Primary skin irritation test

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. 

Skin irritation. Primary skin irritation tests run on this polyether indicate the material should be considered a very irritating substance. 

Hoechst Celanese Corp Primary Skin Irritation Tests with Eighteen Materials in Albino Rabbits EPA Document No. 86-890001277 Fiche No. OTS0520783, 07/27/92... 

The state of the art is a combination of linear low-density polyethylene (PE-LLD) with hmestone for diaper back sheets. By biaxial orientation, the balance of mechanical permeability requirements can be obtained. Because of its PE-like characteristics Ecoflex is a good choice for a biodegradable back sheet. Ecoflex provides a good regulatory basis for these applications because of the positive results of the primary skin irritation test according to OECD 404, as well as the guinea pig test according to OECD 406. 

Two commonly used in vivo, nonclinical tests that are used to evaluate irritation are the intracutaneous and primary skin irritation tests. The intracutaneous reactivity test is aggressive in that it makes use of extracts prepared under exaggerated conditions and places them directly into the skin of test animals, thereby maximizing the chance of finding irritants chemicals if they are present. The primary skin irritation test is less aggressive in that portions of the test material itself are simply placed on the shaved back of albino rabbits. If applicable other irritation tests such as oral, rectal, penile, and vaginal irritation tests are described in annex D of the standard as complements to, not replacements for the primary tests. They are considered relevant for medical devices intended to be applied to those respective mucosal areas of the body. 

Primary Irritancy Studies. These studies are employed to determine the potential of materials to cause local inflammatory effects in exposed body surfaces, notably skin and eye, following acute or short-term repeated exposure. In general, the approach involves applying the test material to the surface of the skin or eye, and observing for signs of inflammation, their duration, and resolution. Reviews have been written about the conduct of primary eye irritation (58,86,87) and primary skin irritation studies (88,89). 

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. 

CTFA Submission of Data by CTFA. CIR Safety Data Test Summary, Primary Skin Irritation and Eye Irritation of Triethanolamine, 1959... 

E. I. Dupont de Nemours. 1977b. Primary skin irritation and sensitization testing on guinea pigs. EPA/OTS doc 86-870001118. 

Other test methods include those in which the induction phase is conducted by intradermal injection together with Freund s adjuvant (a chemical mixture that enhances the antigenic response) and the challenge by dermal application, or tests in which both induction and challenge doses are topical but the former is accompanied by intradermal injections of Freund s adjuvant. It is important that compounds that cause primary skin irritation be tested for skin sensitization at concentrations low enough that the two effects are not confused. 

Monsanto. 1984. Primary skin irritation and Department of Transportation (DOT) skin corrosivity test of p-nitrophenol in rabbits. NTIS/OTS0518156. 

Edwards CC (1972) Hazardous substances Proposed revision of test for primary skin irritants. Fed Reg 37 27635-27636 Guillot JP, Gonnet JF, Clement C et al. (1982) Evaluation of the cutaneous-irritation potential of 56 compounds. Food Chem Toxicol 20(5) 563-572... 

It is unlikely that there will be significant percutaneous toxicity under the usual conditions of exposure to screening smokes. However, if primary and cumulative skin irritation tests suggest that there may be systemic effects, then it will be appropriate to conduct more detailed monitored studies for percutaneous toxicity. 

ASTM F-750 Evaluating Material Extracts by Systemic Injection in the Mouse. ASTM F-719 Testing Biomaterials in Rabbits for Primary Skin Irritation. Eckstein, R, Jackson, M. C., Millman, N. and Sobrero, A. J., Comparison of vaginal tolerance tests of spermicidal preparations in rabbits and monkeys, /. Reprod. Fertil, 20, 85, 1969. 

F 719 Testing biomaterials in rabbits for primary skin irritation... 

Food and Drug Administration (1972) United States - Food and Drug Administration. Hazardous substances. Proposed revisions of test for primary skin irritants. Fed Reg 37 27635 Frankild S, Basketter DA, Andersen KE (1996) The vdue and limitations of rechallenge in the guinea pig maximisation test. Contact Dermatitis 35 135-140... 

IPBC is not a primary skin irritant, but is irritant and corrosive to the eyes. No skin sensitization effects were observed in the guinea pig maximization test. Ames test and micronucleus assay did not show signs of mutagenicity. 

Since the CM-cotton developments were designed for healthcare applications, the CM-products were sterilized with ethylene oxide (EO). The products passed the cell culture, primary skin irritation and intracutaneous irritation tests. Safety evaluation on an animal model is yet to be completed. No adverse toxicological or environmental factors are reported for cellulose ethers in general. In fact, some purified carboxymethylcelluloses, methylcelluloses, and hydroxypropylcelluloses are approved as direct food additive [8]. A significant use of CM-cellulose is also found in pharmaceuticals for skin care products such as ointments, lotions, and creams [9]. 

Primary human skin irritation of tetradecanol, hexadecanol, and octadecanol is nil they have been used for many years ia cosmetic creams and ointments (24). Based on human testing and iudustrial experience, the linear, even carbon number alcohols of 6—18 carbon atoms are not human skin sensitizers, nor are the 7-, 9- and 11-carbon alcohols and 2-ethylhexanol. Neither has iudustrial handling of other branched alcohols led to skin problems. Inhalation hazard, further mitigated by the low vapor pressure of these alcohols, is slight. Sustained breathing of alcohol vapor or mist should be avoided, however, as aspiration hazards have been reported (25). 

Primary irritant-contact dermatitis results from direct cytotoxicity produced on first contact. The cellular injury is characterised by two macro-scopically visible events a reddening of the skin (erythema) and accumulation of fluid (oedema). By observing or measuring these changes, one can estimate the extent of skin damage that has occurred. The most widely used single-exposure irritancy test is based on the Draize rabbit test. ... 

In primary irritation tests no or only slight effects were seen at the skin or in the eyes of the treated rabbits respectively [3.213], [3.214], No skin sensitisation occurred in a Guinea pig maximisation test [3.211]. 

In the typical primary irritation test, the backs of albino rabbits are clipped free of hair and an area of about 5 cm2 on each rabbit is used in the test. This area is then treated with either 0.5 ml or 0.5 g of the compound to be tested and then covered with a gauze pad. The entire trunk of the rabbit is wrapped to prevent ingestion. After 4 to 24 hours the tape and gauze are removed, the treated areas are evaluated for erythematous lesions (redness of the skin produced by congestion of the capillaries) and edematous lesions (accumulation of excess fluid in SC tissue), each of which is expressed on a numerical scale. After an additional 24 to 48 hours, the treated areas are again evaluated. 

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 several types of irritancy testing protocols that are used to comply with federal and international safety regulations. The classic Draize test was developed in 1944 to measure acute primary irritation. The test compound is applied in an occluded fashion to a clipped area of abraded and intact skin of at least six albino rabbits and evaluated 24 hr and 72 hr after patch removal. The degree of erythema and edema, ranging from one to four, is recorded to reflect severity of the irritation. Because these tests are occluded, irritancy is potentiated due to hydration, which reduces the skin barrier. The Draize test may be modified to assess sensitization by preexposing animals to a sensitizing dose of the study chemical and then rechallenging the animals at a later date to illicit the immune-mediated response. 

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