Interspecies differences in perfluoroalkyl substances (PFAS) toxicokinetics and application to health-based criteria.

Toxicokinetics are important for extrapolating health effects and effect levels observed in laboratory animals to humans for purposes of establishing health-based criteria. We conducted a comprehensive review of key absorption, distribution, metabolism, and excretion (ADME) parameters across different mammalian species for five perfluoroalkyl substances (PFAS) and discussed how these data can be used to inform human health risk assessment of these substances. Our analysis revealed several notable differences among the different PFAS regarding species- and substance-specific tissue partitioning, half-life, and transfer to developing offspring via the placenta or lactation, as well as highlighted data gaps for certain substances.

Do individuals with asthma experience airway hyper-responsiveness after exposure to nitrogen dioxide?

The current 100 ppb short-term National Ambient Air Quality Standard for NO, and EPA's determination of a causal association for respiratory effects, are based in part on controlled human exposure studies evaluating airway hyper-responsiveness (AHR). A meta-analysis by Goodman et al. (2009) found increased AHR at 100 ppb NO but no clear concentration-response relationship up to 600 ppb, and an overall lack of an AHR effect for studies involving exercise or exposure to allergens.

Do group responses mask the effects of air pollutants on potentially sensitive individuals in controlled human exposure studies?

To establish primary National Ambient Air Quality Standards (NAAQS) for criteria air pollutants such as nitrogen dioxide (NO2), ozone (O3), and sulfur dioxide (SO2), US EPA relies in part on controlled human exposure studies. It has been suggested that evaluating average responses for all participants in these studies may not reflect the responses of sensitive participants in these studies. To evaluate this, we identified controlled exposure studies with multiple exposure concentrations or durations that provided individual-level lung function data.

Determining soil remedial action criteria for acute effects: the challenge of copper.

Gastrointestinal (GI) symptoms, the primary acute effect of the essential micronutrient copper, paradoxically occur at lower exposure levels than hepatotoxicity, the primary chronic effect. We developed a remedial action criterion (RAC) for copper to protect against GI symptoms, which primarily relate to the stomach copper concentration, and subside within an hour. Using Monte Carlo methods, we generated a distribution of RACs protective against GI symptoms for a 1 h exposure (hourly RACs) based on soil ingestion rate, volume of liquid and food in the stomach, and bioaccessibility.

Meta-analysis of nitrogen dioxide exposure and airway hyper-responsiveness in asthmatics.

The effects of 0.1 to 0.6 ppm nitrogen dioxide (NO2) on airway hyper-responsiveness (AHR) to airway challenges in asthmatics have been evaluated in several controlled exposure studies.

Effects of six months of daily low-dose perchlorate exposure on thyroid function in healthy volunteers.

Context: Perchlorate has been detected in U.S. drinking water supplies at levels ranging from 4 to 200 microg/liter as well as in agricultural products.