Renu Gandhi

Critical Evaluation of Cancer Risk from 2,4-D

2,4-D [(2,4-dichlorophenoxy)-acetic acid] is a widely used postemergent herbicide. It is structurally similar to indoleacetic acid (IAA), a naturally occurring plant hormone (see Fig.1). This similarity allows 2,4-D to mimic IAA and is the basis for its herbicidal action. The synthesis of 2,4-D was first reported in 1941 (ARC 1986I). In 1945, Dow Chemical Co. discovered that a 1:1 mixture of 2,4-D and 2,4,5-T [(2,4,5-trichlorophenoxy)-acetic acid] was a more effective herbicide than either of the two chemicals alone. The mixture was widely used thereafter and referred to as Agent Orange (Lilienfeld and Gallo 1989). Exposure to 2,4-D in the past may have more often been to a mixture of herbicides rather than 2,4-D alone. 2,4-D preparations before 1975 were often contaminated with TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) (IARC 1986;Johnson et al. 1992).

Critical Evaluation of Dichlorvos’ Breast Cancer Risk

Abstract Dichlorvos was once a very popular and commonly used organophosphate pesticide. Dichlorvos applications were not restricted to agriculture. It was widely used as an insecticide in public places and in homes. Its many different non-agricultural applications created the potential for widespread exposure. Dichlorvos use was restricted in response to concerns about its cancer causing potential. For this report, we have used a modification of the International Agency for Research on Cancer (IARC) approach to conduct a detailed evaluation of any direct or related evidence of cancer risk from exposure to dichlorvos, with a focus on breast cancer risk. We have critically evaluated al I the available human, experimental animal, and cancer-related molecular and mechanistic studies on dichlorvos. Chemical and up-to-date regulatory information is included, as well as a discussion of dichlorvos’ environmental fate and potential for human exposure. We have classified dichlorvos in Group 3. In the Program on Breast Cancer and Environmental Risk Factors (BCERF) breast cancer risk classification scheme (see Appendix B), this group represents chemicals that are not classifiable for breast cancer risk in humans. However, studies in experimental animals provide enough evidence to suggest that dichlorvos exposure can increase cancer risk at other sites.

Translational Cancer Research Program on Breast Cancer and Environmental Risk Factors (BCERF) at Cornell University

The American Cancer Society has estimated that in the year 2000, 176,300 women in the United States (U.S.) will be diagnosed with breast cancer, and over 25% of these women will die of this disease (http:/fwww.cancer.org/statistics/). It has been estimated that only about one half of breast cancer risk can be attributed to known risk factors, such as advancing age, genetics, early menarche, late menopause, and late age at first birthlp2. While pesticides may be considered by some to be an unproven risk, there has been widespread public concern about the

Critical Evaluation of Phosmet's Breast Cancer Risk

Abstract Phosmet is an organophosphate insecticide, widely used on fruit trees in orchards. There is a potential for occupational and para-occupational exposure to this insecticide. While there is some evidence of a carcinogenic effect, phosmet has not been through a complete review for its carcinogenic potential by the International Agency for Research on Cancer (IARC), or the United States Environmental Protection Agency (EPA). Health effects from phosmet are undergoing a review at EPA, as part of the procedure for reassessment of tolerances for OP under the Food Quality and Protection Act of 1996 (FQPA). In this evaluation, we have used a modification of the IARC approach to conduct a detailed evaluation of any direct or related evidence of cancer risk, with a focus on breast cancer risk from phosmet. We have critically evaluated all the available human, experimental animal, and cancer-related molecular and mechanistic studies on phosmet. Chemical and up-to-date regulatory information is included, as well as a discussion of phosmets environmental fate and potential for human exposure. Evidence available so far does not indicate that phosmet increases breast cancer risk. We propose that phosmet be classified in Group 3 in the Program on Breast Cancer and Environmental Risk Factors (BCERF) breast cancer risk classification scheme (see Appendix B). This group represents chemicals that are not classifiable for breast cancer risk in humans.

Critical Evaluation of Diazinon's Breast Cancer Risk

Abstract Diazinon is a widely used organophosphate insecticide. Non-agricultural use of diazinon exceeds its agricultural use, creating the potential for widespread non-occupational exposures. Although widely used, there has been no cancer risk classification for diazinon by the US Environmental Protection Agency (EPA), the National Toxicology Program (NTP) or International Agency for Research on Cancer (IARC). For this report, we have used a modification of the IARC approach to conduct a detailed evaluation of any direct or related evidence of cancer risk from exposure to diazinon, with a focus on breast cancer risk. We have critically evaluated all the available human, experimental animal, and cancer-related molecular and mechanistic studies on diazinon. Chemical and up-to-date regulatory information is included, as well as a discussion of diazinons environmental fate and potential for human exposure. Evidence available so far does not indicate that diazinon increases breast cancer risk. It should be noted that this conclusion is based on the limited scientific evidence currently available. We have identified several research gaps in the report. We propose that diazinon be classified in Group 3. In the Program on Breast Cancer and Environmental Risk Factors (BCERF) breast cancer risk classification scheme (see Appendix B), this group represents chemicals that are not classifiable for breast cancer risk in humans.

Critical Evaluation of Chlorpyrifos’ Breast Cancer Risk

Abstract Chlorpyrifos is an organophosphate pesticide extensively used in agricultural and non-agricultural settings. It has been widely used as a termiticide in homes and buildings. There are reports that demonstrate the potential for widespread non-occupational exposure and for children to come in contact with this insecticide. There has been no cancer risk classification for chlorpyrifos by the US Environmental Protection Agency (EPA), the National Toxicology Program (NTP) or the International Agency for Research on Cancer (IARC). For this report, we have used a modification of IARC approach to conduct a detailed evaluation of any direct or related evidence of cancer risk from exposure to chlorpyrifos, with a focus on breast cancer risk. We have critically evaluated all the available human, experimental animal and cancer-related molecular and mechanistic studies on chlorpyrifos. Chemical and up-to-date regulatory information is included, as well as a discussion of chlorpyrifos’ environmental fate and potential for human exposure. Evidence available so far does not indicate that chlorpyrifos increases breast cancer risk. It should be noted that this conclusion is based on the limited scientific evidence currently available and we have identified several research gaps in this evaluation. Thus, we propose that chlorpyrifos be classified in Group 3. In the Program on Breast cancer and Environmental Risk Factors (BCERF) breast cancer risk classification scheme, this group represents chemicals that are not classifiable for breast cancer risk in humans.