Suzanne M. Snedeker

Ochratoxin a: its cancer risk and potential for exposure.

Ochratoxin A (OA) is a naturally occurring mycotoxin known to contaminate a variety of foods and beverages. The cancer risk posed by OA was reviewed as relevant to human exposure, regulatory activities, and risk management efforts occurring worldwide, particularly in Europe. OA moves through the food chain and has been found in the tissues and organs of animals, including human blood and breast milk. Results from the National Toxicology Programs rodent bioassays show significantly increased incidence of mammary gland tumors in female rats and kidney tumors in male and female rats given OA orally. Liver tumors in female mice fed OA in the diet have also been observed. In humans, OA exposure has been most often associated with the kidney disease Balkan endemic nephropathy (BEN), symptoms of which include tumors of the kidney and urinary tract. No epidemiological studies have yet adequately evaluated the cancer risk of OA in human populations. Studies have shown OA to be genotoxic as well as immunotoxic, although its mode of action is not fully understood. Organizations and agencies in many countries are currently promulgating standards for OA in foods and beverages. Increased efforts in farm management and food safety are being made to mitigate the risks to public health posed by OA. The U.S. Food and Drug Administration (FDA) is currently evaluating data on OA levels in domestic and imported commodities but has not established official regulations or guidelines for OA in the U.S. food supply. Funding for this work was provided by the US Department of Agriculture Cooperative State Research, Education and Extension Service. Any findings, conclusions or recommendations are those of the authors and do not necessarily reflect the views of the U.S. Department of Agriculture.

Critical Evaluation of the Cancer Risk of Dibromochloropropane (DBCP)

Dibromochloropropane (1,2-dibromo-3-chloropropane, DBCP), a pesticide used widely for over 20 years to control nematodes on crops, turf and in nurseries, was banned by the United States Environmental Protection Agency (US EPA) in 1977 because of evidence of infertility in men and induction of a variety of tumors in laboratory animals. Despite the ban on the use of DBCP, this pesticide remains persistent in soil and continues to be detected as a groundwater contaminant in areas of past high use, in particular Californias Central Valley. In this review, we present a critical evaluation of the available scientific literature on the potential for DBCP to affect cancer risk, including the results of animal cancer bioassays, human epidemiological studies and in vitro and in vivo genotoxicity studies. In addition, we provide updated information on DBCP chemistry and metabolism, production and past use, current regulations, its environmental fate, potential for human exposure and current remediation efforts. Results from long-term cancer bioassays in rodents show a statistically significant increase in the incidence of malignant and benign mammary gland tumors in female rats treated orally with DBCP compared to controls and some evidence of increased incidence of mammary fibroadenomas in DBCP low-dose treated female rats exposed by inhalation. Significantly increased incidence of tumors of the forestomach occurred in both sexes of rats and mice treated orally. Rats exposed to DBCP by inhalation showed significant increases in tumors of the tunica vaginalis in males; tumors of the pharynx and adrenal gland in females; and tumors of the tongue, nasal turbinate and nasal cavity in both sexes compared to controls. Male and female mice exposed to DBCP by inhalation experienced increased tumor incidence in the lungs and nasal cavity compared to controls. Significant increases in tumors of the lung and forestomach have also been reported in female mice treated by a dermal route. Although high mortality rates in both rat and mouse bioassays limited the ability to detect tumors late in life, the induction of a variety of tumors by multiple routes of exposure in two rodent species provides clear evidence of a DBCP tumorigenic response. In vitro, in vivo and human genotoxicity studies indicate that DBCP is capable of acting as a mutagen and clastogen. Few studies have been conducted to assess whether DBCP workplace or drinking water exposures affect cancer risk in humans. While case-control, cohort and ecological epidemiology studies have not found significant, positive associations between DBCP exposure and cancer in exposed populations, these studies have numerous limitations including small numbers of participants, a lack of control for confounding factors, lack of exposure information on DBCP and other chemicals and short follow-up times. Given the persistent nature of DBCP contamination in areas of past use, efforts should be made to continue remediation efforts and follow previously exposed populations for development of certain human cancers, including breast, ovarian, stomach, respiratory, oral and nasal cancers, among others.

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.

Exploring Cancer Risk Perceptions of Turf and Lawn Pesticide Professionals in New York State

A pilot study was conducted to better understand the knowledge, perceptions, and concerns of turf and lawn care pesticide professionals in New York State (NYS) regarding cancer and other health risks. Data were collected from 31 focus group participants and 104 questionnaire respondents in applicator trainings and other meetings around the state. Three distinct themes emerged from focus group discussions: cultural shift in pesticide management practices, costs and benefits of pesticide regulations, and challenges of understanding and communicating about health risks. Factor analysis yielded three subscales: control disease, reduce chemical risk, and concern. Exploratory regression analysis yielded predictive relationships between work experience, cancer risk knowledge, and attitudes in support of reducing chemical risk, which in turn predicted precautionary pesticide behavior, such as reading the label and using personal protective equipment. Results suggest the need to incorporate cancer risk education into continuing education for turf and lawn care professionals.

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.