The intake of chemicals related to age in long-term toxicity studies--considerations for risk assessment.
The estimation of acceptable daily intake (ADI) is generally based on results from long-term toxicity studies. Long-term exposure of rodent and nonrodent species is extrapolated to lifetime exposure in humans, using uncertainty factors to compensate inter- and intraspecies differences. Special consideration can be given to groups of humans at increased risk, such as children, due to higher susceptibility or higher predicted intake. A retrospective study of long-term carcinogenesis studies was performed at the National Toxicology Program of the National Institute of Environmental Health Sciences to gain insight into the relationship between age and intake of test compounds. In these long-term studies, average intake of feed and drinking water, and consequently chemicals dosed in these, was approximately two times higher on a body weight basis in young animals (postweaning) than in adults. Thus, estimating an ADI from the NOEL of this type of studies already includes a higher dose for the young. When maximum levels for food additives are being set using the already established ADI, it may not be necessary to add an additional uncertainty factor for different ages, unless there are other specific reasons to do so, such as unduly high exposure and toxicity at a certain age. Compared to intake per kilogram of body weight at the end of the study, the ADI already includes an extra uncertainty factor of approximately 2 for young individuals.
Luijckx
N B
NB
National Institute of Public Health and Environmental Protection, Bilthoven, The Netherlands.
Rao
G N
GN
McConnell
E E
EE
Würtzen
G
G
Kroes
R
R
D000375:Aging / Q000502:physiology*; D000821:Animal Feed / Q000032:analysis; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D005260:Female; D008297:Male; D051381:Rats; D011916:Rats, Inbred F344; D012189:Retrospective Studies; D018570:Risk Assessment; D018675:Toxicity Tests; D014481:United States; D014881:Water Supply
D002273:Carcinogens