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Toxicological information

Toxicity to reproduction

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Administrative data

Endpoint:
two-generation reproductive toxicity
Remarks:
based on test type (migrated information)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
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:
Über die Fortpflanzungsfähigkeit der Ratte nach Einwirkung von Diäthylenglykol
Author:
Wegener, H.
Year:
1953
Bibliographic source:
Arch exper Path u Pharmakol, 220:414-417

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
Test material was administered in drinking water of male and female rats through 2 generations.
GLP compliance:
no
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
not specified
Details on test material:
No additional information available.

Test animals

Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
Number of animals: 10/sex/treatment for Parent and F1.

No additional information available.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on exposure:
ADMINISTRATION / EXPOSURE
- Test durations: until F2-generation was 100 days of age
- Premating period: 8 weeks
- Exposure period: 12 weeks (until weaning of F1)
- Route of administration: oral (gavage, dose volume 10 mL/kg)
- Doses: 20% solution in water, ~2000 mg/kg bw
Details on mating procedure:
not indicated (starting when females were between 170 and 215 g)
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No additional information available.
Duration of treatment / exposure:
8-12 weeks (starting before mating and continuing, in females, until weaning).

- Test durations: until F2-generation was 100 days of age
- Premating period: 8 weeks
- Exposure period: 12 weeks (until weaning of F1)
Frequency of treatment:
Daily
Details on study schedule:
- Test durations: until F2-generation was 100 days of age
- Premating period: 8 weeks
- Exposure period: 12 weeks (until weaning of F1)
Doses / concentrations
Remarks:
Doses / Concentrations:
~2000 mg/kg bw
Basis:
nominal conc.
No. of animals per sex per dose:
10/sex/treatment for Parent and F1
Control animals:
yes, concurrent vehicle
Details on study design:
No additional information available.
Positive control:
No data.

Examinations

Parental animals: Observations and examinations:
- Clinical observations: frequency not indicated
- Estrous cycle: in F1 and F2 between 60 and 100 days
- Body weight: in F1 and F2 during day 15 and 60 at 2-day
intervals

Oestrous cyclicity (parental animals):
Estrous cycle: in F1 and F2 between 60 and 100 days
Sperm parameters (parental animals):
Sperm examination: not performed
Litter observations:
Litter size and survival were monitored
Postmortem examinations (parental animals):
No additional information available.
Postmortem examinations (offspring):
ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Organ weights F1 and F2: pituitary, thyroid, adrenals,
ovaries, testicles
- Histopathology F1 and F2: endocrine system organs on 26
animals
Statistics:
No additional information available.
Reproductive indices:
No additional information available.
Offspring viability indices:
No additional information available.

Results and discussion

Results: P0 (first parental generation)

General toxicity (P0)

Clinical signs:
not specified
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Organ weight findings including organ / body weight ratios:
not specified
Histopathological findings: non-neoplastic:
no effects observed
Other effects:
no effects observed

Reproductive function / performance (P0)

Reproductive function: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed

Details on results (P0)

-No effects were found on the reproductive efficiency of the parents.
-Onset of oestrus cycle and weight and microscopy of the endocrine organs were comparable to control values for both F1 and F2 animals.
-In the parent generation all 10 females became pregnant (litter size 9.0, controls 8.1) and in the F1 9/10 females became pregnant (litter size 8.7, controls 8.1).

Effect levels (P0)

Dose descriptor:
NOEL
Effect level:
2 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects observed at 2000 mg/kg/day, highest dose examined.

Results: F1 generation

General toxicity (F1)

Clinical signs:
not specified
Mortality / viability:
no mortality observed
Body weight and weight changes:
no effects observed
Sexual maturation:
no effects observed
Description (incidence and severity):
males not examined
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings:
no effects observed

Details on results (F1)

There was no effect on the growth, fertility and reproductive performance of the F1 generation, and no histological changes occurred in the tissues of both the F1 and F2 generation.

Effect levels (F1)

Dose descriptor:
NOEL
Generation:
F1
Effect level:
2 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects observed at 2000 mg/kg/day, highest dose examined.

Results: F2 generation

Effect levels (F2)

Dose descriptor:
NOEL
Generation:
F2
Effect level:
2 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: No effects observed at 2000 mg/kg/day, highest dose examined.

Overall reproductive toxicity

Reproductive effects observed:
not specified

Any other information on results incl. tables

No effects were found on the reproductive efficiency of the parents, nor on the growth, fertility and reproductive performance of the untreated F1 generation, and no histological changes occurred in the tissues of both the F1 and F2 generation.
Onset of oestrus cycle and weight and microscopy of the endocrine organs were comparable to control values for both F1 and F2 animals.
In the parent generation all 10 females became pregnant (litter size 9.0, controls 8.1) and in the F1 9/10 females became pregnant (litter size 8.7, controls 8.1).

Applicant's summary and conclusion

Conclusions:
Glycerin was administered by oral gavage to groups of male and female rats through two generations. There was no effect noted on growth, fertility and reproductive performance through two generations.
Executive summary:

Glycerin was administered by oral gavage to groups of male and female rats through two generations. There was no effect noted on growth, fertility and reproductive performance through two generations at a dose level of ~2000 mg/kg/day.