Registration Dossier

Administrative data

Description of key information

There are no data for polyglycerine, however data exists 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.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Study period:
Prior to 1960
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 rats were fed for 30 and 45 wk on a purified diet containing 9% PGPR plus 1.0% groundnut oil. Control animals were fed either 10% or 1.0% groundnut oil. During these safety tests, special studies were undertaken to show that PGPR acted as a nutrient and its digestion was comparable to edible fats
GLP compliance:
no
Limit test:
no
Species:
rat
Strain:
other: No data. However based on carcinogenicity study, probably were Colworth Wistar rats.
Sex:
male/female
Details on test animals and environmental conditions:
Entire study is described with results in two paragraphs in publication. See below.
Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
One group of control rats were fed 1.0% groundnut oil in their diet while the other group was fed 10% groundnut oil in their diet. Treated rats were fed 9% PGPR/1% groundnut oil.
Analytical verification of doses or concentrations:
not specified
Details on analytical verification of doses or concentrations:
No data.
Duration of treatment / exposure:
Entire study is described with results in two paragraphs in publication. See below.
Frequency of treatment:
Entire study is described with results in two paragraphs in publication. See below.
Remarks:
Doses / Concentrations:
0 and 9% PGPR
Basis:
nominal in diet
No. of animals per sex per dose:
Entire study is described with results in two paragraphs in publication. See below.
Control animals:
yes
Details on study design:
Entire study is described with results in two paragraphs in publication. See below.
Positive control:
No data.
Observations and examinations performed and frequency:
Body weight, food and water consumption were recorded.
Sacrifice and pathology:
Entire study is described with results in two paragraphs in publication. See below.
Other examinations:
Entire study is described with results in two paragraphs in publication. See below.
Statistics:
No data.
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
no effects observed
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Description (incidence and severity):
increased liver weights
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
See overall remarks which report that the liver changes are due to hypertrophy.
Histopathological findings: neoplastic:
not specified
Details on results:
During wk 5 of the 30-wk study, the rats fed 1.0% groundnut oil were fed no fat in their diet to measure endogenous fat excretion. The other rats continued on their diets containing 9% PGPR/1% groundnut oil or 10% groundnut oil. Faeces were collected for 7 days and analysed for fat. Comparison of fat intake with faecal fat excretion corrected for endogenous fat excretion showed that the digestibility of PGPR was 98.0%. This is nearly equivalent to that of groundnut oil alone, which was 99.8% for the diet containing 10% groundnut oil. Furthermore, when food was restricted for a period of 17 days and then restored ad lib., the energy restricted rats fed PGPR regained the lost body weight in an identical manner to rats fed groundnut oil. Analysis of the carcass and liver for total fat and free fatty acid contents demonstrated that body composition was similar to that of rats fed groundnut oil in their diet. Liver vitamin A values were also similar, indicating that PGPR had no effect on the absorption or utilization of vitamin A. PGPR did not affect the in vitro lipase digestion of groundnut oil, and while PGPR itself did not produce a plasma lipaemia after ingestion, the feeding of 9% PGPR with 9% groundnut oil had no effect on the lipaemia produced by the groundnut oil or on the rate of clearing of this lipaemia.

When rats were fed a purified diet containing 9% PGPR (plus 1% groundnut oil) in feeding trials of 30 or 45 wk duration, no adverse effects were observed on growth, food and water consumption and food utilization compared with rats fed a diet containing 10% groundnut oil. Haematological parameters such as haemoglobin level, haematocrit, erythrocyte count, prothrombin time and red cell fragility were not affected by feeding PGPR. Similarly, PGPR had no effect on the weights of kidneys, spleen, testes, adrenals and pituitary. The livers of rats fed PGPR in the 45-wk test, but not the 30-wk study, were significantly heavier at autopsy. Liver weights in this study were probably affected by the feeding of 18% PGPR prior to killing to see whether PGPR induced a lipaemia

Remarks on result:
not determinable
Remarks:
liver changes are due to hypertrophy
Critical effects observed:
not specified

Entire study is described with results in two paragraphs in publication. See above.

