scholarly journals Analysis of Variability in the Rabbit Skin Irritation Assay

2021 ◽  
pp. 104920
Author(s):  
John P. Rooney ◽  
Neepa Y. Choksi ◽  
Patricia Ceger ◽  
Amber B. Daniel ◽  
James Truax ◽  
...  
Keyword(s):  
Skin Irritation ◽  
Rabbit Skin

Skin irritation testing in man for hazard assessment — evaluation of four patch systems

1995 ◽  
Vol 14 (9) ◽  
pp. 729-734 ◽  
Author(s):  
M. York ◽  
DA Basketter ◽  
JA Cuthbert ◽  
L. Neilson
Keyword(s):  
Skin Irritation ◽  
Research Programme ◽  
Predictive Testing ◽  
Hazard Identification ◽  
Hazard Evaluation ◽  
Rabbit Skin ◽  
Range Finding ◽  
Irritation Test ◽  
Patch Removal ◽  
Skin Irritation Test

1 The limitations of the Draize rabbit skin irritation test for hazard evaluation for man are widely documented. Nevertheless it remains the prescribed method for deter mining acute skin irritation hazard. 2 While the use of human testing for risk assessment of irritants is well established, the use of predictive testing in man for hazard identification has not been explored widely, and this is the object of the research programme. 3 The experiment described in this report evaluates the sensitivity of four patch testing systems (Finn chamber, Hill Top patch, Van der Bend chamber, and Webril patch) using a total of six irritant substances. 4 Following preliminary range-finding experiments, test materials were applied to the upper outer arm for up to 4 h. Assessments were performed immediately after patch removal and at 1, 24, 48 and 72 h. 5 Webril and Hill Top patches generated the greatest lev els of response, although responses with Finn and Van der Bend were observed. Hill Top patches are recom mended for future development work. 6 The use of very small preliminary panels to predict the effects in larger panels using different volunteers was only of limited value as each volunteer was found to have different irritant thresholds.

Dermal and Ocular Irritation Studies of Honeybee (Apis mellifera L.) Venom

2012 ◽  
Vol 40 (04) ◽  
pp. 795-800 ◽  
Author(s):  
Sang Mi Han ◽  
Kwang Gill Lee ◽  
Joo Hong Yeo ◽  
Sok Cheon Pak
Keyword(s):  
Skin Irritation ◽  
Clinical Signs ◽  
Test Material ◽  
Eye Irritation ◽  
Rabbit Skin ◽  
Ocular Irritation ◽  
Mucous Membranes ◽  
Irritation Test ◽  
Skin Irritation Test ◽  
Observation Period

The aim of this study was to access the irritant properties of bee venom (BV) after its application to skin and eye mucous membranes of the rabbit. The animals were also observed for clinical signs and mortality after the application of the test material. Six animals were used for the skin irritation test and nine rabbits for the eye irritation test. The acute BV application to the rabbit skin revealed no appreciable clinical signs throughout the observation period of 72 h and there was no mortality seen. In the eye irritation test, eye reactions were read and graded 24, 48, 72, 96 and 168 h after BV treatment. No changes in the cornea, iris or conjunctivae were observed at all time points of observations. Based on the present findings, it can be concluded that the irritation potential of BV is negligible.

2 Final Report on the Safety Assessment of Benzophenones-1, 3, 4, 5, 9, and 11

1983 ◽  
Vol 2 (5) ◽  
pp. 35-77 ◽  
Keyword(s):  
Safety Assessment ◽  
Skin Irritation ◽  
Metabolic Activation ◽  
Final Report ◽  
Oral Ingestion ◽  
Rabbit Skin ◽  
Animal Data ◽  
Irritation Test ◽  
Skin Irritation Test ◽  
Derivatives Of

