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

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute 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 1970
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:
Groups of rats were dosed with the test material and mortality recorded.
GLP compliance:
no
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Identified as Colworth. Probably Colworth Wistar.
Sex:
male/female
Details on test animals and environmental conditions:
Weanling male and female rats weighing between 77 and 152 grams were used.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Rats were orally gavaged with 20 ml/kg (approximately 20 g/kg) of PGPR
Doses:
20 ml/kg
No. of animals per sex per dose:
55 weanling male and female were dosed with test material. (Number of animals of each sex dosed not specified).

22 weanlings in the control group were intubated with a similar dosage of groundnut oi.
Control animals:
yes
Details on study design:
The acute oral toxicity of the polyglycerol-polyricinoleic acid emulsifier was evaluated by administration of a single oral dose of 20 ml/kg (approx. 20 g/kg) to 55 weanling male and female Colworth rats weighing between 77 and 152 grams. Each of the 22 weanlings in the control group was intubated with a similar dosage of groundnut oil. Due to the high viscosity of PGPR both materials were maintained at 37°C prior to dosing. Animals were observed for 21 days following oral gavage administration.
Statistics:
No additional information available.
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 1 800 mg/kg bw
Based on:
other: polyglycerol
Mortality:
No deaths were observed in rats dosed with PGPR.
Clinical signs:
Other than slight diarrhoea in 42 rats dosed with PGPR and 2 rats dosed with groundnut oil no other untoward toxic effects were observed for any of the parameters measured. .
Body weight:
Body weight gains were comparable to control values.
Gross pathology:
There were no gross pathology findings.
Other findings:
Food consumption and absolute organ weights (organs unspecified) were comparable to control values.

No additional information available.

Interpretation of results:
Category 4 based on GHS criteria
Remarks:
Migrated information
Conclusions:
The acute oral LD50 in rats of polyglycerol is >1800 mg/kg.
Executive summary:

The acute oral toxicity of PolyGlycerol PolyRicinoleic acid (PGPR) was investigated in rats. A group of male and female rats received 20 ml/kg (approximately 20,000 mg/kg) PGPR and were observed for 21 days. (Based on results of metabolism studies, PGPR has been shown to be metabolized in the gut into polyglycerol and polyricinoleic acid. Lower molecular weight polyglycerol is absorbed and excreted unchanged in urine while the higher molecular weight polyglycerols are excreted unchanged in the feces.)

All animals survived with slight diarrhea observed in a number of animals. Based on the amount of polyglycerol present in PGPR, the acute toxicity of polyglycerol is >1800 mg/kg.

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

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
Not stated
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: The study was conducted prior to test guidelines and GLP.
Qualifier:
no guideline available
Principles of method if other than guideline:
Rats were exposed to vapors generated from test material heated at 200C. Exposure time ranged from 1 to 7 hours
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
not specified
Sex:
male
Details on test animals and environmental conditions:
No additional information available.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
Saturated vapor atmosphere generated by passing compressed air throught the test material contained in a fritter-finger glass bubbler immersed in an oil bath heated tp approximately 200°C and introduced into the exposure chamber. For the L(Ct)50 experiment, the same vapor was mixed with room air (1:1) before introduction into the exposure chamber.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
>= 1 - <= 7 h
Concentrations:
Nominal concentration 11.0 mg/L
No. of animals per sex per dose:
Groups of 5 rats were exposed for 1, 2 and a maximum of 7 hours.
Control animals:
not specified
Details on study design:
No additional information available.
Statistics:
No additional information available.
Preliminary study:
Not applicable.
Sex:
male
Dose descriptor:
other: L(Ct)50
Effect level:
4 655 other: mg-min/liter
Based on:
test mat.
Exp. duration:
7 h
Mortality:
See below.
Clinical signs:
other: No additional information available.
Body weight:
No additional information available.
Gross pathology:
See below.
Other findings:
No additional information available.

In a preliminary study, no mortality was observed in rats exposed to a saturated vapor for 1 hour and all animals died within 48 hours after exposure to a saturated vapor for 2 hours.

