Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
197125
Reference Type
Journal Article
Title
Dose-response assessment for developmental toxicity II: Comparison of generic benchmark dose estimates with no observed adverse effect levels
Author(s)
Allen, BC; Kavlock, RJ; Kimmel, CA; Faustman, EM
Year
1994
Is Peer Reviewed?
Yes
Journal
Fundamental and Applied Toxicology
ISSN:
0272-0590
EISSN:
1095-6832
Volume
23
Issue
4
Page Numbers
487-495
Language
English
PMID
7867900
DOI
10.1006/faat.1994.1133
Web of Science Id
WOS:A1994PR07200003
Abstract
Developmental toxicity risk assessment currently relies on the estimation of reference doses (RfDDTs) or reference concentrations (RfDDTs) based on the use of no observed adverse effect levels (NOAELs) divided by uncertainty factors (UFs). The benchmark dose (BMD) has been proposed as an alternative basis for reference value calculations. A large database of 246 developmental toxicity experiments representing 1825 endpoints related to dead implants or malformed fetuses has been compiled for use in evaluating alternative approaches to developmental toxicity risk assessment. Using this database we have compared two approaches for BMD estimation with each other and with corresponding statistically derived NOAELs. Comparisons have been based on proportion of affected litters (litters with one or more affected offspring, a quantal response variable) and on the proportion of affected offspring within each litter (a continuous response variable). A quantal Weibull model was used to calculate generic BMDs for the quantal response variable (QBMDs) and a continuous power model was used to calculate generic BMDs for the continuous response variable (CBMDs) at three levels of additional risk (10, 5, and 1%). CBMD05s (continuous benchmark doses for 5% risk) and CNOAELs (statistically derived NOAELs based on the continuous response variable) were similar, with over 98% of the data subsets having CBMD05 and CNOAEL values that differed by less than an order of magnitude. In contrast, QNOAELs tended to be greater than corresponding QBMD10s. The observed conservatism of the QBMD values relative to the corresponding CBMD values was attributed to two factors, lower maximum likelihood estimates for the quantal model and wider confidence intervals around the maximum likelihood estimates, compared to the continuous model. Comparisons of different quantitative dose-response assessments for developmental toxicity experiments should help to identify appropriate risk assessment approaches for developmental toxicity risk assessment.
Tags
IRIS
•
Methanol (Non-Cancer)
Cited in Final (2013)
Cited in External Review Draft (2013)
Cited in External Review Draft (2011)
•
Trichloroethylene (TCE) (Final, 2011)
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity