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Yu-Sheng Lin,¹ Thomas J. Smith,¹ Karl T. Kelsey,² and David Wypij³

¹Department of Environmental Health, ²Department of Cancer Cell Biology, and ³Department of Biostatistics, Harvard School of Public Health, Boston, Massachusetts, USA

Abstract

1,3-Butadiene (BD) , a suspected human carcinogen, is used as the raw material in industries to make synthetic butyl rubber and plastics. Simulation models using experimental animal data have shown that physiologic factors play an important role in the kinetic behavior of BD. However, human data are limited. The aim of this inhalation study was to identify influential human physiologic factors in the respiratory uptake of BD. We recruited 133 healthy volunteers in Boston, Massachusetts, into this study and tested them under an approved human subjects protocol. Each subject was exposed to 2 ppm (4.42 mg/m³) BD for 20 min, followed by purified air for another 40 min. Five exhaled breath samples collected during exposure were used to determine the respiratory uptake of BD, which was defined as absorbed BD (micrograms) per kilogram of body weight during exposure. Although subjects were given identical administered doses (40 ppm min) , there was a wide range of uptake, 0.6-4.9 µg/kg. Of the studied physiologic factors, the blood:air partition coefficient and alveolar ventilation were most significant in determining the respiratory uptake (p < 0.001 for each) . In addition, in the multiple regression analysis, females had significantly higher respiratory uptake of BD than males on a weight basis. For all subjects, increasing age and cigarette smoking led to significantly decreased respiratory uptake of BD. The results of this human study are consistent with previous kinetic simulations and animal studies. The findings also suggest that interindividual variation in human physiologic factors that affect the exposure-internal dose relationship should be considered while also exploring exposure-disease associations in future epidemiologic research. Key words: alveolar ventilation, blood:air partition coefficient, 1, 3-butadiene, human, physiologic, respiratory uptake, sex. Environ Health Perspect 109:921-926 (2001) . [Online 23 August 2001]
(Correction was made on 30 August 2001) .

http://ehpnet1.niehs.nih.gov/docs/2001/109p921-926lin/ abstract.html

Address correspondence to T.J. Smith, Department of Environmental Health, Harvard School of Public Health, 665 Huntington Avenue, Building 1, Room 1403, Boston, MA USA. Telephone: (617) 432-3315. Fax: (617) 432-0219. E-mail: tsmith@hohp.harvard.edu

We are especially grateful to R.F. Herrick, H.Y. Chang, and E. Moy for helpful discussions.

This study is part of the three-year 1,3-butadiene metabolic study, funded by the National Institute of Environmental Health Sciences (NIEHS) grants 07586 and the NIEHS Center Grant ES00002.

Received 15 January 2001 ; accepted 8 March 2001.