Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0152030 (skin irritation)
 2,146 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Undiluted 2-ethylhexanol (2-EH) was administered by occluded dermal application for 6 hr per day on Gestation Days 6 through 15 to pregnant Fischer 344 rats, in range-finding (R) and main (M) studies. The dermal route is considered to be the most relevant for human exposure. Treatment levels were (R) 0.0, 0.5, 1.0, 2.0, and 3.0 ml/kg/day (equivalent to 0, 420, 840, 1680, and 2520 mg/kg/day) and (M) 0.0, 0.3, 1.0, and 3.0 ml/kg/day (equivalent to 0, 252, 840, and 2520 mg/kg/day). Controls (0.0 ml/kg/day, sham controls) received deionized water at 3.0 ml/kg/day. Dermal-positive control groups received undiluted 2-methoxyethanol (2-ME) at (R) 0.5 and 1.5 ml/kg/day and (M) 1.0 ml/kg/day as a reference compound in a similar regimen. An oral reference compound, valproic acid, was administered by gavage in the range-finding study on Gestation Days 6 through 15 at 400 mg/kg/day. The range-finding study employed an untreated (naive) control group. Numbers of plug-positive females per group were (R) 8 and (M) 25. Maternal weight gain was reduced for 2-EH at 1680 (R) and 2520 (R and M studies) mg/kg/day. Exfoliation and encrustation were seen at the application site in both studies at 840, 1680, and 2520 mg/kg. Maternal liver, kidney, thymus, spleen, adrenal, and uterine weights, and gestational and fetal parameters were unaffected by treatment with 2-EH. There were no treatment-related increases in the incidence of individual or pooled external, visceral, and skeletal malformations or variations following the application of 2-EH. The NOAELs for the maternal toxicity of 2-EH were 252 mg/kg/day based on skin irritation and 840 mg/kg/day based on systemic toxicity. The developmental toxicity NOAEL was at least 2520 mg/kg/day, with no teratogenicity. Administration of 2-ME at 840 mg/kg/day resulted in reduced maternal weight gain and food consumption, increased postimplantation loss, reduced numbers of live fetuses per litter, and reduced fetal body weights per litter. The incidence of fetal malformations and variations was increased. Oral administration of VPA produced maternal toxicity, developmental toxicity, and teratogenicity. The Fischer 344 rat is thus susceptible to known rodent teratogens by both the dermal and oral routes. It is concluded that 2-EH is not developmentally toxic by the dermal route in the Fischer 344 rat at and below treatment levels which produce maternal toxicity.
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PMID:The developmental toxicity of 2-ethylhexanol applied dermally to pregnant Fischer 344 rats. 151 73

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