Irritation testing

Further developments have brought forth polymeric quats having antimicrobial properties (158—160). Different kinds of polyquats have been described with molecular weight from 2,000 to 60,000 (153). Polymeric quats have two characteristics that make them uniquely different from the monomeric quats. One is the absence of foaming, even at high concentrations. The other is their remarkably low toxicity in skin and eye irritation tests and... 

Van Paassen [57,67] reported a synergistic decrease of the skin and eye irritation level of sodium lauryl ether sulfate by combination with lauryl ether carboxylates. The investigations have been carried out using the Draize eye irritation test and human patch test (Tables 13 and 14). Furthermore, measurements by in vitro methods, the Zein test, and the red blood cell test show low to no irritancy [251-253]. 

Generally speaking, up to now the importance of a-sulfo fatty acid esters in cosmetic products has been low [1 p. 367], In the future they may become more interesting because of their mildness. a-Sulfomethyl laurate and most other ester sulfonates are mild to the skin also, they are not human skin sensitizers or primary skin irritants. Tests have shown that a-sulfomethyl laurate is mild enough to be in bath products, such as bubble bath [62]. Three patents for different applications are given to show how ester sulfonates can be used in cosmetics. 

In two studies the cleansing and irritancy behavior of surfactants [106,107] were examined. An automated skin brushing method using a specific test soil and an epicutaneous irritation test on the dorsum of volunteers were applied. A sodium sulfosuccinate monoester based on a fatty alcohol ethoxylate gave very favorable results with respect to skin mildness although this concurred with low detergency. 

Similar results have been obtained at Witco with eye irritation tests on mixtures made from sodium lauryl ether sulfate and the sodium salt of a sulfosuccinate monoester [105], as shown in Fig. 15. Figure 16 shows one third re-... 

If the results of the rabbit eye irritation test can be extrapolated to man, accidental contact of these chlorodibenzodioxins with the eyes... 

III 100 kg—1 tonne p.a. Public (including as part of a formulation) As Category It + eye irritation (unless skin irritation test positive) Skin sensitization... 

In addition to okadaic acid, dinophysistoxin-1 (i.e., 35-methylokadaic acid), 7-0-palmitoyl-okadaic acid, and pectenotoxin 2 are reported to be diarrhetic toxins from shellfish 34). Application of 1 xg of dinophysistoxin-1 to mouse ear caused as strong irritation as the same dose of okadaic acid. Interestingly, the potencies of these compounds in the irritant test on mouse ear correlated well with their potencies as diarrhetic shellfish poisons. Dinophysistoxin-1 induced ODC activity as strongly as okadaic acid. Recently, we found that dinophysistoxin-1 is also a new non-TPA type tumor promoter with as high activity as okadaic acid 35). 

MASAO s, SAiTO H and TAKEO T (1994) Irritation test of skin and eye mucosa on oolong tea water-soluhle extracts , Preclinical Rep of the Central Inst for Exp Animals, 19 (3), 199-203. 

Two in vitro skin irritation tests EpiDerm SIT and SkinEthicTM RHE assay EU... 

Artificial skin models (EpiSkin , EpiDerm ) for skin irritation testing EU... 

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. 

The results of local tissue irritation tests are subject to considerable variability due to relatively small differences in test design or technique. Weil and Scala (1971) arranged and reported on the best known of several intralaboratory studies to... 

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. 

Ocular irritation is significantly different from the other local tissue irritation tests on a number of grounds. For the pharmaceutical industry, eye irritation testing is... 

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

Dose The dose selected is chosen to evaluate the severity of irritation, and represents a concentration that might be used clinically. This volume has been widely used in irritation testing. 

USP (1985). Intramuscular irritation test. United States Pharmacopeia. USP Convention, Rockville, Maryland, pp. 1180-1183. 

Weil, C.S. and Scala, R.A. (1971). Study of intra- and interlaboratory variability in the results of rabbit eye and skin irritation tests. Toxicol. Appl. Pharmacol. 19 276-360. 

Occupational toxicologists from several companies initiated a program to evaluate several experimental models as alternatives to the rabbit eye irritation test... 

Galer, D.M., Curren, R., Gad, S.C., Gautheron, P., Leong, B., Miller, K., Sargent, E., Shah, P.V, Sina, J. and Sussman, R.G. (1993). A 10-company collaborative evaluation of alternatives to the eye irritation test using chemical intermediates. Alternative Methods Toxicol. 9 237. 

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. 

Draize eye irritations test using pharmaceutical intermediates. Fundam. Appl. Toxicol. 26 20-31. 

Society and Toxicology. (1989). SOT Position Paper, comments on the LD50 and acute eye and skin irritation tests. Fundam. Appl. Toxicol. 13 621-623. 

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. 

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