Comparison of the cancer risk of methylene chloride predicted from animal bioassay data with the epidemiologic evidence.
Methylene chloride has been shown to be a lung and liver carcinogen in the mouse; yet, the current epidemiologic data show no adverse health effects associated with chronic exposure to this compound. Hearne et al. have compared the results of a large mortality study on occupational exposure to methylene chloride to the human risk predictions based on the rodent bioassay to point out the inconsistency between the animal toxicologic and human epidemiologic data. The maximum number of lung and liver cancers predicted due to methylene chloride exposure based on the rodent bioassay data was 24 compared to 14 deaths from these cancers actually observed in the Hearne et al. epidemiology study. We assess the minimum risk detectable by the human study in order to calculate the upperbound potency of methylene chloride and compare it to the potency derived from the bioassay data. Results from the epidemiology study imply an upperbound potency of 1.5 x 10(-2) per ppm, compared to 1.4 x 10(-2) per ppm calculated using the most conservative analysis of the animal data. We conclude that the negative epidemiology study of Hearne et al. is not sufficiently powerful to show that the risk is inconsistent with the human risk estimated by modeling the rodent bioassay data. Specifically, the doses to which the workers were exposed, the population studied, and the latency period were not adequate to determine that the risks are outside the bounds of the risk estimates predicted by low-dose modeling of the animal data.
Tollefson
L
L
Office of Nutrition and Food Science, Food and Drug Administration, Washington, D.C. 20204.
Lorentzen
R J
RJ
Brown
R N
RN
Springer
J A
JA
D000395:Air Pollutants, Occupational / Q000009:adverse effects*; D000818:Animals; D004195:Disease Models, Animal; D006801:Humans; D008113:Liver Neoplasms / Q000139:chemically induced* / Q000401:mortality; D008175:Lung Neoplasms / Q000139:chemically induced* / Q000401:mortality; D008297:Male; D008752:Methylene Chloride / Q000633:toxicity*; D051381:Rats; D012306:Risk; D013045:Species Specificity; D016019:Survival Analysis; D015996:Survival Rate
D000395:Air Pollutants, Occupational; D008752:Methylene Chloride