Benzophenones-1 to 12 are substituted derivatives of 2-hydroxybenzophe-none. They are used as photostabilizers in cosmetics and have a photoprotective effect on the skin. When ingested and absorbed, Benzophenones were primarily conjugated and excreted in the urine. Benzophenones were practically nontoxic when chronically administered orally to rats, and Benzophenones-3 and 4 were nontoxic when applied to the skin of rabbits at doses of > 5 g/kg. Subchronic oral ingestion of Benzophenone-3 at 1 % was nontoxic to rats; however, another study showed Benzophenone-3 at 0.5% was toxic. Benzophenone-1 elicited toxic effects in rats at 0.6 g/kg. Benzophenones were nonirritating or mildly irritating to rabbit skin at concentrations of up to 100% and practically nonirritating to the eyes of rabbits. A subchronic skin irritation test indicated that Benzophenone-4 was capable of causing minimal irritation in rabbits at a concentration of 10%. Benzophenone-3 was reported to be nonsensitizing and nonphototoxic in guinea pigs and rabbits. Benzophenones-1, 3, 4, 5, and 9 were nonmutagenic both with and without metabolic activation in the Ames test. Skin irritation and sensitization in humans indicated that Benzophenones were mildly irritating and sensitizing at concentrations greater than those used in cosmetics. On the basis of the available animal data and clinical human experience, it is concluded that Benzophenone-1, 3, 4, 5, 9, and 11 are safe for topical application to humans in the present practices of use and concentration in cosmetics.

The measurement of skin irritation in vitro using ex vivo rabbit skin

1986 ◽  
Vol 115 (s31) ◽  
pp. 45-46 ◽  
Author(s):  
M.A. PEMBERTON ◽  
G.J.A. OLIVER
Keyword(s):  
Ex Vivo ◽  
Skin Irritation ◽  
Rabbit Skin

scholarly journals Are Cosmetics Used in Developing Countries Safe? Use and Dermal Irritation of Body Care Products in Jimma Town, Southwestern Ethiopia

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Wayessa Amasa ◽  
Dante Santiago ◽  
Seblework Mekonen ◽  
Argaw Ambelu
Keyword(s):  
Skin Irritation ◽  
Sun Exposure ◽  
Rabbit Skin ◽  
Adverse Health Effects ◽  
Southwestern Ethiopia ◽  
Dermal Irritation ◽  
Cosmetic Ingredients ◽  
Body Care ◽  
Primary Irritation ◽  
Jimma Town

Background. Rabbit skin model was used to test skin irritation of the most commonly used cosmetic products in Jimma town, southwestern Ethiopia. The most commonly used cosmetics were Dove, Glysolid, College, Top Society, Fair and Lovely, Nivea, Lux, Magic fruit world, Solea, Body talk, Kris, Holly, Victoria, and Sweet Heart.Methods. Intact and abraded rabbit skins were tested for erythema and edema under shade and under sun exposure. Draize Primary Irritation Index (PII) was used to calculate skin irritation of each cosmetic. Cosmetic ingredients were analyzed from the labels.Results and Discussion. Only Dove cream caused no skin irritation except for an abraded skin under sun exposure for five consecutive days. It has been identified that application of cosmetics on abraded skin under sunny condition worsens the irritation. Cosmetic labels revealed that most ingredients used in all products were those restricted chemicals due to their adverse health effects.Conclusion. This study has concluded that use of cosmetics under sunshine and also on abraded skin increases skin irritation. Hence, those users who have abraded skin are advised not to apply those cosmetics on continuous basis specifically under sun exposure.

A Statistical Basis for Using Fewer Rabbits in Dermal Irritation Testing

1990 ◽  
Vol 9 (1) ◽  
pp. 49-60 ◽  
Author(s):  
Nabil S. Hatoum ◽  
Chester L. Leach ◽  
Daniel M. Talsma ◽  
Robert D. Gibbons ◽  
Paul J. Garvin
Keyword(s):  
Statistical Study ◽  
Skin Irritation ◽  
Correlation Coefficients ◽  
Test Group ◽  
In Vivo Studies ◽  
Rabbit Skin ◽  
In Vitro Method ◽  
Dermal Irritation

An acceptable and validated in vitro method to evaluate the potential of a chemical to cause dermal irritation does not exist; therefore, in vivo studies remain the only alternative. Currently most laboratories utilize 6 rabbits per test, but this group size may not be necessary to derive the desired information. Data generated from 6-rabbit skin irritation tests of 105 materials were used to determine the ability of irritation scores from all possible combinations of 5-, 4-, 3-, or 2-rabbit subsets to predict the Draize score derived from 6 rabbits. There are 630, 1575, 2108, and 1575 possible combinations of 105 studies for the 5-, 4-, 3-, and 2-rabbit subseta, respectively. We classify materials using a four-level adjectival rating system based on (among other factors) the Draize score, Comparisons indicated that the 5-, 4-, 3-, and 2-rabbit scores were in 96, 94, 91, and 88% agreement, respectively, with the classification assigned on the basis of the 6-rabbit score. The correlation coefficients for randomly selected subsets of 5-, 4-, 3-, and 2-rabbit scores versus the 6-rabbit Draize score were 0.996, 0.994, 0.986, and 0.977, respectively. This study indicated that 3 rabbits per test group allow for adequate assessment of the dermal irritation potential of a chemical. These results also conformed closely to those obtainetd from a previous statistical study using eye irritancy data from 155 chemicals, where 3-rabbit subsets were 94% predictive of the 6-rabbit tests.

