Dermal irritation tests

For the skin, this scale is used in the primary dermal irritation test, which is performed for those agents that are to be administered to patients by application to the skin. As with all local tolerance tests, it is essential that the material be evaluated in condition of use, that is, in the final formulated form, applied to test animals in the same manner that the agent is to be used clinically. 

PRIMARY DERMAL IRRITATION TEST 11.2.1. Rabbit Screening Procedure... 

The design of vaginal, rectal, and nasal irritation studies is less formalized, but follows the same basic pattern as the primary dermal irritation test. The rabbit is the preferred species for vaginal and rectal irritation studies, but the monkey and dog have also been used for these (Eckstein et al., 1969). Both the rabbit and rat have commonly seen use for nasal irritation evaluations. Defined quantities (typically 1.0 ml) of test solutions or suspensions are instilled into the orifice in question. For the vagina or rectum inert bungs are usually installed immediately thereafter to continue exposure for a defined period of time (usually the same period of hours as future human exposure). The orifice is then flushed clean, and 24 h after exposure it is examined and evaluated (graded) for irritation using the scale in Table 11.1. 

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. 

Some materials, by either their physicochemical or toxicological natures, generate difficulties in the performance and evaluation of dermal irritation tests. The most commonly encountered of these problems are presented below. 

A primary dermal irritation test will be performed prior to the study. 

Hatoum, N.S., Leach, C.L., Talmsa, D.M., Gibbons, R.D., and Garvin, P.F. (1990). A statistical basis for using fewer rabbits in dermal irritation testing. J. Amer. Coll. Toxicol. 9 49-59. 

Hanhijarvi, H., Nevalainen, T. and Mannisto, P. (1985). A six-month dermal irritation test with anthralins in the Gottinger miniature swine. Arch. Toxicol, 8 (Suppl.) 463 168. 

Williams, S. J. (1984). Prediction of ocular irritancy potential from dermal irritation test results. Food. Chem. Toxicol. 22 157-161. 

The test may be considered positive if three or more animals exhibit positive reactions at any observation period. Equivocal tests are repeated. For humane reasons, formulations known to be corrosive or to be severely irritating in the dermal irritation test are assumed to be ocular irritants and not tested. 

Although the correlation between low pHs (acids) and eye damage in the rabbit has not been found to be excellent, all alkalis (pH 11.5 or above) tested have been reported to produce opacities and ocular damage. Many laboratories now use pH cutoffs for testing of 2.0 or lower and 11.5 or 12.0 and higher. If a material falls outside these cutoffs (or is so identified due to other physicochemical parameters), then it is (1) not tested in the rabbit eye and is assumed to be corrosive (2) evaluated in a secondary screen such as an in vitro cytotoxicity test or primary dermal irritation test or (3) evaluated in a single rabbit before a full-scale eye irritation test is performed. It should be kept in mind that the correlation of all the... 

Table 3 In vitro dermal irritation test systems ...

Table 2 Factors governing the selection of animal species for dermal irritation testing...

MMT. No studies were located regarding dermal effects in humans following dermal exposure to MMT. Hinderer (1979) observed that rabbits exposed dermally to commercial neat MMT on shaved skin for 24 hours developed edema and erythema. Further dermal irritation tests performed showed that MMT is a moderate skin irritant. Campbell et al. (1975) exposed male albino rats dermally to MMT for 24 hours on closely clipped dorsolateral aspects of the trunk that were either abraded or allowed to remain intact skin reactions were evaluated and scored at 24 hours and again 48 hours later. By comparing skin reactions following exposure to a test rating that categorized irritancy levels, MMT was determined to be safe for intact or abraded skin contact. However, the authors note that MMT in concentrated form is absorbed... 

Decades of experience have been obtained using the Draize dermal irritation test on albino rabbits, described in OECD guideline 404. However, the use of laboratory animals for skin irritation testing is decreasing due to the development of in vitro models (Ponec 1996) and more frequent use of human... 

DIPHOTERINE solution was noniriitating in the dermal irritation test, with a maximum human irritancy equivalent score of 0.8 [256]. 

Use of tea tree oil for the topical treatment of bum wounds is not recommended due to in vitro inhibition of human epithelial cell and fibroblast viability from 24 h exposure to the oil. Applicatiou of the pure oil to the abraded skin of rabbits (Draize acute dermal irritation test) resulted in increased skin irritation, suggesting that the oil should not be applied in cases of dermatitis. ... 

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