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Description of key information

Two key studies have been identified: one 90d oral toxicity study (K2, The Dow Chemical Company, 1962) and one subchronic toxicity by inhalation study (K2, Renne R., 1992), both performed with the read-across substance glycerol. 
Repeated dose toxicity: oral:
The effect of glycerol following administration for 90 days in a subchronic toxicity study was examined (The Dow Chemical Company, 1962). The test has been performed with the read-across substance glycerol. Animals were exposed orally (via diet) to 0, 5 and 20 % of test substance in diet. A NOAEL of 4850 mg/kg was determined. This study was scored as K2 study (reliable with restrictions) because of read across purposes and was considered as the key study.
Repeated dose toxicity: inhalation:
The subchronic toxicity of glycerol was examined following aerosol exposure. Sprague-Dawley rats were exposed to 33, 165 and 660 mg/m³ (nominal concentration) of test item, during 6 hours/day, 5days a week for 13 weeks. The NOAEL was determined to be 167 mg/m³ (actual dose level) based on local irritant effects on the upper respiratory tract.
Repeated dose toxicity: dermal:
Key studies are available for the oral and inhalation routes of exposure (read across with glycerol). According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
4 580 mg/kg bw/day
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEC
167 mg/m³
Study duration:
subchronic
Species:
rat

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

The information requirements of repeated dose toxicity of glycerine carbonate were covered with studies from the read-across substance glycerol.

Repeated dose toxicity: oral:

The effect of glycerol following oral administration was examined in a subchronic toxicity study. Test material was administered via the diet at 5 and 20% for 90 days. Body weights and feed consumption were measured at selected intervals. At necropsy, lung, heart, liver, kidney, spleen and testes absolute and relative weights were obtained. Basic hematologic and clinical chemistry measurements were made. Rats fed 5 or 20% glycerol in the diet gained weight at a faster rate than control animals. There were no adverse treatment related effects noted in male or female rats fed 5% glycerol in the diet. In the male rats which received 20 percent glycerol, there was an increase in the final liver/body weight ratio and upon microscopic examination generalized cloudy swelling and hypertrophy of the parenchymal cells was observed. The only effect in the female rats on this level was some generalized cloudy selling upon microscopic examination of the liver. A 5% glycerol in the diet corresponded to 4580 and 6450 mg/kg/day for male and female rats, respectively, after 4 weeks and a 20% glycerol in the diet corresponded to 18,750 and 25,800 mg/kg/day for male and female rats, respectively, after 4 weeks.

Repeated dose toxicity: inhalation:

Renne R. (1992) examined the subchronic toxicity of glycerol following aerosol exposure, at concentrations 33, 165 and 660 mg/m³ (nominal concentration). Sprague-Dawley rats were exposed to the test item during 6 hours per day, 5 days per week for 13 weeks. The NOAEL was 167 mg/m³ (actual dose level) based on local irritant effects on the upper respiratory tract.

 

Repeated dose toxicity: dermal:

Two key studies with the read-across substance glycerol are available for the oral and inhalation routes of exposure. According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the dermal or inhalation route of exposure.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Only one reliable study available with the read-across substance glycerol. The justification for this read-across is added to Section 13 of this substance dataset.

Justification for selection of repeated dose toxicity inhalation - systemic effects endpoint:
Only one reliable study available with the read-across substance glycerol. The justification for this read-across is added to Section 13 of this substance dataset.

Justification for selection of repeated dose toxicity inhalation - local effects endpoint:
Only one reliable study available with the read-across substance glycerol. The justification for this read-across is added to Section 13 of this substance dataset.

Justification for selection of repeated dose toxicity dermal - systemic effects endpoint:
A key study is available for the oral and inhalation route of exposure (read-across with glycerol). According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the dermal route of exposure.

Justification for selection of repeated dose toxicity dermal - local effects endpoint:
Key studies are available for the oral and inhalation routes of exposure (read across with glycerol). According to the REACH Regulation, only one route of exposure should be tested for repeated dose toxicity (column 2, annex VIII, section 8.6.1). Therefore, it is not necessary to perform a repeated dose toxicity study via the dermal route of exposure.

Justification for classification or non-classification

The LOAEL (oral route) of the read-across substance glycerol is greater than 4850 mg/kg bw/day and the LOAEC of the read-across substance glycerol is 0.66 mg/l/6 h/d for the inhalation route of exposure (dust/mist/fume). These values are greater than the upper limits of the guidance value range in the CLP Regulation for STOT RE classification category 2 of a 90 day test via the oral and inhalation routes (100 mg/kg and 0.2 mg/l/6h/d respectively). Based on these read-across results, glycerine carbonate should not be classified as STOT RE.

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