hormonal effects including alteration of thyroid hormone levels at very high concentrations animal studies show developmental toxicity from reduced birth size, physical developmental delays, endocrine disruption, and neonatal mortality. pfoa alters lipid metabolism. it is an agonist of pparα and is a peroxisome proliferator in rodents contributing to a well understood form of oxidative stress. humans are considered less susceptible to peroxisome proliferation than rodents. however, pfoa has been found to be a liver carcinogen in rainbow trout via a potential estrogenic mechanism, which may be more relevant to humans. pfoa has been described as a member of a group of "classic non-genotoxic carcinogens". however, a provisional german assessment notes that a 2005 study found pfoa to be genotoxic via a peroxisome proliferation pathway that produced oxygen radicals in hepg2 cells, and a 2006 study demonstrated the induction and suppression of a broad range of genes; therefore, it states that the indirect genotoxic (and thus carcinogenic) potential of pfoa cannot be dismissed. an additional study has shown pfoa to be developmentally toxic, hepatotoxic, immunotoxic, and to have negative effects of thyroid hormone production. criteria have been proposed that would allow pfoa, and other perfluorinated compounds, to be classified as "weakly non-specific genotoxic". endocrine disruption of sexual steroids in 2018, an in vitro toxicology study analyzed the disruptor effect of pfos and pfoa on porcine ovarian cell steroidogenesis. specifically, the study focused on secretion in porcine theca and granulosa cells, controlling gonadotropic stimulation. five ovaries were obtained and dissected to collect theca and granulosa cells. the experimental design included: evaluation of pfos and pfoa on basal steroid secretion, stimulation of lh on theca cells and fsh on granulosa cells, effect of pfos and pfoa on steroidogenesis in the stimulated cells, quantification of steroid hormones by chemiluminescence, protein content determination, statistical analysis. the treatment groups had 9 data points each, from which the mean and standard deviation were calculated. the control group had 15 data points. a multi-factor analysis of variance (anova) and tukey's test were used for the concentrations of p4, a4 and e2. the two groups were compared using a student's "t", with statistical significance set at p < 0.05. results show the disruptor effect of pfos and pfoa depends on cell type. pfos and pfoa inhibit the secretion of steroid hormones in both theca cells and granulosa cells with gonadotropic stimulus. in cells without gonadotropic stimulus, pfos inhibit theca cells but not granulosa, while pfoa inhibit granulosa cells but not theca. these differences are explained by the different types of ppars in cell type. the study used concentrations below the range found in human blood circulation, suggesting that this may occur in human population. these results indicated pfos and pfoa act as endocrine disruptors on ovarian cells which could affect subsequent sexual steroids. human data pfoa is resistant to degradation by natural processes such as metabolism, hydrolysis, photolysis, or biodegradation and has been found to persist in the environment. pfoa is found in environmental and biological fluids as the anion perfluorooctanoate. pfoa can be absorbed from ingestion and can penetrate skin. the acid headgroup of pfoa enables binding to proteins with fatty acid or hormone substrates such as serum albumin, liver fatty acid-binding protein, and the nuclear receptors pparα and possibly car. in animals, pfoa is mainly present in the liver, blood, and kidneys. pfoa does not accumulate in fat tissue, unlike traditional organohalogen persistent organic pollutants. in humans, pfoa has an average elimination half-life of about three years. because of this long half-life, pfoa has the potential to bioaccumulate. the levels of pfoa exposure in humans vary widely. while an average american might have 3 or 4 parts per billion of pfoa present in their blood serum, individuals occupationally exposed to pfoa have had blood serum levels over 100,000 parts per billion (100 parts per million or 0.01%) recorded. in a study of individuals living around dupont's washington works plant, those who had no occupational exposure had a median blood serum level of 329 parts per billion while the median of those with occupational exposure was 775 parts per billion. while no amount of pfoa in humans is legally recognized as harmful, dupont was "not satisfied" with data showing their chinese workers accumulated an average of about 2,250 parts per billion of pfoa in their blood from a starting average of around 50 parts per billion less than a year prior. in late 2012, scientists at emory university compared health risks in workers at a dupont chemical plant in west virginia with high pfoa exposure to the risks of the same diseases in other regional dupont factory workers and in the us population. in comparison with the other dupont workers, workers at the high-pfoa plant were at roughly three times the risk of dying of mesothelioma or chronic kidney disease, and roughly twice the risk of dying of diabetes mellitus. workers were at similarly elevated risk for kidney cancer and for non-cancer kidney diseases. in rodents, pfoa concentrates in the kidneys. consumers single cross-sectional studies on consumers have been published noting multiple associations. blood serum levels of pfoa were associated with an increased time to pregnancy—or "infertility"—in a 2009 study. pfoa exposure was associated with decreased semen quality, increased serum alanine aminotransferase levels, and increased occurrence of thyroid disease. in a study of 2003–2004 us samples, a higher (9.8 milligram per deciliter) total cholesterol level was observed when the highest quartile was compared to the lowest. along with other related compounds, pfoa exposure was associated with an increased risk of attention deficit hyperactivity disorder (adhd) in a study of us children aged 12–15. in a paper presented at the 2009 annual meeting of the international society of environmental epidemiology, pfoa appeared to act as an endocrine disruptor by a potential mechanism on breast maturation in young girls. a c8 science panel status report noted an association between exposure in girls and a later onset of puberty. pfoa exposure and incident cancer research extensive research on pfoa and its role in the causal pathway of cancers exists for animals, however human studies are rare—most studies are mortality studies, which have small sample sizes. a longitudinal study focused on residents living in mid-ohio valley concluded that