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Description of key information

No toxicokinetic studies have been reported for slack waxes, either carcinogenic or non-carcinogenic feed-stock. Read-across data on refined waxes, base oils, and individual aliphatic constituents is used to inform on the toxicokinetics of slack waxes.

There are a number of studies that indicate that highly refined base oils are absorbed from the gut, are distributed to the liver, kidneys, and mesenteric lymph nodes, and excreted primarily via faeces. Mineral hydrocarbons (including lubricant base oils) are chemically inert, and, when ingested, most of the mineral oil (98%) remains unabsorbed in the faeces. Data from studies of “Highly Refined Mineral Oil” (white oil) suggests that small amounts of mineral oil (~2%) are absorbed as such by the animal or human intestinal mucosa and further distributed throughout the body. In toxicokinetic studies analysing tissue distribution paraffin and hydrocarbon 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.

Key value for chemical safety assessment

Bioaccumulation potential:
low bioaccumulation potential
Absorption rate - oral (%):
10

Additional information

Read across justification

No toxicokinetic studies have been conducted with slack waxes (carcinogenic or non-carcinogenic feed-stock). However, toxicokinetic studies of paraffin and microcrystalline waxes, and highly refined base oils are summarized in this review for reference to the primary components of slack wax. Slack waxesare similar in composition to paraffin wax and highly refined lubricant base oils (white oils), so similar toxicokinetic properties would also be expected. 

 

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. A large proportion 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 different pharmacokinetic activity.

In a key tissue distribution toxicokinetic study (Smith et al. 1996), 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. 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 a 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 supporting toxicokinetics study (Halladay et al. 2002) 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. Blood, urine, faeces, liver, and mesenteric lymph nodes were analyzed for the radiolabeled test substance and it 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 in 96 hours 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 supporting tissue disposition study (Low et al. 1992) 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. 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.

 

Mineral hydrocarbons (including lubricant base oils) are chemically inert, and, when ingested, most of the mineral oil (98%) remains unabsorbed in the faeces. Data from studies of “Highly Refined Mineral Oil” (white oil) suggests that small amounts of mineral oil (~2%) are absorbed as such by the animal or human intestinal mucosa and further distributed throughout the body. A very small fraction may undergo further biochemical transformation. Three studies (Albro and Fishbein, 1970, Baldwin et al. 1992, and Ebert et al. 1966) were identified to assess the toxicokinetic activity of highly refined base oils. 

 

In a key basic toxicokinetic study (Baldwin et al. 1992), hydrotreated white oil was mixed with the diet of male and female rats in concentrations of 0, 10, 100, 500, 1000, 5000, 10000, and 20000 ppm for a period of 13 weeks. After sacrifice, haematological, clinical chemistry, gross necropsy, tissue residue, and histopathological examinations were performed. There were no mortalities or adverse effects associated with feeding the rats oleum-treated white oil. Treatment related effects were generally dose-related and more marked in females than in males. After 90 days of treatment moderate multifocal granulomatous changes in mesenteric lymph nodes and liver were observed. Oleum-treated oil caused a greater pathological response then hydrotreated white oil. The hydrotreated white oil (applicable to sufficiently refined hydrocarbons, IP 346 < 3%) is metabolized to the corresponding fatty acids of the same carbon chain length as the parent carbons, suggesting omega oxidation.

 

One supporting toxicokinetics study (Albro et al. 1970) evaluated absorption of hydrocarbon mixtures (IP 346 <3%). Simple mixtures of aliphatic hydrocarbons were administered to rats by gastric intubation at dose levels of up to 500 mg/kg b.w. The percentage retention of the aliphatic hydrocarbons was inversely proportional to the number of carbon atoms and ranged from 60% for C14 to 5% for C28 compounds. The major site of absorption was found to be the small intestine.

 

A supporting toxicokinetics study performed by Ebert et al. 1966 evaluated distribution of tritiated mineral oil (IP 346 <3%) administered orally and via i.p. injections. Male and female rats were dosed with 0.66 mL of radiolabeled mineral oil for thirty-one consecutive days. Radioactivity was measured in extracted tissues after sacrifice. Results indicate that radioactivity is primarily found in liver, fat, kidney, brain, and spleen. Both oral and i.p. routes of administration exhibited the same characteristics of absorption.

 

The Ebert et al. 1966 study also evaluated excretion of tritiated mineral oil (IP 346 <3%) administered orally and via i.p. injections. Male and female rats were dosed with 0.66 mL of radiolabeled mineral oil for thirty-one consecutive days. Urine and faeces were collected and stored daily for radioactivity analysis. 80% of the tritiated mineral oil administered orally was not absorbed but rather excreted in the faeces two days after treatment. Only 11% of the total dose administered by i.p. injection was excreted in the faeces during the first 8 days of the study.