Protective creams fail to prevent solvent-induced cumulative skin irritation - results of a randomized double-blind study.

BACKGROUND: Occupational skin contact with lipophilic substances is a risk factor for the development of irritant hand dermatitis. Skin protection creams form part of the personal protective equipment, and some are claimed to protect against lipophilic irritants. However, their benefit against solvents is under debate. OBJECTIVES: To evaluate the efficacy of barrier creams claimed to protect against lipophilic irritants in a newly developed repetitive irritation model. METHODS: Thirty-five healthy volunteers were enrolled in a double-blind, randomized study, and six barrier creams were evaluated against irritation induced by two occupationally relevant model solvents, n-octane and cumene. Clinical scoring and bioengineering methods (capacitance and transepidermal water loss measurements) were used to quantify the irritant reactions. RESULTS: None of the test products offered protection against n-octane-induced clinical irritation or stratum corneum dehydration. One test product significantly aggravated the skin irritation induced by both irritants, and a second one enhanced dehydration induced by n-octane only. CONCLUSIONS: The lack of efficacy and the aggravation of skin irritation induced by two of six test products stress the need for standardized efficacy testing of occupational skin protection products.

The fate of inhaled octane and the nephrotoxicant, isooctane, in rats.

To determine if inhaled nephrotoxic branched and nonnephrotoxic straight chain alkanes differ substantially in their biological fate, male F344 rats were exposed to 14C-labeled isooctane and octane vapors at approximately 1 and 350 ppm by the nose-only mode for 2 hr. Radioactivity in exhalant, urine, and feces was determined for 70 hr post exposure, after which residual radioactivity in the rat carcasses was determined. Absorbed [14C]isooctane equivalents were eliminated almost exclusively via the kidneys, while absorbed [14C]octane equivalents were excreted about equally via the kidneys and as 14CO2. Kidney excretion of isooctane-introduced 14C was protracted over the entire 70 hr postexposure observation period whereas for octane-introduced 14C, kidney excretion was essentially complete after 10-20 hr. About 5% of the [14C]octane equivalents inhaled at 1 ppm remained in the carcass 70 hr after inhalation exposure. Two percent of the [14C]octane equivalents inhaled at 350 ppm and 1-2% of the [14C]isooctane equivalents inhaled at either 1 or 350 ppm remained in the carcass 70 hr after inhalation exposure. The different patterns of excretion of metabolites of isooctane compared to octane may be a factor affecting the differences in nephrotoxicity between these two compounds.

Histopathology and cell proliferation induced by 2,2,4-trimethylpentane in the male rat kidney.

Unleaded gasoline causes acute and chronic nephrotoxicity and renal tumors in male rats, but not female rats or mice of either sex. An active nephrotoxic component of unleaded gasoline has been identified as 2,2,4-trimethylpentane (TMP). The first objective of this study was to characterize light microscopic renal lesions induced in male F344 rats by a 21-day gavage regimen of 50 to 500 mg/kg TMP. The second objective was to localize and quantitate sites of renal cell proliferation induced by the same TMP dose regimens using histoautoradiographic analysis after [3H]thymidine incorporation. Light microscopic lesions in the proximal convoluted tubule consisted of protein droplet and crystalloid body accumulation, degeneration, and necrosis, and were similar to lesions noted in previous inhalation and gavage studies with other hydrocarbon compounds. The above renal lesions were not dose-related, although tubular dilation of thin limb segments with granular cell debris was dose-related. In cell proliferation studies TMP induced a non-dose-related five- to sixfold increase in the labelling index of the same proximal convoluted tubule portions (P2 segment) that contained severe crystalloid body accumulation, degeneration, and necrosis. Less pronounced, but statistically significant (p less than or equal to 0.05), increases in cell proliferation were also observed in other nephron segments, indicating a generalized regenerative response of the kidney to TMP. The cytotoxic and regenerative renal effects of TMP administered by gavage suggest that similar mechanisms may be involved in the induction of kidney tumors in male rats following chronic inhalation exposure to unleaded gasoline.