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Toxicological information

Carcinogenicity

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Description of key information

The carcinogenic potential of petrolatums is associated with the biologically available/active constituents such as polycyclic aromatic constituents (PAC) found in the entrained oil of these substances. Severely refined petrolatums, produced from feedstocks from which the aromatic constituents have been removed are not carcinogenic. In contrast, carcinogenic potential of insufficiently refined petrolatums may vary depending on the degree of refining severity of feedstocks and their resulting PAC contents.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
5 000 mg/kg bw/day
Study duration:
chronic
Species:
rat

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Study duration:
chronic
Species:
mouse

Additional information

The carcinogenic potential of petrolatums is associated with the biologically available/active constituents such as polycyclic aromatic constituents (PAC) found in the entrained oil of these substances. Severely refined petrolatums, produced from feedstocks from which the aromatic constituents have been removed are not carcinogenic. In contrast, carcinogenic potential of insufficiently refined petrolatums may vary depending on the degree of refining severity of feedstocks and their resulting PAC contents.

 

No inhalation carcinogenicity studies have been reported with petrolatums or similar materials.  

 

Insufficiently Refined Petrolatum (Carcinogenic or Unknown Feed-stock)

 

No oral carcinogenicity studies have been reported with insufficiently refined petrolatum or similar materials. 

In a key dermal carcinogenicity study (Oser et al., 1965) three pharmaceutical and food-grade petrolatum blends were administered subcutaneously into the interscapular region of Swiss-Webster mice. Each mouse was given a single subcutaneous injection of 100 milligrams of the petrolatum blends. A group of 200 rats served as a control and were injected with stripped lard. These animals were observed for 18 months at which time a range of tissues were examined for gross and microscopic changes. There was no specific relationship between tumour incidence and the treatment. Some effects were observed that may have been treatment-related. Chronic inflammatory or fibrotic responses were present in the lymphatic system at the 9- and 12-month periods, but not at 18 months. The site of injection revealed evidence of residual petrolatum with some degree of encapsulation at the 9- and 12-month periods, but not at 18 months. Subcutaneous injection of a 100 mg dose of either of the 3 petrolatum blends was not considered to elicit a carcinogenic response in mice.

In a key read-across carcinogenicity study (Smith et al., 1951), eight crude slack waxes containing 12-29% aromatic mineral oil were tested in a lifetime mouse skin painting study. Approximately 15 milligrams of molten slack waxes were applied 3 days per week to the backs of groups of 30 male albino mice. At 250 days, benign tumours were observed in mice treated with 6 of the 8 waxes and of these malignant tumours had developed in 2 groups. At 450 days, benign tumours had developed in all groups, and malignant tumours had developed in 5 of the 8 wax-treated groups. It was concluded that the slack waxes were weakly carcinogenic.

Supporting data is also available from studies conducted using soft paraffin and yellow vaseline (Schmahl and Reiter, 1953) and slack wax (Dietz et al., 1952). When injected, soft paraffin and yellow vaseline were observed to have a weak, but distinct carcinogenic effect. However, soft paraffin when administered in the feed was negative. Slack waxes were also shown to have a weak carcinogenic effect with the residual oils in slack wax considered responsible for the carcinogenic effects.

Sufficiently Refined Petrolatum (Non-carcinogenic Feed-stock)

There have been several studies on sufficiently refined petrolatums (oral and dermal).  

In a key oral carcinogenicity study (Oser et al., 1965), three pharmaceutical and food-grade petrolatum blends were tested in FDRL rats. To conduct the study, 50 FDRL rats of each sex, individually housed, were given ad libitum access to diets containing 5% (5000 mg/kg/day) of each of the three petrolatum blends for 2 years. A group of 100 rats of each sex served as controls and was fed normal diet that had been supplemented with 1% vitamin mix and 0.2% Aurofac 10. The animals were observed daily for appearance, behaviour and survival. Weekly measurements were made of body weight for the first 12 weeks of the study, and weights were measured biweekly thereafter. Weekly measurements were also made of food intake for the first 12 weeks. Measurements of haematological parameters were made at 12, 26, 52, 72 and 100 weeks. Surviving rats were sacrificed at scheduled termination. These, as well as, rats dying spontaneously were necropsied, and weights of the liver, kidneys, spleen, heart, adrenals, thyroids and pituitary were recorded. Several organs were removed for microscopic examination. Growth rates were unaffected, and there were no differences in survival. There were small, statistically significant differences in food efficiency, but these were judged to have not been toxicologically important. Haematological and clinical parameters were unaffected by treatment. There were no differences at necropsy between petrolatum-exposed and control animals. Furthermore, there were no histological changes that could be attributed to dietary exposure to petrolatum. Finally, none of the petrolatum blends caused an increase in tumour incidence in any tissue or organ examined. Accordingly, petrolatum was judged to be non-carcinogenic following oral administration.

