Experimental methods for immunization and challenge in antigenicity studies in guinea pigs.

Optimal experimental methods for antigenicity studies in guinea pigs were investigated on: (1) the effects of different immunizing methods using complete or incomplete Freund's adjuvants (CFA or IFA), and various injection sites, the number of immunizations, the immunizing doses, and the immunizing periods, (2) the relationship between the severity of active systemic anaphylaxis (ASA) reactions and passive cutaneous anaphylaxis (PCA) titers, (3) positive control for oral administration, and (4) the effects of incubation mixture of drug and serum protein as the challenge for the ASA assay. The following results provided useful information for designing more appropriate methods for antigenicity studies: (1) The optimal immunization method for benzylpenicillin (PcG), cephaloridine, 2,4,6-trinitrobenzene sulfonic acid and adriamycin, which were selected as positive controls for low molecular medicines in this experiment, involved subcutaneous administration of 1 ml of a test substance in CFA (1st immunization) or IFA (2nd and 3rd immunizations) at two doses, 1 and 10 mg/animal, 3 times at 2-week intervals on the back of a guinea pig. Blood collection for PCA assay was needed 2 weeks after the last immunization, and ASA assay, 1 or 2 days after the blood collection.

A subchronic toxicity study of two inhaled aerosolized atropine sulfate formulations in rats and dogs.

The potential subchronic (21 days) toxicity of inhaled metered aerosol formulations (solution and suspension) of atropine sulfate was investigated in rats and dogs. The doses administered to rats were 0.78 and 2.

Quantitative techniques in neuropathology.

In the future, quantitative techniques will probably be used in industry as part of Tier II studies for the evaluation of chemicals and drugs for their neurotoxic potential. Movement towards quantifying some structures or neuropathological changes will be made possible by advances in tissue preparation and computer technology. Emphasis will need to be placed on standardized techniques, good quality samples and sampling techniques in order to produce good quantitative data in a reasonable time.

Correlation between behavioral and pathological changes in the evaluation of neurotoxicity.

Recently the EPA has implemented new guidelines under Section 4 of TSCA to undertake neurotoxicity testing. It is expected that other agencies, both national and international, will follow suit. The evaluation of neurotoxicity will be based primarily on behavioral and morphological observations and particularly on the correlation between them.