Assessment of perfluorocarboxylic acids in fluorinated high-density polyethylene containers and estimation of potential non-cancer risks associated with anticipated use scenarios.

High density polyethylene (HDPE) containers are fluorinated to impart barrier properties that prevent permeation of liquid products filled in the container. The process of fluorination may result in the unintentional formation of certain per- and polyfluoroalkyl substances (PFAS), specifically perfluoroalkyl carboxylic acids (PFCAs), as impurities. This study measured the amounts of PFCAs that may be present in the fluorinated HDPE containers, which could migrate into products stored in these containers. Migration studies were also conducted using water and mineral spirits to estimate the amount of PFCAs that might be found in the products stored in these containers. The migration results were used to conservatively model potential PFCA exposures from use of six product types: indoor-sprayed products, floor products, hand-applied products, manually-sprayed pesticides, hose-end sprayed products, and agricultural (industrial) pesticides. The potential that such uses could result in a non-cancer hazard was assessed by comparing the modeled exposures to both applicable human non-cancer toxicity values and environmental screening levels. Environmental releases were also compared to aquatic and terrestrial predicted no-effect concentrations (PNECs). The results of these analyses indicated no unreasonable non-cancer risk to humans, aquatic species, and terrestrial species from PFCAs in products stored in fluorinated HDPE containers.

Adverse Outcome Pathway Network-Based Assessment of the Interactive Effects of an Androgen Receptor Agonist and an Aromatase Inhibitor on Fish Endocrine Function.

Predictive approaches to assessing the toxicity of contaminant mixtures have been largely limited to chemicals that exert effects through the same biological molecular initiating event. However, by understanding specific pathways through which chemicals exert effects, it may be possible to identify shared "downstream" nodes as the basis for forecasting interactive effects of chemicals with different molecular initiating events. Adverse outcome pathway (AOP) networks conceptually support this type of analysis. We assessed the utility of a simple AOP network for predicting the effects of mixtures of an aromatase inhibitor (fadrozole) and an androgen receptor agonist (17ß-trenbolone) on aspects of reproductive endocrine function in female fathead minnows. The fish were exposed to multiple concentrations of fadrozole and 17ß-trenbolone individually or in combination for 48 or 96 h. Effects on 2 shared nodes in the AOP network, plasma 17ß-estradiol (E2) concentration and vitellogenin (VTG) production (measured as hepatic vtg transcripts) responded as anticipated to fadrozole alone but were minimally impacted by 17ß-trenbolone alone. Overall, there were indications that 17ß-trenbolone enhanced decreases in E2 and vtg in fadrozole-exposed fish, as anticipated, but the results often were not statistically significant. Failure to consistently observe hypothesized interactions between fadrozole and 17ß-trenbolone could be due to several factors, including lack of impact of 17ß-trenbolone, inherent biological variability in the endpoints assessed, and/or an incomplete understanding of interactions (including feedback) between different pathways within the hypothalamic-pituitary-gonadal axis. Environ Toxicol Chem 2020;39:913-922. © 2020 SETAC.