Development of cancer and non-cancer toxicity criteria involves the use of a variety of mathematical and technical tools (e.g., benchmark dose analysis, linear-multistage modeling, meta-analysis, PBPK modeling), along with toxicological, clinical, and epidemiological data to quantify the dose-response relationship, generally the results of which must be consistent with current agency guidelines. Exponent scientists and physicians have specific expertise and considerable experience in developing the toxicity criteria that have been used for site-specific risk assessment, and have been incorporated into chemical risk assessments conducted by OSHA and EPA. We have the experience to identify the pivotal sources of uncertainty and design research that improves the scientific validity of the criteria.
Exponent has designed and conducted original research to develop data for EPA to set a skin-reference dose (S-RfD) in response to the recommendation of their Scientific Advisory Panel (SAP) to generate improved data to assess the health hazard posed by chemicals. Exponent scientists have conducted studies in human volunteers to evaluate allergic contact dermatitis due to occupational and environmental chemical exposure. To ensure the fulfillment of ethical requirements for human-subject studies, study protocols need to be reviewed and approved by institutional review boards (IRBs), and if the study results are to be used by EPA for risk assessment of pesticides, the protocols and final reports also require approval by EPA’s Human Studies Review Board (HSRB). Exponent has experience with securing IRB approval for human research study protocols, as well as with the approval process used by the HSRB.
Our scientists have considerable experience with EPA’s “R”-based program, OPCUMRISK, and the benchmark dose software (BMDS) used to analyze dose-response data for various chemicals, such as hexavalent chromium, pesticides, and volatile organic chemicals. We have conducted data evaluation and benchmark dose (BMD) analyses and developed comments that were submitted to EPA on a variety of issues, such as EPA’s revised risk assessment for Re registration Eligibility Decision of a pesticide. Exponent has an in-depth understanding of EPA’s methodology for pesticide cumulative risk assessment. Our past work with risk assessment has also included an evaluation of safety (uncertainty) factors applicable to various chemicals. In addition, Exponent has analyzed EPA’s quantitative risk assessment approach to deriving BMD estimates for chemicals—work that drew upon our expertise in toxicology, risk assessment, and statistics.
Exponent has been intimately involved in the development of dermal, oral, and inhalation reference doses (RfDs), alternative RfDs, reference concentrations (RfCs), toxicity reference values (TRVs), permissible exposure limits (PELs), and occupational exposure limits (OELs) for a variety of chemicals, including organic alcohols and aldehydes, propylene glycol, lead, petroleum hydrocarbons, dioxin, beryllium, cadmium, and hexavalent chromium. Exponent also has helped develop health-based standards for drinking water, maximum allowable daily levels for chemicals, short-term toxicity value for children’s exposure, and alternative acute RfCs. This work has included comprehensive exposure and toxicological assessment of these chemicals, mathematical modeling, identification of data gaps, and development of toxicological testing study plans.
In addition to non-cancer toxicity criteria, Exponent also has considerable experience in the development of cancer toxicity criteria, such as cancer slope factors and inhalation unit risk factors. This work has involved conducting weight-of-evidence analyses of the carcinogenicity data, analyzing epidemiological data, reconstructing exposures, assessing dose-response and quantitative risk, and testifying before regulatory bodies such as EPA’s SAP, for chemicals including trichloroethylene, hexavalent chromium, and arsenic.
While playing key roles in the development of cancer and non-cancer toxicity criteria, Exponent scientists have served on expert panels working to derive health-protective exposure levels for chemicals. Examples include the National Research Council (NRC) subcommittee for emergency and continuous guidance levels for various chemicals in air in submarines (on behalf of the U.S. Navy), and the subcommittee on spacecraft exposure levels for air and water in spacecraft (on behalf of NASA).