Conclusions:
Liver hypertrophy was observed in rats (and mice) fed high doses of PGPR in the diet.
Executive summary:

Rats were fed up to 9% PGPR in the diet for 30 or 45 weeks. Liver hypertrophy was noted in rats (and mice) fed high doses PGPR in the diet.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Study duration:
subchronic
Species:
rat
Quality of whole database:
acceptable

Repeated dose toxicity: inhalation - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: inhalation
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: The study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study results
Principles of method if other than guideline:
Study design appears to follow intent of OECD 413 but publication does not indicate that OECD 413 was followed.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Rats were obtained from Charles River Breeding Laboratories. Animals were subjected to a 3-week quarantine, health screening five rats of each sex for viral and Mycoplasma infection at the beginning and toward the end of quarantine, physical examinations, body weight measurements, acclimation to the restraining tubes of the nose only exposure system, randomized assignment to exposure groups and individual identification.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Remarks on MMAD:
MMAD / GSD: MMAD <2.0 um (respirable)
Details on inhalation exposure:
A viscous-liquid aerosol generator was used to generate aerosol.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
ANALYSES: target concentration and homogeneity of aerosol
- Method: sampling with aerosol monitor and gravimetric and GC analyses
- Sampling times: actual concentration 2 samples per exposure chamber; homogeneity and uniformity in mock exposure before start of the experiment (6 samples) and during animal exposure (20 samples/concentration)
Duration of treatment / exposure:
6 hours/day
Frequency of treatment:
5 days/week for 13 weeks
Remarks:
Doses / Concentrations:
33, 165 and 660 mg/m3
Basis:
nominal conc.
No. of animals per sex per dose:
15/sex/dose level
Control animals:
yes, concurrent no treatment
Details on study design:
CLINICAL OBSERVATIONS AND FREQUENCY:
- Mortality/clinical signs: twice daily
- Body weight: weekly
- Food consumption: weekly
- Haematology: not specified (complete blood count included)
- Biochemistry: blood urea nitrogen, creatinine, glucose, protein, albumin, albumin/globulin, ASAT, ALAT, LDH, gamma glutamyl transferase, cholesterol, triglycerides and phospholipids

ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Organ weights: lungs, liver, kidneys, brain and heart
- Macroscopic: not specified (complete necropsy).
- Microscopic: total of 40 tissues of high dose and control animals; lungs trachea and anterior nasal cavity were stained with hematoxylin and eosin and duplicate slides with Alcian blue/periodic acid Schiff (Goblet cell changes)

Three rats/sex of control and high dose group were killed during week 10, lung lobes were excised and 2 samples/rat were examined by transmission electron microscopy for abnormalities associated with the Clara cells. The same procedure was followed for 3 rats/sex of all groups during terminal necropsy

ANALYSES: target concentration and homogeneity of aerosol
- Method: sampling with aerosol monitor and gravimetric and GC analyses
- Sampling times: actual concentration 2 samples per exposure chamber; homogeneity and uniformity in mock exposure before start of the experiment (6 samples) and during animal exposure (20 samples/concentration)
Positive control:
No data
Observations and examinations performed and frequency:
CLINICAL OBSERVATIONS AND FREQUENCY:
- Mortality/clinical signs: twice daily
- Body weight: weekly
- Food consumption: weekly
- Haematology: not specified (complete blood count included)
- Biochemistry: blood urea nitrogen, creatinine, glucose, protein, albumin, albumin/globulin, ASAT, ALAT, LDH, gamma glutamyl transferase, cholesterol, triglycerides and phospholipids
Sacrifice and pathology:
ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Organ weights: lungs, liver, kidneys, brain and heart
- Macroscopic: not specified (complete necropsy)
- Microscopic: total of 40 tissues of high dose and control animals; lungs trachea and anterior nasal cavity were stained with hematoxylin and eosin and duplicate slides with Alcian blue/periodic acid Schiff (Goblet cell changes)

Three rats/sex of control and high dose group were killed during week 10, lung lobes were excised and 2 samples/rat were examined by transmission electron microscopy for abnormalities associated with the Clara cells. The same procedure was followed for 3 rats/sex of all groups during terminal necropsy
Other examinations:
No additional information available.
Statistics:
STATISTICAL METHODS: ANOVA, least significant difference
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
triglycerides decreased in males at 33 (34%) and 167 mg/m3 (22%) only.
Urinalysis findings:
not specified
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:
effects observed, treatment-related
Description (incidence and severity):
minimal squamous metaplasia of the epiglottis in 2/25, 1/19, 4/20 and 10/21 rats at 0, 33, 167 and 662 mg/m3; 1 male at 662 mg/m3 showed mild squamous metaplasia. No differences in morphology of the Clara cells in control and high dose rats
Histopathological findings: neoplastic:
not specified
Details on results:
ANALYTICAL ANALYSES:
- Actual dose level: 33, 167 and 662 mg/m3 (100-101% of target)
- Homogeneity (uniformity): relative standard deviation <1% of mean value

