about 1.5% - of all PFAS Binding interactions of perfluoroalkyl substances with thyroid hormone transport proteins and potential toxicological implications. Comparison of polyfluoroalkyl compound concentrations in maternal serum and amniotic fluid: a pilot study. Reproductive Toxicology34, 3 (2012): 312-6. doi:10.1016/j.reprotox.2012.05.039. Search Strategy. Benbrahim-Tallaa L, Lauby-Secretan B, Loomis D, et al. 1Environmental Working Group, Washington, DC 20009, USA; [emailprotected] (D.Q.A. PFAS Cui L., Liao C.Y., Zhou Q.F., Xia T.M., Yun Z.J., Jiang G.B. The following are available online at https://www.mdpi.com/1660-4601/17/5/1668/s1, Table S1: List of abbreviations for reviewed PFAS and data availability for key characteristics. A look at PFAs, 'forever chemicals' and how they're impacting WebPerfluorooctanoic acid (PFOA) and perfluorooctane sulfonate (PFOS) are part of a large group of lab-made chemicals known as perfluoroalkyl and polyfluoroalkyl substances (PFAS). Their potential as breast carcinogens is unclear. A significant body of data from both in vivo and in vitro studies, including mammalian and wildlife species, have confirmed that PFAS are capable of inducing ROS and/or a condition of oxidative stress. Most recently, an occupational cohort study in Italy found a nearly seven-fold increase in liver cancer mortality and a five-fold increase in lymphatic and hematopoietic cancer mortality in the highest tertile of PFOA exposure relative to non-chemical factory workers [36]. Elevated levels of perfluoroalkyl substances in breast cancer Thibodeaux J.R., Hanson R.G., Rogers J.M., Grey B.E., Barbee B.D., Richards J.H., Butenhoff J.L., Stevenson L.A., Lau C. Exposure to perfluorooctane sulfonate during pregnancy in rat and mouse. Low dose perfluorooctanoate exposure promotes cell proliferation in a human non-tumor liver cell line. One study found that both PFOA and PFOS enhanced the effects of estradiol in hormone-dependent human breast cancer cells. PFOA and PFOS both increased proliferation, cell migration and invasion of normal human breast epithelial cells and altered the expression of proteins involved in cell cycle regulation, including cyclin dependent kinase 4 [202,203]. Bouras E., Karakioulaki M., Bougioukas K.I., Aivaliotis M., Tzimagiorgis G., Chourdakis M. Gene promoter methylation and cancer: An umbrella review. Li Y., Fletcher T., Mucs D., Scott J.M., Lindh C.H., Tallving P., Jakobsson K. Half-lives of PFOS, PFHxS and PFOA after end of exposure to contaminated drinking water. ZOF on Twitter: "remember when the breast cancer orgs were Miura R., Araki A., Miyashita C., Kobayashi S., Kobayashi S., Wang S.L., Chen C.H., Miyake K., Ishizuka Y., Iwasaki Y., et al. [25] Kato, Kayoko et al. 26 Jun 2023 13:38:40 Regulatory agencies typically rely on the T cell-dependent antibody response (TDAR) assay in laboratory animals to evaluate immunosuppression [122]. Perfluorinated compounds are related to breast cancer risk in Greenlandic Inuit: A case control study. We conclude that there is strong evidence for an association for PFOA and long-chain PFAS and suggestive evidence for short-chain PFAS and this key characteristic. Importantly, these characteristics aid in cancer hazard classification through integrative evaluation with human and animal evidence of carcinogenicity. Lee J.K., Lee S., Baiek M.C., Lee B.H., Lee H.S., Kwon T.K., Park P.H., Shin T.Y., Khang D., Kin S.H. Chang E.T., Adami H.