An evaluation of genotoxicity tests with Musk ketone.

Musk ketone, a synthetic musk fragrance ingredient that has been found in river water, fish and breast milk, was evaluated for potential genotoxicity in a battery of short-term tests. The mouse lymphoma assay was conducted at musk ketone concentrations ranging from 700 to 4000 micrograms/ml and 2.0 to 35 micrograms/ml in the absence and presence of rat liver S-9, respectively. No increased mutant frequencies were noted. An in vitro cytogenetics assay in Chinese hamster ovary cells was conducted at musk ketone concentrations ranging from 4.3 to 34 micrograms/ml and 1.25 to 10 micrograms/ml in the absence and presence of rat liver S-9, respectively. On the basis of the non-reproducibility of a statistically significant increase at a single concentration and no increases in other test systems, musk ketone was concluded to be negative for chromosome aberrations. An in vitro unscheduled DNA synthesis (UDS) assay was conducted in primary rat hepatocytes at musk ketone concentrations between 0.5 and 5.0 micrograms and 50 micrograms/ml. No increases in net nuclear grain counts were noted. Musk ketone did not show genotoxic potential based on the negative results in the mouse lymphoma, in vitro cytogenetics and in vitro UDS assays.

A report on methods to reduce, refine and replace animal testing in industrial toxicology laboratories.

The Committee to Promote Principles of Reduction, Refinement and Replacement of Animal Testing in Industrial Toxicology Laboratories was established in 1987 to work toward industrywide improvements in laboratory animal testing methods. The committee's goals are to gather information about effective nonanimal testing techniques and other methods of conserving and improving the care of laboratory animals, to work toward the systematic validation of nonanimal alternatives, and to disseminate useful information about progressive programs and policies throughout the industrial toxicology community. This is the first in a continuing series of reports the committee plans to produce as part of an ongoing program to promote communication among industrial toxicologists about successful methods of reducing, refining and replacing animal testing. Here are some of the report's major findings: (1) Animal care and use committees charged with the oversight of laboratory animal use are a universal practice at the companies surveyed. (2) Significant reductions in the number of animals used for acute toxicity testing have taken place at all the companies during the last 5- to 10-year period. (3) Structure-activity relationships (predicting a test compound's properties based on the known properties of familiar chemicals with similar structures) are widely used to minimize, but not replace, the use of animals. (4) Tissue and organ culture systems are being used with increasing frequency for screening and mechanistic studies, but are not completely replacing animal evaluations as a final step. (5) There is a pressing need for the systematic and scientifically sound validation of nonanimal alternative techniques to reduce the use of animals in toxicology testing while satisfying requirements for the protection of public safety.

Monitoring for precursors of health impairment from toxic agents.

It is essential that one be able to diagnose when disorders are caused by drugs and toxic agents. It is also essential that scientists strive toward the ultimate goal of preventing such disorders. To this end, it is necessary to evaluate laboratory procedures for their capability to detect changes which precede disorders of health impairment. To accomplish this, some knowledge of the relationship between the exposure to a chemical agent and the effect owing to that exposure is required. The complexities of the dose-effect relationship are discussed with regard to the estimation of exposure, the effect owing to the exposure and the population exposed to the chemical agent.