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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
prior to 1970
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This study was conducted prior to GLP and test guidelines, but sufficient data is available for interpretation of results

Data source

Reference
Reference Type:
secondary source
Title:
Unnamed
Year:
1998
Report Date:
1998

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Groups of rats were dosed with the test material and mortality recorded.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
not specified
Details on test material:
PGPR is prepared in four stages: preparation of the castor oil fatty acids, condensation of the castor oil fatty acids, preparation of polyglycerol and partial esterification of the condensed castor oil fatty acids with polyglycerol.

The castor oil fatty acids are prepared by hydrolysing castor oil with water and steam at 400 psi pressure without any added catalyst after which the resulting fatty acids are freed from glycerol by water washing. Castor oil contains as its main fatty acid component ricinoleic acid (80–90%), and, it is this fatty acid which is important in the condensation reaction. Other fatty acids present are oleic acid (3–8%), linoleic acid (3–7%) and stearic acid (0–2%).

Fatty acid condensation is brought about by heating the castor oil fatty acids at elevated temperatures under vacuum and in an atmosphere of carbon dioxide to prevent oxidation. Samples are taken at regular intervals and tested for their free fatty acid content until an acid value of 35.0 is achieved. This acid value is equivalent to an average of about five fatty acid residues per molecule of the condensed product. During the condensation phase, ricinoleic acid may react in a number of ways as shown in Fig. 1. Simple linear esterification is the desired reaction but cyclic esterification, which is a chain terminating process, is theoretically possible. However, no evidence was found for the presence of this type of cyclic material in the condensed castor oil fatty acids. Dehydration is also possible, but occurs to only a small extent.

The preparation of the polyglycerol is achieved by heating glycerol to temperatures above 200°C in the presence of a small amount of alkali (potassium hydroxide). In this step, two or more molecules of glycerol condense with a loss of water and the formation of an ether linkage between the glycerol molecules. Carbon dioxide is bubbled through the reaction vessel to prevent oxidation, and unchanged glycerol is removed by distillation at the end of the reaction. The process is controlled by monitoring the rise in the refractive index. The result is a mixture of polyglycerols containing varying numbers of glycerol residues. As the 1- and 3-hydroxy groups of glycerol are more reactive than the 2-hydroxy group, the polyglycerols formed are predominantly straight-chain.

In addition, small amounts of cyclic by-products may be formed in the reaction mixture as a result of condensation between the 1-hydroxy group of one glycerol molecule and the 2-hydroxy group of another. The cyclic diglycerol product is a solid (m.p. 96°C), and is present at 4% in the polyglycerol or 0.4% in PGPR.

The final stage of the preparation involves heating an appropriate amount of polyglycerol with the condensed castor oil fatty acids. The reaction takes place immediately following the preparation of the latter and in the same vessel while the charge is still hot. The esterification conditions are the same as those for fatty acid condensation. The process is continued until a sample withdrawn from the reaction mixture is found to have a suitable acid value.

The JECFA specification for PGPR states that “the polyglycerol moiety shall be composed of not less than 75 percent of the di-, tri- and tetraglycerols and shall contain not more than 10 percent of polyglycerols equal to or higher than heptaglycerol” (FAO, 1992).

PGPR is specified further by the following:Hydroxyl value 85–100Acid value 2.0 max.Iodine value 80–90Refractive index at 65°C 1.4635–1.4665.

According to the FDA submission, polyglycerol represents 9% of the starting material used in the esterification of the condensed castor oil fatty acids with polyglycerol.


Test animals

Species:
rat
Strain:
other: Identified as Colworth. Probably Colworth Wistar.
Sex:
male/female
Details on test animals and environmental conditions:
Weanling male and female rats weighing between 77 and 152 grams were used.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Rats were orally gavaged with 20 ml/kg (approximately 20 g/kg) of PGPR
Doses:
20 ml/kg
No. of animals per sex per dose:
55 weanling male and female were dosed with test material. (Number of animals of each sex dosed not specified).

22 weanlings in the control group were intubated with a similar dosage of groundnut oi.
Control animals:
yes
Details on study design:
The acute oral toxicity of the polyglycerol-polyricinoleic acid emulsifier was evaluated by administration of a single oral dose of 20 ml/kg (approx. 20 g/kg) to 55 weanling male and female Colworth rats weighing between 77 and 152 grams. Each of the 22 weanlings in the control group was intubated with a similar dosage of groundnut oil. Due to the high viscosity of PGPR both materials were maintained at 37°C prior to dosing. Animals were observed for 21 days following oral gavage administration.
Statistics:
No additional information available.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 1 800 mg/kg bw
Based on:
other: polyglycerol
Mortality:
No deaths were observed in rats dosed with PGPR.
Clinical signs:
Other than slight diarrhoea in 42 rats dosed with PGPR and 2 rats dosed with groundnut oil no other untoward toxic effects were observed for any of the parameters measured. .
Body weight:
Body weight gains were comparable to control values.
Gross pathology:
There were no gross pathology findings.
Other findings:
Food consumption and absolute organ weights (organs unspecified) were comparable to control values.

Any other information on results incl. tables

No additional information available.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute oral LD50 in rats of polyglycerol is >1800 mg/kg.
Executive summary:

The acute oral toxicity of PolyGlycerol PolyRicinoleic acid (PGPR) was investigated in rats. A group of male and female rats received 20 ml/kg (approximately 20,000 mg/kg) PGPR and were observed for 21 days. (Based on results of metabolism studies, PGPR has been shown to be metabolized in the gut into polyglycerol and polyricinoleic acid. Lower molecular weight polyglycerol is absorbed and excreted unchanged in urine while the higher molecular weight polyglycerols are excreted unchanged in the feces.)

All animals survived with slight diarrhea observed in a number of animals. Based on the amount of polyglycerol present in PGPR, the acute toxicity of polyglycerol is >1800 mg/kg.