Glycerol tribenzoate

Endpoint summary

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

(Q)SAR

Adequacy of study:

weight of evidence

Study period:

November 2020

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

results derived from a valid (Q)SAR model and falling into its applicability domain, with adequate and reliable documentation / justification

Justification for type of information:

Using the SMILES notation input of Glycerol tribenzoate, confirmed by the computer program by display of the correct CAS number (614-33-5), a predicted for the acute oral toxicity (Rat LD50) was generated.
The prediction was estimated by taking an average of the predicted toxicities from QSAR methods.
Calculations were performed within the TEST v4.2.1 computer modelling programmed issued by the US EPA in 2016.

Qualifier:

no guideline required

Principles of method if other than guideline:

Using the SMILES notation input of Glycerol tribenzoate, confirmed by the computer program by display of the correct CAS number (614-33-5), a predicted for the acute oral toxicity (Rat LD50) was generated.
The prediction was estimated by taking an average of the predicted toxicities from QSAR methods.
Calculations were performed within the TEST v4.2.1 computer modelling programmed issued by the US EPA in 2016.

GLP compliance:

no

Test type:

other: QSAR

Species:

rat

Route of administration:

oral: gavage

Key result

Dose descriptor:

LD50

Effect level:

5 369.95 mg/kg bw

Based on:

test mat.

Predicted Oral rat LD50 for 614-33-5 from Consensus method

Endpoint	Experimental value	Predicted value
Oral rat LD50 -Log10(mol/kg)	N/A	1.88
Oral rat LD50 mg/kg	N/A	5369.95

Method Predicted value -Log10(mol/kg) Hierarchical clustering 1.93 FDA 1.59 Nearest neighbor 2.11

Test chemical

Conclusions:

The predicted Oral rat acute LD50 (mg/kg) was 5369.95, far in excess of the requirement for classification.

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from similar mixture/product

Adequacy of study:

weight of evidence

Study period:

1953

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Qualifier:

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
preparations.
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
irritation.
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:

no

Test type:

other: Bespoke 10-day toxicity study

Species:

rat

Strain:

Long-Evans

Sex:

female

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.

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

Intragastric Administration:

Doses:

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.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

27.2 other: g/kg

Based on:

test mat.

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.

Conclusions:

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

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2021

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

test procedure in accordance with generally accepted scientific standards and described in sufficient detail

Remarks:

This is an in-vitro test which adheres to generally accepted in-vitro validity criteria

Qualifier:

no guideline required

Principles of method if other than guideline:

The detailed method followed, is described in XCellR8 SOP L0064 "Neutral Red Uptake (NRU) Cytoxicity Test Using Human Dermal Fibroblasts in Xeno-Free Culture Conditions"

GLP compliance:

no

Test type:

other: In-vitro: Neutral Red Uptake (NRU) Cytoxicity Test Using Human Dermal Fibroblasts in Xeno-Free Culture Conditions

Specific details on test material used for the study:

Batch: 20118
Purity: 98.1%
Expiry: 24 months from 07/2020

Species:

other: Human Dermal Fibroblast Cells

Strain:

other: Neonatal human dermal fibroblast cultures

Sex:

not specified

Route of administration:

other: A single application of 8 concentratons of the test item (n=6) was applied in cell culture medium with 1% DMSO (dilution factor of 2 in the range-finder, 1.3 in the main test).

Preliminary study:

Cell viability did not reduce to below 50% at 200 ug/mL.

Key result

Sex:

not specified

Dose descriptor:

other: IC50

Effect level:

> 500 other: ug/mL

Based on:

test mat.

Remarks on result:

other: Based on cell viability

Conclusions:

Glycerol tribenzoate was classified as Category 4 or Category 5 or Unclassified (Classification, IC50>500 ug/mL)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed