Glycerol

Developmental toxicity / teratogenicity

Administrative data

Endpoint:

developmental toxicity

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:

Teratological evaluation of glycerin in mice, rats and rabbits.

Author:

N.T.I.S. US Department of Commerce.

Year:

1974

Bibliographic source:

Report No. PB-234876

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Study follows intent of OECD 414 study design. Test material was administered by oral gavage to rats on days 6-15 of gestation. Examination of fetuses: body weight, sex, external abnormalities, visceral (1/3 of fetuses) and skeletal (2/3 of fetuses) examination

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:

FDA 71-89. purity not specified but since the material is identified as FDA, it probably met FDA requirements.

Test animals

Species:

rat

Strain:

Wistar

Details on test animals or test system and environmental conditions:

TEST ORGANISMS
- Age: adult
- Mean weight at study initiation (Day 0): 214-230 g
- Number of animals: 25-28 females/treatment

Virgin adult female albino rats (Wistar derived stock) were individually housed in mesh bottom cages in temperature and humidity controlled quarters with free access to food and fresh tap water. They were mated with adult males and observation of the vaginal sperm plug was considered Day 0 of gestation.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on exposure:

ADMINISTRATION / EXPOSURE
- Test duration: 20 days
- Exposure period: day 6-15 of gestation inclusive
- Definition of day 0: observation of vaginal sperm plug
- Route of administration: oral (gavage)
- Doses: 13.1, 60.8, 282 and 1310 mg/kg bw (dosing volume <6 mL/kg)
- Vehicle: water

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

No data

Details on mating procedure:

1 male/1 female. Observation of the vaginal sperm plug was considered Day 0 of gestation

Duration of treatment / exposure:

Exposure period: day 6-15 of gestation inclusive

Frequency of treatment:

Daily

Duration of test:

Test material was administered on days 6-15 of gestation. Animals were sacrificed on day 20 of gestation

No. of animals per sex per dose:

25-28 females/treatment

Control animals:

yes, concurrent vehicle

other: positive control: Asprin

Details on study design:

PARAMETERS ASSESSED DURING STUDY:
- Mortality/clinical observations: daily
- Body weight: on day 0, 6, 11, 15 and 20
- Food consumption: daily
- Examination of uterine content: no. of implantation sites, resorptions and live and dead fetuses
- Examination of fetuses: body weight, sex, external abnormalities, visceral (1/3 of fetuses) and skeletal (2/3 of fetuses) examination

ORGANS EXAMINED AT NECROPSY: urogenital tract

Examinations

Maternal examinations:

- Mortality/clinical observations: daily
- Body weight: on day 0, 6, 11, 15 and 20
- Food consumption: daily

Ovaries and uterine content:

Examination of uterine content: no. of implantation sites, resorptions and live and dead fetuses

Fetal examinations:

Examination of fetuses: body weight, sex, external abnormalities, visceral (1/3 of fetuses examined using Wilson technique) and skeletal (2/3 of fetuses were cleared in potassium hydroxide, stained with alizarin red S dye and examined for skeletal defects) examination

Statistics:

Not indicated

Indices:

No additional information available.

Historical control data:

No additional information available.

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:

Maternal toxic effects:no effects

Details on maternal toxic effects:
- Mortality: none
- Body weight: no treatment related effects
- Food consumption: no data
- Clinical signs: not reported
- Number pregnant per dose level: 23/25, 24/25, 22/28, 22/25 and 21/25 for controls and at 13.1, 60.8, 282 and 1310 mg/kg bw
- Number aborting: none
- Number of implantations: 11.3, 10.8, 12.3, 11.8 and 11.1 for controls and at 13.1, 60.8, 282 and 1310 mg/kg bw
- Number of resorptions (no of dams involved): 2, 1, 1, 2 and 2 for controls and at 13.1, 60.8, 282 and 1310 mg/kg bw

Effect levels (maternal animals)

Dose descriptor:

NOAEL

Effect level:

> 1 310 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

other: maternal toxicity

Remarks on result:

not determinable due to absence of adverse toxic effects

Results (fetuses)

Details on embryotoxic / teratogenic effects:

Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
- Litter size and weights: No treatment related effects
- Number viable: 11.3, 10.8, 12.3, 11.8 and 11.1 per litter for 0, 13.1, 60.8, 282 and 1310 mg/kg bw
- Sex ratio: no treatment related effects
- External abnormalities: none reported
- Visceral abnormalities: none
- Skeletal abnormalities: delayed ossification in all treatment groups and controls without relationship to treatment

Effect levels (fetuses)

Key result

Dose descriptor:

NOAEL

Effect level:

> 1 310 mg/kg bw/day (actual dose received)

Based on:

test mat.

Basis for effect level:

external malformations

skeletal malformations

visceral malformations

Remarks on result:

not determinable due to absence of adverse toxic effects

Fetal abnormalities

Abnormalities:

not specified

Overall developmental toxicity

Developmental effects observed:

not specified

Any other information on results incl. tables

Table 1 Partial listing of skeletal findings

Dose (mg/kg)	control	Aspirin	13.1	60.8	282	1310
Live fetuses examined (at term)	183/23	157/24	80/24	189/22	182/22	163/21
sternebrae incomplete ossification	54/16	78/21	52/17	37/14	35/11	47/15
ribs incomplete ossification	1/1	9/5				1/1
ribs wavy	26/10	46/17	25/12	5/5	11/8	9/6
ribs more than 13	-/-	126/24	1/1	-/-	-/-	3/1
vertebrae incomplete ossification	45/14	115/23	15/9	14/9	12/5	10/5
extremities incomplete ossification	-/-	2/2	-/-	-/-	-/-	-/-
hyoid; missing	36/13	77/21	10/8	23/11	17/10	19/10
hyoid; reduced	25/10	9/7	14/9	11/8	26/9	14/7

number of fetuses affected/number of litters affected

Applicant's summary and conclusion

Conclusions:

There was no effect on developmental toxicity of offspring of female rats dosed with glycerin.

Executive summary:

A developmental toxicity study was conducted in rats. There was no effect on developmental toxicity of offspring of female rats dosed with glycerin at doses as high as 1310 mg/kg/day.