-O., Boffetta P., Cole P., Starr T.B., Mandel J.S. Perfluorochemicals and human semen quality: the LIFE study. Environmental Health Perspectives123, 1 (2015): 57-63. doi:10.1289/ehp.1307621. [75] Calafat, Antonia M et al. Cui R., Zhang H., Guo X., Cui Q., Wang J., Dai J. Proteomic analysis of cell proliferation in a human hepatic cell line (HL-7702) induced by perfluorooctane sulfonate using iTRAQ. Interestingly, inflammation may mediate PFAS transfer across the blood cerebrospinal fluid barrier in humans through enhanced barrier permeability [120]. A critical review of perfluorooctanoate and perfluorooctanesulfonate exposure and cancer risk in humans. van den Dungen M.W., Murk A.J., Kok D.E., Steegenga W.T. The 63-year-old was diagnosed with early-stage breast cancer following a routine mammogram. [54] PFBA has also been found in donor blood serum samples[55] and in samples from ski wax technicians who were exposed to high levels of PFASs. Importantly over 600 different PFAS were reported in active use over the past decade, yet for the majority of those compounds there is no toxicological information available. NTP Monograph on Immunotoxicity Associated with Exposure to Perfluorooctanoic Acid of Perfluorooctane Sulfonate. In a study of 181 Chinese male adults, the serum concentrations of eleven PFAS, PFOA, PFOS, PFBA, PFBS, PFDA, PFHpA, PFHxA, PFHxS, PFNA, PFUnA and PFDoA, and metabolome changes were evaluated [85]. Stein C.R., McGovern K.J., Pajak A.M., Maglione P.J., Wolff M.S. PFOA interacts with the ligand binding domain of estrogen receptors and while GenX had weaker estrogen binding ability, similar hexafluoropropylene homologues exhibited stronger affinity [178]. For example, exposure to xenobiotic substances that modulate estrogen and testosterone signaling pathways can influence breast and testicular cancer development [144,145,146,147]. One well-studied PFAS, perfluorooctanoic acid (PFOA) was reviewed by the International Agency for Research on Cancer (IARC) in 2016 and classified as group 2B, a possible human carcinogen [1]. Comparative in vivo and in vitro analysis of possible estrogenic effects of perfluorooctanoic acid. Miura and colleagues identified several differentially methylated regions associated with prenatal PFOA and PFOS exposure in this cohort [73]. Data are currently insufficient to assess whether any PFAS promote chronic inflammation, cellular immortalization or alter DNA repair. Interaction effects of polyfluoroalkyl substances and sex steroid hormones on asthma among children. Immunoenhancement can be defined as inappropriate activation of the immune system that can trigger hypersensitivity reactions such as allergies or autoimmune diseases and contribute to chronic inflammation, another key characteristic of carcinogens [121]. Guyton K.Z., Chiu W.A., Bateson T.F., Jinot J., Scott C.S., Brown R.C., Caldwell J.C. A reexamination of the PPAR-alpha activation mode of action as a basis for assessing human cancer risks of environmental contaminants. This state-of-the-science review summarizes the available data for several PFAS for each of the key characteristics of carcinogens and evaluates the strength of evidence for each characteristic. Duchess of York undergoes surgery to treat breast cancer Similarly, in a human liver cell line, PFOA caused hypermethylation of the promoter region of GSTp and upregulation of DNA methyltransferase 3, although no changes in global DNA methylation or promoter regions of other genes were observed [78]. A study of occupationally exposed workers reported a 3.3-fold increase in prostate cancer mortality for each month spent in the chemical division of PFOA production [33], although a re-analysis of this cohort did not detect an association between exposure and cancer mortality or incidence [34]. A study of Inuit women in Greenland showed that women with higher blood serum levels of PFOS, PFOA and total PFAS have an increased risk of breast cancer. In human bronchial epithelial cells, proinflammatory cytokine release resulted following exposure to PFOA and PFOS but not PFBS, PFHxS and the fluorotelomer 8:2 FTOH [119]. [66] Knox, Sarah S et al. 2018;160:152-182. Chemical specific study findings for key characteristic 10modulates receptor-mediated effects. [46] One study found PFBS in household cleaning products between 2007 and 2011. Per-and polyfluoralkyl