Safety evaluation of zinc 2-pyridinethiol 1-oxide in a shampoo formulation.
TL;DR: The dog seems to be the species most susceptible to the effects of the compound itself, but it shows no effects to the shampoo formulation, and the shampoo containing ZnPT did not produce sensitization or undue irritation of the skin.
About: This article is published in Toxicology and Applied Pharmacology.The article was published on 1965-05-01. It has received 57 citations till now. The article focuses on the topics: Shampoo.
Citations
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TL;DR: There is concern that organic booster biocides in the antifouling paints which will replace tributyltin (TBT)-based coatings could cause serious environmental damage.
205 citations
TL;DR: Management of scalp psoriasis requires long term strategies in order to reach an optimal improvement of the condition, while avoiding the adverse effects associated with the long term use of treatments.
Abstract: Coal tar shampoos, containing 2 to 10% coal tar solution, are effective in scalp psoriasis. However, no double-blind studies are available to support such an assumption. Salicylic acid 5 to 10% has a pronounced keratolytic effect. Salicylic acid should be formulated in an ointment, which can be washed off easily. Crude coal tar is the most effective tar available for the treatment of psoriasis. An important feature of coal tar is its potent efficacy against pruritus. At the scalp, the application of crude coal tar is difficult. Therefore coal tar solution is the most frequently applied tar preparation in scalp psoriasis. Dithranol 0.1 to 3% is manufactured in various formulations. Treatment is initiated at a low concentration and the concentration is increased stepwise until a slight irritation, the feeling of warmth, is reached. In the treatment of scalp psoriasis, cream formulations are used. Imidazole antifungals have been used with success in scalp psoriasis. Overgrowth of the scalp with pityrosporon is a well-known feature of scalp psoriasis and seborrheic dermatitis. In case of resistance to other topical treatments use of a topical or systemic imidazole derivative might be helpful. So far, topical corticosteroids are the most frequently used treatments for psoriasis of the scalp. Corticosteroids inhibit epidermal proliferation, inhibit inflammation and modulate immune functions. Topical corticosteroids are fast acting: within 3 to 4 weeks maximal efficacy is reached. No data are available to support the efficacy and safety of topical corticosteroids during long term use. However, from epidemiologic surveys we know that these treatments are used by the majority of patients for more than 8 weeks. Since 1992 vitamin D3 formulations have been developed for the treatment of psoriasis. Calcipotriol is available in most countries. Tacalcitol is available in Japan and several other countries. Vitamin D3 analogues inhibit epidermal proliferation, enhance cornification and inhibit inflammation. Therefore, vitamin D3 analogues have a substantial antipsoriatic effect. Systemic treatments such as methotrexate, cyclosporine and acitretin are indicated in patients with recalcitrant disease. Management of scalp psoriasis requires long term strategies in order to reach an optimal improvement of the condition, while avoiding the adverse effects associated with the long term use of treatments.
124 citations
TL;DR: It is demonstrated for the first time that cultured primary human skin keratinocytes and melanocytes display an exquisite vulnerability to nanomolar concentrations of ZnPT resulting in pronounced induction of heat shock response gene expression and impaired genomic integrity.
Abstract: The differentiated epidermis of human skin serves as an essential barrier against environmental insults from physical, chemical, and biological sources. Zinc pyrithione (ZnPT) is an FDA-approved microbicidal agent used worldwide in clinical antiseptic products, over-the-counter topical antimicrobials, and cosmetic consumer products including antidandruff shampoos. Here we demonstrate for the first time that cultured primary human skin keratinocytes and melanocytes display an exquisite vulnerability to nanomolar concentrations of ZnPT resulting in pronounced induction of heat shock response gene expression and impaired genomic integrity. In keratinocytes treated with nanomolar concentrations of ZnPT, expression array analysis revealed massive upregulation of genes encoding heat shock proteins (HSPA6, HSPA1A, HSPB5, HMOX1, HSPA1L, and DNAJA1) further confirmed by immunodetection. Moreover, ZnPT treatment induced rapid depletion of cellular ATP levels and formation of poly(ADP-ribose) polymers. Consistent with an involvement of poly(ADP-ribose) polymerase (PARP) in ZnPT-induced energy crisis, ATP depletion could be antagonized by pharmacological inhibition of PARP. This result was independently confirmed using PARP-1 knockout mouse embryonic fibroblasts that were resistant to ATP depletion and cytotoxicity resulting from ZnPT exposure. In keratinocytes and melanocytes, single-cell gel electrophoresis and flow cytometric detection of γ-H2A.X revealed rapid induction of DNA damage in response to ZnPT detectable before general loss of cell viability occurred through caspase-independent pathways. Combined with earlier experimental evidence that documents penetration of ZnPT through mammalian skin, our findings raise the possibility that this topical antimicrobial may target and compromise keratinocytes and melanocytes in intact human skin.
78 citations
Cites background from "Safety evaluation of zinc 2-pyridin..."
