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Administrative data

Key value for chemical safety assessment

Effects on fertility

Description of key information
No additional information available.
Link to relevant study records
Reference
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
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
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.
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)
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.
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.
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: oestrous cycle:
no effects observed
Reproductive function: sperm measures:
not specified
Reproductive performance:
no effects observed
-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).

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.
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
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.
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.
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.
Reproductive effects observed:
not specified

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).

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.

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
2 000 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
good
Additional information

Although data do not exist for polyglycerine, data do exist for the major component, glycerine and also for polyglycerine polyricinoleate (PGPR) which breaks down in the gastrointestinal tract releasing polyglycerine (called Polyglycerine-Heavy in Justification document). There was no evidence of an effect on fertility based on a two-generation reproduction study with either glycerin (~2000 mg/kg/day) or polyglycerine ricinoleate (1.5% in the diet). The PGPR study did not convert percent PGPR in the diet to mg/kg/day consumed. Using the following assumptionsa, Males-26 grams food consumed/day, at 549 grams and Females-20 grams food consumed/day at 358 grams, a 9% PGPR in the diet corresponds to 4255 mg/kg/day for males and 5005 mg/kg/day for females. This corresponds to 383 mg Polyglycerine-heavy/kg/day for the males and 450 mg Polyglycerine-heavy/kg/day for the females).

aBody weights and feed consumption came from F0 generation values in report on 2 generation rat reproduction study DR-0189 -9383 -005.


Short description of key information:
There are no data for polyglycerine, however data exist for the major component, Glycerine and also for polyglycerine polyricinolate (PGPR) which breaks down in the body releasing polyglycerine (called Polyglycerine-Heavy in Justification document). Justification for the use of these data is in the document attached at section 13 of the IUCLID.

Justification for selection of Effect on fertility via oral route:
Several studies on source analogues are used in a Weight of Evidence.

Effects on developmental toxicity

Description of key information
There are no data for polyglycerine, however data exist for the major component, glycerine and also for polyglycerine polyricinolate (PGPR) which breaks down in the body releasing polyglycerine. Justification for the use of these data is in the document attached at section 13 of the IUCLID.
Link to relevant study records
Reference
Endpoint:
developmental toxicity
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
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 rabbits on days 6-18 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
Species:
rabbit
Strain:
Dutch
Details on test animals and environmental conditions:
TEST ORGANISMS
- Age: adult
- Mean weight at study initiation (Day 0: 2.09-2.38 kg
- Number of animals: 15-20 females/treatment

Virgin, adult, Dutch-belted female rabbits were individually housed in mesh bottom cages in temperature and humidity controlled quarters with free access to food and fresh tap-water.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on exposure:
ADMINISTRATION / EXPOSURE
- Test duration: 20 days
- Exposure period: day 6-18 of gestation inclusive
- Definition of day 0: observation of vaginal sperm plug
- Route of administration: oral (gavage)
- Doses: 11.8, 54.8, 254.5 and 1180 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:
On Day 0, each doe was given an injection of 0.4 ml of human chorionic gonadotropin (400 IU) via the marginal ear vein. Three hours later, each doe was inseminated artificially with 0.3 ml of diluted semen from a proven donor buck using approximately 20 x 10 (6) motile sperm according to the procedure described by Vogin et al (Pharmacologist 11, 282 (1969).
Duration of treatment / exposure:
Exposure period: day 6-18 of gestation inclusive
Frequency of treatment:
Daily
Duration of test:
Test material was administered on days 6-18 of gestation. Animals were sacrificed on day 29 of gestation
No. of animals per sex per dose:
15-20 females/treatment
Control animals:
yes, concurrent vehicle
other: positive control: 6-aminonicotinamide
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
Maternal examinations:
PARAMETERS ASSESSED DURING STUDY:
- Mortality/clinical observations: daily
- Body weight: on day 0, 6, 12, 18 and 29
- Food consumption: daily

Ovaries and uterine content:
Examination of uterine content: no. of corpora lutea, implantation sites, resorptions and live and dead fetuses
Fetal examinations:
Examination of fetuses: body weight, sex, external abnormalities on day 29, neonatal survival (live fetuses of each litter were placed in an incubator for 24 hours for the evaluation of neonatal survival), visceral (by dissection) and skeletal examination (fetuses were cleared in potassium hydroxide, stained with alizarin red S dye and examined for skeletal effects) on day 30
Statistics:
Not indicated
Indices:
No additional information available.
Historical control data:
No additional information available.
Details on maternal toxic effects:
Maternal toxic effects:no effects

