Percutaneous absorption and skin irritation upon low-level prolonged dermal exposure to nonane, dodecane and tetradecane in hairless rats.
Even though the dermal toxicity of hydrocarbon fuels has been well established in the literature, there is little information available on the dermal penetration kinetics and irritation potential of the individual hydrocarbons. The penetration and skin retention of nonane, dodecane and tetradecane was assessed in vitro using hairless rats' skin. The effects of unocclusive dermal exposures of these chemicals (15 microL every 2 h for 8 h a day for four days) on the transepidermal water loss (TEWL) and erythema were measured in CD hairless rats. The expression of interleukin 1alpha (IL- 1alpha) and TNF-alpha in the skin and blood were measured at the end of dermal exposures. The flux of dodecane was 3- and 77-fold higher than nonane and tetradecane. The retention of chemicals in stratum corneum (SC) was in the order of tetradecane > dodecane > nonane, and directly correlated to the log Kp (r2 = 0.9900) and molecular weight of the chemicals (r2 = 0.8782). The TEWL and erythema data indicate that irritation was in the following order: tetradecane > dodecane > nonane. Likewise, the expression of IL-lalpha in the blood and TNF-alpha in the skin after dermal exposures was higher for tetradecane followed by dodecane and nonane compared to control. In conclusion, the aliphatic hydrocarbon chemicals of the present study induced cumulative irritation upon low-level repeat exposures for a four-day period. The affinity of the chemicals to SC and their gradual accumulation in the skin in the present study is the probable cause for the differences in the skin irritation profiles of different aliphatic chemicals. The findings of the present study will be helpful in understanding the skin irritation response of the chemicals in humans; indeed the reality check arises from dermal exposures in humans and human experience in occupational handling of these chemicals.
Babu
R J
RJ
College of Pharmacy and Pharmaceutical Sciences, Florida A & M University, Tallahassee, FL 32307, USA.
Chatterjee
A
A
Ahaghotu
E
E
Singh
M
M
D000279:Administration, Cutaneous; D000473:Alkanes / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000633:toxicity; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D004890:Erythema / Q000139:chemically induced*; D006838:Hydrocarbons / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity*; D066298:In Vitro Techniques; D007375:Interleukin-1 / Q000096:biosynthesis; D008297:Male; D051381:Rats; D012867:Skin / Q000378:metabolism; D012869:Skin Absorption; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis; D014870:Water Loss, Insensible / Q000187:drug effects
D000473:Alkanes; D015415:Biomarkers; D006838:Hydrocarbons; D007375:Interleukin-1; D014409:Tumor Necrosis Factor-alpha; C024713:n-tetradecane; C007548:n-dodecane; C017573:nonane