8 Final Report on the Safety Assessment of Triethanolamine, Diethanolamine, and Monoethanolamine

1983 ◽  
Vol 2 (7) ◽  
pp. 183-235 ◽  
Keyword(s):  
Skin Testing ◽  
Skin Irritation ◽  
Laboratory Animals ◽  
Final Report ◽  
Oral Toxicity ◽  
Rabbit Skin ◽  
Patch Tests ◽  
Prolonged Contact ◽  
Cosmetic Formulations

Triethanolamine (TEA), Diethanolamine (DEA), and Monoethanolamine (MEA) are amino alcohols used in cosmetic formulations as emulsifiers, thickeners, wetting agents, detergents, and alkalizing agents. The nitrosation of the etha-nolamines may result in the formation of N-nitrosodiethanolamine (NDELA) which is carcinogenic in laboratory animals. In single-dose oral toxicity for rats, TEA was practically nontoxic to slightly toxic, and DEA and MEA were slightly toxic. Long-term oral ingestion of the ethanolamines by rats and guinea pigs produced lesions limited mainly to the liver and kidney. Long-term cutaneous applications to animals of the ethanolamines also produced evidence of hepatic and renal damage. TEA and DEA showed little potential for rabbit skin irritation in acute and subchronic skin irritation tests. MEA was corrosive to rabbit skin at a 30% concentration in a single semioccluded patch application and at a >10% concentration in 10 open applications over a period of 14 days. The ethanolamines were nonmutagenic in the Ames test and TEA is also nonmutagenic to Bacillus subtilis. TEA did not cause DNA-damage inducible repair in an unscheduled DNA synthesis test. TEA had no carcinogenic or cocarcinogenic activity when dermally applied to mice for 18 months. Clinical skin testing of TEA and cosmetic products containing TEA and DEA showed mild skin irritation in concentrations above 5%. There was very little skin sensitization. There was no phototoxicity or photosensitization reactions with products containing up to 20.04% TEA. A formulation containing 11.47% MEA and a formulation containing 1.6% DEA and 5.9% MEA were irritating to human skin in patch tests. The Panel concludes that TEA, DEA, and MEA are safe for use in cosmetic formulations designed for discontinuous, brief use followed by thorough rinsing from the surface of the skin. In products intended for prolonged contact with the skin, the concentration of ethanolamines should not exceed 5%. MEA should be used only in rinse-off products. TEA and DEA should not be used in products containing N-nitrosating agents.

2 Final Report on the Safety Assessment of p-Hydroxyanisole

1985 ◽  
Vol 4 (5) ◽  
pp. 31-63 ◽  
Keyword(s):  
Guinea Pigs ◽  
Safety Assessment ◽  
Skin Irritation ◽  
Tumor Promoter ◽  
Final Report ◽  
Skin Sensitization ◽  
Cosmetic Products ◽  
Rabbit Skin ◽  
Ames Assay

p-Hydroxyanisole is used as an antioxidant in cosmetic products at concentrations of up to 1.0 percent. The acute oral LD50 of p-Hydroxyanisole in rats was estimated as 1630 mg/kg. Undiluted p-Hydroxyanisole is a severe skin and ocular irritant in rabbits but produced minimal eye irritation at 0.1 percent and minimal rabbit skin irritation at 5 percent. Skin sensitization to p-Hydroxyanisole occurred when guinea pigs were treated at 0.5 M. p-Hydroxyanisole is a skin-depigmenting agent at concentrations approximating those used in cosmetic products. p-Hydroxyanisole was nonmutagenic in the Ames assay. No local toxic changes or tumors were observed following long-term application of 5 and 10 percent p-Hydroxyanisole. The antioxidant was inactive as a tumor promoter. Solutions of p-Hydroxyanisole produced embryotoxicity but not teratogenicity. The function of p-Hydroxyanisole in cosmetics is that of an antioxidant; it is not intended for use as a skin lightener or skin-depigmenting agent. Because of the depigmenting action of p-Hydroxyanisole in black guinea pigs at reported concentrations approaching those used in cosmetics, it is concluded that p-Hydroxyanisole is unsafe for use as a cosmetic ingredient.