In the L(Ct)50 experiments, compressed air at the rate of 500 ml/minute was bubbled through glycerine which was heated to 200C. The rate of vaporization of glycerine under these conditions, was gravimetrically determined and calculated to be 11.0 mg/minute. The vapor-laden air was diluted by adding make-up air at the rate of 500 ml/minute. The total airflow (volume of air emerged from heated compound plus the volume of make-up air added per unit time), entering the exposure chamber was 1 liter/minute. The nominal concentration of glycerine in the experimental atmosphere was therefore 11.0 mg/L.

During the initial four hours of exposure, no significant adverse effect was observed. However, after approximately 240 minutes, signs of mild irritation, indicated by hyperemia of the eyelids and nasal discharges were observed. These conditions became more severe as the exposure progressed. The animals eventually salivated profusely and exhibited dyspneic respiratory patterns. After approximately 360 minutes, all animals began gasping for air and lay in prostration. Two animals died at approximately the 419 minute timepoint. The third one died shortly after the termination of the exposure. The fourth animal succumbed at approximately 30 minutes post-exposure. The remaining animal succumbed on the fourth post-exposure day. Based upon the time-to-death data, an approximate Lt50 was graphically determined to be 423 minutes.

The L(Ct)50 was obtained by multiplying the nominal chamber concentration, C, with the estimated Lt50 and was equal to 4655 mg-min/liter.

Necropsies of the animals which succumbed revealed: 1) desquamation of the epithelium of the trachea, 2) hyperemia and slight edema of the lung tissues, and 3) extreme distention of the stomach and intestines with air. No significant gross pathological condition was detected in other organs or tissues.

Interpretation of results:
Category 5 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Under the conditions of the study, the acute inhalation exposure of rats for two hours to saturated vapors generated at 200°C produced 100 per cent mortality, while for exposures of one hour, no mortality was observed. The nominal concentration was 11 mg/L and this study is of a condensation aerosol. Thus the 1 hour LC50 based on nominal concentration was >11 mg/L. Under the OECD GHS guidelines, a 4 hr LC50 can be determined from a 1 hour LC50 by dividing by 4. Thus a calculated 4 hour LC50 value based on nominal concentration would be >2.75 mg/L.
Executive summary:

The acute toxicity following 1 or 2 hours exposure to saturated vapors of glycerine (generated by passing air through test material heated to 200C) was determined. Under the conditions of the study, the acute inhalation exposure of rats for two hours to saturated vapors generated at 200°C produced 100 per cent mortality, while for exposures of one hour, no mortality was observed. The nominal concentration was 11.0 mg/L and this study is of a condensation aerosol. Thus the 1 hour LC50 based on nominal concentration was >11.0 mg/L. Under the OECD GHS guidelines, a 4 hr LC50 can be determined from a 1 hour LC50 by dividing by 4. Thus a calculated 4 hour LC50 value based on nominal concentration would be >2.75 mg/L.

In addition the L(Ct)50 was determined following exposure to 1100 mg/L. The L(Ct)50 for Glycerine was 4655 mg minute/liter.

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

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
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
Qualifier:
no guideline available
Principles of method if other than guideline:
Test material was administered dermally to groups of guinea pigs. The material remained in dermal contact for 4 days. Animals were observed for two weeks after removal of the dermal bandage
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
guinea pig
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
No additional information available.
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
The hair was removed with electric clippers from a band of skin about three inches wide, completely encircling the animal between the fore and hind legs. One day was then allowed for healing of any small accidental skin nicks. Then the animal was weighed and the dose calculated in terms of millitliters of material per kilo body weight. A piece of three-inch adhesive tape was cut, long enough to encircle the clipped area about twice. On this a flat pad of absorbent cotton was laid, thick enough and large enough to retain the entire calculated dose. For the larger doses, this cotton pad was about 2 x 10 cm., and the full thickness of cotton in a standard one pound roll. For smaller doses the pad was made proportionately smaller and thinner. This cotton pad then received the measured dose and the tape and pad were wrapped about the pig, covering the clipped area, the cotton over the abdomen. About three, or in most cases four days, the tape was removed without the use of solvents, the skin area observed for signs of irritation other than that due to the tape.
Duration of exposure:
three or four days
Doses:
16, 40, 50 and 60 ml/kg
No. of animals per sex per dose:
5 guiinea pigs (mixed sex) were dosed at 50 and 60 ml/kg, 8 guinea pigs were dosed at 40 ml/kg and 1 guinea pig was dosed at 16 ml/kg. One male was dosed with 16 ml/kg, 3 males and 5 females were dosed with 40 ml/kg, 1 male and 4 females were dosed with 50 ml/kg and 4 males and 1 female were dosed with 60 ml/kg.
Control animals:
not specified
Details on study design:
Following removal of the bandage the animals were kept under observation for two weeks, or until they died.
Statistics:
No additional information available.
Preliminary study:
Not applicable.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
45 mL/kg bw
Based on:
test mat.
Mortality:
See Table below
Clinical signs:
After about 12 hours the animals became accustomed to the restriction of the bandage and ate and in general behaved as usual, those having large doses being weak with low body temperature and dying; those with small doses apparently not being affected.

