Pharmacodynamic Responses of F344 Rats to the Mouse Hepatocarcinogen Oxazepam in a 90-Day Feed Study

Cunningham, Michael L.; Bucher, John R.

doi:10.1006/taap.1997.8330

Cited by 4 publications

(1 citation statement)

References 14 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Example S. Species differences in carcinogenicity with differences in enterohepatic recirculation (oxazepam) Oxazepam, a benzodiazepine drug (summary of various studies by Cunningham and Bucher, 1998), was shown to produce liver tumors in two different strains of mice, but not in rats. Oxazepam and its metabolites are excreted primarily in the feces in both rats and mice; however, the metabolites differ significantly between the two species.…”

Section: Enterohepatic Recirculationmentioning

confidence: 98%

The Acquisition and Application of Absorption, Distribution, Metabolism, and Excretion (ADME) Data in Agricultural Chemical Safety Assessments

Barton

Pastoor

Baetcke

et al. 2006

Critical Reviews in Toxicology

128

View full text Add to dashboard Cite

A proposal has been developed by the Agricultural Chemical Safety Assessment (ACSA) Technical Committee of the ILSI Health and Environmental Sciences Institute (HESI) for an improved approach to assessing the safety of crop protection chemicals. The goal is to ensure that studies are scientifically appropriate and necessary without being redundant, and that tests emphasize toxicological endpoints and exposure durations that are relevant for risk assessment. Incorporation of pharmacokinetic studies describing absorption, distribution, metabolism, and excretion is an essential tool for improving the design and interpretation of toxicity studies and their application for safety assessment. A tiered approach is described in which basic pharmacokinetic studies, similar to those for pharmaceuticals, are conducted for regulatory submission. Subsequent tiers provide additional information in an iterative manner, depending on pharmacokinetic properties, toxicity study results, and the intended uses of the compound.

show abstract

Section: Enterohepatic Recirculationmentioning

confidence: 98%

The Acquisition and Application of Absorption, Distribution, Metabolism, and Excretion (ADME) Data in Agricultural Chemical Safety Assessments

Barton

Pastoor

Baetcke

et al. 2006

Critical Reviews in Toxicology

128

View full text Add to dashboard Cite

show abstract

Doses in Rodent Cancer Studies: Sorting Fact From Fiction

Bucher

2000

Drug Metabolism Reviews

View full text Add to dashboard Cite

The belief that rodent cancer bioassays predict for human cancers is a fundamental public health precept based on sound biological principles. Nonetheless, it is appropriate to periodically debate this point as scientific understanding of cancer causation advances. This presentation addresses one of the many factors that determines the predictive value of rodent tumor bioassay results for human health. This is the issue of dose. Examination of several recent National Toxicology Program (NTP) studies demonstrates that the applied dose often far overestimates the actual effective dose, or maximum blood concentration attained in a rodent, when compared with similar relationships in humans. Further examination of the NTP database on rodent toxicity and carcinogenicity studies revealed summary information on factors that were pivotal in prechronic studies for selecting doses for chronic studies. Contrary to popular belief, target organ toxicity was a determining factor in only about half of the studies. The typically minimal nature of the lesions which limit doses for chronic studies is described for several common target sites. Taken together, these facts paint a far different picture than the common public perception of the "massive" doses used in chronic rodent studies and suggest that, in some cases, dose limitations are actually so severe as to limit the sensitivity of a chronic bioassay to detect a carcinogenic effect.

show abstract

Aflatoxicosis in Chickens (Gallus gallus): An Example of Hormesis?

2008

View full text Add to dashboard Cite

Poultry has commonly been considered highly susceptible to aflatoxins. However, among domestic fowl there is wide variability in specific species sensitivity to these mycotoxins. Comparative toxicological studies in avian species have shown that ducklings and turkey poults are the most sensitive species to aflatoxins, quails show intermediate sensitivity, whereas chickens are the most resistant. Hormesis is a dose-response phenomenon characterized by low-dose stimulation and high-dose inhibition. The low-dose stimulation is typically maximal at only about 30 to 60% greater than controls. Hormesis has been noted in regards to changes in body weight in numerous studies, including those performed for the US National Toxicology Program, with over 50 chemicals. The present paper assesses how relatively low levels of aflatoxin consumption in feed may affect the growth rate of chickens. In general, multiple independent investigations have shown that such aflatoxin consumption affects growth in a hormetic-like biphasic manner with a low dose stimulation and a high dose inhibition. Such observations were then generalized to other toxic agents and animal models, suggesting that low doses of stressor agents induce adaptive responses as reflected in accelerated growth rates. The implications of such hormetic dose responses are briefly discussed.

show abstract

Pharmacodynamic Responses of F344 Rats to the Mouse Hepatocarcinogen Oxazepam in a 90-Day Feed Study

Cited by 4 publications

References 14 publications

The Acquisition and Application of Absorption, Distribution, Metabolism, and Excretion (ADME) Data in Agricultural Chemical Safety Assessments

The Acquisition and Application of Absorption, Distribution, Metabolism, and Excretion (ADME) Data in Agricultural Chemical Safety Assessments

Doses in Rodent Cancer Studies: Sorting Fact From Fiction

Aflatoxicosis in Chickens (Gallus gallus): An Example of Hormesis?

Contact Info

Product

Resources

About