Gerald A. Gellin

Detection of environmental depigmenting substances

We systematically screened the depigmenting capacity of several phenols, catechols and organic antioxidants. Clear‐cut depigmentation was achieved with monomethyl ether of hydroquinone (MMH) and tertiary butyl catechol (TBC) using black guinea pigs and black mice as animal models. A goal was to establish a reliable in vivo method to demonstrate or to predict the depigmenting action of chemicals on mammalian melanocytes. There was no universal solvent or optimal body site, although all tested areas could be depigmented. Irritation induced by some vehicles and test materials produced false positive responses. False negative responses with known depigmenting chemicals were observed. Utilising these observations, we propose a model for screening medicinal and industrial chemicals for depigmenting capacity.

Fibrous Glass Dermatitis

Investigations have been conducted in fibrous glass plants to assess the prevalence and significance of work-related dermatitis. Fibrous glass can cause skin irritation in most people. This is usually transient. Persons with dermographism are more likely to be intolerant of this discomfort. Allergy does not play a role in this dermatitis. Methods of control in the plant and in the home are presented.

Reduction in eumelanin by the activation of glutathione reductase and γ-glutamyl transpeptidase after exposure to a depigmenting chemical

Topical application of 4-tertiary butyl catechol (TBC) causes vitiligo in the skin of man and animals, and previous electron microscopic studies showed pheomelanin formation in the affected areas. In the present study, we investigated changes of enzyme activities, eumelanin content and amount of sulfur in tissue cultured human melanoma cells exposed to the depigmenting chemical. TBC enhanced glutathione reductase activity without changing the eumelanin content by 24 hr after exposure and subsequently (by 42 hr) increased gamma-glutamyl transpeptidase activity and sulfur content in the cells with a decrease in eumelanin content. It is suggested that this chemical alters the types of melanin formed by modulation of these enzyme activities.

Is the antioxidant butylated hydroxytoluene a depigmenting agent in man

Because of the allegation that butylated hydroxytoluene produced depigmentation in man, a prospective study was performed. Sixteen adult darkly pigmented males received daily occlusive applications for 60 days. Depigmentation was not observed.

Stimulation of pheomelanogenesis in cultured B16 melanoma cells by 4-tertiary butylcatechol

Intermediates of pheomelanin in tissue cultured B16 melanoma cells were analyzed by high performance liquid chromatography, and reduced glutathione (GSH), L-dopa, 2-[(L)-S-cysteinyl]-L-dopa (2-SCD) and 5-[(L)-S-cysteinyl]-L-dopa (5-SCD) were quantified. The effects of 4-tertiary butylcatechol (TBC), an antioxidant which causes skin depigmentation, on the levels of the intermediate were then examined. A concentration of 10(-4) M TBC increased the intracellular levels of GSH, 2-SCD and 5-SCD, whereas the L-dopa level was unchanged. The time-course of the increased intermediates corresponded to the elevation of glutathione-metabolizing enzyme activities previously reported by Kawashima et al. [J. invest. Derm. 82, 53 (1984)] in the same cell line exposed to 10(-4) M TBC. The findings establish chemical evidence that TBC stimulates pheomelanogenesis in melanocytes.

Glutathione reductase activity in skin exposed to 4-tertiary butyl catechol

SummaryThe effect of 4-tertiary butyl catechol (TBC), a potent depigmenting chemical, on glutathione reductase (GR) in pigmented ear skin of hairless mice was investigated. Three topical applications of TBC, which cause neither skin color changes nor melanocyte degeneration, induced an increase in enzyme activity. Since the same treatment resulted in pheomelanin formation as evidenced by electron microscopy, it is suggested that the GR increase correlates at least in part with changes in melanocyte metabolism. This enzyme generates a reduced form of glutathione which may be involved in the formation of glutathionedopas, substrates for hydrolytic enzymes to produce cysteinyldopas, and pheomelanin. Elevation of GR may be an indication of melanogenesis before clinical skin color changes due to TBC appear. It may be used for the early detection of occupational leukoderma.