substances (PFAS) in American Red Cross adult blood donors, 20002015. This stability renders the PFAS family of chemicals non electrophilic, relatively metabolically inert and resistant to metabolic activation [47]. Using evidence from established carcinogens, ten characteristics commonly exhibited by and shared among carcinogenic agents were identified (Table 1). Perfluorinated chemicals, PFOS and PFOA, enhance the estrogenic effects of 17-estradiol in T47D human breast cancer cells. Journal of Applied Toxicology36, 6 (2016): 790-801. doi:10.1002/jat.3210. Polyfluorinated compounds in serum linked to indoor air in office environments. Environmental Science & Technology46, 2 (2012): 1209-15. doi:10.1021/es2038257. DuPonts Teflon changed our lives, but also polluted our bodies. Song P., Li D., Wang X., Zhong X. Our findings contribute evidence supporting positive associations between serum PFOS and hormone receptor-positive tumors, and possibly between PFOA and receptor-negative tumors. This year, Breast Cancer Awareness Month coincides with deliberations in Congress on how to address PFAS in a must-pass military spending bill, the National Defense Authorization Act for FY 2020. Guyton K.Z., Rusyn I., Chiu W.A., Corpet D.E., van den Berg M., Ross M.K., Christiani D.C., Beland F.A., Smith M.T. Additionally, PFNA exposure in males was positively associated with elevated TSH levels [163]. Overall, there is somewhat suggestive evidence from epidemiological, animal and in vitro studies that PFOA, PFOS, PFDA and PFUnA may promote chronic inflammation, yet the number of studies are limited and biomarkers of chronic inflammation and identification of inflammatory diseases which are specific to PFAS exposures are needed to more fully characterize the relationship between exposure, chronic inflammation and risk for cancer development (Table 5). Bonefeld-Jorgensen E.C., Long M., Bossi R., Ayotte P., Asmund G., Kruger T., Ghisari M., Mulvad G., Kern P., Nzulumiki P., et al. [34] PFHxS along with other PFASs have been detected in breast milk, and it was concluded that breastfeeding is a considerable source of exposure to perfluorinated chemicals for infants. Instead, use ceramic coated non-stick or well-seasoned cast iron cookware. Gimenez-Bastida J.A., Surma M., Zielinski H. In vitro evaluation of the cytotoxicity and modulation of mechanisms associated with inflammation induced by perfluorooctanesulfonate and perfluorooctanoic acid in human colon myofibroblasts CCD-18Co. PFNA may lead to developmental and reproductive toxicity to males. Perfluorooctanoic acid induces oxidative damage and mitochondrial dysfunction in pancreatic -cells. Recently, research by the Halifax Project environmental mixtures task force highlighted that chemicals commonly present in human environment cause a variety of effects associated with hallmarks of cancer [194,214]. [46] Biomonitoring California. [54] Blaine, Andrea C, et al. Perfluoroalkyl acids: a review of monitoring and toxicological findings. Toxicological Sciences99, 2 (2007): 366-94. doi:10.1093/toxsci/kfm128. Environ Res. Polyfluoroalkyl substances (PFASs) are persistent pollutants that may cause breast cancer. Heres who is eligible for money from 3M PFAS Toxicogenomic study of triazole fungicides and perfluoroalkyl acids in rat livers predicts toxicity and categorizes chemicals based on mechanisms of toxicity. Trends in exposure to polyfluoroalkyl chemicals in the U.S. Population: 1999-2008. Environmental Science & Technology45, 19 (2011): 8037-45. doi:10.1021/es1043613. Butt C.M., Muir D.C.G., Mabury S.A. Biotransformation pathways of fluorotelomer-based polyfluoroalkyl substances: A review. Similarly, PFOA-treated male mice exhibited dose-dependent reductions in testosterone and progesterone levels, reduced sperm quality, damaged seminiferous tubules and increased testicular oxidative stress at doses of 0.31 to 20 mg/kg/day [91,165]. For