Petrolatum (petroleum), oxidized, calcium salt

Endpoint summary

Description of key information

A read-across approach was used to fill data gaps for sufficiently refined petrolatum using paraffin and hydrocarbon waxes and highly refined base oil (white mineral oil) analogs. Primarily the basis for the read-across is the similar physical chemical properties shared by the sufficiently refined petrolatum and paraffin and hydrocarbon waxes and highly refined base oils (white mineral oil). 
In toxicokinetic studies analyzing tissue distribution, paraffin and microcrystalline waxes accumulated in the greatest amounts in the liver and mesenteric lymph nodes. The majority of the administered dose of these substances is excreted in the urine and faeces. Results indicated that typically around 10% of the total dose gets absorbed.

Additional information

Several criteria justify the use of the read across approach to fill data gaps for sufficiently refined petrolatum using paraffin and hydrocarbon waxes and highly refined base oil (white mineral oils) analogs. Petrolatums are complex substances containing primarily branched and linear paraffinic hydrocarbons with varying amount of naphthenics and aromatics. No toxicokinetic studies have been conducted with petrolatums specifically because petrolatum physical chemical properties are very similar to paraffin and hydrocarbon waxes and highly refined lubricant base oils. This provides the basis for performing a read-across study. 

In toxicokinetic studies analyzing tissue distribution, paraffin and microcrystalline waxes were found in the greatest amounts in the liver and mesenteric lymph nodes and in smaller amounts in the kidneys and spleen following oral exposure. The majority of the administered dose of these substances is excreted in the urine and faeces. Results indicate that typically around 10% of the total dose gets absorbed. Differences in the pharmacokinetic activity of waxes were seen between males and females. Different components of the test substances also exhibit distinct pharmacokinetic activity.

In a key tissue distribution toxicokinetic study (Klimisch score = 2), groups of 4 week old Fischer 344 rats (5 per sex) were fed a control diet or diets containing one of five microcrystalline or paraffin waxes (low melting point wax, intermediate melting point wax, high melting point wax, mix of high and low melting point wax, and high sulphur wax) for 90 days at a concentration of 20,000 ppm (Smith et al. 1996). Extra groups of rats (5 per sex), used to determine whether effects were reversible, were fed control diet or one of 5 waxes for 90 days followed by exposure to control diet only for an additional 28 to 85 days. The waxes were distributed mostly in the liver, mesenteric lymph nodes, and perirenal fat. Less than 0.1 mg/g was distributed in the spleen and kidneys. Accumulation of the waxes in the liver and mesenteric lymph nodes was greater in females than males. After an 85 -day reversal period, the accumulation levels in the liver decreased by 80 to 90%. However, there was minimal reduction of the wax accumulation in the mesenteric lymph nodes after a 28 -day reversal period. Data from the 85 -day reversal period in the mesenteric lymph nodes was not available.

A key toxicokinetics study (Klimisch score = 2) measured distribution, excretion, and metabolite activity in female Sprague-Dawley and F-433 rats orally administered by gavage either 1.8 g/kg or 0.18 g/kg of [1 -14C]1 -eicosanylcyclohexane, a mineral hydrocarbon, in olive oil (Halladay et al. 2002). Blood, urine, faeces, liver and mesenteric lymph nodes were analyzed for the radiolabeled test substance and its metabolites. Livers and mesenteric lymph nodes of F-344 rats retained a greater percentage of mineral hydrocarbons than did Sprague-Dawley rats. Faecal excretion was the major route of elimination for both strains and doses. 92 and 88% of the administered high dose was recovered after 96 hours in the F-344 and Sprague-Dawley rats, respectively. The amount of radioactivity removed in the urine was dose-dependent in both strains. The major urinary metabolite identified in both Sprague-Dawley and F-344 rats was 12 -cyclohexyldodecanoic acid. 10 -cyclohexyldodecanoic acid was also identified.

In a key tissue disposition study (Klimisch score = 2) male and female F-344 rats were fed a diet of 20,000 ppm dose (2% w/w) of naphthenic white oil with radiotracer surrogates for each chemical class, during a one hour feeding session (Low et al. 1992). Cycloparaffin, isoparaffin, and n-paraffin components of the white oil were radiolabelled and accumulation was analyzed in the liver, mesenteric lymph nodes, spleen, adipose tissue, brain, blood, urine, and faeces. Three animals were sacrificed at 2, 4, 8, 16, 24, 48, and 72 hours. Results indicate that n-paraffins are less readily absorbed than either cycloparaffins or isoparaffins. Cycloparaffins are the most extensively absorbed component of the white oil, they are found at higher concentrations in the liver and mesenteric lymph nodes than isoparaffins. There was so significant difference in the absorption and distribution response of males and females.