- Hematology: No differences between the exposed rats in any group of either sex when compared to their respective control group.
- Clinical chemistry: triglycerides decreased in males at 33 (34%) and 167 mg/m3 (22%) only.
- Gross lesions: few gross lessions observed with no evidence of changes attributed to exposure to glycerol.
- Histopathology: minimal squamous metaplasia of the epiglottis in 2/25, 1/19, 4/20 and 10/21 rats at 0, 33, 167 and 662 mg/m3; 1 male at 662 mg/m3 showed mild squamous metaplasia.
No differences in morphology of the Clara cells in control and high dose rats

STATISTICAL RESULTS: all effects mentioned showed statistical significance (squamous metaplasia only significant at high concentration)

Dose descriptor:
NOAEL
Effect level:
167 mg/m³ air (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: based on local irritant effects on the upper respiratory tract.
Critical effects observed:
not specified

No additional information available.

Conclusions:
The NOAEL was 167 mg/m3 based on local irritant effects on the upper respiratory tract..
Executive summary:

The subchronic toxicity of glycerol was examined following aerosol exposure. The NOAEL was 167 mg/m3 based on local irritant effects on the upper respiratory tract..

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Study duration:
subchronic
Species:
rat
Quality of whole database:
acceptable

Repeated dose toxicity: inhalation - local effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: inhalation
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: The study was not conducted according to guideline/s and GLP but the report contains sufficient data for interpretation of study results
Principles of method if other than guideline:
Study design appears to follow intent of OECD 413 but publication does not indicate that OECD 413 was followed.
GLP compliance:
not specified
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
Rats were obtained from Charles River Breeding Laboratories. Animals were subjected to a 3-week quarantine, health screening five rats of each sex for viral and Mycoplasma infection at the beginning and toward the end of quarantine, physical examinations, body weight measurements, acclimation to the restraining tubes of the nose only exposure system, randomized assignment to exposure groups and individual identification.
Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
air
Remarks on MMAD:
MMAD / GSD: MMAD <2.0 um (respirable)
Details on inhalation exposure:
A viscous-liquid aerosol generator was used to generate aerosol.
Analytical verification of doses or concentrations:
yes
Details on analytical verification of doses or concentrations:
ANALYSES: target concentration and homogeneity of aerosol
- Method: sampling with aerosol monitor and gravimetric and GC analyses
- Sampling times: actual concentration 2 samples per exposure chamber; homogeneity and uniformity in mock exposure before start of the experiment (6 samples) and during animal exposure (20 samples/concentration)
Duration of treatment / exposure:
6 hours/day
Frequency of treatment:
5 days/week for 13 weeks
Remarks:
Doses / Concentrations:
33, 165 and 660 mg/m3
Basis:
nominal conc.
No. of animals per sex per dose:
15/sex/dose level
Control animals:
yes, concurrent no treatment
Details on study design:
CLINICAL OBSERVATIONS AND FREQUENCY:
- Mortality/clinical signs: twice daily
- Body weight: weekly
- Food consumption: weekly
- Haematology: not specified (complete blood count included)
- Biochemistry: blood urea nitrogen, creatinine, glucose, protein, albumin, albumin/globulin, ASAT, ALAT, LDH, gamma glutamyl transferase, cholesterol, triglycerides and phospholipids

ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Organ weights: lungs, liver, kidneys, brain and heart
- Macroscopic: not specified (complete necropsy).
- Microscopic: total of 40 tissues of high dose and control animals; lungs trachea and anterior nasal cavity were stained with hematoxylin and eosin and duplicate slides with Alcian blue/periodic acid Schiff (Goblet cell changes)

Three rats/sex of control and high dose group were killed during week 10, lung lobes were excised and 2 samples/rat were examined by transmission electron microscopy for abnormalities associated with the Clara cells. The same procedure was followed for 3 rats/sex of all groups during terminal necropsy

