Introduction
1-Bromopropane (CAS No. 106-94-5) is a brominated hydrocarbon currently used as a solvent in a variety of industrial and commercial applications. Workers are exposed to 1-bromopropane from its production and use as an adhesive (highest levels), an aerosol solvent, and a vapor degreaser, and in dry cleaning. Several of these uses resulted from the substitution of bromopropane for substances identified as suspected carcinogens or ozone-depleting chemicals. People living near industrial facilities may be exposed to 1-bromopropane, albeit at lower levels than via occupational exposure.
Methods
The National Toxicology Program (NTP) evaluated evidence for cancer studies in experimental animals and mechanisms of carcinogenesis by evaluating study quality and integrating evidence across studies. Using established criteria, NTP reached conclusions on the strength of evidence for the carcinogenicity of 1-bromopropane; the final listing recommendation was reached by applying Report on Carcinogens (RoC) listing criteria to the body of evidence. Some information on worker exposure is available but no epidemiological studies or case reports were identified that evaluated the relationship between human cancer and exposure specifically to 1-bromopropane.
Results and discussion
Cancer studies in experimental animals
NTP concluded that there was sufficient evidence of carcinogenicity in animals based on its review of studies, which showed that inhalation exposure to 1-bromopropane caused tumors in two rodent species and at several different tissue sites. In male rats, 1-bromopropane caused significant dose-related increases in the incidences of several types of benign and/or malignant skin tumors. Both female and male rats showed an increased incidence of large-intestine tumors, which are rare tumors in rats. In female mice, 1-bromopropane caused significant dose-related increases in the incidence of benign and malignant lung tumors.
Mechanistic data
Exposure to 1-bromopropane has been shown to cause molecular alterations related to carcinogenicity, including genotoxicity (mutations and DNA damage), oxidative stress, glutathione depletion, and immunomodulation. Reactive metabolites (or intermediates) of 1-bromopropane may be responsible for some of the carcinogenic effects observed in rodents. 1-Bromopropane can bind to macromolecules; it formed S-propylcysteine–globin adducts in exposed animals and humans. Studies showed it caused mutations in cultured mammalian cells with or without addition of mammalian metabolic activation and DNA damage in cultured human cells without metabolic activation. There is limited evidence of DNA damage in leukocytes from 1-bromopropane-exposed workers. Glutathione is an important cellular defense mechanism, and its reduction can lead to oxidative stress, increased toxicity, and carcinogenicity; numerous studies have shown 1-bromopropane induces both oxidative stress and glutathione depletion. Recent studies have shown 1-bromopropane causes immunosuppression in rodents as well as dose-related increases in gene expression and production of proinflammatory cytokines in mouse macrophages and an inflammatory response in rats.
Human cancer studies
No epidemiological studies or case reports were identified that evaluated the relationship between human cancer and exposure specifically to 1-bromopropane. NTP concluded that the data available from exposure studies in humans were inadequate to evaluate the relationship between human cancer and exposure to 1-bromopropane.
NTP cancer hazard conclusion
The conclusion of the cancer hazard evaluation was that 1-bromopropane should be listed as reasonably anticipated to be a human carcinogen in the RoC. The Secretary of Health and Human Services approved the listing of 1-bromopropane in the 13th RoC. The rationale for the listing was sufficient evidence of carcinogenicity of 1-bromopane from studies in experimental animals.
National Toxicology Program (NTP). 2013. Report on Carcinogens monograph on 1-bromopropane. Research Triangle Park, NC: National Toxicology Program. RoC Monograph 01. https://doi.org/10.22427/ROC-MGRAPH-01