...Topical safety and toxicity profile of this OTC-drug have been studied to some extent previously, and it has been established that ZnPT does not display a potential for primary irritation or sensitization of human skin (Snyder et al. 1965; Brandrup and Menne 1985; Skoulis et al. 1993)....
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...Topical safety and toxicity profile of this OTC-drug have been studied to some extent previously, and it has been established that ZnPT does not display a potential for primary irritation or sensitization of human skin (Snyder et al. 1965; Brandrup and Menne 1985; Skoulis et al. 1993)....
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TL;DR: The authors' conclusion is that zinc pyrithione is not only a safe and effective antimicrobial but that its use in certain alcohol-based formulations results in antimicrobial efficacy exceeding that of iodine and chlorhexidine gluconate.
72 citations
Cites background or methods from "Safety evaluation of zinc 2-pyridin..."
...Of some 1350 compounds screened, ZPT was one of the most active antifungal and antibacterial compounds examined.(20,21) For example, Pityrosporum ovale is thought to play a pathogenic role in skin conditions such as seborrheic dermatitis and dandruff....
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...This led one well-known pharmaceutic company to conduct safety evaluations of ZPT in a shampoo formulation.(21) The result was an antidandruff product, Head & Shoulders (Procter & Gamble, Cincinnati, Ohio) that is currently sold over-the-counter with 1....
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TL;DR: A single chemical dose of dipyrithione was applied to the ventral forearm, forehead, and scalp of human volunteers and no evidence of a significant difference in penetration was noted when (a) the various anatomic sites were compared or (b) intact skin was compared with stripped skin.
Abstract: A single chemical dose of dipyrithione (2,2′-dithiobispyridine-l, 1′-dioxide), 4 or 12 μ/cm2 (containing 1 μCi of 2–6-14C material), was applied to the ventral forearm (intact skin, methyl alcohol vehicle [MeOH]), forehead (intact and stripped skin; cosmetic cream and MeOH vehicle), and scalp (intact and stripped skin; shampoo and MeOH vehicle) of human (white and black) volunteers. The urinary excretion of 14C was measured over the 7-day study period. Percutaneous penetration data were corrected for incomplete urinary recovery using data from intravenous studies (Wedig et al1). The results obtained in this study suggested: (1) means from the complete analysis indicated 34% less (p
50 citations
References
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01 Mar 1948
TL;DR: The method provides means for the rapid test of parallelism of two curves and easy computation of relative potency with its confidence limits and its accuracy is commensurate with the nature of dose-per cent effect data.
Abstract: 1. A rapid graphic method for approximating the Median Effective Dose and the Slope of dose-per cent effect curves is presented. Confidence limits of both of these parameters for 19/20 probability are given by the method. In addition, confidence limits for any other probability or for a dose other than the Median Effective Dose are readily estimated. 2. The data are used throughout the method in their original form without transformation to logarithms and probits. 3. An effective means for plotting and using 0 and 100 per cent effects is provided. 4. The calculations have been simplified by means of nomographs to the extent that a slide rule is a convenience but not a necessity. 5. A simple means is provided for detecting a poorly fitted line or significantly heterogeneous data, In the former case, the line may be refitted; in the latter, the confidence limits are corrected for the degree of heterogeneity. 6. The method provides means for the rapid test of parallelism of two curves and easy computation of relative potency with its confidence limits. 7. Although the method is rapid (10-15 minutes), its accuracy is commensurate with the nature of dose-per cent effect data.
7,221 citations
Journal Article•
TL;DR: In this article, a rapid graphic method for approximating the median effective dose and the slope of dose-per-cent effect curves is presented, and confidence limits of both of these parameters for 19/20 probability are given by the method.
Abstract: 1. A rapid graphic method for approximating the Median Effective Dose and the Slope of dose-per cent effect curves is presented. Confidence limits of both of these parameters for 19/20 probability are given by the method. In addition, confidence limits for any other probability or for a dose other than the Median Effective Dose are readily estimated. 2. The data are used throughout the method in their original form without transformation to logarithms and probits. 3. An effective means for plotting and using 0 and 100 per cent effects is provided. 4. The calculations have been simplified by means of nomographs to the extent that a slide rule is a convenience but not a necessity. 5. A simple means is provided for detecting a poorly fitted line or significantly heterogeneous data, In the former case, the line may be refitted; in the latter, the confidence limits are corrected for the degree of heterogeneity. 6. The method provides means for the rapid test of parallelism of two curves and easy computation of relative potency with its confidence limits. 7. Although the method is rapid (10-15 minutes), its accuracy is commensurate with the nature of dose-per cent effect data.
7,217 citations
125 citations
TL;DR: It is suggested that direct instillation of moderately irritating substances into the rabbit eye is not a satisfactory method for predicting possible hazard, and that new procedures such as the cup-aspirator must be developed and used to enable toxicologists to predict the safety of these materials.
64 citations
TL;DR: The principal objectives of this communication are to demonstrate the activity of some simple mercaptans as an interesting class of water-soluble allergens, the utility of the guinea pig in predicting the allergenicity of new compounds for man, and an improved patch test method which more clearly distinguishes between primary irritation and sensitization in human subjects.
55 citations