Th. Maurer

The optimization test in the guinea pig in relation to other predictive sensitization methods

The allergenicity of various compounds was tested by means of the optimization procedure in the guinea-pig. Results with antibiotics, preservatives, fragrance raw materials and miscellaneous contactants are reported. Their relevance is critically discussed in relation to other animal sensitization methods (Draize, Bühler, open epicutaneous and maximization tests). Predictive animal tests are compared with those used in human allergy (Shelanski & Shelanski; maximization test). The importance of animal methods entailing the use of adjuvants is underlined.

Predictive evaluation in animals of the contact allergenic potential of medically important substances. II. Comparison of different methods of cutaneous sensitization with "weak" allergens.

Results of the optimization method and of other methods used to assess contact allergy in laboratory animals were compared with known epidemiological data on the occurrence of hypersensitivity reactions in man. Tests were performed with preservatives {formalin, ethylenediamine and sorbic acid), drugs (penicillin G, benzocaine and sulphathiazole) and other contactants belonging to widely different chemical classes (p‐phenylenediamine, triclosan, pyrazole derivatives, nickel and chrome salts, eugenol, isoeugenol and mercaptobenzothiazole). The degree of sensitization achieved in guinea pigs by the optimized procedure (intradermal test with adjuvant combination) and the maximization procedure was invariably superior to that produced by the epidermal method using prior irritation of the site of application. Both the optimized procedure and the maximization test seem to be capable of identifying contact allergens that cause hypersensitivity reactions in as few as t in 10,000 of the human population as a whole. The optimization test merits consideration as a standardized and efficiently predictive procedure.

The optimization test in the guinea-pig. A method for the predictive evaluation of the contact allergenicity of chemicals

Guinea-pigs were sensitized with various substances (DNCB, penicillin G, PPL, ethylaminobenzoate, formalin) by the Draize method, the maximization method and the new optimization method (intracutaneous test employing adjuvant). The advantages of the optimization method favouring its adoption as a standard sensitization test are discussed in the light of the results obtained by this method and with the two established tests.

A standard protocol for phototoxicity testing : results from an interlaboratory study

Based on experience accumulated in a number of laboratories, a standardized protocol for phototoxicity testing in experimental animals by the dermal route is presented. By conducting a limited interlaboratory study, demonstrating a high degree of consistency using 8‐methoxypsoralen {8‐MOP) and acridine, the sensitivity and reproducibility of the proposed methodology is demonstrated. Important aspects of performing phototoxicity testing are discussed.

Predictive animal testing for photocontact allergenicity

The purpose of this investigation was to establish a standardized animal model to predict the photoallergenic potential of new chemical compounds. In a first series of experiments the main factors influencing the induction of photoallergenicity were evaluated (induction concentration, pH of the test solution, pretreatment of the irradiation site with sodium lauryl sulphate, additional use of adjuvant injections and routes of administration). Osram Ultravitalux lamps were utilized for these studies.

Predictive evaluation in animals of the contact allergenic potential of medically important substances I. Comparison of different methods of inducing and measuring cutaneous sensitization

Groups of guinea pigs were sensitized with a 0.1% solution of dinitrochlorobenzene (DNCB) by the Draize intracutaneous method, The course of the induction process, the influence of the vehicles used and the extent to which the reactions are amenable to assessment according to objective criteria were examined. The sensitivity of the standardized Draize test was then compared with that of various other sensitization techniques, including:

Guinea-pig contact sensitization assays

After reviewing general aspects and the historical development of predictive animal skin sensitization tests, the recommended tests of the OECD and EC are discussed. Background information is given on the changes which occurred in the last 2 years. From the many factors known to influence induction and challenge of contact allergy in animals, the discussion is focused on the choice of induction concentration and the vehicle. The difference of general screening strategies in Europe and the USA is presented and discussed. The paper closes with a discussion on the importance of inhouse validation of the methods used for proper prediction of the sensitizing potential of chemicals and with remarks on predictive in vitro tests.

The maximization test for skin sensitization potential—Updating the standard protocol and validation of a modified protocol

Since Magnusson and Kligman (1969) first described the maximization test, for assessing skin sensitization potential, the test has been substantially validated and data have been obtained on dose-activity relationships. The original method remains acceptable for qualified risk assessment but several modified protocols have been developed to overcome problems with particular test materials. A modified maximization test is described for compounds that are not soluble in the standard vehicles and, therefore, not injectable, and for formulations, to simulate user exposure conditions. The test compounds 2,4-dinitrochlorobenzene, p-phenylenediamine, 1-(3-chlorophenyl)-3- (4-chlorophenyl)-2-pyrazoline, formaldehyde, benzocain, penicillin G, benzylsalicylate, potassium dichromate and isoeugenol, all gave positive reactions. The incidences of positive reactions varied with the sensitization potentials of the compounds. The results for the first six compounds listed above were compared with those obtained by the standard procedure and were found to be similar. We propose that testing guidelines for skin sensitization should accommodate validated modifications of existing standard procedures.

Sensitization potential of benzotriazole

Predictive guinea pig sensitization studies have been performed with commercial and purified 1H‐benzotriazole. In only 3 animals, induced and challenged according to the maximization protocol with more than 100 times the normal use concentration, were slight erythemas elicited with the commercial grade of benzotriazole. The optimization test with commercial and purified materials, as well as the test with the purified material, was negative. We conclude that benzotriazole has a very low sensitization potential.

Evaluation of the photocontact allergenic potential of 6‐methylcoumarin in the guinea pig

6‐Methylcoumarin was tested in a new animal model developed for the predictive evaluation of photocontact allergenic potential. Negative results were obtained and these are discussed with respect to inherent limitations of the animal model.