title: Critical evaluation of the cancer risk of dibromochloropropane (DBCP).
abstract: 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 California's 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.
authors.affiliation: Program on Breast Cancer and Environmental Risk Factors, Sprecher Institute for Comparative Cancer Research, College of Veterinary Medicine, Cornell University, Ithaca, NY 14853, USA. hac4@cornell.edu
authors.forename: Heather A
authors.initials: HA
authors.lastname: Clark
authors.forename: Suzanne M
authors.initials: SM
authors.lastname: Snedeker
mesh_terms: D000818:Animals; D000969:Antinematodal Agents / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity*; D002273:Carcinogens / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D004784:Environmental Monitoring; D004785:Environmental Pollutants / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D016021:Epidemiologic Studies; D062665:Epidemiological Monitoring; D006801:Humans; D009152:Mutagenicity Tests; D009369:Neoplasms / Q000139:chemically induced* / Q000453:epidemiology; D011407:Propane / Q000031:analogs & derivatives* / Q000032:analysis / Q000493:pharmacokinetics / Q000633:toxicity; D018570:Risk Assessment
chemical_list: D000969:Antinematodal Agents; D002273:Carcinogens; D004785:Environmental Pollutants; C007318:1,2-dibromo-3-chloropropane; D011407:Propane