Skin Irritation and Corrosion

Any application of substances onto the skin, for instance, cosmetic products, must not cause damage to human health when applied under normal conditions. Therefore, any compound considered for application on human skin needs to be tested for reversible disadvantageous effects (skin irritation) and irreversible skin damage (skin corrosion). 

To test the irritancy potential of substances, two tests which can reliably distinguish between skin corrosives and noncorrosives are endorsed by the European Centre for the Validation of Alternative Methods (ECVAM). The testing procedures are based on the transcutaneous electrical resistance (TER) measurements of rat skin and on a human skin model. Both test systems [141-145] will be briefly outlined below. Nevertheless, these tests are not suited for the group of mild irritants which do not induce an acute effect on the barrier function. For those substances, new markers need to be evaluated. First results are available for heat shock protein 27 where higher levels were observed in skin models after exposure to mildly irritating chemicals [146, 147]. 

The rat skin TER assay enables to reliably discriminate between skin corrosives and noncorrosive substances [148], The assay relies on the change in the bioelectrical properties of the skin in response to the application of test chemicals. For the measurements, small discs of rat skin are necessary onto which the substances are applied to the epidermal surface for up to 24 h. In 

For the experiment, the dorsal skin of young rats (Wistar or a comparable strain) is shaved and washed with an antibiotic solution (containing, e.g., streptomycin, penicillin, chloramphenicol, and amphotericin in concentrations inhibiting bacterial growth). After skin excision, excess fat is peeled off and the skin is placed over the end of a polytetrafluoroethylene tube with the epidermal side in touch with the hollow cylinder. The skin is fixed with an O-ring and the tube interior is sealed. The side of the dermis is then submersed in a magnesium sulphate solution (154 mM). The samples are applied at 30°C to the epidermal side of the skin in such a way that the skin interface is fully covered. After the incubation time, the substances are removed with prewarmed water the skin surface tension is decreased with ethanol which is subsequently replaced with magnesium sulphate solution (154 mM). 

As positive control, 10 M hydrochloric acid (36%) is recommended distilled water will work as a negative control. 

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Draize Scoring System for Evaluation of Skin Irritating and Corrosive Properties... 

BgW The BgVV database has been used to develop specific S AR models for predicting skin irritation and corrosion. These models have been incorporated into a decision support system (DSS). The DSS is mainly a rule based approach, the rules being developed are not only based on substructural features but additionally incorporate specific physicochemical properties such as Log P, molecular weight, and aqueous solubility. The rules have been developed and validated on a total of 1508 compounds of which 199 are classified as hazardous. The DSS is designed to predict EU risk phrases. 

European Centre for Ecotoxicology and Toxicology of Chemicals, Skin Irritation and Corrosion Reference Chemicals Data Bank, ECETOC Technical Report No. 66, p. 247, Brussels, Belgium, 1995. 

Barratt, M.D., Quantitative structure-activity relationships for skin irritation and corrosivity of neutral and electrophilic organic chemicals, Toxicol, in vitro, 10, 247-256, 1996a. 

Hulzebos, E.M., Maslankiewicz, L., and Walker, J.D., Verification of literature-derived SARs for skin irritation and corrosion, QSAR Combinatorial Sci., 22, 351-363, 2003. 

Handling and Toxicity. Tungsten hexafluoride is irritating and corrosive to the upper and lower airways, eyes, and skin. It is extremely corrosive to the skin, producing bums typical of hydrofluoric acid. The OSHA permissible exposure limits is set as a time-weighted average of 2.5 mg/kg or 0.2 ppm (22). 

The acute oral toxicity and the primary skin and acute eye irritative potentials of dimer acids, distilled dimer acids, trimer acids, and monomer acids have been evaluated based on the techniques specified ia the Code of Eederal Regulatioas (CER) (81). The results of this evaluatioa are showa ia Table 7. Based oa these results, monomer acids, distilled dimer acids, dimer acids, and trimer acids are classified as nontoxic by ingestion, are not primary skin irritants or corrosive materials, and are not eye irritants as these terms are defined ia the Eederal regulatioas. 

Toxic Reactions of the Skin Irritation is the most common reaction of the skin. Skin irritation is usually a local inflammatory reaction. The most common skin irritants are solvents dehydrating, oxidizing, or reducing compounds and cosmetic compounds. Acids and alkalies are common irritants. Irritation reactions can be divided into acute irritation and corrosion. Necrosis of the surface of the skin is typical for corrosion. Acids and alkalies also cause chemical burns. Phenols, organotin compounds, hydrogen fluoride, and yellow phosphorus may cause serious burns. Phenol also causes local anesthesia, in fact it has been used as a local anesthetic in minor ear operations such as puncture of the tympanous membrane in cases of otitis. ... 