ANALYSES: target concentration and homogeneity of aerosol
- Method: sampling with aerosol monitor and gravimetric and GC analyses
- Sampling times: actual concentration 2 samples per exposure chamber; homogeneity and uniformity in mock exposure before start of the experiment (6 samples) and during animal exposure (20 samples/concentration)
Positive control:
No data
Observations and examinations performed and frequency:
CLINICAL OBSERVATIONS AND FREQUENCY:
- Mortality/clinical signs: twice daily
- Body weight: weekly
- Food consumption: weekly
- Haematology: not specified (complete blood count included)
- Biochemistry: blood urea nitrogen, creatinine, glucose, protein, albumin, albumin/globulin, ASAT, ALAT, LDH, gamma glutamyl transferase, cholesterol, triglycerides and phospholipids
Sacrifice and pathology:
ORGANS EXAMINED AT NECROPSY (MACROSCOPIC AND MICROSCOPIC):
- Organ weights: lungs, liver, kidneys, brain and heart
- Macroscopic: not specified (complete necropsy)
- Microscopic: total of 40 tissues of high dose and control animals; lungs trachea and anterior nasal cavity were stained with hematoxylin and eosin and duplicate slides with Alcian blue/periodic acid Schiff (Goblet cell changes)

Three rats/sex of control and high dose group were killed during week 10, lung lobes were excised and 2 samples/rat were examined by transmission electron microscopy for abnormalities associated with the Clara cells. The same procedure was followed for 3 rats/sex of all groups during terminal necropsy
Other examinations:
No additional information available.
Statistics:
STATISTICAL METHODS: ANOVA, least significant difference
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
not examined
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
triglycerides decreased in males at 33 (34%) and 167 mg/m3 (22%) only.
Urinalysis findings:
not specified
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:
effects observed, treatment-related
Description (incidence and severity):
minimal squamous metaplasia of the epiglottis in 2/25, 1/19, 4/20 and 10/21 rats at 0, 33, 167 and 662 mg/m3; 1 male at 662 mg/m3 showed mild squamous metaplasia. No differences in morphology of the Clara cells in control and high dose rats
Histopathological findings: neoplastic:
not specified
Details on results:
ANALYTICAL ANALYSES:
- Actual dose level: 33, 167 and 662 mg/m3 (100-101% of target)
- Homogeneity (uniformity): relative standard deviation <1% of mean value

- Hematology: No differences between the exposed rats in any group of either sex when compared to their respective control group.
- Clinical chemistry: triglycerides decreased in males at 33 (34%) and 167 mg/m3 (22%) only.
- Gross lesions: few gross lessions observed with no evidence of changes attributed to exposure to glycerol.
- Histopathology: minimal squamous metaplasia of the epiglottis in 2/25, 1/19, 4/20 and 10/21 rats at 0, 33, 167 and 662 mg/m3; 1 male at 662 mg/m3 showed mild squamous metaplasia.
No differences in morphology of the Clara cells in control and high dose rats

STATISTICAL RESULTS: all effects mentioned showed statistical significance (squamous metaplasia only significant at high concentration)

Dose descriptor:
NOAEL
Effect level:
167 mg/m³ air (analytical)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: based on local irritant effects on the upper respiratory tract.
Critical effects observed:
not specified

No additional information available.

Conclusions:
The NOAEL was 167 mg/m3 based on local irritant effects on the upper respiratory tract..
Executive summary:

The subchronic toxicity of glycerol was examined following aerosol exposure. The NOAEL was 167 mg/m3 based on local irritant effects on the upper respiratory tract..

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
167 mg/m³
Study duration:
subchronic
Species:
rat
Quality of whole database:
Acceptable

Repeated dose toxicity: dermal - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting 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
Qualifier:
no guideline available
Principles of method if other than guideline:
Test material was applied to rabbit skin for 8 hours/day, 5 days/week for 45 weeks. The Draize method was used to evaluate the skin. Body weights, urinalysis and selected tissues were examined histopathologically.
GLP compliance:
no
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
other: No occlusion at the two lower dose levels and occlusion at the two upper dose levels.
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
8 hours/day
Frequency of treatment:
5 days/week for 45 weeks
Remarks:
Doses / Concentrations:
0.5-4.0 ml/kg
Basis:
nominal per unit body weight
No. of animals per sex per dose:
6/dose level
Control animals:
not specified
Dose descriptor:
NOEL
Effect level:
other: 4.0 ml/kg
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: No effects noted in 90 day study at dose levels as high as 4.0 ml/kg.
Critical effects observed:
not specified

No signs of local irritation after 90 days of application.

OTHER EFFECTS: no treatment related effects on the other parameters measured.

Conclusions:
There were no effects noted in rabbits dosed 8 hours/day, 5 days/week for 45 weeks with dose levels as high as 4.0 ml/kg.
Executive summary:

The effects following repeated dermal application of glycerin were examined. There were no local or systemic effects noted in rabbits dosed 8 hours/day, 5 days/week for 45 weeks with dose levels as high as 4.0 ml/kg. Using a density of 1.2611 g/cm3 at 20 °C, a dose of 4.0 ml/kg corresponds to 5040 mg/kg/day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
5 040 mg/kg bw/day
Study duration:
subchronic
Species:
rabbit
Quality of whole database:
Acceptable

Repeated dose toxicity: dermal - local effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting 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
Qualifier:
no guideline available
Principles of method if other than guideline:
Test material was applied to rabbit skin for 8 hours/day, 5 days/week for 45 weeks. The Draize method was used to evaluate the skin. Body weights, urinalysis and selected tissues were examined histopathologically.
GLP compliance:
no
Limit test:
no
Species:
rabbit
Strain:
not specified
Sex:
not specified
Type of coverage:
other: No occlusion at the two lower dose levels and occlusion at the two upper dose levels.
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
8 hours/day
Frequency of treatment:
5 days/week for 45 weeks
Remarks:
Doses / Concentrations:
0.5-4.0 ml/kg
Basis:
nominal per unit body weight
No. of animals per sex per dose:
6/dose level
Control animals:
not specified
Dose descriptor:
NOEL
Effect level:
other: 4.0 ml/kg
Based on:
test mat.
Sex:
not specified
Basis for effect level:
other: No effects noted in 90 day study at dose levels as high as 4.0 ml/kg.
Critical effects observed:
not specified

No signs of local irritation after 90 days of application.

OTHER EFFECTS: no treatment related effects on the other parameters measured.

Conclusions:
There were no effects noted in rabbits dosed 8 hours/day, 5 days/week for 45 weeks with dose levels as high as 4.0 ml/kg.
Executive summary:

The effects following repeated dermal application of glycerin were examined. There were no local or systemic effects noted in rabbits dosed 8 hours/day, 5 days/week for 45 weeks with dose levels as high as 4.0 ml/kg. Using a density of 1.2611 g/cm3 at 20 °C, a dose of 4.0 ml/kg corresponds to 5040 mg/kg/day.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
acceptable

Additional information

There are no data for polyglycerine. Studies on the major component, glycerine, demonstrate the low level of concern about glycerine via the dietary, dermal and respiratory route. The only effect observed was upper respiratory tract irritation in the subchronic inhalation toxicity study, possibly an adaptive effect due to glycerol’s recognizedhygroscopic properties Subchronic dietary toxicity studies on the higher molecular weight polyglycerine polyricinoleate (PGPR) identified liver hypertrophy in rats ingesting 9% PGPR for 35 weeks. PGPR has been shown to be metabolized in the GI tract releasing polyglycerine (called Polyglycerine-Heavy in Justification document) which is excreted unchanged in the urine (diglycerine and triglycerine) and feces (higher MW glycerine oligomers) (Detailed in Sections 7.1.1 and 13). Castor oil, used in the preparation of PGPR, likewise affects the liver probably due to an adaptive hypertrophy, without toxic damage, through the need to metabolize ricinoleic acid. Thus the subchronic effects observed with PGPR are believed to not be due to polyglycerine but rather are attributed solely to the polyricinoleate portion of the molecule.

PGPR consists of 9% polyglycerine. 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; 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.

a Body weights and feed consumption came from F0 generation values in a report on a 2-generation rat reproductive toxicity study, DR-0189-9383-005.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Adverse effects were observed in studies of PGPR. Minor liver hypertrophy effects observed. However, these effects occurred at high oral doses by a non-relevant route. In addition a long history of use as a food additive indicates that the effects observed are not likely to be of significance in human risk assessment.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
There are no data for polyglycerine. Data do exist for glycerine, a major component of polyglycerine. In the 13-week aerosol study of glycerine, there were no systemic effects noted.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
There are no data for polyglycerine. Data do exist for glycerine, a major component of polyglycerine. In the 13-week aerosol study of glycerine, irritation of the upper respiratory tract was noted.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
There are no data for polyglycerine. Data do exist for glycerine, a major component of polyglycerine. In the subchronic toxicity study in rabbits the NOAEL was 5040 mg/kg/day.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
There is no data for polyglycerine. Data does exist for glycerine, a major component of polyglycerine. In the subchronic toxicity study in rabbits the NOAEL was 5040 mg/kg/day.

Justification for classification or non-classification

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