As a part of continued progress and investigation into the toxicological profile of chemicals, pharmaceuticals, and consumer products, Federal Agencies will require additional testing when they believe there is merit in evaluating new endpoints of interest or concern. Two such focal areas have become active areas of research and investigation for pesticidal active ingredients and these are related to endocrine activity and immunotoxicity evaluation. Many pesticides have undergone testing for these endpoints, and chlorpyrifos is amongst that group. More specific information on chlorpyrifos and these evaluations follows.

Endocrine Disruption: Definition

Endocrine disruptor - Generally, a substance that interacts with one or more components of the endocrine system to cause adverse effects.

Endocrine Disruption: Discussion

Historically, exposure to some chemicals was shown to interfere with proper function of endocrine-related hormone systems of some wildlife species which gave rise to potential concern for human health. The US EPA initiated a program some 15+ years ago to begin to evaluate the endocrine-modulating potential of chemicals. After years of work related to testing approaches and validation, chlorpyrifos was one of 67 chemicals selected for EPA’s Endocrine Disruptor Screening Program (EDSP) based on widespread use and potential for human and environmental exposures (EPA 2002, 2007). The purpose of the program is to screen pesticide chemicals for their potential to interact with the estrogen, androgen, or thyroid systems.

A battery of 11 EDSP assays covering the scope of the program was completed for chlorpyrifos based on the EDSP data call-in and in accordance with test guidelines developed for EDSP Tier 1 testing. To assist with scientific interpretation of the EDSP screening results for chlorpyrifos and within the context of existing data from regulatory guideline studies and published literature, a weight-of-evidence (WoE) evaluation was completed (Juberg et al. 2012). This WoE approach was based on the OECD conceptual framework for testing and assessment of potential endocrine-disrupting chemicals and consisted of a systematic evaluation of data, progressing from simple to complex across multiple levels of biological organization. The conclusion of the WoE evaluation is that chlorpyrifos demonstrates no potential to interact with the endocrine system, including estrogen, androgen, and thyroid pathways. Dow AgroSciences has recently submitted this evaluation for publication in the peer-reviewed scientific literature and submitted all testing results to EPA for its evaluation.

Immunotoxicity: Definitions

Immunotoxic - Harmful to the immune system.

Immunosuppressant - Substance that depresses the function of the immune system.

Immunosensitizer - Substance that makes the immune system more reactive to antigens.

Immunotoxicity: Discussion

Similar to the enhanced investigation of chemicals for endocrine-modulating potential, recent revision of the toxicology data requirements for US registered chemical pesticides includes the requirement to assess potential effects on immune function through the conduct of what is referred to as the T-cell dependent antibody response (TDAR) assay. Pesticide registrants have completed and submitted more than 80 guideline-compliant TDAR studies, thus fulfilling the requirement and providing an opportunity to evaluate potential implications for hazard identification and risk assessment. Dow AgroSciences has completed this work for chlorpyrifos and the results indicated no impacts to the immune system and thus chlorpyrifos is negative for immunotoxic potential.

In the recently published preliminary human health assessment for chlorpyrifos, the EPA concluded that “there was no sign of immunotoxicity in the guideline study at the highest dose tested.” (EPA, 2011)

Further Resources

“Endocrine Disruptor Screening Program, Proposed Chemical Selection Approach for Initial Round of Screening; Request for Comment.” U.S. Environmental Protection Agency, Federal Register. Vol. 67, No. 250 /Monday, December 30, 2002.

“Draft List of Initial Pesticide Active Ingredients and Pesticide Inerts to be Considered for screening under the Federal Food, Drug, and Cosmetic Act.” U.S. Environmental Protection Agency, Federal Register. Vol. 72, No. 116. Monday, June 18, 2007.

“Chlorpyrifos: Preliminary Human Health Risk Assessment for Registration Review.” U.S. Environmental Protection Agency, Memorandum, DP No. D388070, June 30, 2011.

Juberg, D.R. et al. “Chlorpyrifos: Weight of Evidence Evaluation of Potential Interaction with the Estrogen, Androgen, or Thyroid Pathways”. Regulatory Toxicology and Pharmacology, 2013 (in press).

U.S. Department of Health & Human Services. Environmental Health & Toxicology site. IUPAC glossary:

SOT glossary