Toxicology & Risk Sciences

Example Projects


The potential human health impacts of chemical exposures in the environment, workplace, or from products we use in our daily lives are concerns that often demand a rigorous understanding of underlying chemical toxicology and cause-effect relationships. Gradient brings formidable scientific strengths to bear on these issues. Our scientists have a long history of advancing the field of risk sciences by developing novel approaches, authoring noteworthy peer-reviewed publications, serving on scientific advisory panels, and providing scientific input on health risk issues underlying environmental regulations.

Gradient Risk Science Expertise:

  • Chemical causation analysis
  • Toxicity mechanisms
  • Dose-response determination
  • Pharmacokinetic modeling
  • Benchmark dose analysis
  • Characterization of uncertainty
  • Historical state-of-knowledge

Example publications:

Cohen, SM; Arnold, LL; Beck, BD; Lewis, AS; Eldan, M. 2013. "Evaluation of the carcinogenicity of inorganic arsenic." Crit. Rev. Toxicol. 43(9):711-752.

Prueitt, RL; Rhomberg, LR; Goodman, JE. 2013. "Hypothesis-based weight-of-evidence evaluation of the human carcinogenicity of toluene diisocyanate." Crit. Rev. Toxicol. 43(5):391-435.

Rhomberg, LR; Bailey, LA; Goodman, JE; Hamade, A; Mayfield, D. 2011. "Is exposure to formaldehyde in air causally associated with leukemia? - A hypothesis-based weight-of-evidence analysis." Crit. Rev. Toxicol. 41(7):555-621.

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Example Projects

Evaluation of the Scientific Basis for Revisions to Ozone, Lead, NO2, SO2, and PM National Ambient Air Quality Standards

Full Description

Gradient assessed the validity and appropriateness of key health studies comprising the basis for US EPA's revisions to its NAAQS.  We presented our analyses to US EPA, congressional subcommittees, and in peer-reviewed literature.

Weight-of-evidence Analysis of Low Dose Health Effects of Bisphenol A

Full Description

Gradient critically reviewed studies of low exposures to Bisphenol A affecting reproduction and development via endocrine disruption by evaluating the repeatability of outcomes and consistency with an endocrine-modulation mode of action. We provided testimony in hearings on proposed state and municipal legislation.

Evolution of Knowledge of Toxicology

Full Description

Gradient researched the historical knowledge of the toxicity of PCBs and manufactured gas plant compounds. We contrasted historical understanding of environmental issues with current risk assessment methods that provide the basis of modern-era environmental cleanups.

Non-cancer Health Effects of Dioxin

Full Description

Gradient conducted a weight-of-evidence evaluation of the epidemiological data available for selected health endpoints for dioxin. We identified datasets suitable for performing quantitative dose-response evaluations and illustrated the impact of toxicity assessment choices and key sources of uncertainty on quantitative toxicity estimates.

Dioxin Reassessment - TEF and Integrated Risk Characterization Peer Review

Full Description

A Gradient principal served on a scientific consultation panel convened by US EPA to evaluate its Science Advisory Board review of the draft dioxin reassessment. Gradient's review focused on pharmacokinetics and representations of uncertainty as well as margins of exposure analyses.

Toxicity Evaluation Methodology for PFOA and PFOS

Full Description

Gradient analyzed the scientific validity of US EPA's approach to oral reference dose (RfD) development for Perfluorooctane Sulfonate (PFOS) and Perfluorooctanoic Acid (PFOA). We provided alternate methods for development of RfDs that considered mode of action understandings and incorporated findings from human biomonitoring data.