Abstract
Biologically rational regulatory policies with regards to developmental toxicity are often based on the extrapolation of standard laboratory rodent bioassay results to the human population. Significantly contributing to the difficulty of this task is the possibility that general toxic effects on the maternal organism may affect the developing conceptus. This review examines maternal factors which may bear directly or indirectly upon developmental outcome, with emphasis on those of greatest relevance to the hazard assessment process. Standard teratology testing protocols call for top dosage levels that induce overt maternal toxicity, and the developmental effects of this toxicity (both alone, and with concurrent embryo/fetal insult) continue to present regulators with considerable interpretive difficulties. In response to these problems, there have been both research and literature review efforts dealing with the relationship of maternal and developmental toxicity. Maternally mediated developmental toxicity occurs with a number of agents, and toxicant-induced alterations in maternal physiology may affect the conceptus at dosages not causing overt maternal toxicity. Relevant studies are reviewed here, and suggestions for avenues of future research are offered including the identification of any syndromes of developmental effects occurring at maternally toxic levels irrespective of the causative agent, and experimental approaches for the characterization of maternal toxicity.
| Original language | English (US) |
|---|---|
| Journal | Toxicology and Applied Pharmacology |
| Volume | 207 |
| Issue number | 2 SUPPL. |
| DOIs | |
| State | Published - Sep 1 2005 |
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Keywords
- Fetal toxicity
- Hazard evaluation
- Maternal stress
- Maternal toxicity
- Teratology
ASJC Scopus subject areas
- Pharmacology
- Toxicology
Cite this
Evaluation and interpretation of maternal toxicity in Segment II studies : Issues, some answers, and data needs. / Rogers, John M.; Chernoff, Neil; Keen, Carl L; Daston, George P.
In: Toxicology and Applied Pharmacology, Vol. 207, No. 2 SUPPL., 01.09.2005.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Evaluation and interpretation of maternal toxicity in Segment II studies
T2 - Issues, some answers, and data needs
AU - Rogers, John M.
AU - Chernoff, Neil
AU - Keen, Carl L
AU - Daston, George P.
PY - 2005/9/1
Y1 - 2005/9/1
N2 - Biologically rational regulatory policies with regards to developmental toxicity are often based on the extrapolation of standard laboratory rodent bioassay results to the human population. Significantly contributing to the difficulty of this task is the possibility that general toxic effects on the maternal organism may affect the developing conceptus. This review examines maternal factors which may bear directly or indirectly upon developmental outcome, with emphasis on those of greatest relevance to the hazard assessment process. Standard teratology testing protocols call for top dosage levels that induce overt maternal toxicity, and the developmental effects of this toxicity (both alone, and with concurrent embryo/fetal insult) continue to present regulators with considerable interpretive difficulties. In response to these problems, there have been both research and literature review efforts dealing with the relationship of maternal and developmental toxicity. Maternally mediated developmental toxicity occurs with a number of agents, and toxicant-induced alterations in maternal physiology may affect the conceptus at dosages not causing overt maternal toxicity. Relevant studies are reviewed here, and suggestions for avenues of future research are offered including the identification of any syndromes of developmental effects occurring at maternally toxic levels irrespective of the causative agent, and experimental approaches for the characterization of maternal toxicity.
AB - Biologically rational regulatory policies with regards to developmental toxicity are often based on the extrapolation of standard laboratory rodent bioassay results to the human population. Significantly contributing to the difficulty of this task is the possibility that general toxic effects on the maternal organism may affect the developing conceptus. This review examines maternal factors which may bear directly or indirectly upon developmental outcome, with emphasis on those of greatest relevance to the hazard assessment process. Standard teratology testing protocols call for top dosage levels that induce overt maternal toxicity, and the developmental effects of this toxicity (both alone, and with concurrent embryo/fetal insult) continue to present regulators with considerable interpretive difficulties. In response to these problems, there have been both research and literature review efforts dealing with the relationship of maternal and developmental toxicity. Maternally mediated developmental toxicity occurs with a number of agents, and toxicant-induced alterations in maternal physiology may affect the conceptus at dosages not causing overt maternal toxicity. Relevant studies are reviewed here, and suggestions for avenues of future research are offered including the identification of any syndromes of developmental effects occurring at maternally toxic levels irrespective of the causative agent, and experimental approaches for the characterization of maternal toxicity.
KW - Fetal toxicity
KW - Hazard evaluation
KW - Maternal stress
KW - Maternal toxicity
KW - Teratology
UR - http://www.scopus.com/inward/record.url?scp=24644459507&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=24644459507&partnerID=8YFLogxK
U2 - 10.1016/j.taap.2005.03.026
DO - 10.1016/j.taap.2005.03.026
M3 - Article
C2 - 15982694
AN - SCOPUS:24644459507
VL - 207
JO - Toxicology and Applied Pharmacology
JF - Toxicology and Applied Pharmacology
SN - 0041-008X
IS - 2 SUPPL.
ER -