1 Final Report on the Safety Assessment of Laureths 4 and 23

1983 ◽  
Vol 2 (7) ◽  
pp. 1-15 ◽  
Keyword(s):  
Clinical Studies ◽  
Skin Irritation ◽  
Lauryl Alcohol ◽  
Male Rats ◽  
Final Report ◽  
Rabbit Skin ◽  
Safety Test ◽  
Cosmetic Ingredients ◽  
Rats And Mice ◽  
Primary Irritation

The Laureths, polyethoxyethers of lauryt alcohol, are used in a wide variety of cosmetic products. Laureth-4 was “practically nontoxic” when administered orally to rats and mice. Acute, subchronic, and chronic dermal tests with diluted formulations on rabbits were negative for systemic toxicity. In eye irritation studies in rabbits, undiluted Laureth-4 was moderately and minimally irritating in the unrinsed and rinsed eye, respectively; 10 and 20% dilutions were both classified as minimally and nonirritating. The acute oral LD50s for Laureth-23 were 8.6 and 3.5 g/kg for fasted male rats and mice, respectively. Undiluted Laureth-23 caused no primary irritation when applied to the rabbit skin. Undiluted Laureth-23 caused a slight conjunctival reaction in rabbits. Review of safety test data on closely-related Laureths and other lauryl alcohol ethoxylated compounds indicated no teratological, multiple generation and fertility, and mutagenicity effects for these compounds. No skin irritation or sensitization was reported in clinical studies with undiluted Laureth-4. A 6% Laureth-4 product produced no evidence of phototoxicity. No primary cutaneous irritation was observed in clinical studies using 60% Laureth-23. No evidence of sensitization was reported when a 25% solution of Laureth-23 was used in a repeated insult patch test on 168 subjects, nor was there evidence of phototoxicity when tested on a subset of this population. It is concluded that Laureth-4 and Laureth-23 are safe as cosmetic ingredients in the present practices of use and concentration.

scholarly journals Review of skin irritation/corrosion hazards on the basis of human data: a regulatory perspective

2012 ◽  
Vol 5 (2) ◽  
pp. 98-104 ◽  
Author(s):  
David Basketter ◽  
Dagmar Jírova ◽  
Helena Kandárová
Keyword(s):  
Patch Test ◽  
Skin Irritation ◽  
Alternative Methods ◽  
Test Protocol ◽  
Rabbit Skin ◽  
Irritation Test ◽  
Skin Irritation Test

Abstract Regulatory classification of skin irritation has historically been based on rabbit data, however current toxicology processes are transitioning to in vitro alternatives. The in vitro assays have to provide sufficient level of sensitivity as well as specificity to be accepted as replacement methods for the existing in vivo assays. This is usually achieved by comparing the in vitro results to classifications obtained in animals. Significant drawback of this approach is that neither in vivo nor in vitro methods are calibrated against human hazard data and results obtained in these assays may not correspond to situation in human. The main objective of this review was to establish an extended database of substances classified according to their human hazard to serve for further development of alternative methods relevant to human health as well as resource for improved regulatory classification. The literature has been reviewed to assemble all the available information on the testing of substances in the human 4 h human patch test, which is the only standardized protocol in humans matching the exposure conditions of the regulatory accepted in vivo rabbit skin irritation test. A total of 81 substances tested according to the defined 4 h human patch test protocol were found and collated into a dataset together with their existing in vivo classifications published in the literature. While about 50% of the substances in the database are classified as irritating based on the rabbit skin test, on using the 4 h HPT test, less than 20% were identified as acutely irritant to human skin. Based on the presented data, it can be concluded that the rabbit skin irritation test largely over-predicts human responses for the evaluated chemicals. Correct classification of the acute skin irritation hazard will only be possible if newly developed in vitro toxicology methods will be calibrated to produce results relevant to man.

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