Primary dermal irritation test

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. 

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

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... 

Organophosphate Ester Hydraulic Fluids. Repeated application of a patch treated with 0.2 pL of Skydrol 500B-4 for 5 weeks (3 times/week) resulted in mild cumulative erythema confined to the contact site in 14 of 53 human test subjects, beginning with the third dose during the first week. No evidence of immediate primary dermal irritation was observed (Monsanto 1980). 

The Primary Dermal Irritation Index is calculated for the test substance or control substance by dividing the sum of the Total Irritation Scores by the number of observations (three days x six animals = 18 observations). 

The test substance will not be studied for eye irritation if it is a strong acid (pH of 2.0 or less) or strong alkali (pH of 11.0 or greater) and/or if the test substance is a severe dermal irritant (with a primary dermal irritation index (PDll) of 5-8) or causes corrosion of the skin. 

MB Research Laboratories (1988d) Test substance ethyl tertiary butyl ether. Primary Dermal Irritation in rabbits. Unpublished report MB 88-9107C for ARCO Chemical Company, PA... 

The Federal Flazardous Substances Acts (FHSA) of 1940 and of 1960 define five areas of acute toxicity/irritation that are of primary importance for the development and sale of consumer products acute oral toxicity, dermal toxicity, primary dermal irritation, eye irritation, and acute inhalation toxicity. The FHSA act describes recommended test conditions in detail for these toxicity/irritation phenomena. Some knowledge of the potential for sensitization and phototoxicity are also relevant, and to provide longterm safety assurance, potential carcinogenicity and mutagenicity must also be considered. 

Dermal Irritation and Sensitization. There are tests for dermal irritation caused by topical application of chemicals. These fall into four general categories primary irritation, cutaneous sensitization, phototoxicity, and photosensitization. Because many foreign chemicals come into direct contact with the skin, including cosmetics, detergents, bleaches, and many others, these tests are considered essential to the proper regulation of such products. Less commonly, dermal effects may be caused by systemic toxicants. 

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. 

Test sample Concentration ratio of Cl-MTT(wt%) Primary irritation index (PE) Dermal irritation toxicity categories... 

Testing is performed to evaluate the potential occurrence of two different, yet related, endpoints, irritation and sensitization. The broadest application of these is evaluation of the potential to cause skin irritation, characterized by erythema (redness) and edema (swelling). Severity of irritation is measured in terms of both the degree of these two parameters and how long they persist. Primary irritation, cutaneous sensitization, phototoxicity, and photosensitization are possible types of dermal irritation resulting from dermal application. There are three types of irritation tests, each designed to address a different concern ... 

PBO was tested in both primary eye irritation and skin irritation studies in rabbits, dogs and cals. In all such studies, the compound was found to have minimal or no irritating effects. Sensitization studies performed on guinea pigs and rabbits (dermal exposure showed that PBO was not a sensitizing agent. 

In New Zealand white rabbits, patches soaked with 0.5 mL of undiluted 2-butoxyethanol acetate were applied to one site of the prepared skin surface (Jacobs et al. 1989). The untreated skin was used as a control. Erythema scores were obtained 1, 24, 48, and 72 hours after application of the undiluted substance for 4 hours. The erythema scores of exposure to 100% 2-butoxyethanol acetate for 4 hours in rabbits showed a ranking of 2, which is the minimal mean erythema needed to classify substances as skin irritants. New Zealand rabbits exposed dermally to unspecified doses of 2-butoxyethanol acetate for 24 hours exhibited dermal effects (Truhaut et al. 1979). When 2-butoxyethanol acetate was tested for primary irritation of the skin, four of six rabbits showed slight erythema (grade 1) at 24 hours. Dermal irritation from exposure to 2-butoxyethanol acetate has been studied in rabbits using both the Draize protocol (24-hour occluded exposure) and the European Economic Communities protocol (4-hour occluded exposure) (Zissu 1995). For both protocols, 0.5 mL of undiluted 2-butoxyethanol acetate was placed on the skin. 2-Butoxyethanol acetate was considered a moderate irritant by the Draize protocol and non-irritating by the European Economic Communities protocol. 

SM is widely known for its vesicating properties. There are no documented studies that conform to any standard regulatory test method for dermal irritation/corrosivity. However, there is sufficient information from observations and tests in humans to establish SM as a primary irritant, and further tests in animals are not required. 

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],... 

RTECS CLASS OF COMPOUND Primary Irritant - toxic by ingestion. Acute oral toxicity (LD50) 1780 mg/kg [Rat] acute dermal toxicity (LD50) 4 mL/kg [Rabbit], Since APTES is sensitive to hydrolysis, which may occur during testing, observed toxicity is likely due to the hydrolysis products ethanol and trisilanols. 

The following studies have been conducted with the tilanequat (a) acute oral, (b) acute ocular, (c) acute and subacute dermal, (d) acute vapor inhalation, (e) primary skin sensitization and irritation, (Q sub-acute vaginal irritation, (g) four-day static fish toxicity, (h) teratogenic evaluation, fi) sub-acute human wear test (socks), (j) human repeated insult patch test, Ot) iit-vitro Ames Microbial Assay with and wi ut metabolic activation, (1) in-vitro mammalian cell transfinmation in the presence and absence of exogenous metabolic... 

---