pfoa concentrations are positively associated with kidney and testicular cancers . the study consisted of 32,254 residents with 2,507 reported cancer diagnoses occurring during study period. pfoa serum concentrations were measured at baseline and three to six year follow-up meetings. retrospective yearly pfoa serum levels were estimated for each subject from 1952 through 2011. initial subject recruitment was performed using eligibility criteria and surveys—subjects were eligible if they lived or worked in one of the six contaminated water districts for at least one year between 1950 and december 3, 2004. follow-up surveys were administered and remaining subjects (completion of at least one survey) were then included in the analysis dataset—selection bias was assessed and the final subjects did not differ significantly from the original population. retrospective pfoa serum concentrations were calculated using the published method of shin et al. 2011a, 2011b). historical regional data including emission rates by the dupont facility, temporal patterns and groundwater flow are incorporated in the model as well as individual specific occupational exposure level was included. a job-exposure matrix was developed to assess estimated pfoa levels for workers across times and job roles. incident data was self-reported by study participants and followed up with a medical chart review. cancer diagnoses were verified using ohio/west virginia cancer registries. a proportional hazards regression model was used for each cancer type with the cancer as the outcome and pfoa serum level included as a time-varying covariate. participants were followed from age 20 (or age in 1952) to the age of cancer diagnosis. models were adjusted for time-varying- smoking and alcohol consumption, as well as sex, education and five-year birth cohort. the outcome of pfoa serum level was log-transformed due to the scarcity of very high cumulative exposure values. participants who worked at the dupont facility had higher pfoa serum levels and higher estimated annual pfoa levels than subjects who never worked at the facility. after cancer diagnosis validation, thyroid, kidney and testicular cancer risk were found to increase with an increase in the pfoa serum concentration (log-transformed), with testicular cancer being significantly associated (α =0.05). the results are consistent with previous mortality analyses performed using dupont data. there is a positive exposure-response trend for cancer incidence and pfoa serum levels. kidney and testicular cancer are of interest given that animal studies have found that pfoa is distributed mainly in the kidneys and because pfoa has been found to induce testicular tumors in rats. impact of in utero exposure on reproductive organs due to the fact that pfoa is able to readily pass through the placental barrier, exposure is of particular concern during in utero development. numerous studies have analyzed the impacts of pfoa on fetal development of reproductive organs. one study that followed a danish pregnancy cohort suggests that in utero exposure to pfoa could be associated with lower levels of sperm concentration and total sperm count in adult males, reduced testicular size, and higher adjusted levels of luteinizing hormone and follicle-stimulating hormone. in utero pfoa exposure is also demonstrated to impact female development. for example, a study following a danish population-based cohort found a 5.3 month later age of menarche in girls exposed to higher levels of pfoa in utero. delayed onset of menarche is associated with lower bone mineral density and may have psychosocial impacts. other impacts on exposure in utero pfoa exposure on thyroid function has also been a topic of concern, and has found to negatively impact thyroid stimulating hormone even at low levels when exposed during fetal development. pfoa is also shown to have obesogenic effects, and an experimental study found a positive correlation to low-dose prenatal exposure of pfoa and prevalence of overweight and high waist circumference in females at age 20. a correlation between in utero pfoa exposure and mental performance has yet to be established, as many studies have resulted in insignificant results. for example, a study conducted near parkersburg, west virginia did not find a significant association between in utero pfoa exposure and performance of math skills or reading performance in children ages 6 to 12 living in the pfoa-contaminated water district. based on a cohort study conducted in the mid-ohio valley, no clear association was found between prenatal exposure to pfoa and birth defects, although a possible association with brain defects was observed and requires further research and assessment. pfoa has been associated with signs of reduced fetal growth including lower birth weight. however, other studies have not replicated the lower birth weight finding including a study on the dupont exposed community. extrapolated epidemiological data suggests a slight association between pfoa exposure and low birth weight. this was consistent based on blood levels of pfoa metabolites regardless of the geographic residence of subjects. generally, the findings among human fetuses exposed to the chemical were considerably less drastic than what was seen in mice studies. because of this, studies linking exposure to low birth weight can be considered inconclusive. pfoa exposure in the danish general population was not associated with an increased risk of prostate, bladder, pancreatic, or liver cancer. maternal pfoa levels were not associated with an offspring's increased risk of hospitalization due to infectious diseases, behavioral and motor coordination problems, or delays in reaching developmental milestones. employees and dupont exposed community in 2010, the three members of the c8 science panel published a review of the epidemiological evidence on pfoa exposure in environmental health perspectives. insufficient evidence exists to conclude pfoa causes adverse health effects in humans, but consistent evidence exists on associations with higher cholesterol and uric acid. whether or not these potential effects result in an increase in cardiovascular disease is unknown. further data on the 69,030 member cohort that is being studied by the panel is scheduled for release through 2012. a 2011 epidemiological study demonstrated "probable link" between pfoa and kidney cancer, testicular cancer, thyroid disease, high cholesterol, pre-eclampsia and ulcerative colitis. facial birth defects, an effect observed in rat offspring, occurred with the children of two out of seven female dupont employees from the washington works facility from 1979 to 1981. bucky bailey is