Repeat insult patch test

There are 4 basic predictive human sensitization tests in current use (1) single induction/ single challenge patch tests (2) repeated insult patch tests (RIPT) (3) RIPT with continuous exposure (modified Draize) and (4) the maximization test. Principal features of human sensitization assays are summarized in Table 2. 

Stotts (1980) presented detailed examples of proper interpretation of human repeat insult patch tests. Sensitization is characterized by challenge reactions stronger than reactions early in the induction phase, by persistence of responses through delayed readings, by delayed appearance of a response, or by weak responses in a few subjects when the material has not produced irritation in the panel. 

Phenylmercuric salts are irritant to the skin at 0.1% w/w concentration in petrolatum. In solution, they may give rise to erythema and blistering 6-12 hours after administration. In a modified repeated insult patch test, a 2% w/v solution was found to produce extreme sensitization of the skin. ° ... 

There are several acceptable ways to evaluate DTH responses in nonclinical species. Of these, the most common are the guinea pig assays used to assess contact sensitization. Both the Magnusson and Kligman model (guinea pig maximization test) and the Buehler model measure the elicitation phase of the hypersensitivity response, though the tests vary in their methods of chemical application and utilization of adjuvants. Most recently, the local lymph node assay has been accepted as a stand alone test for chemical hypersensitivity. This assay is conducted in mice and measures the induction phase of sensitization. In humans, the most common methods to assess delayed hypersensitivity are the patch test (contact sensitivity for diagnostic purposes) and the human repeat insult patch test (contact sensitivity for predictive purposes). Additionally, intradermal... 

Pew data on the acute toxicity of NMP in humans are available. Volunteers exposed to <12 ppm NMP for 8 h did not experience any eye or respiratory tract irritation, symptoms such as headache, dizziness, or nausea, or changes in pulmonary function measured by spirometry. At 12 ppm NMP, two of six subjects reported an acetone-like odor. NMP did not produce signs of sensitization in a repeated-insult patch test with NMP, although a minor and transient irritation was observed. 

Many industries regularly conduct repeat insult patch tests on human volunteers to evaluate topical irritancy. Groups of human volunteers are patched with test substance. One to five concentrations can be tested simultaneously, a wide enough range to yield results relevant to the usage. Cumulative skin irritancy is measured by applying patch applications each day for 3 weeks. Skin irritation is usually assessed visually, but blood flow and skin temperature can be measured objectively by laser Doppler flowmetry, ultrasound Doppler, heat flow disk measurement, sensitive thermocouple devices, or noncontact infrared radiative techniques. In these tests, dose-response curves can be obtained. Skin thickness can be measured with calipers as a measure of edema formation. 

Human volunteers are also used in many industries in tests for allergic sensitization by cosmetic substances and formulations. The repeat insult patch test includes an induction phase (repeat applications during 3 weeks) and a 2 week rest period (incubation phase), followed by a challenge to see if sensitization has occurred. A pilot study of 20 human volunteers can be followed by more extensive testing (80-100 subjects). Positive results at more than the 10% level in the human volunteers would suggest a major problem with the formulation. User tests with the sensitized individuals and nonreactive matched control subjects can often determine the importance... 

CMA. 1992. Repeated insult patch test to evaluate sensitization potential of ethylene glycol monobutyl ether with cover letter dated 05/26/93. EPA/OTS Doc 86-930000207. 

Greenspan AH, Reardon RC, Gingell R. 1995. Human repeated insult patch test of 2-butoxyethanol. Contact Dermatitis 33 59-60. 

Skin Irritation and Sensitization. If there are species variations in the response to laboratory tests to assess local cutaneous toxicity, or if the findings are marginal or equivocal, then it may be considered appropriate to confirm, or otherwise, the cutaneous reaction in humans. This may be conveniently conducted using patch tests or repeated insult patch tests (Hermansky, 1999). 

Sensitization of the Skin or Respiratory System Evidence of adverse effects in humans Weight of evidence demonstrates potential for adverse effects in humans GHS Category 1 —(skin or respiratory) or Positive responses in predictive Human Repeat Insult Patch Tests (HRIPT) (skin) Suggestive animal studies Analog data or Chemical class known to produce toxicity No basis for concern identified... 

In repeated-insult patch tests, 0 or 5% of subjects became sensitized after being treated with 10% ylang ylang essential oil in a petroleum base. In a rechallenge patch test... 

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... 

There are four basic predictive human sensitization tests in current use (1) a single-induction/single-challenge patch test (2) repeated-insult patch test (RIPT) (3) RIPT with continuous exposure (modified Draize) and (4) the maximization test all of these use similar customized patches (Frosch and Kligman 1979 Kaminsky et al. 1986). Principal features of human sensitization assays are summarized in Table 1, and further details can be found in MarzuUi and Maibach (1996). For assays other than maximization, 150-200 subjects are usually tested. Henderson and Riley (1945) statistically showed that if no positive reactions are observed in 200 randomly selected subjects, as many as 15/1000 of the general population may react (95% confidence). As sample size is reduced, the likelihood of unpredicted adverse reactions in the general population increases. 

For humans, the most widely known methods are the human maximisation test (HMT) and the modified Draize repeated-insult patch test (Kligman 1966 Marzulli and Maibach 1973). GPMT and HMT were developed in parallel and the results were in close conformity, which has been adduced as support for extrapolating guinea pig findings to man. 

Skin Repeated Insult Patch Test Not a primary irritant or sensitizer (humans)... 

None of the tests produced responses which could be attributed to an allergic reaction [103-106]. On the evidence of these tests, alkyl polyglycoside does not require classification or labeling. This was confirmed by a human repeated insult patch test in which alkyl polyglycoside did not induce any sensitization in volunteers. Thus, the animal model provided clear predictions of effects on human beings. 

In the last 50 years, skin sensitisation potential assessment has been of paramount importance for ensuring the safety of cosmetic products. Different human sensitisation tests, such as Schwartz-Peck test (Schwartz, 1969), human repeated insult patch tests (Marzulli and Maibach, 1973 Griffith and Buehler, 1976) and human maximisation test (Kligman and Epstein, 1975), have been used but standardised test guideUnes are not available and the tests have not undergone an official validation process. 

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