No evidence of skin irritation from the dose in the cotton pad was observed.
Body weight:
At 60 ml/kg, the body weight of the surviving male was 130 gram greater than on the day of dosing.
At 60 ml/kg, the body weight of the surviving female was 3 grams less than on the day of dosing.

At 50 ml/kg, the body weight of the surviving female was 3 grams greater than on the day of dosing.

At 40 ml/kg, the body weight of the two surviving males was 8 and 34 grams less than on the day of dosing.
At 40 ml/kg, the body weight of the three surviving females was -12, -38 and 14 grams from the predosing level.

At 16 ml/kg, the body weight of the surviving male was 23 grams less than on the day of dosing.
Gross pathology:
No additional information available.
Other findings:
No additional information available.

Mortality

 Dose Level (ml/kg)  Number dosed  Number survived
16   1  0
 40  8  3
 50  5  4
 60  5  3

Interpretation of results:
study cannot be used for classification
Remarks:
Migrated information
Conclusions:
The acute dermal toxicity of glycerin was examined in guinea pigs. The dermal LD50 was determined to be 45 ml/kg (56,750 mg/kg) in guinea pigs.
Executive summary:

The acute dermal toxicity of glycerin was examined in guinea pigs. The dermal LD50 was determined to be 45 ml/kg (56,750 mg/kg) in guinea pigs.

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

Additional information

Acute Oral toxicity:

There are no data for polyglycerine. Data exist for the components. The acute oral LD50 of glycerol was determined in three species, rat, mice and guinea pigs. In all three species the oral LD50 was >/= 11,500 mg/kg. For the higher MW polyglycerols, data exist for polyglycerol ricinoleate (PGPR) where a dose of 20,000 mg/kg resulted only in diarrhea (no deaths). Since polyglycerol (called Polyglycerine-Heavy in Justification document) represents 9% MW of PGPR, the oral LD0 was1800 mg/kg in rats. For further information on justification for using PGPR data, see Section 13.

Inhalation:

There are no data for polyglycerine. Data exist for the main component, glycerine. In an inhalation study, rats were exposed to vapors from test material heated to 200°C for 1 or 2 hours. Under the conditions of the study, the acute inhalation exposure of rats for two hours to saturated vapors generated at 200°C produced 100 percent mortality, while for exposures of one hour, no mortality was observed. The nominal concentration was 1100 mg/L and this study is of a condensation aerosolproduced from glycerol heated to 200°C. Thus the 1-hour LC50 based on nominal concentration was >1100 mg/L. Under the OECD GHS guidelines, a 4-hr LC50 can be determined from a 1-hour LC50 by dividing by 4. Thus a calculated 4-hour LC50 value of products of glycerol heated to 200°C, based on nominal concentration, would be >275 mg/L

Dermal:

There are no data for polyglycerine. Data exist for the main component, glycerine. A dose of 45 ml/kg produced no adverse effects. Based on the lack of significant oral toxicity in the study of PGPR, dermal exposure to polyglycerine is also not expected to produce significant toxicity.


Justification for selection of acute toxicity – oral endpoint
Data for major component of target substance, in addition to data for other components and in a number of laboratory species. Weight of Evidence suggests low acute toxicity by oral route and no adverse effects were observed in several studies.

Justification for selection of acute toxicity – inhalation endpoint
Data for major component, glycerine, with lowest molecular weight and hence highest vapour pressure.

Justification for selection of acute toxicity – dermal endpoint
Data for major component of target substance.

Justification for classification or non-classification

Based on the study data of the major component, glycerine and polyglycerol (as part of polyglycerol polyricinoleate) for oral, inhalation and dermal endpoints, the classification according to GHS and the Directive 67/584/EEC (DSD) is not warranted.