A key read-across oral carcinogenicity study (Shubik et al., 1962) was conducted on five paraffin waxes (3 of the waxes were microcrystalline and the other two were unidentified). The paraffin waxes were selected on the basis of aromatic content and represented the range of material available in commerce at the time of the study (~ 1960).  Each of the paraffin waxes was ground into powder and added to the feed in a 1:9 w/w proportion.  Each of the five waxes was fed ad libitum to male and female Sprague-Dawley rats (50 -55/sex) at a dietary concentration of 10% for 2 years.  An additional group of 140 male and 157 female rats were fed a control diet.

The rats were inspected and weighed every second week, and all gross lesions were recorded.  This was continued until all the rats died or were sacrificed moribund, then the animals were submitted to a complete autopsy followed by histological examination of all abnormal tissues. Survival rates and growth rates were unaffected by oral exposure to any of the waxes tested.  A number of tumours were found in all groups at necropsy.  The most common tumours were those of the mammary regions (fibrocarcinomas, adenocarcinomas, fibromas, and sarcomas), of the adrenal glands (cortical adenomas with a few carcinomas and pheochromocytomas) and of the pituitary.  The number of tumour-bearing animals and the incidence of tumours of each type were similar across groups.  No other toxic effects were found at histological examination. The authors concluded that the five paraffin waxes were devoid of carcinogenic or other toxic action when fed at a level of 10% in the diet (Shubik et al., 1962). Based on the body weights, this equates to a daily dose of approximately 5700 mg/kg/day.

In a key dermal carcinogenicity study (Kane et al., 1984), carcinogenicity of severely refined petrolatum (CAS No. 8009-03-8) was evaluated as part of a series of mouse skin painting bioassays with 46 clearly defined samples of refinery streams associated with lubricant base oil processing. Male C3H mice, 6 to 8 weeks old, were allowed to acclimate and were housed individually or in small groups. The animals were shaved biweekly, and the undiluted test material was applied to the shaven interscapular regions. The petrolatum that had been produced by a solvent extraction process was painted on the skin of 50 male C3H mice at 25 milligrams twice weekly for 80 weeks. Positive control groups were treated with solutions of benzo(a) pyrene, and negative control groups included an inactive oil-treated group and a no-treatment group. No tumours developed in any of the mice to which the highly refined petrolatum was applied. The study was repeated in 25 animals using the same application dose of 25 mg/application, twice weekly for 80 weeks, and, again, none of the animals developed tumours.

In another key dermal carcinogenicity study (Lijinsky et al., 1966), amber petrolatum (NF grade) was evaluated for carcinogenicity in Swiss mice. The petrolatum was dissolved in isooctane to make a 15% solution and applied twice weekly to the skin of 40 male and 30 female mice throughout the life of each animal. A control group of 50 males and 50 females received skin application of isooctane only. Tumour incidence in the petrolatum-treated group (5 tumours in three animals, 3 tumours regressed) was similar to that from the vehicle control group (2 tumours in two animals).  It was concluded that amber petrolatum was not carcinogenic.

Supporting dermal carcinogenicity data is available from a read-across lifetime skin painting carcinogenicity study of paraffin waxes (Shubik et al., 1962) in mice and rabbits. In this study five paraffin waxes were selected from 36 samples on the basis of their ultraviolet absorptivity, representing the range of aromatic contents. Each of the five waxes was dissolved in warm benzene to achieve 15% solutions. The five waxes tested did not demonstrate any carcinogenic potential via dermal exposure in either sex of mice.

Justification for selection of carcinogenicity via oral route endpoint:

One of two available oral carcinogenicity studies.

Justification for selection of carcinogenicity via dermal route endpoint:

One of 7 available dermal carcinogenicity studies.

Carcinogenicity: via dermal route (target organ): other: skin

Justification for classification or non-classification

Sufficiently Refined Petrolatum (Non-carcinogenic Feed-stock)

Sufficiently refined petrolatums are not classified for carcinogenicity according to EU guidelines. Refined petrolatum were found to be non carcinogenic in oral carcinogenicity study in rats and dermal exposure studies in mice and do not meet the EU criteria for classification.  

Insufficiently Refined Petrolatum (Carcinogenic or Unknown Feed-stock)

Insufficiently refined petrolatums were found to produce skin tumours in mice following dermal exposure and meet the criteria for classification as Carcinogen 1B (H350) according to EU CLP Regulation (EC No. 1272/2008).