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Administrative data

Description of key information

All repeated dose toxicity data is based on the read across substances glycerol and Polyglycerol Polyricinoleate (PGPR). See "Read across report" attached to the dossier.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEL
10 000 mg/kg bw/day
Study duration:
chronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Dose descriptor:
NOAEC
660 mg/m³
Study duration:
subchronic
Species:
rat

Additional information

Repeated dose toxicity studies with Polyglycerin are not available. The results of experimental studies with the read across substance glycerol are presented below.

Oral exposure (key study):

A 1-year chronic toxicity study with natural and synthetic glycerol was carried on males and females of Long-Evans rats. Based on the absence of treatment related effects in high dose animals, the NOAEL was calculated as 10000 mg/kg bw.

Inhalation route (key study):

In a 2-week inhalation study in rats (0, 1, 2 or 4 mg/L), a decrease in mean body weight gain was noted for all exposure groups; decreases were statistically significant in females with an inverse relationship between exposure concentrations and body weight gain. Furthermore, a decreased in blood glucose values was in females (inverse dose response). No further changes were noted in food consumption, haematology, clinical biochemistry, organ weights and macroscopy.At histopathology, minimal to mild squamous metaplasia of the epithelium lining of the base of the epiglottis in larynx was observed in most rats of all concentration groups. The increase incidence of this finding was statistically significant at all dose groups.

The toxicological significance of the inverse dose response on mean body weight gain and blood glucose levels in female rats remains unclear. In absence of further data and since the reductions in body weight gain were significant (42-62% of controls), these findings are considered toxicologically relevant and therefore the NOAEC for systemic effects is < 1 mg/L. Based on the observed increased in laryngeal squamous metaplasia, the LOAEC for local effects is < 1 mg/L.

In a 13-week inhalation study in rats (0, 0.033, 0.165 or 0.66 mg/L) no effects on mortality, clinical signs, body weight and food consumption, hematology, organ weights and gross pathology were reported. In clinical biochemistry, a statistically significant increase in triglyceride values in the low and medium male exposure groups (134 and 123% of controls) were observed; an inverse relation between exposure and triglyceride values. In females, slightly lower values were measured at the low and medium exposure groups (83 and 93% of controls). No further changes were reported for clinical biochemistry.

At histopathology, minimal squamous metaplasia of epithelium lining of the base of the epiglottis was observed half of the animals of the high dose group, one high dose animal showed mild laryngeal squamous metaplasia.

The toxicological relevance of the observed changes in triglycerides at the low and medium dose groups is unclear. However, since no corroborative findings were reported in the liver (clinical biochemistry, liver weight and histopathology) and no effect on body weight was reported, this finding is not considered adverse. Therefore the NOAEC for systemic effects is ≥ 0.66 mg/L. Based on the laryngeal squamous metaplasia at the high dose group, the NOAEC for local effects is 0.165 mg/L.

Other available information on the read across substance glycerol

More information on repeated dose toxicity is presented in the OECD SIDS dossier of glycerol. Please find hereafter the conclusion on the repeated dose toxicity of glycerol (text copied from OECD SIDS dossier of glycerol, page 18):

 

A considerable number of studies have been performed. However, many of these studies are considered to be of indeterminable reliability due to deficiencies in reporting or methodology, primarily because they were performed before internationalised guidelines were available.

 

Based on the studies of better quality, it can be concluded that repeated oral exposure by gavage to glycerol does not induce adverse effects other than local irritation of the gastro-intestinal tract. The lowest effect value was 950 mg/kg bw and found in a 3 day study with rats (Staples 1967). The design of this study was considered not to be representative for a repeateddose study, because the duration of exposure was only 3 days and only irritantproperties were investigated. The 2-year study of Hine (1953) was chosen to establish the overall NOAEL after prolonged treatment of rats with glycerol. It was concluded that the NOEL is 10,000 mg/kg bw (20% in diet), which is in agreement with most of the findings. At this dose level no systemic or local effects were observed in the parameters investigated. However, it is noted that gavage dosing with bolus administration of glycerol may enhance the local toxicity to the gastrointestinal tract compared with continuous administration via the diet, however, toxic effects are still only seen at relatively high dose levels and do not raise concern.

 

For inhalation exposure, irritant effects were observed at 662 mg/m3. No other target organ involvement was identified. The NOAEL for local effects on the respiratory tract following exposure by inhalation is 165 mg/m3.

 

Other available information on the read across substance Polyglycerol Polyricinoleate (PGPR)

In the sections on “Carcinogenicity” and “Toxicity for reproduction” information on the repeated dose toxicity ofPolyglycerol Polyricinoleate (PGPR) has been reported. A dose of 2000 mg/kg bw was considered a NOAEL for repeated dose toxicity.

Justification for classification or non-classification

The test substance is not classified for repeated dose toxicity since no adverse effects in repeated dose toxicity studies were observed.