Guidelines for Combining Neoplasms for Evaluation of Rodent Carcinogenesis Studies

McConnell, Ernest E.; Solleveld, Hendricus A.; Swenberg, James A.; Boorman, Gary A.

doi:10.1007/978-3-642-61364-7_21

Cited by 60 publications

(74 citation statements)

References 19 publications

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“…Pathology specimens and diagnoses from the study laboratory were subjected to NTP pathology quality assessment and Pathology Working Group review; details of these review procedures have been described, in part, by Maronpot and Boorman (1982) and Boorman et al (1985). For subsequent analyses of the pathology data, the decision of whether to evaluate the diagnosed lesions for each tissue type separately or combined was generally based on the guidelines of McConnell et al (1986).…”

Section: Methodsmentioning

confidence: 99%

Comparative toxicity and carcinogenicity of soluble and insoluble cobalt compounds

et al. 2015

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Section: Methodsmentioning

confidence: 99%

Comparative toxicity and carcinogenicity of soluble and insoluble cobalt compounds

et al. 2015

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“…The increase was not statistically significant for either tumor type considered individually, but a significant (P = 0.014) increase was observed for combined liver neoplasms in female mice (6/50; 6/50; 16/50). In our opinion and as recommended by McConnell et al [29] and others, the most appropriate evaluation for responses in rodent (and especially mouse) liver should be made on the combined incidences of benign and malignant neoplasms. This is particularly important if one morphologic type increases and one decreases, thus in essence 'cancelling' the apparent response.…”

Section: Resultsmentioning

confidence: 99%

Occurrence and relevance of chemically induced benign neoplasms in long-term carcinogenicity studies

1989

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Recent carcinogenicity studies conducted and evaluated by the National Toxicology Program/National Institute of Environmental Health Sciences were examined to determine the frequency of chemically increased incidences of neoplasia. Many of the chemicals originally selected for study were chosen because of an a priori suggestion that they might be carcinogens. Of the 143 chemical studies evaluated, usually involving male and female rats and mice, 42 (29%) did not induce any neoplasms, 20 (14%) gave marginal or equivocal neoplastic responses, and 81 (57%) showed positive neoplastic responses in one or more of the 524 species-gender experiments. Of these 81 positive studies, 60 (74%) were considered positive based on malignant neoplasia, 16 (20%) were positive due primarily to benign neoplasia, but had supporting evidence of malignant neoplasia in the same organ/tissue, and 5 (6%) were positive based only on benign neoplasia. These five chemicals are a) allyl isothiocyanate (transitional cell papillomas of the urinary bladder in male rats), b) 2-amino-4-nitrophenol (tubular cell adenomas of the kidney in male rats), c) asbestos intermediate range chrysotile (adenomatous polyps of the large intestine in male rats), d) decabromodiphenyl oxide (neoplastic nodules of the liver in male and female rats), and e) nitrofurazone (fibroadenomas of the mammary gland in female rats and benign mixed tumors and granulosa cell tumors of the ovary in female mice). For all but one of these lesions (mammary gland), the occurrence in historic controls is low. Thus, only 5 of the 143 chemicals studied (3.5%) induced benign neoplasia alone, and those observed benign neoplasms are known to progress to malignancy. Accordingly, we consider chemically induced benign neoplasia to be an important indicator of a chemical's carcinogenic potential in rodents, and believe it should continue to be made an integral part of the overall weight-of-the-evidence evaluation process for identifying potential human health hazards.

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“…Benign and malignant neoplastic incidences were evaluated separately and combined, where appropriate. The criteria for combination were based on the work of McConnell et al (1986).…”

Section: Resultsmentioning

confidence: 99%

Two-year Carcinogenicity Study in Rats with a Nonnucleoside Reverse Transcriptase Inhibitor

et al. 2014

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Administration of lersivirine, a nonnucleotide reverse transcriptase inhibitor, daily by oral gavage to Sprague-Dawley rats for up to 2 yr was associated with decreased survival, decreased body weights, and an increase in neoplasms and related proliferative lesions in the liver, thyroid, kidney, and urinary bladder. Thyroid follicular adenoma and carcinoma, the associated thyroid follicular hypertrophy/hyperplasia, hepatocellular adenoma/adenocarcinoma, altered cell foci, and hepatocellular hypertrophy were consistent with lersivirine-related induction of hepatic microsomal enzymes. Renal tubular adenoma and renal tubular hyperplasia were attributed to the lersivirine-related exacerbation of chronic progressive nephropathy (CPN), while urinary bladder hyperplasia and transitional cell carcinoma in the renal pelvis and urinary bladder were attributed to urinary calculi. Renal tubular neoplasms associated with increased incidence and severity of CPN, neoplasms of transitional epithelium attributed to crystalluria, and thyroid follicular and hepatocellular neoplasms related to hepatic enzyme induction have low relevance for human risk assessment.

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Guidelines for Combining Neoplasms for Evaluation of Rodent Carcinogenesis Studies

Cited by 60 publications

References 19 publications

Comparative toxicity and carcinogenicity of soluble and insoluble cobalt compounds

Comparative toxicity and carcinogenicity of soluble and insoluble cobalt compounds

Occurrence and relevance of chemically induced benign neoplasms in long-term carcinogenicity studies

Two-year Carcinogenicity Study in Rats with a Nonnucleoside Reverse Transcriptase Inhibitor

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