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1,3-Butadiene: exposure estimation, hazard characterization, and exposure-response analysis.

https://arctichealth.org/en/permalink/ahliterature186649
Source
J Toxicol Environ Health B Crit Rev. 2003 Jan-Feb;6(1):55-83
Publication Type
Article
Author
K. Hughes
M E Meek
M. Walker
R. Beauchamp
Author Affiliation
Existing Substances Division, Environmental Health Directorate, Health Canada, Environmental Health Centre, Tunney's Pasture PL0802B1, Ottawa, Ontario, Canada K1A 0L2.
Source
J Toxicol Environ Health B Crit Rev. 2003 Jan-Feb;6(1):55-83
Language
English
Publication Type
Article
Keywords
Animals
Butadienes - metabolism - toxicity
Canada - epidemiology
Carcinogens, Environmental - toxicity
Environmental Exposure
Hazardous Substances - toxicity
Humans
Mutagens - toxicity
Neoplasms - chemically induced - epidemiology
Occupational Diseases - chemically induced - epidemiology
Risk assessment
Abstract
1,3-Butadiene has been assessed as a Priority Substance under the Canadian Environmental Protection Act. The general population in Canada is exposed to 1,3-butadiene primarily through ambient air. Inhaled 1,3-butadiene is carcinogenic in both mice and rats, inducing tumors at multiple sites at all concentrations tested in all identified studies. In addition, 1,3-butadiene is genotoxic in both somatic and germ cells of rodents. It also induces adverse effects in the reproductive organs of female mice at relatively low concentrations. The greater sensitivity in mice than in rats to induction of these effects by 1,3-butadiene is likely related to species differences in metabolism to active epoxide metabolites. Exposure to 1,3-butadiene in the occupational environment has been associated with the induction of leukemia; there is also some limited evidence that 1,3-butadiene is genotoxic in exposed workers. Therefore, in view of the weight of evidence of available epidemiological and toxicological data, 1,3-butadiene is considered highly likely to be carcinogenic, and likely to be genotoxic, in humans. Estimates of the potency of butadiene to induce cancer have been derived on the basis of both epidemiological investigation and bioassays in mice and rats. Potencies to induce ovarian effects have been estimated on the basis of studies in mice. Uncertainties have been delineated, and, while there are clear species differences in metabolism, estimates of potency to induce effects are considered justifiably conservative in view of the likely variability in metabolism across the population related to genetic polymorphism for enzymes for the critical metabolic pathway.
PubMed ID
12587254 View in PubMed
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Health risk assessment of 1,3-butadiene as a Priority Substance in Canada.

https://arctichealth.org/en/permalink/ahliterature194411
Source
Chem Biol Interact. 2001 Jun 1;135-136:109-35
Publication Type
Article
Date
Jun-1-2001
Author
K. Hughes
M E Meek
M. Walker
Author Affiliation
Environmental Health Directorate, Health Canada, Tunney's Pasture PL0802B1, Ottawa, Ontario, Canada K1A 0L2. kathy_hughes@hc-sc.gc.ca
Source
Chem Biol Interact. 2001 Jun 1;135-136:109-35
Date
Jun-1-2001
Language
English
Publication Type
Article
Keywords
Animals
Butadienes - metabolism - toxicity
Canada - epidemiology
Carcinogens, Environmental - toxicity
Environmental Exposure
Hazardous Substances - toxicity
Humans
Mutagens - toxicity
Neoplasms - chemically induced - epidemiology
Occupational Diseases - chemically induced - epidemiology
Risk assessment
Abstract
1,3-Butadiene was included in the second list of Priority Substances to be assessed under the Canadian Environmental Protection Act. Potential hazards to human health were characterized on the basis of critical examination of available data on health effects in experimental animals and occupationally exposed human populations, as well as information on mode of action. Based on consideration of all relevant data identified as of April 1998, butadiene was considered highly likely to be carcinogenic to humans, and likely to be a somatic and germ cell genotoxicant in humans. In addition, butadiene may also be a reproductive toxicant in humans. Estimates of the potency of butadiene to induce these effects have been derived on the basis of quantitation of observed exposure-response relationships for the purposes of characterization of risk to the general population in Canada exposed to butadiene in the ambient environment.
PubMed ID
11397385 View in PubMed
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Tools for the prioritization of substances on the Domestic Substances List in Canada on the basis of hazard.

https://arctichealth.org/en/permalink/ahliterature148466
Source
Regul Toxicol Pharmacol. 2009 Dec;55(3):382-93
Publication Type
Article
Date
Dec-2009
Author
K. Hughes
J. Paterson
M E Meek
Author Affiliation
Safe Environments Directorate, Health Canada, AL 4904D, Ottawa, Ontario, Canada K1A 0K9. Kathy_hughes@hc-sc.gc.ca
Source
Regul Toxicol Pharmacol. 2009 Dec;55(3):382-93
Date
Dec-2009
Language
English
Publication Type
Article
Keywords
Animals
Canada
Environmental Exposure - adverse effects
Environmental Health - methods
Hazardous Substances - toxicity
Humans
Risk Assessment - methods
Abstract
A precedent setting legislative mandate under the Canadian Environmental Protection Act 1999 to establish priorities for assessment based on systematic consideration of all of the approximately 23,000 Existing Chemicals in Canada required the development and refinement of methodology in a number of important areas. This included development of simple and complex exposure and hazard tools for priority setting which draw maximally and efficiently on available data to systematically identify substances that are highest priorities in relation to their potential to cause adverse effects on the general population. The hierarchical approach in the simple and complex hazard tools described here efficiently and effectively sets substances aside as non-priorities, or prioritizes them for consideration additionally in assessment. The hazard tools efficiently incorporate previous work, contributing to consistency internationally, and involve hierarchical consideration of sources of information based on their relative weighting. They are health protective, based on their incorporated degree of conservatism, and provide direction for additional assessment for substances deemed to be priorities. Although designed for prioritization of Existing Substances in Canada, these tools have potential for broader application in other national and international programs to provide focus and increase efficiency in human health risk assessment.
PubMed ID
19766685 View in PubMed
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