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Acute Toxicity: oral

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acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Study period:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference Type:
Report date:

Materials and methods

Test guideline
no guideline available
Principles of method if other than guideline:
THIS STUDY was undertaken in order to determine whether there are differences in toxicity between synthetic and natural glycerin and whether synthetic
glycerin would he suitable and safe to use in cosmetic, pharmaceutical, and food
The acute toxicity was compared in rodents by intragastric administration to
mice, guinea pigs, and rats and by application to the skin of rabbits. Chronic
toxicity was evaluated by feeding rats for two years on diets containing 5,
10, or 20% of glycerin. The response of skin to chronic exposure was determined
by applying glycerin to the skin 'of rabbits repeatedly over a period of 18 weeks.
Guinea pigs were used for sensitization tests, and rabbits for determining ocular
The synthetic glycerin used was a commercial product manufactured by the
Shell Chemical Corporation from propylene and chlorine by a number of different
unit processes, including chlorination, chlorohydrination, and hydrolysis. These
processes are depicted in the flow diagram. A series of purification treatments,
including extraction and distillation, resulted in glycerin which averaged 99.5%
by weight in purity. The nonglycerin content was mostly water, and there was no
spectroscopic evidence of benzene or naphthalene nuclei or any other aromatic compounds. Apart from the impurities indicated by the U. S. P. specification tests, the
only specific contaminants identified have been glycerin polymers and glYceraldehyde.
GLP compliance:
Test type:
other: Bespoke 10-day toxicity study

Test material

Constituent 1
Chemical structure
Reference substance name:
EC Number:
EC Name:
Cas Number:
Molecular formula:
Test material form:

Test animals

Details on test animals or test system and environmental conditions:
Animals were obtained from local suppliers and were quarantined for about two weeks prior to use. Metal cages bedded with sawdust housed them in approximately equal groups, which were sep- arated according to species and sex. The temperature of the animal room varied between 15 and 17 C. The animals were fed commercial animal food pellets of known composition, supple- mented weekly with greens.

Administration / exposure

Route of administration:
oral: gavage
unchanged (no vehicle)
Details on oral exposure:
Intragastric Administration:
Twelve rats (114 -1-.8 gm. after fasting 22 to 24 hours) received 2726 gm./kg., reported by von Oettingen 2 to be the L.D50. Feed was offered two hours after the treatment, and water was available at all times.
No. of animals per sex per dose:
12 F
Control animals:
not specified
Details on study design:
Mortality, weight changes, and physiologic signs were recorded over a 10-day period. Exam- inations were made for gross lesions in all animals that died and in selected survivors that were killed for the purpose. Specimens of brain, heart, liver, spleen, stomach, intestine, and kidney were taken routinely for histologic study. Tissue specimens were fixed in 10% formalin, preserved in 80% alcohol, embedded in paraffin, sectioned, mounted, and stained with hematoxylin
and eosin.

Results and discussion

Effect levels
Key result
Dose descriptor:
Effect level:
27.2 other: g/kg
Based on:
test mat.

Any other information on results incl. tables

Deaths of rats were also preceded by muscle spasms and clonic convulsions ; respiratory failure occurred 15 minutes to two and one-quarter hours after administration. Survivors appeared normal within two and one-half hours after administration. The approximate L. D.50 values rats was 27.2 gm./kg., respectively, for both glycerins. Lesions.—Hyperemia of the small intestine and lungs occurred in some mice of both groups at the higher dosage levels. The only other lesion of interest was slight hyperemia of the kidneys and of the mucosa of the small intestine. In rats, there was invariably hyperemia of the pylorus and of the small intestine. The lungs were usually congested, and the spleen was pale. Three rats showed hyperemia of the cerebral meninges. Similar changes appeared in the guinea pigs with either glycerin.

Results were negative; apparently neither glycerin was absorbed in quantities sufficient to produce a pharmacologic effect.

Applicant's summary and conclusion

The approximate L. D.50 values 5 for mice and rats were 23.0 and 27.2 gm./kg.,
respectively, for both glycerins.