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Query: UMLS:C0920652 (skin irritant)
 188 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Skin irritation, inflammation and hyperplasia appear to be intimately associated with the phenomenon of tumour promotion, but the mechanism of action remains elusive. Prostaglandins and leukotrienes play an important role in skin inflammation and prostaglandin E(2) (PGE(2)) modulates several events associated with phorbol ester-induced tumour promotion. This study investigated the release of eicosanoids (PGE(2) and leukotriene B(4)) and markers of cytotoxicity [neutral red (NR) uptake and intracellular acid phosphatase (AP) activity], after exposure of rat tongue epithelial (RTE) keratinocyte cultures to chemicals of different irritating and tumour promoting activity. The potent phorbol ester tumour promoter phorbol-12-myristate-13-acetate (PMA), and the less potent, structurally related diterpene ester, mezerein (MEZ) were compared with the known skin irritant sodium dodecyl sulfate (SDS). Cytotoxicity data reflected the in vivo skin irritation potential of the test chemicals and intracellular AP activity was increased after exposure to SDS (160 mug/ml), but did not appear to be increased by the more cytotoxic chemicals PMA and MEZ. Extracellular levels of PGE(2) were increased (200 to > 1000% of control levels) after an 18-hr exposure to PMA or MEZ over a concentration range of 0.01 to 20 mug/ml (NR(50) values 8.0 +/- 6.6 and 15.5 +/- 4.8 mug/ml, respectively). These data indicated that PGE(2) release occurred in the absence of cytotoxicity. In contrast, SDS only elicited PGE(2) release after exposure to 80 mug/ml (a cytotoxic dose level, NR(50) 82.5 +/- 9.9 mug/ml). The potency of a chemical to elicit PGE(2) release in keratinocytes in the absence of a cytotoxic response may reflect intracellular pathways intimately associated with the initiation of an inflammatory response and possibly with tumour promoting activity.
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PMID:Measurement of eicosanoid release in keratinocyte cultures to investigate skin irritation and tumour promoting activity. 2065 89

An in vitro cell culture approach was evaluated for its ability to provide data pertinent to the assessment of skin irritation potential. The hypothesis of this approach is that a direct toxic insult to the epidermal keratinocyte in vivo may lead to release of inflammatory mediators, which are responsible for initiation of a local primary skin irritant reaction. This paper presents data on the cytotoxic potential of a number of structurally unrelated chemicals (chloroform, 2-methoxyethanol, 2-butoxyethylacetate, toluene, 1-butanol, acetaldehyde, n-hexane, sodium dodecyl sulfate, benzalkonium chloride, silver nitrate, dibutyltin dichloride and tributyltin chloride). Cytotoxicity (neutral red uptake and intracellular acid phosphatase activity) of a number of structurally unrelated chemicals, representative of a wide range of skin irritation potential, was evaluated in cultures of rat and human epidermal keratinocytes. The sensitivity of human and rat keratinocytes to the test chemicals was very similar, irrespective of the endpoint of cytotoxicity. The neutral red uptake assay appeared more generally applicable to the diverse range of chemical structures represented in this study, since not all test chemicals elicited an early increase in intracellular acid phosphatase activity. The results were very encouraging, as a good correlation was evident between cytotoxicity in rat keratinocytes and the degree of erythema and oedema associated with an in vivo skin irritant response in rabbits. Keratinocyte cytotoxicity data may provide an indication of the potential of a chemical to induce a severe skin irritant reaction, or if a chemical is more likely to be a marginal or non-irritant. However, the data illustrate that such assays appear unable to discriminate correctly between more subtle classes of irritancy, such as non-irritant, mild, moderate or severe. Available human in vivo skin irritation data were insufficient to conclude which cell type is preferable for evaluation of human skin irritation potential.
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PMID:Use of human and rat keratinocyte cultures to assess skin irritation potential. 2065 Feb 13

Biochemical parameters of cytotoxicity, such as the release of intracellular enzymes, appear to be useful for classification of irritant substances following in vivo chemical insult to the skin. Changes in activity of acid phosphatase (AP), a lysosomal enzyme, appear to parallel the development of the inflammatory response in laboratory animals after treatment with the known skin irritant sodium dodecyl sulphate (SDS). Neutral red (NR) uptake and AP were chosen as endpoints of cytotoxicity. NR and AP were measured in cultures of human epidermal keratinocytes, prepared from separate individuals, and in 3T3 cells following treatment with SDS. The NR(50) value (concentration producing a 50% reduction in NR uptake compared with controls) was similar in both cell types. AP in human keratinocyte cultures exhibited a peak activity, before declining at higher concentrations. This phenomenon was time dependent and was observed within 4 hr of treatment, but was not evident after a 24-hr exposure. The peak produced in 3T3 cells was negligible in comparison. The rate of NR uptake was also studied within the first 4 hr of exposure to SDS, which was comparable to the earlier time points at which AP was determined. The degree of inhibition of NR uptake was greater in human keratinocyte cultures than in 3T3 cells and a response was also elicited at lower dose levels in keratinocytes. AP may be a sensitive indicator of cytotoxicity in human keratinocytes and the data may be interpreted in relation to changes in lysosomal membrane function. This assay may be of value in assessment of skin irritation potential of aqueous soluble surfactants and chemicals that possess the ability to damage biological membranes.
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PMID:Surfactant-induced cytotoxicity in cultures of human keratinocytes and a commercially available cell line (3T3). 2073 18