Dermal sensitization tests

Gad, S. C. et al., Development and validation of an alternative dermal sensitization test the mouse ear swelling test (MEST), Toxicol. Appl. Pharmacol., 84, 93, 1986. 

Gad S.C., Dunn, B.J., Dobbs, D.W. and Walsh, R.D. (1986) Developmental and validation of an alternative dermal sensitization test The Mouse Ear Swelling Test (MEST), Topical Appl. Pharmacol. 84 93-114. 

Life Science Research Submission of Data by CTFA (2-5-50).Dermal Sensitization Test in Guinea Pigs (TEA), 1975... 

Information regarding levels of chromium(III) compounds that result in death is available only for the oral route. Systemic effects of acute- and intermediate-duration inhalation exposure to chromium(III) are limited to the respiratory system. Information on systemic effects of chronic inhalation exposure to chromium(III) is limited to a study that used a mixture of chromium(VI) and chromium(III). Studies of intermediate- and chronic duration oral exposure to chromium(III) failed to find any systemic, neurological, developmental, reproductive, or carcinogenic effects. The immunological and genotoxic effects of chromium(III) in animals have not been tested by the oral route. Information regarding effects of dermal exposure of animals to chromium(III) is limited to a study of skin ulceration after acute exposure and dermal sensitization tests. 

The importance of hydrolysis potential, ie, whether moisture or water is present, is illustrated by the following example. In the normal dermal toxicity test, namely dry product on dry animal skin, sodium borohydride was found to be nontoxic under the classification of the Federal Hazardous Substances Act. Furthermore, it was not a skin sensitizer. But on moist skin, severe irritation and bums resulted. 

As discussed imder dermal effects, people can develop hypersensitivity to trichloroethylene. The effects observed in hypersensitive individuals include skin effects (Conde-Salazar et al. 1983 Nakayama et al. 1988 Phoon et al. 1984 Waller et al. 1994) and liver effects (Phoon et al. 1984). Dermal sensitivity was confirmed with patch testing in only two cases (Conde-Salazar et al. 1983 Nakayama et al. 1988). The woman described by Conde-Salazaer et al. (1983) reacted positively to both vapor exposure and a dermal application of 5% trichloroethylene in olive oil. 

F. Both the age of the test animal and the application site (saddle of the back versus flank) can markedly alter test outcome. Both of these factors are also operative in humans, of course (Mathias, 1983), but in dermal irritation tests, the objective is to remove all such sources of variability. In general, as an animal ages, sensitivity to irritation decreases. For the dermal test, the skin middle of the back (other than directly over the spine) tends to be thicker (and therefore less sensitive to irritations) than that on the flanks. 

FIGURE 15.4. Line chart for modified Buehler test for delayed contact dermal sensitization in the guinea pig. 

FIGURE 15.5. Line chart for guinea pig maximization test for dermal sensitization. 

Ellis HV, Hodgson JR, Hwang SW, et al. 1978. Mammalian toxicity of munitions compounds. Phase I Acute oral toxicity, primary skin and eye irritation, dermal sensitization, disposition and metabolism and Ames tests of additional compounds. NTIS/AD-A069 333. [Unpublished study to be peer-reviewed],... 

There are sufficient data to determine that chromium or its compounds affect the immune system. More sensitive tests of the immune function after inhalation, oral, or dermal exposure to chromium or its compounds would be useful to determine the threshold levels for effects in humans. Additional studies that explore changes in cytokine levels (Snyder et al. 1996) caused by chromium exposure should prove helpful since they may provide mechanistic information as to how chromium may affect immune function. 

Although sensitising properties can be also detected in the classical development program of a drug substance, the need for dermal sensitization studies is of importance for the development of certain drugs. The increasing importance of trans-dermal formulations demonstrate the need of testing for dermal sensitization on the one side, on the other side, there are classical examples which cause dermal sensitization (e.g. neomycin, procaine, sulphonamides). 

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