Assessing susceptibility from early-life exposure to carcinogens.
Cancer risk assessment methods currently assume that children and adults are equally susceptible to exposure to chemicals. We reviewed available scientific literature to determine whether this was scientifically supported. We identified more than 50 chemicals causing cancer after perinatal exposure. Human data are extremely limited, with radiation exposures showing increased early susceptibility at some tumor sites. Twenty-seven rodent studies for 18 chemicals had sufficient data after postnatal and adult exposures to quantitatively estimate potential increased susceptibility from early-life exposure, calculated as the ratio of juvenile to adult cancer potencies for three study types: acute dosing, repeated dosing, and lifetime dosing. Twelve of the chemicals act through a mutagenic mode of action. For these, the geometric mean ratio was 11 for lifetime exposures and 8.7 for repeat exposures, with a ratio of 10 for these studies combined. The geometric mean ratio for acute studies is 1.5, which was influenced by tissue-specific results [geometric mean ratios for kidney, leukemia, liver, lymph, mammary, nerve, reticular tissue, thymic lymphoma, and uterus/vagina > 1 (range, 1.6-8.1); forestomach, harderian gland, ovaries, and thyroid < 1 (range, 0.033-0.45)]. Chemicals causing cancer through other modes of action indicate some increased susceptibility from postnatal exposure (geometric mean ratio is 3.4 for lifetime exposure, 2.2 for repeat exposure). Early exposures to compounds with endocrine activity sometimes produce different tumors after exposures at different ages. These analyses suggest increased susceptibility to cancer from early-life exposure, particularly for chemicals acting through a mutagenic mode of action.
Barton
Hugh A
HA
Office of Research and Development, National Center for Computational Toxicology, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, USA.
Cogliano
V James
VJ
Flowers
Lynn
L
Valcovic
Larry
L
Setzer
R Woodrow
RW
Woodruff
Tracey J
TJ
D000293:Adolescent; D000328:Adult; D000375:Aging / Q000502:physiology*; D000818:Animals; D002273:Carcinogens / Q000633:toxicity*; D002648:Child; D002657:Child Development; D002675:Child, Preschool; D004198:Disease Susceptibility; D004781:Environmental Exposure; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D009153:Mutagens / Q000633:toxicity*; D009369:Neoplasms / Q000139:chemically induced*; D018570:Risk Assessment / Q000379:methods
D002273:Carcinogens; D009153:Mutagens