Cancer risk assessment for 1,3-butadiene: Dose–response modeling from an epidemiological perspective

Sielken, Robert L.; Valdez‐Flores, Ciriaco; Gargas, Michael L.; Kirman, Christopher R.; Teta, M. Jane; Delzell, Elizabeth

doi:10.1016/j.cbi.2006.06.004

Cited by 23 publications

(22 citation statements)

References 6 publications

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“…In vitro metabolism data and Hb adduct levels indicate that humans generate low doses of DEB and, as for rat, high exposure levels are most probably required to reach a sufficient in vivo dose of the epoxides to cause a detectable genotoxic/carcinogenic response. A causal relationship between leukemia and high cumulative exposure and high intensity of exposure to BD is supported by a study using an excess relative risk model, similar to the model used in the present evaluation (47). The DD estimated from the linear regression was 595 ppm-year.…”

Section: Discussionsupporting

confidence: 56%

Evaluation of Cancer Tests of 1,3-Butadiene Using Internal Dose, Genotoxic Potency, and a Multiplicative Risk Model

2008

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In cancer tests with 1,3-butadiene (BD), the mouse is much more sensitive than the rat. This is considered to be related to the metabolism of BD to the epoxide metabolites, 1,2-epoxy-3-butene (EB), 1,2:3,4-diepoxybutane, and 1,2-epoxy-3,4-butanediol. This study evaluates whether the large difference in outcome in cancer tests with BD could be predicted quantitatively on the basis of the concentration over time in blood (AUC) of the epoxide metabolites, their mutagenic potency, and a multiplicative cancer risk model, which has earlier been used for ionizing radiation. Published data on hemoglobin adduct levels from inhalation experiments with BD were used for the estimation of the AUC of the epoxide metabolites in the cancer tests. The estimated AUC of the epoxides were then weighed together to a total genotoxic dose, by using the relative genotoxic potency of the respective epoxide inferred from in vitro hprt mutation assays using EB as standard. The tumor incidences predicted with the risk model on the basis of the total genotoxic dose correlated well with the earlier observed tumor incidences in the cancer tests. The total genotoxic dose that leads to a doubling of the tumor incidences was estimated to be the same in both species, 9 to 10 mmol/LÂh EB-equivalents. The study validates the applicability of the multiplicative cancer risk model to genotoxic chemicals. Furthermore, according to this evaluation, different epoxide metabolites are predominating cancer-initiating agents in the cancer tests with BD, the diepoxide in the mouse, and the monoepoxides in the rat.

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Section: Discussionsupporting

confidence: 56%

Evaluation of Cancer Tests of 1,3-Butadiene Using Internal Dose, Genotoxic Potency, and a Multiplicative Risk Model

2008

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“…(The Akaike information criterion (AIC) could have been used Table 2 Statistical significance (p-value) of the effect of adding one of the exposure variables to the Cox proportional hazards model with no exposure variables. 1 1 Cumulative exposure in this table and only this table excludes exposures received early than 40 years before the current age (as in Table 6 in Sielken et al [24]). a,b,c Rank of the maximum log-likelihood for the specified endpoint ( a Implies the best fitting model, b Implies second best, and c Implies third best).…”

Section: Exposure-response Modelingmentioning

confidence: 98%

“…As indicated in Sielken et al [24], the analyses of myeloid neoplasm and lymphoid neoplasm have two important caveats: (1) the diagnoses are based on death certificates and oftentimes the medical records are not detailed enough to assess the level of specificity needed to distinguish among different types of neoplasm and (2) the classification for myeloid neoplasm and lymphoid neoplasm used here assumes a common etiology for the groupings, which has not been well-established in epidemiological studies.…”

Section: Analysesmentioning

confidence: 99%

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A comprehensive review of occupational and general population cancer risk: 1,3-Butadiene exposure–response modeling for all leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, myeloid neoplasm and lymphoid neoplasm

Sielken¹,

Valdez‐Flores²

2015

Chemico-Biological Interactions

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“…Beane Freeman et al [17] found that the risk of lymphohematopoietic tumors was associated with peak exposure to formaldehyde but not with cumulative or average exposure. Sielken et al [18] reported that the prediction of leukemia risk from cumulative butadiene exposure was significantly improved when age and peak exposure were included in the risk assessment model. Charbotel et al [19] found an effect of trichloroethylene peak exposure on renal cell carcinoma.…”

Section: Discussionmentioning

confidence: 99%

Biologic Implications from an Epidemiologic Study of Chromate Production Workers

Gibb¹

2011

TOEPIJ

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This analysis of an epidemiologic study of chromate production workers evaluates several variables related to the biologic understanding of chromate-induced lung cancer. Age at hire was found to be negatively associated with lung cancer risk. Reducing exposure was found to have benefits that extended into older age, and the benefits were greater when the reduction began at an earlier age. The same cumulative exposure over a short period of time (30 days) had more effect than if the exposure occurred over 10 years. The greater carcinogenic effect among those exposed at an early working age is consistent with an ability to more efficiently reduce hexavalent chromium intracellularly at younger ages. The greater effect at younger ages may also explain why short-term cumulative hexavalent chromium exposure was found to have more effect than the equivalent cumulative exposure spread over a longer term. The SMR for lung cancer was highest in the decade following cessation of exposure and may reflect the extremely irritating nature of hexavalent chromium.

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Cancer risk assessment for 1,3-butadiene: Dose–response modeling from an epidemiological perspective

Cited by 23 publications

References 6 publications

Evaluation of Cancer Tests of 1,3-Butadiene Using Internal Dose, Genotoxic Potency, and a Multiplicative Risk Model

Evaluation of Cancer Tests of 1,3-Butadiene Using Internal Dose, Genotoxic Potency, and a Multiplicative Risk Model

A comprehensive review of occupational and general population cancer risk: 1,3-Butadiene exposure–response modeling for all leukemia, acute myelogenous leukemia, chronic lymphocytic leukemia, chronic myelogenous leukemia, myeloid neoplasm and lymphoid neoplasm

Biologic Implications from an Epidemiologic Study of Chromate Production Workers

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