title: DNA damage in leukocytes of workers occupationally exposed to 1-bromopropane.
abstract: 1-bromopropane (1-BP; n-propyl bromide) (CAS No. 106-94-5) is an alternative to ozone-depleting chlorofluorocarbons that has a variety of potential applications as a degreasing agent for metals and electronics, and as a solvent vehicle for spray adhesives. Its isomer, 2-brompropane (2-BP; isopropyl bromide) (CAS No. 75-26-3) impairs antioxidant cellular defenses, enhances lipid peroxidation, and causes DNA damage in vitro. The present study had two aims. The first was to assess DNA damage in human leukocytes exposed in vitro to 1- or 2-BP. DNA damage was also assessed in peripheral leukocytes from workers with occupational exposure to 1-BP. In the latter assessment, start-of- and end-of-work week blood and urine samples were collected from 41 and 22 workers at two facilities where 1-BP was used as a solvent for spray adhesives in foam cushion fabrication. Exposure to 1-BP was assessed from personal-breathing zone samples collected for 1-3 days up to 8h per day for calculation of 8h time weighted average (TWA) 1-BP concentrations. Bromide (Br) was measured in blood and urine as a biomarker of exposure. Overall, 1-BP TWA concentrations ranged from 0.2 to 271 parts per million (ppm) at facility A, and from 4 to 27 ppm at facility B. The highest exposures were to workers classified as sprayers. 1-BP TWA concentrations were statistically significantly correlated with blood and urine Br concentrations. The comet assay was used to estimate DNA damage. In vitro, 1- or 2-BP induced a statistically significant increase in DNA damage at 1mM. In 1-BP exposed workers, start-of- and end-of-workweek comet endpoints were stratified based on job classification. There were no significant differences in DNA damage in leukocytes between workers classified as sprayers (high 1-BP exposure) and those classified as non-sprayers (low 1-BP exposure). At the facility with the high exposures, comparison of end-of-week values with start-of-week values using paired analysis revealed non-sprayers had significantly increased comet tail moments, and sprayers had significantly increased comet tail moment dispersion coefficients. A multivariate analysis included combining the data sets from both facilities, log transformation of 1-BP exposure indices, and the use of multiple linear regression models for each combination of DNA damage and exposure indices including exposure quartiles. The covariates were gender, age, smoking status, facility, and glutathione S-transferase M1 and T1 (GSTM1, GSTT1) polymorphisms. In the regression models, start-of-week comet tail moment in leukocytes was significantly associated with serum Br quartiles. End-of-week comet tail moment was significantly associated with 1-BP TWA quartiles, and serum Br quartiles. Gender, facility, and GSTM1 had a significant effect in one or more models. Additional associations were not identified from assessment of dispersion coefficients. In vitro and in vivo results provide limited evidence that 1-BP exposure may pose a small risk for increasing DNA damage.
authors.affiliation: National Institute for Occupational Safety and Health, 4676 Columbia Parkway, Cincinnati, OH 45226, USA. mtoraason@cdc.gov
authors.forename: Mark
authors.initials: M
authors.lastname: Toraason
authors.forename: Dennis W
authors.initials: DW
authors.lastname: Lynch
authors.forename: D Gayle
authors.initials: DG
authors.lastname: DeBord
authors.forename: Narendra
authors.initials: N
authors.lastname: Singh
authors.forename: Edward
authors.initials: E
authors.lastname: Krieg
authors.forename: Mary Ann
authors.initials: MA
authors.lastname: Butler
authors.forename: Christine A
authors.initials: CA
authors.lastname: Toennis
authors.forename: Jeffrey B
authors.initials: JB
authors.lastname: Nemhauser
mesh_terms: D000328:Adult; D020552:Comet Assay; D004249:DNA Damage; D005260:Female; D005982:Glutathione Transferase / Q000235:genetics; D006801:Humans; D006842:Hydrocarbons, Brominated / Q000009:adverse effects; D007587:Job Description; D007962:Leukocytes; D008297:Male; D016273:Occupational Exposure; D011110:Polymorphism, Genetic; D012307:Risk Factors; D012737:Sex Factors
chemical_list: D005982:Glutathione Transferase; D006842:Hydrocarbons, Brominated; C118559:1-bromopropane