TY - JOUR

T1 - Enhancement of developmental toxicity effects of chemicals by gestational stress. A review

AU - Hougaard, Karin S

AU - Hansen, Åse Marie

PY - 2007/4/17

Y1 - 2007/4/17

N2 - Risk assessment of developmental toxicants is almost exclusively based on single chemicals studied in animals under controlled experimental conditions, as to reduce stress. Although humans may be exposed simultaneously to numerous hazards, little is known about the interaction of prenatal chemical exposures with other factors, such as maternal stress, itself a modifier of fetal development. Gestational stress has been hypothesized to enhance the developmental toxicity of chemicals. This review identified 36 animal studies investigating if maternal stress may enhance the effects of prenatal chemical exposure, and evaluated the presented hypothesis. Studies of a broad range of chemicals and developmental endpoints support the notion, that maternal stress is able to enhance the effects of developmental toxicants, although stress mitigated chemically induced effects in a few cases. Maternal stress most often enhanced chemical developmental toxicity at dose levels associated with severe maternal toxicity or where test agents were already above threshold for effect. Thus, LOAEL(chemical) was generally similar to LOAEL(chemical+stress), although not necessarily for the same endpoint. It should be noted that the database contained a limited number of studies, and only a single high dose level was applied in most studies, rendering establishment of NOAELs for combined exposures impossible. Furthermore, for some compounds, the margin between human exposure levels and the LOAEL(chemical+stress) seems small. Future studies are recommended to investigate compounds, for which maternal stress was already proven as an enhancer, at lower dose levels. Interactive response seems to depend on stressor severity and timing of chemical exposure relative to maternal stress which should be further scrutinized.

AB - Risk assessment of developmental toxicants is almost exclusively based on single chemicals studied in animals under controlled experimental conditions, as to reduce stress. Although humans may be exposed simultaneously to numerous hazards, little is known about the interaction of prenatal chemical exposures with other factors, such as maternal stress, itself a modifier of fetal development. Gestational stress has been hypothesized to enhance the developmental toxicity of chemicals. This review identified 36 animal studies investigating if maternal stress may enhance the effects of prenatal chemical exposure, and evaluated the presented hypothesis. Studies of a broad range of chemicals and developmental endpoints support the notion, that maternal stress is able to enhance the effects of developmental toxicants, although stress mitigated chemically induced effects in a few cases. Maternal stress most often enhanced chemical developmental toxicity at dose levels associated with severe maternal toxicity or where test agents were already above threshold for effect. Thus, LOAEL(chemical) was generally similar to LOAEL(chemical+stress), although not necessarily for the same endpoint. It should be noted that the database contained a limited number of studies, and only a single high dose level was applied in most studies, rendering establishment of NOAELs for combined exposures impossible. Furthermore, for some compounds, the margin between human exposure levels and the LOAEL(chemical+stress) seems small. Future studies are recommended to investigate compounds, for which maternal stress was already proven as an enhancer, at lower dose levels. Interactive response seems to depend on stressor severity and timing of chemical exposure relative to maternal stress which should be further scrutinized.

KW - Animals

KW - Female

KW - Fetal Development

KW - Humans

KW - Maternal-Fetal Relations

KW - Noxae

KW - Pregnancy

KW - Prenatal Exposure Delayed Effects

KW - Review Literature as Topic

KW - Stress, Physiological

KW - Journal Article

KW - Review

U2 - 10.1016/j.ntt.2007.02.003

DO - 10.1016/j.ntt.2007.02.003

M3 - Journal article

C2 - 17433620

VL - 29

SP - 425

EP - 445

JO - Neurotoxicology and Teratology

JF - Neurotoxicology and Teratology

SN - 0892-0362

IS - 4

ER -