Increasing the utility of epidemiologic studies as key evidence in chemical risk assessment.

The Society of Toxicology 2024 meeting assembled risk assessors, epidemiologists, and toxicologists to discuss the utility of integrating epidemiologic data into the derivation of reference values. Advantages of the use of epidemiologic evidence include (i) human relevance; (ii) increased likelihood that exposure levels are relevant to risk assessment; and (iii) incorporation of uncertainties attributed to co-exposures or other population-based considerations. The workshop panelists discussed the challenges of incorporating epidemiologic evidence due to uncertain exposure measurements, confounding, heterogeneity, and inherent study design limitations.

Retrospective analysis of dog study data from food and color additive petitions.

As part of the US FDA CFSAN's efforts to explore alternatives to animal testing, we retrospectively analyzed a sample of food additive (FAP) and color additive petitions (CAP) submitted to the FDA for the utility of dog study data in safety assessment. FAPs and CAPs containing dog studies (161 petitions) were classified as decisive (38%), supportive (27%), supplemental (29%) or undermined (6%) based on the impact the dog study data had on the final safety decision. Petitions classified as decisive were further categorized based on if the dog study data were used to a) address a safety concern (35/61); b) calculate an acceptable daily intake (ADI) (11/61); c) withdraw a petition (4/61); d) the effect was unique to the dog (2/61); or e) unclear (9/61).

Reassessment of the cadmium toxicological reference value for use in human health assessments of foods.

The U.S. Food and Drug Administration (FDA) developed an oral toxicological reference value (TRV) for characterizing potential health concerns from dietary exposure to cadmium (Cd).

A systematic review of adverse health effects associated with oral cadmium exposure.

Scientific data characterizing the adverse health effects associated with dietary cadmium (Cd) exposure were identified in order to make informed decisions about the most appropriate toxicological reference value (TRV) for use in assessing dietary Cd exposure. Several TRVs are available for Cd and regulatory organizations have used epidemiologic studies to derive these reference values; however, risk of bias (RoB) evaluations were not included in the assessments. We performed a systematic review by conducting a thorough literature search (through January 4, 2020).

Cadmium physiologically based pharmacokinetic (PBPK) models for forward and reverse dosimetry: Review, evaluation, and adaptation to the U.S. population.

The goal of this study was to assess a cadmium (Cd) physiologically based pharmacokinetic (PBPK) model to evaluate Cd toxicological reference values (e.g. reference dose, tolerable intake, minimum risk level) adapted to the U.

A scoping review of infant and children health effects associated with cadmium exposure.

The U.S. FDA initiative, Closer to Zero, identifies actions the agency will take to reduce toxic element exposure from foods eaten by babies and young children with the goal for exposure to be as low as possible.

Cadmium: Mitigation strategies to reduce dietary exposure.

Cadmium has long been recognized as an environmental contaminant that poses risks to human health. Cadmium is of concern since nearly everyone in the general population is exposed to the metal through the food supply and the ability of the element to accumulate in the body over a lifetime. In support of the United States Food and Drug Administration's (FDA) Toxic Element Working Group's efforts to reduce the risks associated with elements in food, this review sought to identify current or new mitigation efforts that have the potential to reduce exposures of cadmium throughout the food supply chain.

Guidelines for performing systematic reviews in the development of toxicity factors.

The Texas Commission on Environmental Quality (TCEQ) developed guidance on conducting systematic reviews during the development of chemical-specific toxicity factors. Using elements from publicly available frameworks, the TCEQ systematic review process was developed in order to supplement the existing TCEQ Guidelines for developing toxicity factors (TCEQ Regulatory Guidance 442). The TCEQ systematic review process includes six steps: 1) Problem Formulation; 2) Systematic Literature Review and Study Selection; 3) Data Extraction; 4) Study Quality and Risk of Bias Assessment; 5) Evidence Integration and Endpoint Determination; and 6) Confidence Rating.

Development of an inhalation unit risk factor for ethylene dibromide.

The Texas Commission on Environmental Quality (TCEQ) follows standard scientific methods to develop up-to-date toxicity factors for chemicals emitted in the state of Texas. An inhalation unit risk factor (URF) was developed for ethylene dibromide (EDB, CAS 106-93-4) based on an increased incidence of nasal cavity adenocarcinomas observed in female rats in a 2-year inhalation cancer bioassay conducted by the National Toxicology Program (NTP). The NTP study provided evidence of several EDB-induced tumors in male and female rats and in female mice.