Validation of 1,3-butadiene exposure estimates for workers at a synthetic rubber plant

Sathiakumar, Nalini; Delzell, Elizabeth; Cheng, Hong; Lynch, Jeremiah; Sparks, W. J.; Macaluso, Maurizio

doi:10.1016/j.cbi.2006.08.016

Cited by 15 publications

(20 citation statements)

References 16 publications

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“…After the HEI report was finalized, an exposure estimate validation study was conducted on the updated UAB BD exposure estimates. ( 8 ) At lower concentrations, there was reasonably good agreement between measured versus estimated BD exposures, whereas at higher exposures, the estimates tended to be less than the measured values. On average, estimates were about 10% lower than measurements.…”

Section: Introductionmentioning

confidence: 77%

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Development of a Unit Risk Factor for 1,3‐Butadiene Based on an Updated Carcinogenic Toxicity Assessment

et al. 2009

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The Texas Commission on Environmental Quality (TCEQ) has developed an inhalation unit risk factor (URF) for 1,3-butadiene based on leukemia mortality in an updated epidemiological study on styrene-butadiene rubber production workers conducted by researchers at the University of Alabama at Birmingham. Exposure estimates were updated and an exposure estimate validation study as well as dose-response modeling were conducted by these researchers. This information was not available to the U.S. Environmental Protection Agency when it prepared its health assessment of 1,3-butadiene in 2002. An extensive analysis conducted by TCEQ discusses dose-response modeling, estimating risk for the general population from occupational workers, estimating risk for potentially sensitive subpopulations, effect of occupational exposure estimation error, and use of mortality rates to predict incidence. The URF is 5.0 x 10(-7) per microg/m(3) or 1.1 x 10(-6) per ppb and is based on a Cox regression dose-response model using restricted continuous data with age as a covariate, and a linear low-dose extrapolation default approach using the 95% lower confidence limit as the point of departure. Age-dependent adjustment factors were applied to account for possible increased susceptibility for early life exposure. The air concentration at 1 in 100,000 excess leukemia mortality, the no-significant-risk level, is 20 microg/m(3) (9.1 ppb), which is slightly lower than the TCEQ chronic reference value of 33 microg/m(3) (15 ppb) protective of ovarian atrophy. These values will be used to evaluate ambient air monitoring data so the general public is protected against adverse health effects from chronic exposure to 1,3-butadiene.

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Section: Introductionmentioning

confidence: 77%

“…On average, estimates were about 10% lower than measurements. Based on the validation study of Sathiakumar et al , ( 8 ) the updated exposure estimates of Macaluso et al . ( 4 ) have a higher confidence than original exposure estimates.…”

Section: Introductionmentioning

confidence: 99%

Development of a Unit Risk Factor for 1,3‐Butadiene Based on an Updated Carcinogenic Toxicity Assessment

et al. 2009

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“…BD and the ET metabolite, ethylene oxide (EO), have been classified as human carcinogens [120]. Occupational exposure to butadiene has been associated with increased risk for leukemia in workers exposed to BD in synthetic rubber production [121-123] and an increase in lymphohematopoietic cancers in BD monomer production workers that was not exposure related [124]. Olefins are mainly metabolized by P450s to the corresponding epoxides that are known to form DNA adducts, including N 7-guanine adducts via S N 2 reactions (Figure 3).…”

Section: Formation Of N7-guanine Adducts In Animal Modelsmentioning

confidence: 99%

The formation and biological significance of N7-guanine adducts

Boysen

Pachkowski

Nakamura

et al. 2009

Mutation Research/Genetic Toxicology and Environmental Mutagene

185

182

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DNA alkylation or adduct formation occurs at nucleophilic sites in DNA, mainly the N7-position of guanine. Ever since identification of the first N7-guanine adduct, several hundred studies on DNA adducts have been reported. Major issues addressed include the relationships between N7-guanine adducts and exposure, mutagenesis, and other biological endpoints. It became quickly apparent that N7-guanine adducts are frequently formed, but may have minimal biological relevance, since they are chemically unstable and do not participate in Watson Crick base pairing. However, N7-guanine adducts have been shown to be excellent biomarkers for internal exposure to direct acting and metabolically activated carcinogens. Questions arise, however, regarding the biological significance for N7-guanine adducts that are readily formed, do not persist, and are not likely to be mutagenic. Thus, we set out to review the current literature to evaluate their formation and the mechanistic evidence for the involvement of N7-guanine adducts in mutagenesis or other biological processes. It was concluded that there is insufficient evidence that N7-guanine adducts can be used beyond confirmation of exposure to the target tissue and demonstration of the molecular dose. There is little to no evidence that N7-guanine adducts or their depurination product, apurinic sites, are the cause of mutations in cells and tissues, since increases in AP sites have not been shown unless toxicity is extant. However, more research is needed to define the extent of chemical depurination versus removal by DNA repair proteins. Interestingly, N7-guanine adducts are clearly present as endogenous background adducts and the endogenous background amounts appear to increase with age. Furthermore, the N7-guanine adducts have been shown to convert to ring opened lesions (FAPy), which are much more persistent and have higher mutagenic potency. Studies in humans are limited in sample size and differences between controls and study groups are small. Future investigations should involve human studies with larger numbers of individuals and analysis should include the corresponding ring opened FAPy derivatives.

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“…This concerns the exposure dose estimates, which are explained by uncertainties in the measured exposure levels and duration, and because of varying exposure conditions, e.g. simultaneous exposures to other compounds (Goel et al, 2013;Sathiakumar et al, 2007). The Hb adduct level increments could be afflicted with uncertainties, particularly when the measured adduct levels are close to the LOQ of the analytical method or close to background adduct levels from other sources as measured in the controls (this particularly concerns the adduct from DEB in humans).…”

Section: Discussionmentioning

confidence: 99%

In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: An inter-species extrapolation approach

Motwani

Törnqvist

2014

Toxicology and Applied Pharmacology

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Validation of 1,3-butadiene exposure estimates for workers at a synthetic rubber plant

Cited by 15 publications

References 16 publications

Development of a Unit Risk Factor for 1,3‐Butadiene Based on an Updated Carcinogenic Toxicity Assessment

Development of a Unit Risk Factor for 1,3‐Butadiene Based on an Updated Carcinogenic Toxicity Assessment

The formation and biological significance of N7-guanine adducts

In vivo doses of butadiene epoxides as estimated from in vitro enzyme kinetics by using cob(I)alamin and measured hemoglobin adducts: An inter-species extrapolation approach

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