Environmental Engineering Reference
In-Depth Information
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significant data gaps; and
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major assumptions.
12.5.10.2 Characterisation of Dose-Response
1. What data were used to develop the dose-response curve? Would the result have
been significantly different if based on a different data set?
If animal data were used:
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What species were used? The most sensitive, average of all species, or other?
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Were any studies excluded? Why?
If epidemiological data were used:
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Which studies were used? Only positive studies, all studies, or some other
combination?
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Were any studies excluded? Why?
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Was a meta-analysis performed to combine the epidemiological, studies?
What approach was used? Were studies excluded? Why?
2. What model was used to develop the dose-response curve? What rationale sup-
ports this choice? Is chemical-specific information available to support this
approach?
For non-carcinogenic hazards:
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How was the Tolerable Intake (or the acceptable range) estimated?
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What assumptions or uncertainty factors were used?
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What is the confidence in the estimates?
For carcinogenic hazards:
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What dose-response model was used? What is the basis for the selection of
the particular dose-response model used? Are there other models that could
have been used with equal plausibility and scientific validity?
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What is the basis for selection of the model used in this instance?
3. Discuss the route and level of exposure observed in the toxicology or epidemiol-
ogy studies, as compared to the expected human exposures in the situation under
appraisal.
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Are the available data from the same route of exposure as the expected human
exposures? If not, are pharmacokinetic data available to extrapolate across
route of exposure?
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What is the degree of extrapolation from the observed data in the toxico-
logical or epidemiological studies to the expected human exposures in the
situation under appraisal (one to two orders of magnitude? multiple orders of
magnitude)? What is the impact of such an extrapolation?
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