Evaluation of Reduced Protocols for Carcinogenicity Testing of Chemicals: Report of a Joint EPA/NIEHS Workshop

Lai, David Y.; Baetcke, Karl P.; Vu, Vanessa; Cotruvo, Joseph A.; Eustis, Scot L.

doi:10.1006/rtph.1994.1017

Cited by 22 publications

(4 citation statements)

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“…This is incorrect. The excellent agreement between carcinogenic responses in male and female rats is similar to that seen for male and female mice [Haseman and Huff, 1987;Huff et al, 1991;Haseman and Lockhart, 1993;Lai et al, 1994]. Moreover, even if one focuses on site-specific tumor responses, the correlation between sexes is quite high, as reported elsewhere [e.g., Haseman and Lockhart, 1993].…”

supporting

confidence: 82%

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Transgenic assays and the identification of carcinogens

Tennant

Haseman

Stoll

2001

Environ. Mol. Mutagen.

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supporting

confidence: 82%

“…From the data presented in Johnson's own Table I This high concordance reflects a significant (P Ͻ 0.0001) correlation, an association that was reported previously by numerous investigators [e.g., Haseman and Huff, 1987;Huff et al, 1991;Lai et al, 1994]. This is incorrect.…”

mentioning

confidence: 68%

Transgenic assays and the identification of carcinogens

Tennant

Haseman

Stoll

2001

Environ. Mol. Mutagen.

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“…In the U.S. FDA, U.S. NTP, and CPD databases only 22, 26, and 33%, respectively, of all compounds with positive findings produced tumor findings in at least one common site in the rat and mouse (18,19,22). The lack of site specificity has been cited as part of the rationale for a reduced 2-year study protocol using only male rats and female mice (28,29). If tumor site cannot be reliably predicted between rodent species, extrapolation of rodent tumor sites to humans is also questionable (30).…”

Section: Introductionmentioning

confidence: 99%

In Vivo Transgenic Bioassays and Assessment of the Carcinogenic Potential of Pharmaceuticals

Contrera¹,

DeGeorge²

1998

Environmental Health Perspectives

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There is general agreement in the scientific community on the need to improve carcinogenicity testing and the assessment of human carcinogenic risk and to incorporate more information on mechanisms and modes of action into the risk assessment process. Advances in molecular biology have identified a growing number of genes such as protooncogenes and tumorsuppressor genes that are highly conserved across species and are assocjated with a wide variety of human and animal cancers. In vivo transgenic rodent models incorporating such mechanisms are used to identify mechanisms involved in tumor formation and as selective tests for carcinogens. Transgenic methods can be considered an extension of genetic manipulation by selective breeding, which long has been employed in science and agriculture. The use of two rodent species in carcinogenicity testing is especially important for identifying transspecies carcinogens. The capacity of a substance to induce neoplasia across species suggests that the mechanism(s) involved in the induction of the neoplasia are conserved and therefore may have significance for humans. Based on available information there is sufficient experience with some in vivo transgenic rodent carcinogenicity models to support their application as complementary second species studies in conjunction with a single 2-year rodent carcinogenicity study. The optional substitution of a second 2-year rodent carcinogenicity study with an alternative study such as an in vivo transgenic carcinogenicity study is part of the International Conference on Harmonization guidance Si B: Testing for Carcinogenicity of Pharmaceuticals. This guidance is intended to be flexible enough to accommodate a wide range of possible carcinogenicity assessment models currently under consideration or models that may be developed in the future. The use of an in vivo transgenic mouse model in place of a second 2-year mouse study will improve the assessment of carcinogenic risk by contributing insights into the mechanisms of tumorigenesis and potential human relevance not available from a standard 2-year bioassay. It is envisioned that this will stimulate the further development of more efficient and relevant methods for identifying and assessing potential human carcinogenic risk, which will benefit public health.Environ Health Perspect 106(Suppl 1): 71-80 (1998). http.//ehpnet1.niehs.nih.gov/ docs/1998/Suppl-1/71-80contrera/abstract.html

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“…Proper dose selection continues to be an important issue (5,8,15,26,33). It has been suggested that a reduced protocol (e.g., male rats and female mice or male and female rats) may be sufficient for detecting the majority of important carcinogens (3,14,21,39,40 (9,13). This is an important issue, since the questioned tumor sites constitute a significant portion of the carcinogenic effects found in rodent studies (35), and determining definitive mechanisms of carcinogenic action may be difficult (31,32).…”

mentioning

confidence: 99%

Value of Historical Control Data and Other Issues Related to the Evaluation of Long-Term Rodent Carcinogenicity Studies

1997

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One of the most important of these factors is consistency of gross necropsy and histopathology procedures, including the interpretation and classification of lesions. National Toxicology Program experimental protocols are structured to ensure that standard procedures are followed and that the data receive a thorough quality assurance and peer review before the nonneoplastic and neoplastic diagnoses are finalized (6,16,54 Other factors that may produce differences in control tumor rates from study to study include caging protocols, diet, environmental factors, genetic drift, study duration, and survival differences (20,24). In practice, the number

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Evaluation of Reduced Protocols for Carcinogenicity Testing of Chemicals: Report of a Joint EPA/NIEHS Workshop

Cited by 22 publications

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Transgenic assays and the identification of carcinogens

Transgenic assays and the identification of carcinogens

In Vivo Transgenic Bioassays and Assessment of the Carcinogenic Potential of Pharmaceuticals

Value of Historical Control Data and Other Issues Related to the Evaluation of Long-Term Rodent Carcinogenicity Studies

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