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Description of key information

Paraffin and hydrocarbon waxes were found to be of low acute toxicity by the oral, and dermal routes.  There are no reports of acute inhalation toxicity studies of paraffin and hydrocarbon waxes; however, due to the very low vapour pressures of these substances, exposure by inhalation is not expected.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 500 mg/kg bw/day
Study duration:
chronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

Paraffin and hydrocarbon waxes were found to be of low acute toxicity by the oral and dermal routes. There are no reports of acute inhalation toxicity studies of paraffin and hydrocarbon waxes; however, due to the very low vapour pressures of these substances, exposure by inhalation is not expected. For the dermal repeat dose toxicity endpoint, data was read across from lubricant base oils because of similarities to the feedstocks used to produce finished paraffin and hydrocarbon waxes.

 

Among the repeated dose toxicity data are results of a number of 90-day repeat oral studies of paraffin and hydrocarbon waxes. Few findings were noted in these studies, and those that were regarded as toxicologically important to rats were not judged to be relevant to humans. For purposes of human health risk assessment, the no observed adverse effect level (NOAEL) was the highest concentration tested (2% in the diet), equivalent to approximately 1500 mg/kg/day. No repeated dermal or repeated inhalation studies of paraffin or hydrocarbon waxes have been reported.

 

In a 90-day oral feeding study, three different waxes (low melting point wax, high melting point wax, and high sulphur wax) were administered to rats at dose levels of 0.002, 0.02, 0.2, or 2.0% in diet (equivalent to approximate average daily consumption values of 1.5, 15, 150, 1500 mg mineral hydrocarbon/kg body weight/day) for 90 days. In general the magnitude of effects was greatest with the low melting point wax. The high melting point wax and high sulphur wax were without effect. Accordingly, the overall no observed adverse effect level (NOAEL) for high melting point wax and high sulphur was is the highest concentration tested (2% in the diet) or approximately 1500 mg/kg bw/day. Almost without exception, the effects seen during the study were much more severe in females than in males. For the low melting point wax, the NOAEL is equal to 0.002% in diet (equivalent to 1.5 mg/kg/day) for males and females based on histiocytosis in the mesenteric lymph nodes, granuloma in the liver, and inflammation of cardiac mitral valve.

 

In a second study, 3 waxes designated as low melting point wax, a 1:1 mix of low and high melting point wax, and intermediate melting point wax were administered via the diet (at 2% only, at 0.02, 0.2, and 2.0%, and at 0.02, 0.2, and 2.0%, respectively). There were no effects on food intake, growth rate, or clinical conditions of animals fed paraffin waxes (low melting point wax, intermediate melting point wax or mixed melting point wax).  Changes in the liver, mesenteric lymph nodes, and the cardiac mitral valve were considered to have been treatment-related. The effects were dose-related, more severe in females than males, and greater with low melting point wax than either of the other two. 

 

In a 90-day dietary feeding study to compare the effects of paraffin wax in Fischer-344 and Sprague-Dawley rats. Female rats were fed diet containing low melting point wax at concentrations of 0, 0.2% or 2.0%.  There were no treatment-related effects on survival, clinical signs, body weight gain, or food consumption with low melting point wax in either rat strain. Treatment-related changes either occurred only in Fischer-344 rats or were considerably more severe in Fischer-344 rats than in Sprague-Dawley rats.  A NOEL was not established experimentally in either strain; however, the results demonstrated the differential response to dietary mineral hydrocarbon between rat strains.

 

Differential effects of dietary exposure to 2% low melting point wax on female Fischer-344 and Sprague-Dawley rats was also examined in a 60-day study.  While mean body weights were not affected in either strain throughout the course of the study, a number of changes within the livers of Fischer-344 rats were observed, but not in livers from Sprague-Dawley rats.  Total white blood cell and neutrophil counts were significantly elevated in blood of Fischer-344 rats.  The observed differences in KC function between the two species may account for the strain differences in the response to low melting point wax. No significant changes in these functions were observed in KC isolated from Sprague-Dawley rats exposed to low melting point wax or from control rats. A NOEL was not established from this study.

 

In 28- and 90-day feeding studies, groups of female Fischer-344 rats were administered 0 or 2% low melting point wax.  There were no overall differences in body weight during the course of either the 28- or 90-day studies. At the end of the 28-day feeding study, a statistically significant increase in absolute and relative weights of the mesenteric lymph nodes was seen in the group of rats given low melting point wax. At the end of the 90-day study, statistically significant increases were seen in absolute and relative weights of the livers and spleens in the low melting point group over the control group. Both the proximal and distal mesenteric lymph nodes showed statistically significant increases in absolute and relative weights in the low melting point group.  A NOEL was not established from this study.

 

A series of 180-day feeding studies in rats were performed on chewing-gum bases containing hydrocarbon wax in proportions ranging from 2 to 57% of the gum.  Calculated feeding levels for the waxes were reported to vary from 0.16% to 4.75% of the diet.  Test animals were fed diets consisting of 75% basal diet, 8.3% gum base, and 16.67% wood flour.  No treatment-related effects were observed from these studies.

