Review of the Environmental Protection Agency's Draft IRIS Assessment of Formaldehyde (2011) / Chapter Skim
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Appendix B: Weight-of-Evidence Descriptions from U.S. Environmental Protection Agency Guidelines
Appendix B: Weight-of-Evidence Descriptions from U.S. Environmental Protection Agency Guidelines
Pages 174-190
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From page 174... ...
. When human exposures occur, effects on postgonial stages should be weighted by the relative sensitivity and the duration of the stages.
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From page 175... ...
5. Suggestive evidence for a chemical's interaction with mammalian germ cells, together with valid positive mutagenicity evidence from two assay systems as described under 4, above.
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From page 176... ...
The criteria for establishing causal significance can be found in Appendix C In general, the following factors enhance the weight of evidence on a chemical: Clear evidence of a dose-response relationship; Similar effects across sex, strain, species, exposure routes, or in multiple experiments; Biologically plausible relationship between metabolism data, the postulated mechanism of action, and the effect of concern; Similar toxicity exhibited by structurally related compounds; Some correlation between the observed chemical toxicity and human evidence.
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From page 177... ...
The WOE scheme was the subject of a considerable number of public comments, and was one of the major concerns of the SAB. The concern of public commentors was that the reference to human developmental toxicity in this scheme suggested that a chemical could be prematurely designated, and perhaps labeled, as causing developmental toxicity in humans prior to the completion of the risk assessment process.
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From page 178... ...
of action and likelihood of human cancer hazard and risk. The cancer guidelines recognize the growing sophistication of research methods, particularly in their ability to reveal the modes of action of carcinogenic agents at cellular and subcellular levels as well as toxicokinetic processes.
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From page 179... ...
There are five recommended standard hazard descriptors: "Carcinogenic to Humans," "Likely to Be Carcinogenic to Humans," "Suggestive Evidence of Carcinogenic Potential," "Inadequate Information to Assess Carcinogenic Potential," and "Not Likely to Be Carcinogenic to Humans." Each standard descriptor may be applicable to a wide variety of data sets and weights of evidence and is presented only in the context of a weight of evidence narrative. Furthermore, as described in Section 2.5 of these cancer guidelines, more than one conclusion may be reached for an agent (EPA 2005b, Pp 1-11 to 1-12)
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From page 180... ...
, available information on the epidemiologic or experimental conditions that characterize expression of carcinogenicity (e.g., if carcinogenicity is possible only by one exposure route or only above a certain human exposure level) , a summary of potential modes of action and how they reinforce the conclusions, indications of any susceptible populations or lifestages, when available, and a summary of the key default options invoked when the available information is inconclusive.
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From page 181... ...
For example, if an agent causes point-of-contact tumors by one exposure route but adequate testing is negative by another route, then the agent could be described as likely to be carcinogenic by the first route but not likely to be carcinogenic by the second. Another example is when the mode of action is sufficiently understood to conclude that a key event in tumor development would not occur below a certain dose range.
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From page 182... ...
there is strong evidence of an association between human exposure and either cancer or the key precursor events of the agent's mode of action but not enough for a causal association, and (b) there is extensive evidence of carcinogenicity in animals, and (c)
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From page 183... ...
association between human exposure and cancer, in most cases with some supporting biological, experimental evidence, though not necessarily carcinogenicity data from animal experiments; an agent that has tested positive in animal experiments in more than one species, sex, strain, site, or exposure route, with or without evidence of carcinogenicity in humans; a positive tumor study that raises additional biological concerns beyond that of a statistically significant result, for example, a high degree of malignancy, or an early age at onset; a rare animal tumor response in a single experiment that is assumed to be relevant to humans; or a positive tumor study that is strengthened by other lines of evidence, for example, either plausible (but not definitively causal) association between human exposure and cancer or evidence that the agent or an important metabolite causes events generally known to be associated with tumor formation (such as DNA reactivity or effects on cell growth control)
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From page 184... ...
Some examples include: little or no pertinent information; conflicting evidence, that is, some studies provide evidence of carcinogenicity but other studies of equal quality in the same sex and strain are negative. Differing results, that is, positive results in some studies and negative results in one or more different experimental systems, do not constitute conflicting evidence, as the term is used here.
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From page 185... ...
, convincing and extensive experimental evidence showing that the only carcinogenic effects observed in animals are not relevant to humans, convincing evidence that carcinogenic effects are not likely by a particular exposure route (see Section 2.3) , or convincing evidence that carcinogenic effects are not likely below a defined dose range.
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From page 186... ...
Finally, the extent of the database is summarized, and assumptions made in the assessment are explicitly detailed. Further details about EPA's WOE approach can be found in the Methods for Derivation of Inhalation Reference Concentrations and Application of Inhalation Dosimetry (U.S.
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From page 187... ...
Statistical Power is the ability of a study to detect effects of a given magnitude. Corroboration means that specific effects are replicated in similar studies, similar effects are observed under varied conditions and /or similar effects are observed in multiple laboratories.
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From page 188... ...
1985. Guidelines as to what constitutes an adverse respira tory health effect, with special reference to epidemiologic studies of air pollu tion.
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From page 189... ...
1994. Methods for Derivation of Inhala tion Reference Concentrations and Application of Inhalation Dosimetry.
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From page 190... ...
1988. Using weight-of-evidence classification schemes in the assessment of non-cancer health risks.
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