Incorporating human exposure information in a weight of evidence approach to inform design of repeated dose animal studies.

Human health risks from chronic exposures to environmental chemicals are typically estimated from potential human exposure estimates and dose-response data obtained from repeated-dose animal toxicity studies. Various criteria are available for selecting the top (highest) dose used in these animal studies. For example, toxicokinetic (TK) and toxicological data provided by shorter-term or dose range finding studies can be evaluated in a weight of evidence approach to provide insight into the dose range that would provide dose-response data that are relevant to human exposures.

Opportunities and challenges related to saturation of toxicokinetic processes: Implications for risk assessment.

Top dose selection for repeated dose animal studies has generally focused on identification of apical endpoints, use of the limit dose, or determination of a maximum tolerated dose (MTD). The intent is to optimize the ability of toxicity tests performed in a small number of animals to detect effects for hazard identification. An alternative approach, the kinetically derived maximum dose (KMD), has been proposed as a mechanism to integrate toxicokinetic (TK) data into the dose selection process.

Reducing the need for animal testing while increasing efficiency in a pesticide regulatory setting: Lessons from the EPA Office of Pesticide Programs' Hazard and Science Policy Council.

As part of EPA's commitment to reducing animal testing, the Office of Pesticide Programs (OPP) created the Hazard and Science Policy Council (HASPOC). This group considers requests for waiving animal study requirements for human health risk assessments and makes recommendations based on a weight-of-the-evidence approach. Since its inception in 2012, the HASPOC has evaluated over one thousand requests to waive animal studies required by default for pesticide evaluation.

Stressful life events and the tripartite model: relations to anxiety and depression in adolescent females.

Although the tripartite model reliably distinguishes anxiety and depression in adolescents, it remains unclear how negative affectivity (NA) and positive affectivity (PA) influence developmental pathways to internalizing problems. Based on models which propose that affectivity shapes how youth react to stress, the present study attempted to investigate the relative roles of NA, PA, and stressful life events in characterizing and differentiating adolescent anxiety and depression. A sample of adolescent females (N=63), including a sub-sample of adolescent mothers, completed measures of NA, PA, negative life event (NLE) occurrence, anxiety, and depression.