PFOA, PFOS and PFHxS, half-lives in humans range between 2.7 to 5.3 years [49,50]. [7] These findings are consistent with the observation that PFASs are found in breast milk and passed on to the infant during breastfeeding. Vriens A., Nawrot T.S., Janssen B.G., Baeyens W., Bruckers L., Covaci A., De Craemer S., De Henauw S., Den Hond E., Loots I., et al. Further research aimed at measuring specific biomarkers of oxidative stress in connection with PFAS exposures in human populations as well as for short-chain PFAS would provide additional information regarding this key characteristic of carcinogens. All rights reserved. Mice exposed to PFOS during gestation exhibited decreased global DNA methylation in the liver as well as increased methylation of the glutathione-S-transferase Pi (GSTp) promoter [77]. Exploring the Relationship between PFAS Exposure and Breast Cancer Per-and polyfluoroalkyl substances (PFAS) are synthetic chemicals commonly found in everyday products due to their water and grease resistance properties. Steenland K., Kugathasan S., Barr D.B. Perfluorodecanoic acid stimulates NLRP3 inflammasome assembly in gastric cells. IARC Monographs on the Identification of Carcinogenic Hazard to Humans Preamble. 2007;115:1596-1602. [22] Parida, Sheetal, and Dipali Sharma. breast A critical review of perfluorooctanoate and perfluorooctanesulfonate exposure and immunological health conditions in humans. Published 2023. Washington, DC 20005. As documented in this state-of-the-science review, different PFAS chemicals exhibit multiple key characteristics of carcinogens and PFAS exposure can lead to a variety of Hallmarks of Cancer phenotypes, such as inflammation, dysregulated metabolism, change in intra- and extra-cellular signaling as well as weakening or suppression of immune response which is essential for defense against cancer. PFAS Therefore, there is strong evidence for an association between PFOA and other long-chain PFAS and this key characteristic (Table 4). Thompson P.A., Khatami M., Baglole C.J., Sun J., Harris S.A., Moon E.Y., Al-Mulla F., Al-Temaimi R., Brown D.G., Colacci A., et al. Glge J, Scheringer M, Cousins IT, et al. Biomonitoring of emerging contaminants, perfluoroalkyl and polyfluoroalkyl substances (PFAS), in New Jersey adults in 20162018. (2018) [5] for each key characteristic in combination with PFAS, perfluoro* or names, abbreviations and Chemical Abstract Services (CAS) numbers of individual chemicals. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (, GUID:8D464E92-4864-4E0C-B297-59A1E87BAFED, key characteristics of carcinogens, PFAS, oxidative stress, immunotoxicity, environmental carcinogen. 2021 Apr 5;18(7):3794. doi: 10.3390/ijerph18073794. Association between serum perfluorooctanoic acid (PFOA) and thyroid disease in the U.S. National Health and Nutrition Examination Survey. In rats, PFOA and PFOS increased serum estradiol level and protein expression of estrogen receptor alpha in uterus [175]. Recently, the Key Characteristics of Carcinogens framework was developed in order to facilitate the organization and characterization of mechanistic data for cancer hazard identification [5,6]. While hundreds of research studies have been published on the health harms due to individual PFAS, significant data gaps remain, particularly with respect to PFAS other than PFOA and PFOS, and for PFAS mixtures. 