Dermal sensitization

Enslein K, Gombar VK, Blake BW, Maibach HI, Hostynek JJ, Sigman CC et al. A quantitative structure-activity relationships model for the dermal sensitization guinea pig maximization assay. Food Chem Toxicol 1997 35 1091-8. 

As discussed imder dermal effects, people can develop hypersensitivity to trichloroethylene. The effects observed in hypersensitive individuals include skin effects (Conde-Salazar et al. 1983 Nakayama et al. 1988 Phoon et al. 1984 Waller et al. 1994) and liver effects (Phoon et al. 1984). Dermal sensitivity was confirmed with patch testing in only two cases (Conde-Salazar et al. 1983 Nakayama et al. 1988). The woman described by Conde-Salazaer et al. (1983) reacted positively to both vapor exposure and a dermal application of 5% trichloroethylene in olive oil. 

Isolated cases of dermal sensitivity and allergic responses in humans have been reported (Bauer and Rabens 1974 Conde-Salazar et al. 1983 Czirjak et al. 1993 Goh andNg 1988 Nakayama et al. 1988 Phoon et al. 1984 Schattner and Malnick 1990 Waller et al. 1994). An increase in the symptoms of systemic lupus erythematosus has been reported in persons exposed to trichloroethylene in their drinking water (Kilbum and Warshaw 1992). 

Another approach builds on the notion, widely accepted among immunotoxicologists (and probably true), that respiratory sensitizers (at least small molecular-weight chemicals) represent a subset of dermal sensitizers [42], Thus, assays for ACD, such as... 

Gad, S. C. et al., Development and validation of an alternative dermal sensitization test the mouse ear swelling test (MEST), Toxicol. Appl. Pharmacol., 84, 93, 1986. 

Arts, J.H.E. et al., Airway morphology and function of rats following dermal sensitization and respiratory challenge with low molecular weight chemicals, Toxicol. Appl. Pharmacol., 152, 66, 1998. 

Details on the cellular immune responses occurring following the recognition of xenobiotic haptens as antigens by the immune system are described in chapters 33-35 of this volume. Ultimately, a certain combination of mediators is selectively activated and subsequently helps determine and differentiate the characteristic immune response (e.g., Thl vs. Th2). For example, dermal sensitizing chemicals (e.g., oxazolone and dinitrochlorobenzene) elicit a higher proportion of Thl cytokines such as IFNy and... 

Much of the methods development and validation efforts in the past have been focused on evaluation of immunosuppression and contact or dermal sensitization. Currently available animal models and assays are not valid to assess the potential for systemic hypersensitivity and, at this time, reliable models to assess autoimmunity are not available. 

Dearman, R.J., et al., Influence of dibutyl phthalate on dermal sensitization to fluorescein isothiocyanate. Fundam. Appl. Toxicol., 33, 24, 1996. 

Hexachloroethane did not act as a sensitizer in guinea pigs when a challenge dose was given 2 weeks after the end of a 3-week sensitization period (Weeks et al. 1979). Accordingly, it did not stimulate antibody formation during sensitization. The NOAEL for dermal sensitization is reported in Table 2-3. 

Cell counts (lymphocytes, neutrophils, monocytes, eosinophils) were unaffected by u-hexane exposure. No reports of dermal sensitization after exposure to -hexane in humans were located. 

The reader should note that this scoring scheme is the same one used for dermal sensitization scoring, whereas the scoring method for the rabbit model discussed previously is that used for dermal irritation studies.)... 

FIGURE 15.4. Line chart for modified Buehler test for delayed contact dermal sensitization in the guinea pig. 

FIGURE 15.5. Line chart for guinea pig maximization test for dermal sensitization. 

Gad S.C., Dunn, B.J., Dobbs, D.W. and Walsh, R.D. (1986) Developmental and validation of an alternative dermal sensitization test The Mouse Ear Swelling Test (MEST), Topical Appl. Pharmacol. 84 93-114. 

Toxicology. p-Aminophenol is of moderately low toxicity but has caused dermal sensitization and kidney injury the potential for producing methemoglobin is of relatively minor importance. 

Toxicology. Benomyl causes dermatitis and dermal sensitization in experimental animals it is a reproductive toxin and teratogen. 

Contact dermatitis has been reported in Japanese women who worked in a greenhouse where benomyl had been used. Eruptions on the backs of the hands and on the forearms consisted of redness and edema. Cases of dermal sensitization have also been reported. In animal studies benomyl has low acute toxicity. The oral LDso for rats was greater than lOg/kg, and the dermal LDso in rabbits was also greater than lOg/kg. There was mild irritation when benomyl was placed on the skin of the rabbit or in the rabbit eye. 

Whether or not chlorothalonil is a true dermal sensitizer in humans or strictly a skin irritant remains controversial. Some investigators suggest that repeated exposure results in an enhanced irritant response, whereas others suggest that it is a potent contact allergen. It is noted that relatively few cases of allergy to chlorothalonil have been reported despite widespread use for over 20 years. Furthermore, at a plant that produces the chemical cases of work-related contact dermatitis have not been reported for years after adoption of good hygienic practices. ... 

DMEP did not cause dermal sensitization in guinea pigs. In the eyes of rabbits, it was not irritating. 

Dermal sensitization to EHA has been documented from exposure to its presence in adhesive tape. This potential has been confirmed in the guinea pig. ... 

Dermal sensitization to formaldehyde is an often-reported phenomenon. After skin contact, a symptom-free induction period typically ensues for 7-10 days. With subsequent contact there is itching, redness, swelling, multiple small blisters, and scaling in sensitized individuals. Repeated contact tends to cause more severe reactions, and sensitization usually persists for life. 

Toxicology. Methylene bis-(4-hexylisocyan-ate) (HMDI) is an irritant of the eyes, nose, and upper respiratory tract and causes dermal sensitization. 

Texaco Chemical Company Dermal Sensitization Study. FYI-OTS-0685-0402 FLWP Seq. I. Washington, DC, US Environmental Protection Agency, Office of Toxic Substances, 1985... 

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