Cutaneous toxicity

Allen, D.G., Riviere, J.E., and Monteiro-Riviere, N.A., Cytokine induction as a measure of cutaneous toxicity in primary and immortalized porcine keratinocytes exposed to jet... 

CUTANEOUS TOXICITY Victor A. Drill and Paul Lazar, editors, 288pp., 1984... 

Topical drug preparations are applied for days or even weeks, cosmetics for a lifetime and skin contact is probably the most common form of exposure to industrial chemicals. Therefore, a knowledge of the cutaneous toxicity is important for an overall hazard assessment. Cutaneous toxicity or localised skin injury can be considered as a primary event, because the compound could be irritant or corrosive, or as a secondary immunologically mediated event causing a delayed hypersensitivity response. 

Worobeck SM, DiBeneditto JP Perspectives on occupational dermatoses. In Drill VA, Lazar P eds. Cutaneous Toxicity, pp 253. New York, Raven Press, 1984... 

Mathur AK, Gupta BN, Singh S, et al. 1992. Cutaneous toxicity of sodium lauryl sulphate, nickel, and their combination in guinea pigs Biochemical and histopathological observations. Bull Environ Contam Toxicol 49 871-878. 

In 1971 M T Chemicals (USA) began marketing 1-para-chlorophenylsilatrane as a new rodenticide under the trade mark RS-15030, 3 ). This first organosilicon pesticide had an advantage over other known toxicants. This highly toxic compound is rapidly inactivated in poisoned rodents, so their corpses are not harmful to other animals. Furthermore, RS-150 penetrates very poorly through the skin (its cutaneous toxicity is 3000 mg/kg for rats)31). Finally, rats do not become resistant to l-(4 -chlorophenyl)silatrane as was the case with other 1-arylsilatranes. Practically complete lack of smell is another important advantage of this preparation and other 1-arylsilatranes. 

Griffith JF (1969) Predictive and Diagnostic test for contact sensitization. Toxicol. Appl Pharmacol 3 90-102 Griffith JF, Buehler E (1976) Prediction of skin irritancy and sensitization potential by testing with animals and man. In Drill V, Lazer P (eds) Cutaneous Toxicity. Academic Press, New York, pp 155-173... 

Frosch PJ, Kligman AM (1977) The chamber scarification test for assessing irritancy of topically applied substances. Cutaneous Toxicity. Academic Press, NY, pp 127-144 Frosch PJ, Kligman AM (1979) The soap chamber test. A new method for assessing the irritancy of soaps. J Am Acad Dermatol 1 35-41... 

Frosch PJ, Kligman AM (eds) (1993) Noninvasive methods for the quantification of skin functions. Karger, Basel Griffith JF, Weaver JE, Whitehouse HS et al. (1969) Safety evaluation of enzyme detergents. Oral and cutaneous toxicity, irritancy and skin sensitization studies. Food Cosmet Toxicol 7 581-593... 

Other toxicities. The patient should be methodically questioned about the development of any other side-effects of treatment. Severe grades of toxicity may again necessitate dose adjustment (e.g. severe neurotoxicity, cutaneous toxicity). 

Drill, V. A., and Lazar, P. Cutaneous Toxicity, Raven Press, New York, 1984. 

Triplet states of the amiodarone, an antiarrhythmic drug which shows cutaneous toxicity, are involved in its photolysis. The lowest triplet states of the drugs codeine and morphine and their molecular sub units veratrole and guaiacol are. ... 

An unusually high incidence of skin eiythema (70-85%) was noted in patients who received aldesleukin after autologous bone marrow transplantation. Histological examination showed features of cutaneous graft-versus-host disease or T cell epidermal infiltrates, but cutaneous toxicity was not reproduced in patients receiving low-dose aldesleukin (100,101). 

The potential role of localized vertebral palhative radiotherapy before aldesleukin treatment was denied, since the area of cutaneous toxicity was broader than the irradiated field. 

Chlormezanone is a tranquillizer with central muscle relaxant effects. In reaction to some case reports of serious, sometimes fatal, cutaneous toxicity and after intervention by drug regulatory authorities in some European countries, all major manufacturers have stopped production of chlormezanone. It may still be available in combination products in some Asian countries. 

The dose and duration of protracted infusional fluorouracil is hmited by mucositis, diarrhea, and/or palmar-plantar erythrodysesthesia. Typically, palmar-plantar dysesthesia begins several weeks to months after starting treatment. Although the dysesthesia abates within several weeks of discontinuing the infusion, it rapidly recurs when the infusion is resumed. Five patients who developed palmar-plantar dysesthesia during infusion of fluorouracil were treated with oral pyridoxine, 50 or 150 mg/day, once it reached moderate severity (149). The severity of the skin toxicity improved, with resolution of pain in four of the five patients, despite continued administration of fluorouracil. The abihty of pyridoxine to modulate fluorouracil-induced cutaneous toxicity is currently undergoing evaluation in the randomized trial (150). 

Alley E, Green R, Schuchter L. Cutaneous toxicities of cancer therapy. Curr Opin Oncol 2002 14(2) 212-16. 

Lacouture ME. Mechanisms of cutaneous toxicities to EGFR inhibitors. Nat Rev Cancer. 2006 6(10) 803-812. 

Table 13 Instrumental methods for assessing cutaneous toxicity...

Drill VA and Lazar P (eds.) (1984) Cutaneous Toxicity. New York Raven Press. 

Finally, cell culture studies are often used to assess direct cutaneous toxicity to skin cells such as keratinocytes. As discussed above, this can be used to define if a potential topical chemical that penetrates the skin can cause epidermal cell dysfunction. However, systemically administered chemicals can also distribute to skin and modify keratinocytes cell function. Damage to skin, especially if the mechanism of action is immunological, does not require topical exposure. 

Weingand DA, Haygood C, Gaylor JR, et al. Racial variations in the cutaneous barrier. In Drill VA, Lazar P, eds. Current Concepts in Cutaneous Toxicity. New York Academic Press, 1980 221-235. 

Hermansky, S.J., Cutaneous toxicity, in General and Applied Toxicology, Volume 2, Second Edition, Ballan-tyne, B., Marrs, T.C., and Syversen, T., Eds., Macmillan Reference Ltd., London, 1999, pp. 827-852. 

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