Details on maternal toxic effects:
MATERNAL TOXIC EFFECTS BY DOSE LEVEL:
- Mortality: 1 animal at 54.8 mg/kg bw, 2 at 254.5 mg/kg bw and 1 at 1180 mg/kg bw
- Body weight: no treatment related effects, significant decrease only at 254.5 mg/kg bw (14%) compared to controls.
- Food consumption: no data
- Clinical signs: not reported
- Number pregnant per dose level: 14/15, 12/15, 10/18, 13/20 and 13/15 for 0, 11.8, 54.8, 254.5 and 1180 mg/kg bw
- Number aborting: 2 at 254.5 mg/kg bw
- Number of corpora lutea: 9.7, 11.7, 5.6, 8.2 and 11.2 for controls and at 11.8, 54.8, 254.5 and 1180 mg/kg bw
- Number of implantations: 6.1, 5.1, 5.4, 7.3 and 6.4 for controls and at 11.8, 54.8, 254.5 and 1180 mg/kg bw
- Number of resorptions (no of dams involved): 5, 2, 4, 2 and 6 for controls and at 11.8, 54.8, 254.5 and 1180 mg/kg bw
Dose descriptor:
NOAEL
Effect level:
1 180 mg/kg bw/day (actual dose received)
Based on:
test mat.
Basis for effect level:
other: maternal toxicity
Details on embryotoxic / teratogenic effects:
Embryotoxic / teratogenic effects:no effects

Details on embryotoxic / teratogenic effects:
FETAL DATA:
- Litter size: No treatment related effects
- Fetal weight: decreased(14%) at 254.5 mg/kg bw compared to controls.
- Number viable: 5.1, 4.7, 4.8, 5.9 and 5.5 per litter for 0, 11.8, 54.8, 254.5 and 1180 mg/kg bw mg/kg bw
- Sex ratio: no treatment related effects
- External abnormalities: none reported
- Visceral abnormalities: no treatment related effects
- Skeletal abnormalities: delayed ossification increased at 254.5 mg/kg bw (without relationship to treatment)
Dose descriptor:
NOAEL
Effect level:
1 180 mg/kg bw/day
Based on:
test mat.
Basis for effect level:
other: No effects were observed in offspring of dams dosed with glycerin.
Abnormalities:
not specified
Developmental effects observed:
not specified

Table 1 Partial listing of skeletal findings in rabbits

 Dose (mg/kg) control   6 -AN  11.8  54.8  254.5  1180
 live fetuses examined (at term)  71/13  49/10  56/12  43/8  65/9  72/12
sternebrae incomplete ossification   1/1  ND  1/1  1/1  8/5  6/2

number of fetuses affected/number of litters affected

6 -AN = 6 -aminonicotinamide

Conclusions:
There was no effect on developmental toxicity of offspring of female rabbits dosed with glycerin.
Executive summary:

A developmental toxicity study was conducted in rabbits. There was no effect on developmental toxicity of offspring of female rabbits dosed with glycerin at doses as high as 1180 mg/kg/day.

Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 180 mg/kg bw/day
Study duration:
subacute
Species:
rabbit
Quality of whole database:
acceptable
Additional information

Although no data exist for polyglycerine, data do exist for the major component, glycerine. There was no evidence of a developmental toxicity effect in rats (1310 mg/kg/day), mice (1280 mg/kg/day) or rabbits (1180 mg/kg/day) administered glycerine orally. Although no developmental toxicity study has been conducted on the higher MW glycerine present in polyglycerine, there were no developmental toxicity effects noted in a rat 3-generation reproduction study of polyglycerine polyricinoleate (PGPR). PGPR has been shown to be metabolized in the GI tract releasing polyglycerine which is excreted unchanged in the urine (diglycerine and triglycerine) and feces (higher MW glycerines) (Detailed in Sections 7.1.1 and 13).


Justification for selection of Effect on developmental toxicity: via oral route:
Several studies on major glycerol component are used in a Weight of Evidence.

Toxicity to reproduction: other studies

Additional information

No additional information available.

Justification for classification or non-classification

There is no justification for classification based on data from available studies.