Registration Dossier

Administrative data

Endpoint:
developmental toxicity
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
no data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No data on uterus weights, no of corpora lutea and food consumption were included in the report. No analyses of the test substance concentration were included. For foetal external, visceral and skeletal examinations only summary tables were included.

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, 1974 (82)

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
not applicable
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
CAS 56-81-5 (glycerin) (syrup), purity not specified

Test animals

Species:
rat
Strain:
Wistar
Details on test animals and environmental conditions:
TEST ORGANISMS
- Age: adult
- Mean weight at study initiation: 214-230 g
- Number of animals: 25-28 females/treatment

Administration / exposure

Route of administration:
oral: gavage
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: none
Analytical verification of doses or concentrations:
not specified
Details on mating procedure:
MATING PROCEDURES: most probably 1 male/1 female
Duration of treatment / exposure:
day 6 to day 15 of gestation inclusive
Frequency of treatment:
daily
Duration of test:
20 days
Doses / concentrations
Remarks:
Doses / Concentrations:
13.1-1310 mg/kg bw
Basis:
nominal in diet
Control animals:
yes, sham-exposed
Details on study design:
Doses 13.1-1310 mg/kg bw

Examinations

Maternal examinations:
- Mortality/clinical observations: daily
- Body weight: on day 0, 6, 11, 15 and 20
- Food consumption: daily
- Examination of uterine content
Ovaries and uterine content:
Examination of uterine content: no. of implantation sites, resorptions and live and dead foetuses
Fetal examinations:
- Examination of foetuses: body weight, sex, external
abnormalities, visceral (1/3 of foetuses) and skeletal (2/3
of foetuses) examination
Statistics:
not indicated

Results and discussion

Results: maternal animals

Maternal developmental toxicity

Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
MATERNAL TOXIC EFFECTS BY DOSE LEVEL:
- 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)

open allclose all
Dose descriptor:
NOAEL
Effect level:
1 310 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: developmental toxicity
Dose descriptor:
NOAEL
Effect level:
1 310 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity

Results (fetuses)

Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
FETAL DATA:
- Litter size and weights: No treatment related effects
- Number viable: 10.8, 11.1, 11.2, 11.0 and 10.2 per litter for controls and at 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)

Dose descriptor:
NOAEL
Effect level:
ca. 1 310 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: no effects oberserved

Fetal abnormalities

Abnormalities:
not specified

Overall developmental toxicity

Developmental effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Although the presented teratogenicity study on rats with glycerol is does not follow current standards, it allows for deriving the NOAEL values:
NOAEL maternal toxicity = 1310 mg/kg bw
NOAEL teratogenicity = 1310 mg/kg bw