To convert a 70-y exposure to a 24-h exposure:
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OCR for page 194
Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals Appendix H Example of a Carcinogenicity Assessment Appendix in A Technical Support Document CARCINOGENICITY ASSESSMENT OF DIMETHYLHYDRAZINE Slope factors for 1,1-dimethylhydrazine and 1,2-dimethylhydrazine were available but have been withdrawn from the U.S. EPA Integrated Risk Information System (IRIS) (U.S. EPA 1986). For a preliminary carcinogenicity assessment, the withdrawn inhalation slope factor for 1,1-dimethylhydrazine (cited in ATSDR 1994) will be used. The assessment follows previously described methodologies (NRC 1985; Henderson 1992). The withdrawn slope factor for 1,1-dimethylhydrazine was 3.5 (mg/ kg·d)−1, which, based upon a human inhalation rate of 20 m3/d and a body weight of 70 kg, is equivalent to 1 (mg/m3)−1. To convert to a level of monomethylhydrazine that would cause a theoretical excess cancer risk of 10−4: Risk of 1×10−4=(1×10−4/1)×1 mg/m3 =1×10−4 mg/m3 (virtually safe dose) To convert a 70-y exposure to a 24-h exposure:
OCR for page 195
Standing Operating Procedures for Developing Acute Exposure Guideline Levels for Hazardous Chemicals 24-h exposure =d×25,600 =(1×10−4 mg/m3)×25,600 d =2.56 mg/m3 To account for uncertainty regarding the variability in the stage of the cancer process at which monomethylhydrazine or its metabolites may act, a multistage factor of 6 is applied (Crump and Howe 1984): (2.56 mg/m3)/6=0.43 mg/m3 (0.18 ppm) Therefore, based upon the potential carcinogenicity of monomethylhydrazine, an acceptable 24-h exposure would be 0.9 mg/m3 (0.5 ppm). If the exposure is limited to a fraction (f) of a 24-h period, the fractional exposure becomes 1/f×24 h (NRC 1985). 24-h exposure =0.43 mg/m3 (0.18 ppm) 8-h =1.3 mg/m3 (0.5 ppm) 4-h =2.6 mg/m3 (1.1 ppm) 1-h =10.3 mg/m3 (4.2 ppm) 0.5 h =20.6 mg/m3 (8.5 ppm) Because the AEGL-2 values based upon acute toxicity were equivalent to or lower than the 10−4 risk values derived based on potential carcinogenicity, the acute toxicity data were used for the AEGLs for dimethylhydrazine. For 10−5 and 10−6 risk levels, the 10−4 values are reduced by 10-fold or 100-fold, respectively.
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