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Toxicological information

Carcinogenicity

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Description of key information

Carcinogenicity results are based on the read across substances glycerol or Polyglycerol esters (PGPR). See "Read across report" attached to the dossier.
Key study: 2-year repeated dose study with Polyglycerol Polyricinoleate (PGPR) in rats and mice. Identified NOEL value was ca. 2.5 g/kg b.w. per day based on the overall effects.

Key value for chemical safety assessment

Carcinogenicity: via oral route

Endpoint conclusion
Dose descriptor:
NOAEL
2 500 mg/kg bw/day

Additional information

Carcinogenicity studies with Polyglycerol-3 are not available.However information on the read across substances Polyglycerol Polyricinoleate (PGPR) and glycerol is available.

2-year repeated dose study with Polyglycerol Polyricinoleate (PGPR) in Rats and Mice (key-study):

The carcinogenic potential and chronic toxicity of the food emulsifier ADMUL WOL brand of polyglycerol polyricinoleate (PGPR) was evaluated in rats and mice. Groups of 60 male and 60 female rats were given purified diets containing 5% of either PGPR or groundnut oil for 2 years. Groups of 25 male and 25 female mice were given purified diets containing 5% of either PGPR or groundnut oil for 80 weeks.

The authors state that no carcinogenic effect of PGPR was observed. In addition, dietary PGPR had no adverse effect on growth, food consumption, longevity and hematology. Organ weight analysis revealed an increase in liver and kidney weight in both male and female rats and female mice. Histological analysis of tissues revealed no treatment related adverse effects.As the slightly increased liver and kidney weights were not accompanied by correlating findings, these effects were not considered adverse.

The NOAEL value for carcinogenicity and chronic toxicity for both test species rats and mice was calculated as approx. 2500 mg/kg bw/day based on the overall effects.

Available information on glycerol:

 

Please find hereafter the text on thecarcinogenicityof glycerol (text copied from OECD SIDS dossier of glycerol, page 20):

In a limited and non OECD Guideline 12-24 month dietary study in rats, evidence of malignant neoplasms were reported in 5/26, 1/22, 5/22, 0/22, 0/21, 5/22 and 0/22 animals in controls and at 5%, 10%, 20% (natural glycerol) and at 5%, 10%, 20% (synthetic glycerol). At the top dose, the treatment period was one year. Benign neoplasms were encountered including pheochromacytomas and granulosa cell tumours in 0/26, 2/22, 1/22, 0/22, 4/21, 4/22 and 1/22 animals in controls and at 5%, 10%, 20% (natural glycerol) and at 5%, 10%, 20% (synthetic glycerol), respectively.The authors concluded that glycerol does not initiate tumor development in the rat (Hine 1953).

In male ddY mice administration of glycerol (5% in drinking water during 1-20 weeks) after a single s. c. injection with 4-nitroquinoline 1-oxide (4-NQO) was reported to enhance lung tumor development. Histopathologically most lung tumors were identified as adenomas (Nagahara 1987, Inayama 1986). The mechanism of tumor induction was independent from pulmonary cell kinetics (Nagahara 1987).

Conclusion: No studies conducted to modern regulatory guidelines are available. The studies that are available are therefore of lower quality. No increase in tumor formation was observed in a limited dietary carcinogenicity study in the rat. Data from non-guideline studies designed to investigate tumor promotion activity in male mice suggest that oral administration of glycerol up to 20 weeks had a weak promotion effect on the incidence of lung tumor formation. In the same studies, treatment with glycerol alone (administered in the drinking water) did not result in an increase in the number of tumor bearing mice relative to controls. Overall, these data do not raise concern for carcinogenic potential.

Justification for classification or non-classification

Based on the read-across substance (Polyglycerol Polyricinoleate PGPR) and supporting information (glycerol), Polyglycerol-3 does not possess any carcinogenic properties. No classification as carcinogen is required.