Alternatives To Using Human Experience In Assessing Health Risks

Rall, D.

doi:10.1146/annurev.publhealth.8.1.355

Cited by 6 publications

(10 citation statements)

References 12 publications

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“…Exposure assessment includes external and internal exposure; determination of exposure dose, frequency, and duration; and biological changes for monitoring of subclinical or clinical eects (Rall et al 1987). However, some biochemical alterations may not produce clinically recognizable symptoms, which may lead to underestimation of the toxicological potential of agricultural chemicals.…”

Section: Introductionmentioning

confidence: 99%

Occupational exposure to agricultural chemicals: effect on the activities of some enzymes in the blood of farm workers

Panemangalore¹,

Dowla²,

Byers³

1999

International Archives of Occupational and Environmental Health

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Section: Introductionmentioning

confidence: 99%

Occupational exposure to agricultural chemicals: effect on the activities of some enzymes in the blood of farm workers

Panemangalore¹,

Dowla²,

Byers³

1999

International Archives of Occupational and Environmental Health

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“…These 19 chemicals (13% of those studied) caused neoplasia in both sexes of both species. Considering the 'weight-of-the-evidence' concept, perhaps these chemicals need the most attention from a public health view and as potential candidates for epidemiologic studies [25]. To complete the subsets of the 81 positive studies (Tables 2 and 3 For those 81 chemicals showing a positive neoplastic response in these NTP studies, chemically induced benign neoplasia was the predominant or contributing effect in 21 (26%) ( Table 3).…”

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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“…Clearly the accumulated experience in the field of carcinogenesis supports this concept." (Rall et al, 1987) Because rodents appear to be more susceptible to development of cancer in a wider variety of tissues (Grisham, 1996), in contrast to humans, doesn't make them less valuable as research and testing tools. There is credence, however, to the notion that if humans underwent as complete pathology/histopathology as do rodents, the cancer gap would be substantially reduced or even eliminated.…”

Section: Species Differences and Similarities In Carcinogenesismentioning

confidence: 99%

Relevance of Animal Carcinogenesis Findings to Human Cancer Predictions and Prevention

2004

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Use of laboratory animals to identify carcinogenic potential of chemicals, mixtures, and other agents has a modern history of greater than 40 years from which much useful scientific and public health information can be derived. While laboratory animals differ from humans in some respects that may affect responses to hazardous exposures, use of such models is based on experimental evidence indicating that there are more genetic, genomic, physiological, biochemical, and metabolic similarities than differences among mammalian species. Issues of concordance of responses between rodent species and between rodents and humans as well as repeatability and site-specificity are important considerations in evaluating laboratory animal carcinogenicity results. Variables in experimental design such as animal strain, diet, route of exposure, and study, duration as well as single-site versus multisite carcinogenic responses all influence interpretation and intelligent use of study data. Similarities and differences in site-specific laboratory animal and corresponding human cancers should also be considered in study evaluation. Recent attempts to explore genetically engineered mice and to humanize the mouse for more relevant identification of carcinogen hazard identification have yielded mixed results. In the end we are confronted by the realization that virtually all animal cancer models are useful but imperfect surrogates for humans. Assuming the percentage of chemicals currently in commerce that are estimated to be potent animal or human carcinogens is quite low, the task of identifying agents with significant carcinogenic potential is daunting and important. The biological conundrum of scientific debate regarding the relevance of carcinogenicity studies in laboratory animals is likely to continue. Nonetheless public health considerations must take precedence when deciding human safety issues.

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Alternatives To Using Human Experience In Assessing Health Risks

Cited by 6 publications

References 12 publications

Occupational exposure to agricultural chemicals: effect on the activities of some enzymes in the blood of farm workers

Occupational exposure to agricultural chemicals: effect on the activities of some enzymes in the blood of farm workers

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

Relevance of Animal Carcinogenesis Findings to Human Cancer Predictions and Prevention

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