Quantitative risk analysis for quantal reproductive and developmental effects

Journal Article · Wed Feb 01 04:00:00 EST 1989 · Environmental Health Perspectives; (USA)

DOI:https://doi.org/10.1289/ehp.8979243· OSTI ID:5584651

Gaylor, D W ^[1]

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1. National Center for Toxicological Research, Jefferson, AR (USA)

Animal experiments are generally conducted at higher dose levels than anticipated human dose levels in order to elicit otherwise subtle changes in reproduction or developmental effects with relatively few animals. Based on animal data, regulatory strategy generally has been to postulate a no-observed-effect level (NOEL) for toxic effects and to divide this by a safety factor, usually 100, to establish acceptable levels for humans. Various authors have discussed the shortcomings of using NOEL and have suggested the use of an estimable effect level determined from a dose-response curve fitted to bioassay data, e.g., the dose at which 1% of the animals are adversely affected, and employing some form of conservative low dose extrapolation to control risks at lower doses. In this paper, 10 sets of bioassay data on fetal mortality or anomalies were used to compare the estimated upper limits of risk estimated at the NOEL/100 and the lower 95% confidence limit estimate of the dose producing adverse effects in 1% of the embryonic implants or fetuses divided by 100 (LED{sub 01}/100). The latter quantity is expected to result in a risk (proportion affected) of less than 10{sup {minus}4} (1 in 10,000). The estimated upper limits of risk associated with the NOEL/100 were from 2 {times} 10{sup {minus}4} to 6 x 10{sup {minus}4} for the 10 data sets investigated.

• OSTI ID: 5584651
• Journal Information: Environmental Health Perspectives; (USA), Journal Name: Environmental Health Perspectives; (USA) Vol. 79; ISSN 0091-6765; ISSN EVHPA
• Country of Publication: United States
• Language: English

Related Subjects

560300* -- Chemicals Metabolism & Toxicology
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
ANTITHYROID DRUGS
AROMATICS
AZAARENES
BIOLOGICAL EFFECTS
CARBONIC ACID DERIVATIVES
CONGENITAL MALFORMATIONS
DIOXIN
DOSE-RESPONSE RELATIONSHIPS
DRUGS
HAMSTERS
HETEROCYCLIC COMPOUNDS
HORMONE ANTAGONISTS
MALFORMATIONS
MAMMALS
MATHEMATICAL MODELS
MICE
MORTALITY
ONTOGENESIS
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANIC SULFUR COMPOUNDS
PATHOLOGICAL CHANGES
PURINES
RABBITS
RATS
REPRODUCTION
RISK ASSESSMENT
RODENTS
TERATOGENS
THIOUREA
THIOUREAS
VERTEBRATES
XANTHINES