Assessing cancer risks from short-term exposures in children.
For the vast majority of chemicals that have cancer potency estimates on IRIS, the underlying database is deficient with respect to early-life exposures. This data gap has prevented derivation of cancer potency factors that are relevant to this time period, and so assessments may not fully address children's risks. This article provides a review of juvenile animal bioassay data in comparison to adult animal data for a broad array of carcinogens. This comparison indicates that short-term exposures in early life are likely to yield a greater tumor response than short-term exposures in adults, but similar tumor response when compared to long-term exposures in adults. This evidence is brought into a risk assessment context by proposing an approach that: (1) does not prorate children's exposures over the entire life span or mix them with exposures that occur at other ages; (2) applies the cancer slope factor from adult animal or human epidemiology studies to the children's exposure dose to calculate the cancer risk associated with the early-life period; and (3) adds the cancer risk for young children to that for older children/adults to yield a total lifetime cancer risk. The proposed approach allows for the unique exposure and pharmacokinetic factors associated with young children to be fully weighted in the cancer risk assessment. It is very similar to the approach currently used by U.S. EPA for vinyl chloride. The current analysis finds that the database of early life and adult cancer bioassays supports extension of this approach from vinyl chloride to other carcinogens of diverse mode of action. This approach should be enhanced by early-life data specific to the particular carcinogen under analysis whenever possible.
Ginsberg
Gary L
GL
Connecticut Department of Public Health, Division of Environmental Epidemiology & Occupational Health, PO Box 340308, MS 11CHA, Hartford, CT 06134-0308, USA. gary.ginsberg@po.state.ct.us
D000367:Age Factors; D000818:Animals; D015197:Carcinogenicity Tests; D002273:Carcinogens / Q000008:administration & dosage / Q000633:toxicity*; D002648:Child; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D009153:Mutagens / Q000008:administration & dosage / Q000633:toxicity; D009369:Neoplasms / Q000139:chemically induced*; D009374:Neoplasms, Experimental / Q000139:chemically induced; D051381:Rats; D018570:Risk Assessment; D014481:United States; D014484:United States Environmental Protection Agency; D014752:Vinyl Chloride / Q000008:administration & dosage / Q000633:toxicity
D002273:Carcinogens; D009153:Mutagens; D014752:Vinyl Chloride