U.S. EPA Contaminated Site Cleanup Information (CLU-IN)


U.S. Environmental Protection Agency
U.S. EPA Technology Innovation and Field Services Division

Dense Nonaqueous Phase Liquids (DNAPLs)

Toxicology

Halogenated Alkanes

1,2-Dibromo-3-chloropropane

Human Health Toxicity

Although the general population might be exposed to 1,2-dibromo-3-chloropropane (DBCP), potential exposure typically is limited to those agricultural areas of the United States where DBCP was heavily employed as a soil fumigant (ATSDR 1992). Residual amounts of DBCP can persist in once-fumigated soil and might be present in groundwater contaminated from agricultural applications. Human exposure to DBCP-contaminated groundwater can occur through drinking water consumption and from showering via inhalation and dermal absorption. Also, crops irrigated with contaminated groundwater might contain residual DBCP.

Few studies exist on human or animal absorption of DBCP through any exposure route; however, it has been inferred from the evidence that the compound is readily absorbed. Laboratory rodent studies indicate that a large percentage of an oral dose of DBCP is absorbed rapidly from the gastrointestinal tract. Once absorbed, DBCP is distributed quickly to all tissues, including fetal tissues, suggesting that it readily crosses the placental barrier.

The majority of the absorbed dose of DBCP undergoes metabolism, and while most of the final products of metabolism are excreted in urine, fecal excretion also occurs. Carbon dioxide derived from DBCP is exhaled. DBCP is detoxified mainly in the mammalian liver by a series of glutathione conjugation reactions, but paradoxically, these same reactions in the testes can be responsible for the formation of reactive intermediates that are genotoxic. The resulting DNA damage is related to testicular necrosis.

Although DBCP is acutely toxic to laboratory animals via inhalation, dermal absorption, and ingestion, there are no reported human deaths from acute toxicity of this compound. The effects of chronic, long-term exposures to DBCP have been investigated in laboratory animals, and epidemiological studies have been conducted on workers who were occupationally exposed during DBCP manufacture and agricultural applications. Studies of the effects of DBCP on male rats show testicular atrophy and reduced production of sperm after 13 weeks of intermittent exposure to 25 mg DBCP. Female rats showed no change in fertility when similarly exposed.

Several epidemiological studies show that the male reproductive system appears to be the target of DBCP toxicity. Occupational exposure resulted in low sperm counts and in some cases, the absence of sperm; atrophy of the seminiferous epithelium; and decreased testicular size. Changes in the levels of reproductive hormones also were reported in workers whose testicular biopsy showed histopathological changes. Workplace exposure resulted in reduced fertility and testicular atrophy that was reversible in some cases. Reversibility was related to the length of worker exposure.

Although adverse effects on the human male reproductive system were described in various investigations, no increase in congenital malformations or cytogenetic abnormalities were seen in 34 children of men occupationally exposed to DBCP.

EPA's Integrated Risk Information System (IRIS) reports a reference concentration (RfC) of 2 x 10-4 mg/m3 for DBCP inhaled from ambient air. This RfC represents an estimate of a daily inhalation exposure of the human population that is likely to be without appreciable risk of deleterious effects during a lifetime.

In addition to the non-carcinogenic reproductive toxicity exhibited by DBCP, long-term laboratory rodent studies suggest that the compound is carcinogenic in these species. Oral exposure of mice and rats resulted in cancers of the forestomach in both sexes and cancers of the mammary gland in female rats. Inhalation exposure of rats to DBCP produced cancers of the nasal passages and tongue in both sexes, and it produced cancers of the pharynx in female rats. Both sexes of mice developed lung cancer and cancer of the nasal passages in response to inhalation exposure to DBCP.

Although laboratory animal studies indicate that DBCP is carcinogenic, the epidemiological evidence is insufficient to conclude that it is a human carcinogen. Results from epidemiological studies have been confounded by the exposure of workers to multiple pesticides, such that any increase in the rate of cancer cannot be attributed solely to DBCP. Two studies were conducted in California to determine whether an association exists between groundwater concentrations of DBCP and the development of gastric cancers and leukemia in the human population. One of the studies reported a trend of increasing cancer risk with increasing DBCP concentration, but the trend did not rise to the level of significance. No association was identified by the other study, and neither of these investigations is considered conclusive (Rice 1999).

