Glycerol

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Not stated

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:

publication

Title:

Comparative toxicity of synthetic and natural glycerin

Author:

Hine, C.

Year:

1953

Bibliographic source:

Arch Ind Hyg Occup Med 7:282-291

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Test material was administered in the diet for up to 2 years. Study design followed intent of OECD 452. The number of animals/dose level used was less than required and minimal histopathology was conducted.

GLP compliance:

no

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:

propane-1,2,3-triol

Details on test material:

Natural glyerine, achieved from market stock, although purity was not indicated (impurities were fatty acids and esters) it was USP grade material.
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)
- Number of animals: 22/sex/treatment, 26/sex for controls
- Source: Institute of Experimental Biology of University of California

Upon arrival at the laboratory, each rat was assigned to an individual numbered cage. Distribution among the experimental groups was accomplished by reference to a standard random number table.

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

ADMINISTRATION / EXPOSURE
- Exposure period: 2 year (1 year for the high dose group)
- Route of administration: oral in diet. Diet consisted of a standard dog-food meal with which the glycerin was thoroughly mixed. Feed was prepared once a week and stored in stoneware crocks. The crocks were weighed and refilled weekly, and the unconsumed feed was discarded.
- Doses: 5, 10 and 20% in diet; males 2000, 4000 and 8000 mg/kg bw, females 2500, 5000 and 10000 mg/kg bw
- Water was allowed freely.

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

Not applicable.

Duration of treatment / exposure:

Continuous

Frequency of treatment:

Daily for up to two years

Doses / concentrations

Remarks:

Doses / Concentrations:
5, 10 and 20% in diet; males 2000, 4000 and 8000 mg/kg bw, females 2500, 5000 and 10000 mg/kg bw
Basis:
nominal in diet

No. of animals per sex per dose:

22/sex/treatment, 26/sex for controls

Control animals:

yes, concurrent no treatment

Details on study design:

No additional information available.

Positive control:

No data.

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 hr 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:

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

Statistics:

Chi-sqare test, student t-test, ANOVA (Fisher) were used as appropriate.

Results and discussion

Results of examinations

Clinical signs:

not specified

Mortality:

not specified

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

slightly increased (significant) in males at 5 and 10% natural glycerin

Food efficiency:

not specified

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

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not specified

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not specified

Details on results:

TOXIC RESPONSE/EFFECTS BY DOSE LEVEL:
- 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

1

Dose descriptor:

NOAEL

Effect level:

> 8 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male

Basis for effect level:

other:

Remarks on result:

not determinable due to absence of adverse toxic effects

2

Dose descriptor:

NOAEL

Effect level:

> 10 000 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other:

Remarks on result:

not determinable due to absence of adverse toxic effects

Target system / organ toxicity

Critical effects observed:

no

Any other information on results incl. tables

No additional information available.

Applicant's summary and conclusion

Conclusions:

The NOAEL was 8000-10,000 mg/kg bw based on the absence of treatment related effects in high dose animals.

Executive summary:

The chronic toxicity of glycerin was examined in rats fed the test material in the diet at concentrations of 5, 10 and 20% for up to two years. The NOAEL was 8000-10,000 mg/kg bw based on the absence of treatment related effects in high dose animals.