Assessing Susceptibility from Early-Life Exposure to Carcinogens

Abstract

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.

Perspectivas da investigação sobre determinantes sociais em câncer

“…Estudos da exposição aos fatores de risco ao longo do curso da vida são úteis para uma visão mais abrangente da etiologia do câncer. Exposições a cancerígenos na vida intra-uterina ou na infância precoce têm sido implicadas na ocorrência de câncer na vida adulta (BAIK et al, 2005;BARTON et al, 2005;FORMAN et al, 2005). Muitas das situações de vulnerabilidade nas fases iniciais da vida estão socialmente determinadas (UAUY; SOLOMONS, 2005).…”

Integrating Field Analyses with Laboratory Exposures to Assess Ecosystems Health

“…An analysis by the Environmental Protection Agency (2005) indicated that there can be greater susceptibility for the development of tumours as a result of exposures to mutagenic chemicals early in life compared with later stages of life (see also Barton et al, 2005). In general, there are limited data to elucidate the mode(s) of action that leads to differences in tumour incidence following exposure early in life or later.…”

Maternal Exposure to Particulate Air Pollution and Engineered Nanoparticles: Reproductive and Developmental Effects

“…In humans, maternal exposure to air pollution during pregnancy has been associated with genotoxicity in the children. Early-life exposure might therefore predispose to cancer and other diseases later in life (Barton et al 2005).…”