Extensive literature pertinent to the genotoxicity of DBCP is available. A wide variety of in vivo and in vitro tests that employ mammalian, human, and bacterial test systems have been performed. DBCP has been shown to be clastogenic (inducing breaks and other microscopically visible alterations in chromosomes) and mutagenic. Evidence of the mutagenic effects of DBCP in exposed workers has been reported, including a change in the sex ratio of their offspring, with a percentage of newborn boys of 16.6. DBCP reduced the fertility of sperm bearing the Y chromosome, which is capable of producing male offspring.

The International Agency for Research on Cancer's (IARC) evaluation of DBCP concluded that "there is inadequate evidence in humans for the carcinogenicity of 1,2-dibromo-3-chloropropane"; however, "there is sufficient evidence in experimental animals for the carcinogenicity of 1,2-dibromo-3-chloropropane." The eleventh Report on Carcinogens states that "1,2-dibromo-3-chloropropaneis is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity in experimental animals" (NTP 2005).

References

1,2-Dibromo-3-Chloropropane Adobe PDF Logo
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Re-Evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide. International Agency for Research on Cancer (IARC), Vol. 71, p 479-500, 1999

1,2-Dibromo-3-Chloropropane, CAS No.96-12-8 Adobe PDF Logo
Report on Carcinogens, Twelfth Edition. U.S. Department of Health and Human Services, Public Health Service, National Toxicology Program (NTP), 2011

1,2-Dibromo-3-Chloropropane (DBCP) (CASRN 96-12-8)
U.S. EPA, Integrated Risk Information System (IRIS)

Public Health Goal for 1,2-Dibromo-3-Chloropropane in Drinking WaterAdobe PDF Logo
Rice, D.
California Environmental Protection Agency, Office of Environmental Health Hazard Assessment, 50 pp, 1999

Toxicological Profile for 1,2-Dibromo-3-Chloropropane
Agency for Toxic Substances and Disease Registry (ATSDR), 164 pp, 1992

Ecological Toxicity

Although many studies have been performed on laboratory rodents to determine the mode of action and the effects of chronic exposure to DBCP, there are very few studies of its toxicity to wildlife. Existing wildlife studies generally employ aquatic species and are designed to determine the concentration at which DBCP could become acutely toxic. These range-finding investigations are usually LC50 studies. An LC50 is defined as the median lethal concentration-specifically, the concentration of a chemical required to kill 50 percent of the test subjects in a stated time.

DBCP has exhibited slightly toxic effects on the following species of snails: mud snail (Cipangopaludina malleata), snail (Indoplanorbis exustus), marsh snail (Semisulcospira libertina), and European bladder snail (Physella acuta) with 48-hr LC50 values of 53, 57, 50, and 24 mg/L, respectively. DBCP is highly toxic to another mollusk, the hard clam (Mecenaria meceneria), with an LC50 value of 0.78 mg/L (Kegley et al. 2009).

A 48-hr LC50 value of 18 mg/L has been determined for the mayfly (Cloeon dipterum) (Kegley et al. 2009).

Reports exist of toxic effects on fish. One study has shown DBCP to be slightly toxic to fingerling largemouth bass (Micropteris salmoides) with a 48-hr LC50 value of 20 mg/L. Year old danios (Danio rerio) were exposed to an addition of 20 µg/L DBCP to their water every 2 weeks for an 8-week period. After the final addition of DBCP, the animals were maintained in uncontaminated water for a further 12 weeks. Nine of the 21 surviving fish (21/100) developed liver tumors (IARC 1999).

References

1,2-Dibromo-3-ChloropropaneAdobe PDF Logo
IARC Monographs on the Evaluation of Carcinogenic Risks to Humans: Re-Evaluation of Some Organic Chemicals, Hydrazine and Hydrogen Peroxide. International Agency for Research on Cancer (IARC), Vol. 71, p 479-500, 1999

DBCP: Identification, Toxicity, Use, Water Pollution Potential, Ecological Toxicity and Regulatory Information
Kegley, S.E., B.R. Hill, S. Orme, and A.H. Choi.
PAN Pesticide Database. Pesticide Action Network, San Francisco, CA, 2009



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