Lethal concentrations and doses are parameters of acute, systemic poisoning. There are also specific protocols to evaluate the irritant and corrosive effects on skin, eyes and mucous membranes. 

The platform includes different decision trees for the following endpoints the estimation of Threshold of Toxicological Concern (TTC), aquatic modes of action [44], skin and eye irritation and corrosion, mutagenicity and carcinogenicity [45], in vivo micronucleus assay, identification of Michael Acceptors and biodegradation potential [46]. 

Cyanide solutions or cyanide aerosols generated in humid atmospheres have been reported to cause irritation of the upper respiratory tract (primarily nasal irritation) and skin. Skin contact with solutions of cyanide salts can cause itching, discoloration, or corrosion, most likely due to the alkalinity of the solutions. Skin irritation and mild systemic symptoms (e.g., headache, dizziness) have been caused by solutions as dilute as 0.5% potassium cyanide. ... 

Toxicology. Sulfur tetrafluoride is extremely irritating and corrosive to the respiratory tract, skin, and eyes. 

First, it is important to distinguish between toxic effects occurring at the point or site of exposure (e.g., the stomach), so-called local effects, and those toxic effects occurring at a site distant from the site of exposure, known as systemic effects. Local effects are usually limited to irritancy and corrosive damage such as from strong acids, which occur immediately but can be reversible. The one exception is sensitization, which involves the immune system but is often manifested at the site of the exposure (e.g., skin) although may be delayed. 

Acrylonitrile is highly toxic if ingested, with an acute LDLo value for laboratory rats of 113 mg/kg. Tl is moderately loxic if inhaled (rat T.CLo — 500 ppm/4 h>, and it is extremely irritating and corrosive to skin and eyes. Aoylomtnle is categorized as a cancer hazard by OSHA. 

Highly irritating and corrosive to eyes, skin, and mucous membranes.1 Causes severe burns and is irritating to respiratory system. If taken by mouth, causes severe local and internal irritation and damage.1 7... 

The solid and solution are irritant and corrosive to skin and eyes. Irritant and poisonous if taken by mouth.5... 

The importance of MP can be related to the physical state of the substance under the conditions of Draize test. In this study, it was assumed that chemicals with a MP less than or equal to 37°C would exist as liquids in the test procedure and that, in general, liquids would be more likely than solids to cause corrosion and irritation. The results confirm that there is indeed a relationship between physical state and the potential for acute skin toxicity. The fact that some solids are corrosive or irritant may relate to the fact that their MPs are not much higher than 37°C and that they exist as wax-like substances, which are more capable of penetrating into the skin than are solids with higher MPs. For example, carvacrol, and thymol, which are both irritant and corrosive, have predicted MPs of 38°C and 38.1°C, respectively. In the case of other solids, such as benzene sulfonyl chloride (MP = 61°C), the corrosive response may be due to a more toxic derivative (e.g., benzene sulfonic acid). 

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

Basketter DA, Whittle E, Chamberlain M (1994) Identification of irritation and corrosion hazard in skin An alternative strategy to animal testing. Food and Chemical Toxicology 32 539-542... 

Tungsten hexafluoride is an irritating and corrosive gas. In the presence of moisture, hydrogen fluoride may be formed. Special care should be taken to avoid inhalation of the vapors or contact with skin. For disposal of tungsten hexafluoride, it can be diluted with an inert gas and scrubbed in water and a caustic solution. Small amounts of tungsten hexafluoride can be decomposed by passing through columns of soda lime or slaked lime. 

SAFETY PROFILE Intensely irritating and corrosive to skin, eyes, and mucous membranes. Large doses cause central nervous system depression. Mutation data reported. Reaction with molecular sieve produces toxic hydrogen bromide gas. See also BROMIDES. 

DOT CLASSIFICATION 8 Label Corrosive SAFETY PROFILE Poison by ingestion, intraperitoneal, and intravenous routes. Irritating and corrosive to skin and mucous membranes. Mutation data reported. When heated to decomposition it emits toxic fumes of Br". See also BROMIDES. 

DOT CLASSIFICATION 8 Label Corrosive SAFETY PROFILE Moderately toxic by ingestion and skin contact. An eye and severe skin irritant. A corrosive material. It fumes in moist air, releasing HCl. Combustible when exposed to heat or flame. When heated to decomposition it... 

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