1,2,3-Propanetriol, mono- and diformates

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No individual data were included and microscopy was performed on distinct organs only.

Data source

Reference

Reference Type:

publication

Title:

Comparative toxicity of synthetic and natural glycerin.

Author:

Hine, C.

Year:

1953

Bibliographic source:

Arch Ind Hyg Occup Med 7:282-291, 1953 (47)

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 452 (Chronic Toxicity Studies)

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Glycerol

EC Number:

200-289-5

EC Name:

Glycerol

Cas Number:

56-81-5

Molecular formula:

C3H8O3

IUPAC Name:

glycerol

Details on test material:

CAS 56-81-5 (glycerine),
Natural glycerine, achieved from market stock, purity not
indicated (impurities were fatty acids and esters)
Synthetic glycerin, purity 99.5% (rest mainly water with
very small amounts of glycerin polymers and glyceraldehyde)

Test animals

Species:

rat

Strain:

Long-Evans

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ORGANISMS
- Age: not indicated
- Weight at study initiation: 96-109 g (males), 92-108 g
(females)
- Source: Institute of Experimental Biology of University of
California

Administration / exposure

Route of administration:

oral: feed

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

- Exposure period: 2 year (1 year for the high dose group)

Doses / concentrations

Remarks:

Doses / Concentrations:
5, 10 and 20% in diet calculated to be equivalent to doses of: males 2000, 4000 and 8000 mg/kg bw, females 2500, 5000 and 10000 mg/kg bw
Basis:

No. of animals per sex per dose:

22/sex/treatment, 26/sex for controls

Control animals:

yes

Examinations

Observations and examinations performed and frequency:

CLINICAL OBSERVATIONS AND FREQUENCY:
- Clinical signs: daily in cage and weekly examination outside the home cage
- Mortality: daily
- Body weight: weekly
- Food consumption: weekly
- Haematology: erythrocyte and leucocyte count and haemoglobin after 3, 6, 12, 18 and 24 months
- Urinalysis: albumin, glucose, casts and red and white blood cells after 3, 6, 12, 18 and 24 months (24-48 urine collection)

Sacrifice and pathology:

ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Organ weights: liver, kidneys, heart, spleen and lungs
- Macroscopic: no details provided
- Microscopic: liver, spleen, adrenals, kidney, small intestine, gonads and urinary bladder

Other examinations:

OTHER EXAMINATIONS: glycogen and lipid content of the liver of surviving rats at 0 and 20% glycerol.

Statistics:

STATISTICAL METHODS: Chi-sqare test, student t-test, ANOVA (Fisher)

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

not examined

Urinalysis findings:

effects observed, treatment-related

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

not examined

Details on results:

- Mortality and time to death: not indicated

- Clinical signs: not reported

- Body weight gain: no statistically significant differences between treated and control animals

- Food consumption: slightly increased (significant) in males at 5 and 10% natural glycerin

- Haematology: no treatment related effects

- Urinalysis: albumin: no significant treatment related effects (92% incidence in females at 20% natural glycerin compared to 54-64% in controls); glucose, casts, red and white blood cells: no treatment related effects

- Organ weights: incidental increases and decreases were reported without apparent relationship to treatment

- Gross pathology: no lesions related to treatment.

- Histopathology: Incidental bronchiectasis, pneumonia, pulmonary abcesses, taenia infestation of the liver, hydronephosis and pyelonephritis (total 27 rats were affected).

- Other: liver glycogen and lipid did not significantly differ between 0 and 20% glycerin (liver glycogen natural glycerin 4.2-4.3% and synthetic glycerin 3.7-4.2%)

Effect levels

Dose descriptor:

NOAEL

Effect level:

10 000 mg/kg bw (total dose)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: absence of adverse effects

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

No adverse effect has been reported in an chronic feeding studies in rat at concentrations up to 10.000 mg/kg bw.

Executive summary:

In a chronic toxicity study glycerol was administered to 22 Long-Evans rats/sex/dose in diet at dose levels of 2000, 4000 and 8000 mg/kg bw for males and 2500, 5000 and 10000 mg/kg bw for females for 2 years (1 year for high dose group).

There were minimal compound related effects in food consumption, urinalysis, organ weights and histopahology and no compound related effects in other measured parameters. The NOAEL is 10000 mg/kg bw based on the lack of adverse effects. 

This chronic study in the rat is acceptable and satisfies the guideline requirement for a chronic oral study (OPPTS 870.4100), OECD 452 in rodents. Deficiencies include no individual data included and microscopy was performed on distinct organs only.