2014;15:924-925. International Agency for Research on Cancer. Prenatal perfluorooctyl sulfonate exposure and Alu DNA hypomethylation in cord blood. Poly- and perfluoroalkyl substance concentrations in human breast milk and their associations with postnatal infant growth. The Science of the Total Environment713 (2020): 136417. doi:10.1016/j.scitotenv.2019.136417. PFAS NTP Technical Report on the Toxicity Studies of Perfluoroalkyl Sulfonates (Perfluorobutane Sulfonic Acid, Perfluorohexane Sulfonate Potassium Salt, and Perfluorooctane Sulfonic Acid) Administered by Gavage to Sprague Dawley (Hsd:Sprague Dawley SD) Rats. Association between perfluorooctanoic acid exposure and degranulation of mast cells in allergic inflammation. As yet, information on the effects of other members of the PFAS family on proliferation, nutrient supply and cell death is not available. The 63-year-old was diagnosed with early-stage breast cancer following a routine mammogram. LONDON, UK Sarah, the Duchess of York, underwent surgery after being diagnosed with breast cancer, according to a spokesperson. [16] United States Environmental Protection Agency. [5] Mller, M H B et al. As noted in the Key Characteristics of Carcinogens framework by Smith et al. [11],[12] This has led manufacturers to begin replacing the longer-chain PFAS chemicals such as PFOA and PFOS with shorter-chain acids. Aside from the Reduced circulating levels of testosterone and estradiol were observed in children age 6 to 9 exposed to PFOA and PFOS and reduced levels of insulin-like growth factor-1 were observed in children exposed to PFNA and PFOS [155]. Received 2020 Jan 17; Accepted 2020 Feb 12. Developmental neurotoxicity of perfluorinated chemicals modeled in vitro. Environmental Health Perspectives116, 6 (2008): 716-22. doi:10.1289/ehp.11253. Liew Z., Goudarzi H., Oulhote Y. Developmental exposures to perfluoralkyl substances (PFASs): An update of associated health outcomes. Anogenital distance as a marker of androgen exposure in humans. International Agency for Research on Cancer . Di Nisio A., Sabovic I., Valente U., Tescari S., Rocca M.S., Guidolin D., DallAcqua S., Acquasaliente L., Pozzi N., Plebani M., et al. Overall, we identified strong evidence indicating that PFOA, several long-chain PFAS and short-chain PFAS can modulate receptor-mediated effects. Exposure to PFAS may result in elevated cholesterol, uric acid, and liver enzymes and changes in immune response. 27 Jun 2023 23:34:29 Steenland K., Zhao L., Winquist A. If two types of evidence had studies limited in number and/or design or reported largely inconsistent findings, the data were considered Insufficient to make an assessment. [9] Breastfeeding is still the best option for newborn and infant nutrition. Kingsley S.L., Kelsey K.T., Butler R., Chen A., Eliot M.N., Romano M.E., Houseman A., Koestler D.C., Lanphear B.P., Yolton K., et al. In the same adult study, serum PFOS and PFHxS levels were positively and negatively associated with mitochondrial DNA content respectively [198]. PFAS interactions with biological tissues and organisms are distinct from those of other environmentally persistent halogenated synthetic chemicals. In vitro evaluation of the immunotoxic potential of perfluorinated compounds (PFCs), Corsini E., Sangiovanni E., Avogadro A., Galbiati V., Viviani B., Marinovich M., Galli C.L., DellAgli M., Germolec D.R. a The following long-chain PFAS are not presented in the table since no data were avaible to assess this key characteristic: PFUnA, PFDoA, PFTrDA, PFTeDA, 8:2 monoPAP, 8:2 diPAP, 8:2 triPAP, 10:2 diPAP. PMC Exposure to perfluoroalkyl substances and thyroid function in pregnant women and children: A systematic review of epidemiologic studies. PFOA is a suspected endocrine (hormone) disruptor and possible carcinogen, and PFOS has been linked to fertility problems. [29], PFHxS (Perfluorohexane sulfonic acid) is also ubiquitous in the environment. ), formation of DNA and protein adducts, DNA damage (DNA strand breaks, DNA-protein cross-links, unscheduled DNA synthesis), intercalation, gene mutations, cytogenetic changes (e.g., chromosome aberrations, micronuclei), 3Alters DNA repair or causes genomic instability, Alterations of DNA replication or repair (e.g., topoisomerase II, base-excision or double-strand break repair, DNA methylation, histone modification, microRNAs, Oxygen radicals, oxidative stress, oxidative damage to macromolecules (e.g., DNA, lipids), Elevated white blood cells, myeloperoxidase activity, altered cytokine and/or chemokine production, Decreased immunosurveillance, immune system dysfunction, Receptor in/activation (e.g., ER, PPAR, AhR) or modulation of endogenous ligands (including hormones), Inhibition of senescence, cell transformation, 10Alters cell proliferation, cell death or nutrient supply, Increased proliferation, decreased apoptosis, changes in growth factors, energetics and signaling pathways related to cellular replication or cell-cycle control, angiogenesis. Perfluorinated chemicals: differential toxicity, inhibition of aromatase activity and alteration of cellular lipids in human placental cells. Toxicology and Applied Pharmacology277, 2 (2014): 124-30. doi:10.1016/j.taap.2014.03.012. Maternal plasma concentrations of perfluoroalkyl and polyfluoroalkyl substances during pregnancy and anogenital distance in male infants. [23] Fassler, Cecily S et al. If only one type of evidence provided positive findings, or if findings for distinct PFAS were inconsistent, then the overall evidence was considered Suggestive. PFOA also induces oxidative stress in a dose-dependent manner from 0.5 to 5 mg/kg/day in the mouse liver and pancreas [25], and a variety of tissues including rat pancreatic -cells [92], mouse testes and epididymis [93], and mouse ovary [94]. Mike remember when the breast cancer orgs were talking about how the rates of breast cancer were skyrocketing? sharing sensitive information, make sure youre on a federal Vetvicka V., Vetvickova J. Perfluoroalkyl Acid Uptake In Lettuce (lactuca Sativa) and Strawberry (fragaria Ananassa) Irrigated with Reclaimed Water. Environmental Science & Technology48, 24 (2014): 14361-14368. doi:10.1021/es504150h. (2010) [70] analyzed global DNA methylation in human umbilical cord serum from 30 newborns and reported an association between PFOA levels and global DNA hypomethylation. Rhee J, Barry KH, Huang WY, Sampson JN, Hofmann JN, Silverman DT, Calafat AM, Botelho JC, Kato K, Purdue MP, Berndt SI. NCI CPTC Antibody Characterization Program. Calafat A.M., Kato K., Hubbard K., Jia T., Botelho J.C., Wong L.Y. Breast cancer risk and serum levels of per- and poly-fluoroalkyl Impact on olfactory tissue were also observed for PFHxA, PFBS and PFHxS. Ng C.A., Hungerbuehler K. Exploring the use of molecular docking to identify bioaccumulative perfluorinated alkyl acids (PFAAs). Limitations in these epidemiologic studies include differences in reporting disease (incidence versus mortality) and different approaches for estimating PFAS exposure (job matrix estimates and water measurements versus direct biological serum measurements). WebResearch shows that exposure to PFAS (per- and polyfluoroalkyl substances) can cause breast cancer, according to a study in the Journal of Applied Toxicology. Hanahan D., Weinberg R.A. However, there was an association with higher PFHxS levels and the risk of hormone receptor negative (ER-/PR-) breast cancer. [53] A 2014 study found high accumulation levels on lettuce and strawberries irrigated with reclaimed water. a The following long-chain PFAS are not presented in the table since no data were avaible to assess this key characteristic: PFNA, PFDoA, PFTrDA, PFTeDA, PFOSA, 8:2 monoPAP, 8:2 diPAP, 8:2 triPAP, 10:2 diPAP; b The following short-chain PFAS are not presented in the table since no data were avaible to assess this key characteristic: PFHxA, PFBA, PFPeA, PFHpA, GenX (HFPO-DA); PMOH, PMPP/ADONA, 4:2 FTOH, 6:2 FTOH, 4:2 diPAP, 6:2 diPAP. Data concerning epigenetic effects of chemicals are becoming increasingly important for carcinogen hazard identification and are expected to become even more important in future cancer risk assessments [69]. Son H.Y., Lee S., Tak E.N., Cho H.S., Shin H.I., Kim S.H., Yang J.H. [28], PFOSA (Perfluorooctane sulfonamide) is a PFAS compound that breaks down to PFOS in the environment.