 

In a long-term repeat-dose toxicity study, 5 types of paraffin wax were tested in male and female Sprague-Dawley rats over a 2-year period at a dose of 10% in diet given ad libitum. No pathologic finding attributable to the treatment was observed in rats fed 10% wax in their diet for a period of two years and then observed until their deaths. The incidence of tumours observed is consistent with that in untreated controls. No other toxic effects were found at histological examination and the survival rates and average weights show no abnormality. This study indicates that the five waxes tested by feeding at the level of 10% in the diet in rats are devoid of carcinogenic or other toxic action by this route of administration.

 

In 2001, a panel of medical and veterinary pathologists was convened to review published and unpublished reports dealing with studies of various white mineral oils and waxes in both Fischer-344 and Sprague-Dawley rats. They also examined histological slides from both subchronic and chronic studies of certain mineral hydrocarbons (90-day oral study of low melting point wax in female Fischer-344 and Sprague-Dawley rats; 90-day studies of low viscosity (P15) and medium viscosity (P70) white oil and high melting point wax in male and female Fischer-344 rats, and 24 month study of P70 white oil in male and female Fischer-344 rats). The Panel also reviewed mineral oil-induced alterations in tissues of human patients (liver, hepatic lymph node and spleen). The panel agreed that certain of the mineral hydrocarbons (MHCs) produced lesions in the mesenteric lymph nodes and liver of the Fischer-344 rat and these lesions were best described as microgranulomas/granulomas. The lesions were fundamentally similar in both organs, although varying in severity with dose and type of MHCs. The panel agreed that hepatic lesions with inflammatory cell infiltration, necrosis, and fibrosis were produced only by feeding of low melting point wax and that the lesions were confined to Fischer-344 rats; and not found in Sprague-Dawley rats. The most severe granulomatous lesions in the mesenteric lymph nodes were found in high dose low melting point wax-fed Fischer-344 rats, however, the severity did not differ greatly between control and treated groups, and there was no clear evidence of a dose response. The microgranulomas were similar in subchronic and chronic studies. The panel agreed that some slight reversibility existed for these lesions, but also agreed that the lesions observed in the liver and mesenteric lymph nodes of Fischer-344 rats exposed to MHCs, especially the low melting point wax, were different morphologically from changes observed in lymph node, liver, and spleen of humans that were mineral oil-users. (These changes in humans are usually found incidentally in tissues taken at biopsy or autopsy from the general population). The Panel agreed that a minimal severity infiltrate of mononuclear inflammatory cells occurred in the base of the cardiac mitral valve in a slightly increased incidence in Fischer-344 rats fed low melting point wax. The Panel concluded that these mitral valve alterations had little, if any, toxicological significance as the focal infiltrate was minimal in severity, occurred in controls, occurred in association with murine cardiomyopathy (frequent in Fischer-344 rats), and was unlike the responses in the liver and mesenteric lymph nodes.

 

The overall conclusions of the panel were that the MHC-associated alterations in humans are ubiquitous, present after a certain age in most, if not all humans, and consist of intra-and-extra-cellular oil droplets with a minimal macrophage (including giant cells) response. Thus, the granulomatous lesions experimentally induced by MHC-feeding, particularly in the livers of Fischer-344 rats, are an exaggerated toxicological response. The MHC-induced lesions can be considered incidental and inconsequential in humans.

 

In a 28-day read across from lubricant base oils dermal toxicity study, hydrotreated heavy naphthenic distillate was applied to the skin of New Zealand White rabbits three times per week for four weeks at dose levels of 0, 200, 1000, or 2000 mg/kg. Minimal to slight epidermal hyperplasia and hyperkeratosis of the skin were present in two male and two female rabbits treated topically with 2000 mg/kg of hydrotreated heavy naphthenic distillate. A slight to moderately severe multifocal or diffuse hepatocytomegaly accompanied by a minimal to moderate multifocal subacute hepatitis was present in the liver of nine of the ten rabbits treated with 2000 mg/kg hydrotreated heavy naphthenic distillate.

 

In a 90-day dermal toxicity study read across from lubricant base oils (Cruzan 1983, Klimisch score = 1), mineral oil base stock was applied to the skin of Sprague-Dawley rats at a dose level of 0 or 2 g/kg/day for 13 weeks.  Treatment-related pathologies occurred in all groups, were never severe, and included liver enlargement and microscopic skin changes.  The absolute liver weight was 19% larger in males treated with mineral oil base stock than in control males.  The relative liver weight was 17% larger. The skin of most test-treated animals showed epidermal hyperplasia {trace to mild, in excess of that in the controls} and/or trace chronic inflammation of the superficial dermis. Both findings were very minimal in animals treated with mineral oil base stock. The study authors concluded that these findings are not biologically significant.

 

In accordance with Column 2 of REACH Annex VIII, testing by the inhalation route was not conducted as exposure to humans via this route is not expected to occur due to the very low vapour pressure of substances that comprise this category of substances.

 

Justification for classification or non-classification

The repeat dose toxicity of paraffin and hydrocarbon waxes are not classified according to EU guidelines due to the lack of effects at the high doses.