Registration Dossier

Administrative data

Description of key information

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
2 000 mg/kg bw/day
Study duration:
chronic
Species:
rat
Quality of whole database:
To determine the potential of the test substance to produce systemic toxicity when administered repeatedly, the public available literature was checked for sientific papers. Two carcinogenicity tests performed in rats (2y) and in mice (80 wk) with the source substance Polyglycerol polyricinoleate (PGPR), i.e. the read across substance, are available. Justification of read-across: Both chemicals are of comparable structures and can be characterized as esters of polyglycerol and fatty acids and undgo the same metabolism (Refer to Read Across Justification presented in Section 13).
Justification of reliability of 2: scientifically well-performed study

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 study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

A read across approach is used to fill the data gap for subchronic toxicity.The read-across to PGPR is justifed as both chemicals are of comparable structures. They can be characterized as esters of polyglycerol and fatty acids and undergo the same metabolism (Refer to "Read Across Justification" presented in Section 13).

No adverse effects were observed in rats after 45 week feeding a diet containing 9 % PGPR (source substance).

Haematological parameters were not affected. No effects on organ weight (kidneys, spleen, testes, adrenals and pituitary) were observed. The livers of rats fed 45 weeks were heavier but not the livers from animals fed 30 weeks (Wilson et al., 1998). In a separate experiment (Wilson et al., 1998) DNA of livers was determined to distinguish between hyperplasia and hypertrophy. The total DNA content of enlarged livers was not increased indicating that enlargement was not due to an increase in the number of parenchymal cells (hyperplasia). Therefore, the findings of increased liver weight are considered to be an physiological effect of adaptive metabolic response.

The findings are supported by two carcinogenicity tests (Smith et al., 1998) performed in rats (2 y) and in mice (80 wk) with the read across analogue substance Polyglycerol polyricinoleate (PGPR) (i.e. source substance). Rats and mice received purified diets containing 5 % of PGPR. No carcinogenic effect of PGPR was observed in rats and mice. In addition, dietary PGPR had no adverse effect on growth, food consumption, longevity and haematology. 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. The effect on liver weight might be interpreted as adaptive physiological response. Based on the results, it was concluded that treatment of 5% (approx. 2500 mg/kg bw/day) in the diet did not induce adverse effects in rats and mice.

During 1964 to 1965, PGPR (source chemical) was fed to 19 human volunteers (8 male and 11 female). Subjects received a diet containing constant levels of fat and protein. During the first week the subjects received a diet without PGPR, then 5g PGPR/day was fed in the second week and 10 g PGPR/day was fed in the third week. PGPR was fed in soups, cakes and toffee bars. Fat balance and blood tests showed that digestion, absorption and excretion of PGPR took place and no consistent effect of PGPR on various parameters was observed (Wilson R. and Smith M., 1998).The quantities consumed, up to 10 g/day, was equivalent to approximately 63 times the estimated maximum per capita mean daily intake by man of 2.64 mg/kg body weight/day [FAC (1992) Food Advisory Committee Report on the Review of the Emulsifiers and Stabilisers in Food Regulations FdAC/REP/11. pp. 1-71. HMSO, London]. It is therefore concluded from this study that the consumption of ADMUL WOL, a brand of PGPR, has no adverse effects in man.

Furthermore, the source chemical PGPR is well assessed as food additive. Polyglycerol esters of fatty acids have been evaluated for acceptable daily intake by the Joint FAO/WHO Expert Committee on Food Additives in 1966. In its evaluation of PGPR in 1974, the Joint FAO/WHO Expert Committee on Food Additives (JECFA 17th report) considered that the rat reproduction study (Wilson R. and Smith M., 1998), with a dietary level of PGPR of 1.5%, should be used to estimate an acceptable daily intake (ADI) of PGPR for man since the study showed a no-effect level for liver enlargement. Accordingly, a rat intake equivalent to 750 mg PGPR/kg body weight was used to set the ADI for PGPR of 7.5 mg/kg body weight. This intake is more than maximum likely from the use of PGPR in tin-greasing emulsions or in block chocolate and chocolate couverture.

No study is provided for the systemic inhalation toxicity. Inhalation of the registered test substance is unlikely due to the following reason: The vapour pressure is very low with 0.001 Pa (20°C). During manufacturing and processing inhalation exposure is unlikely due to efficient control measures in place.

No study is provided for the systemic dermal toxicity. Systemic exposure via repeated dermal application of the registered test substance is considered to be of no concern due to the following reason: The manufacture is performed in closed systems. The test substance is shown to be of low acute and systemic toxicity. Even when absorbed through the skin, due to the demonstrated low systemic toxicity of the test item it would be of no concern. Further, the test substance is not a skin irritant or skin sensitizer, neither in rats nor in human (patch tests). This assumption is well supported by the finding that the analogue source chemical PGPR is well evaluated and used as food additive.

Based on the similar structure and the same metabolism of both the target and source chemical (refer to Section 13: “Justification for Read Across”) and taken all the available data on repeated dose toxicity with the source chemical together, it is considered that the target substance is of low toxicity. Therefore, the NOAEL for repeated dosing is determined to be 2000 mg/kg bw/day. This value will be used as NOAEL for the repeated oral toxicity of the target chemical.

Justification for classification or non-classification

Based on the results from the available repeated dose toxicity data, it is concluded that the registered substance is not subject to classification and labelling according to the criteria of the EU Dangerous Substances Directive (67/548/EEC) (DSD) and of the EU Classification, Labelling and Packaging Regulation (1972/2008/EC) (CLP).