Perfluorooctanoic acid (PFOA) is a member of a family of synthetic perfluorinated compounds with extremely high stabilities. PFOA has been widely used in the production of numerous industrial and consumer products (flame retardants, water and oil repellent coatings for fabrics and food packaging, paint additives, electrical insulation and many others). PFOA is one of the most common persistent organic pollutants in the environment. Biomonitoring studies have shown that PFOA and other perfluorinated chemicals are found as global pollutants in air, water and soil, and also are detected in blood samples from almost all organisms sampled including human populations. The Breast Cancer and Environment Research Centers Epidemiology Project identified a subgroup of girls in the University of Cincinnati cohort who had above average concentrations of PFOA in their serum. The peripubertal period in females is thought to be an important window of breast susceptibility to environmental exposures that may affect breast cancer risk later in life. The effects of PFOA in pubertal girls is not known.
We have examined the effect of PFOA exposure in female mice during the peripubertal period (21 through 50 days of age). The effects of PFOA (doses 0.1 – 10 mg/kg BW) were examined in two strains of mice (Balb/c and C57BL/6) which are known to have genetically determined differences in mammary gland development and responses to hormones. PFOA treatment caused: 1) pathological changes in the liver, 2) delayed onset of puberty, 3) changes in uterine development, and 4) alterations in mammary gland development. Changes in the liver and delayed onset of puberty were similar in the 2 mouse strains. However, while Balb/c mice exhibited only inhibition of mammary gland and uterine development (5, 10 mg/kg doses), C57BL/6 mice exhibited stimulatory effects in both organs at low dose (5 mg/kg) and inhibition at higher dose (10 mg/kg).
Summary: These results demonstrate in mice that peripubertal exposure to PFOA has detrimental effects in the liver, uterus, onset of puberty and mammary gland development. However, there were significant differences in the effects based on genetic background. This underscores the need for caution when drawing conclusions about the effects of PFOA and possibly other environmental pollutants on the basis of studies in a single mouse strain. This is particularly relevant for identifying the effects of PFOA in the genetically heterogeneous human population.
This study was supported by the Breast Cancer and the Environment Research Center Grant 1-UO1 ESO12800 01 from National Institute of Environmental Health Sciences