ABSTRACT
While conducting a guinea pig sensitization protocol, using the maximization test, it was discovered, at challenge, that the test animals were more responsive to the vehicle (acetone) than they were to the proprietary test material. During rechallenge, conducted to clarify the specific immune status of the test animals, it was determined that they were also hyperreactive to an alternate vehicle (diethyl phthalate), to which they were naïve. This bizarre set of data is presented and it is suggested that this type of response is the prototype for the presence of false-positive responses experienced by toxicologists using this test. The test conditions imposed on the immune system by the maximization test that could result in these anomalous results are discussed. These data suggest that investigators need cautiously to interpret data that are produced by the injection of Freund's complete adjuvant (FCA).
Subject(s)
Freund's Adjuvant/adverse effects , Hypersensitivity/etiology , Acetone/administration & dosage , Animals , Disease Models, Animal , Dose-Response Relationship, Immunologic , False Positive Reactions , Female , Freund's Adjuvant/administration & dosage , Guinea Pigs , Hypersensitivity/immunology , Male , Phthalic Acids/administration & dosageABSTRACT
Currently, the European Community is in the process of discussing the details of how to conduct various protocols for safety assessment. Additionally, there is a desire that these protocols be harmonized internationally. This presentation attempts to describe the critical and non-critical parameters of the protocol for detecting potential contact allergens in the guinea pig and also discusses some controversial issues. It is also emphasized that the identification of a test material as a potential sensitizer is only the first step in the risk-assessment exercise.
Subject(s)
Dermatitis, Contact , Disease Models, Animal , Guinea Pigs , Hypersensitivity, Delayed/chemically induced , Patch Tests/methods , Animal Identification Systems , Animals , Female , Hair Removal , Male , Patch Tests/standards , Restraint, PhysicalABSTRACT
The potential of 4 related nitro musk substances (musk tibetene, musk ketone, musk xylol, and musk moskene) to cause photoallergy, phototoxicity, and/or contact sensitivity was compared to that of musk ambrette, a known photoallergen. Musk ambrette caused a high incidence of photoallergy as indicated by the severity of the skin grades as compared to a control group. Musk tibetene and musk moskene were negative for phototoxicity, photoallergenicity and contact sensitivity under the test conditions. Musk xylol was shown to be a weak contact sensitizer. Musk ketone gave challenge responses suggestive of a weak phototoxin and a weak contact sensitizer. The latter was not affected by light exposure. These data suggest that except for musk ambrette, the nitro musks as a group do not have the potential to produce photoallergy. Some members of this type of perfume raw material could be classified as weak sensitizers (musk xylol, musk ketone) or weakly phototoxic (musk ketone). These latter biological qualities have not been expressed clinically.
Subject(s)
Dermatitis, Contact/etiology , Dinitrobenzenes/adverse effects , Fatty Acids, Monounsaturated , Fatty Acids, Unsaturated/adverse effects , Nitrobenzenes/adverse effects , Perfume/adverse effects , Photosensitivity Disorders/chemically induced , Animals , Guinea PigsABSTRACT
Guinea-pig tests were conducted on a known photocontact allergen, tetrachlorosalicylanilide (TCSA), a known phototoxin, 8-methoxypsoralen, two reportedly weak photoallergens, musk ambrette and 6-methylcoumarin, and a negative control, octylphenoxy polyethoxyethanol (Triton X-15). The data show that under the test conditions used, photosensitivity responses can be produced, and combinations of these as well as the other biological responses can be readily defined. The results indicate that musk ambrette is photoallergenic, that 8-methoxypsoralen is phototoxic and that Triton X-15 is only a slight irritant. On the other hand, results with TCSA suggest that it is a strong contact allergen and photoallergen, while 6-methylcoumarin would be considered to be a weak contact allergen with weak phototoxic properties. Previous reports that barrier destruction or adjuvanticity is necessary to produce photoallergy to musk ambrette were not confirmed; by ensuring occlusion using standard methods, the photoallergic nature of the response to this material was clearly demonstrated. A device described elsewhere (Newmann & Parker, Fd Chem. Toxic. 1985, 23, 683) has made it possible to develop methods that can be used to differentiate clearly among the possible biological responses that can occur in guinea-pigs when photoreactive materials are applied to their skin and irradiated. The probable biological responses that need to be defined, under the above conditions, are primary irritation, delayed contact hypersensitivity, phototoxicity and/or photoallergenicity.
Subject(s)
Allergens/radiation effects , Hypersensitivity, Delayed/etiology , Photosensitivity Disorders/etiology , Ultraviolet Rays/adverse effects , Animals , Coumarins/toxicity , Dinitrobenzenes/toxicity , Drug Evaluation, Preclinical , Guinea Pigs , Methoxsalen/toxicity , Salicylanilides/toxicityABSTRACT
For toxicologists who are actively involved in safety testing and risk assessment, the ideal animal model should accurately predict the biologic response of humans after any contact with potentially hazardous materials. Unfortunately this goal is seldom, if ever, approached. Therefore, the toxicologist must design and execute experiments that will define to a higher degree of accuracy the inherent toxicity of the chemical and the biological response of the model. If the biologic response can be defined and understood and if the relevant information is available for comparable human responses, then the extrapolation to the human situation, although not always precise, can be made with a measure of assurance. Finally, and perhaps most importantly, it is essential that follow-up on human exposures be in sufficient detail so that the variations in biologic response can be further defined. In this way the precision and accuracy of the safety assessment can be checked.
Subject(s)
Drug Hypersensitivity/etiology , Animals , Dermatitis, Contact/etiology , Disease Models, Animal , Guinea Pigs , Humans , Hypersensitivity, Delayed/etiology , Skin Tests , Species SpecificitySubject(s)
Allergens/analysis , Dermatitis, Contact/immunology , Hypersensitivity, Delayed/immunology , Adjuvants, Immunologic , Allergens/immunology , Animals , Antigens/immunology , Dermatitis, Contact/diagnosis , Disease Models, Animal , Dose-Response Relationship, Immunologic , Guinea Pigs , Hypersensitivity, Delayed/diagnosis , Immunity, Cellular , Naphthalenesulfonates/immunology , Skin/immunology , T-Lymphocytes/immunologyABSTRACT
A new method was developed to permit the contact of haptens exclusively with the vaginal mucosal surfaces of the guinea pig. The method described has some unique characteristics that make it potentially useful, not only for studies of the immune response but also for other areas of toxicologic concern. Utilizing this approach it was demonstrated that delayed contact hypersensitivity was as readily produced in the vagina as it was in the skin. Grossly, the vaginas of sensitized animals appeared normal when challenged with a non-irritating concentration of hapten but, histologically, a perivascular lymphocytic cuffing, that is the hallmark of the delayed hypersensitivity response, was demonstrated.
