PMID- 15451557 OWN - NLM STAT- MEDLINE DCOM- 20041116 LR - 20161124 IS - 0378-4274 (Print) IS - 0378-4274 (Linking) VI - 153 IP - 2 DP - 2004 Nov 2 TI - Assessment of skin irritation and molecular responses in rat skin exposed to nonane, dodecane and tetradecane. PG - 255-66 AB - Aliphatic hydrocarbons constitute a major portion of jet fuels, kerosene and other solvents. This study investigated the effects of dermal exposures of selected aliphatic hydrocarbons (nonane, dodecane and tetradecane) on the skin irritation (erythema), transepidermal waterloss (TEWL) and expression of interleukin-1alpha (IL-1alpha), tumor necrosis factor (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) in the skin and blood of hairless rats. Dermal exposures were carried out by occlusive application of chemicals (230 microl for 1 h, using Hill Top Chambers) for 1 h. The expression of IL-1alpha, TNF-alpha and MCP-1 was measured by enzyme immunoassay (EIA), and the regulatory proteins NFkappaB and IkappaBalpha were measured by Western blot analysis. The skin irritation and TEWL data indicate that the irritation was in the following decreasing order: nonane > dodecane > tetradecane. Likewise, nonane significantly increased the expression of IL-1alpha, TNF-alpha and MCP-1 in skin and blood as compared to control at different time points. Dodecane and tetradecane did not show any increase in the expression of IL-1alpha and MCP-1 as compared to control (P > 0.05), but the expression of TNF-alpha by dodecane and tetradecane was significantly higher than control at all time points. The release of cytokines by nonane exposure was further supported by activation of NFkappaB p65 and corresponding degradation of IkappaBalpha in the skin. In conclusion, this study demonstrates that the biophysical parameters (TEWL and erythema scores) were correlated to the biomarker expressions after dermal exposures with nonane but not with dodecane and tetradecane. Dodecane produced only mild irritation in response to experimental conditions of the present study and further did not show significant differences in IL-1alpha and MCP-1 levels in skin and blood. However, TNF-alpha was well expressed in response to all the chemicals. Tetradecane did not show any visible signs of skin irritation and also did not produce any significant difference in IL-1alpha and MCP-1 release profiles as compared with control. The expression of TNF-alpha in skin due to tetradecane support the fact that visually indistinguishable skin irritation reactions can induce significant changes in the biological marker profile. FAU - Babu, R J AU - Babu RJ AD - College of Pharmacy and Pharmaceutical Sciences, Florida A&M University, Tallahassee, FL 32307, USA. FAU - Chatterjee, A AU - Chatterjee A FAU - Singh, M AU - Singh M LA - eng PT - Journal Article PT - Research Support, U.S. Gov't, Non-P.H.S. PT - Research Support, U.S. Gov't, P.H.S. PL - Netherlands TA - Toxicol Lett JT - Toxicology letters JID - 7709027 RN - 0 (Alkanes) RN - 0 (Biomarkers) RN - 0 (Chemokine CCL2) RN - 0 (I-kappa B Proteins) RN - 0 (Interleukin-1) RN - 0 (Irritants) RN - 0 (NF-kappa B) RN - 0 (Nfkbia protein, rat) RN - 0 (Transcription Factor RelA) RN - 0 (Tumor Necrosis Factor-alpha) RN - 03LY784Y58 (n-tetradecane) RN - 11A386X1QH (n-dodecane) RN - 139874-52-5 (NF-KappaB Inhibitor alpha) RN - T9W3VH6G10 (nonane) SB - IM MH - Alkanes/*toxicity MH - Animals MH - Biomarkers MH - Body Water/metabolism MH - Chemokine CCL2/analysis MH - I-kappa B Proteins/analysis MH - Interleukin-1/analysis MH - Irritants/*toxicity MH - Male MH - NF-KappaB Inhibitor alpha MH - NF-kappa B/analysis MH - Rats MH - Skin/chemistry/*drug effects/metabolism MH - Transcription Factor RelA MH - Tumor Necrosis Factor-alpha/analysis EDAT- 2004/09/29 05:00 MHDA- 2004/11/17 09:00 CRDT- 2004/09/29 05:00 PHST- 2004/02/23 00:00 [received] PHST- 2004/04/29 00:00 [revised] PHST- 2004/04/30 00:00 [accepted] PHST- 2004/09/29 05:00 [pubmed] PHST- 2004/11/17 09:00 [medline] PHST- 2004/09/29 05:00 [entrez] AID - S0378427404002632 [pii] AID - 10.1016/j.toxlet.2004.04.036 [doi] PST - ppublish SO - Toxicol Lett. 2004 Nov 2;153(2):255-66. doi: 10.1016/j.toxlet.2004.04.036.