Oxybispropanediol

Endpoint summary

Description of key information

Repeated dose inhalation toxicity is read-across from glycerol: a 14-day and 90-day study available. And a 2-year oral repeated dose toxicity study is available with glycerol.

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

662 mg/m³

Study duration:

subchronic

Species:

rat

Additional information

An oral toxicity study with glycerol is available.

In a dietary study, groups of 22 rats (Long-Evans)/sex/treatment received 5, 10 and 20% glycerol (natural or synthetic) in their diet (males 2000, 4000 and 8000 mg/kg bw; females 2500, 5000 and 10000 mg/kg bw) for 2 years. Routine clinical observations were made, and bodyweight and food consumption was determined weekly. Deviations from the OECD guideline included the absence of clinical chemistry investigation and a limited range of haematological and urinary analyses were performed. A limited range of organs was investigated at necropsy and the liver, spleen, adrenals, small intestine, gonads and urinary bladder were examined microscopically. Glycogen and fat content of the liver was determined in surviving rats from the 0 and 20 % dose groups. No individual data were reported. For high dosed animals treatment was discontinued after 1 year. No data on mortality and clinical observations were reported. Food consumption was slightly increased in males treated with 5 and 10% natural glycerol. Incidental observations considered by the report-authors to be without relationship to treatment included: bronchiectasis, pneumonia, pulmonary abcesses, hydronephrosis and pyelonephritis. Although the results were not described in detail, based on this limited dietary study it can be concluded that no adverse effects were observed at up to 10,000 mg/kg bw.

A 14-day and 90 -day inhalation study in rats is available for glycerol.

In a 2 -week inhalation study in rats (0, 1000, 2000 or 4000 mg/m3, 5d/week, 6 h/d), 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 MMAD was reported to be < 1.5 micrometres.

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 LOAEC for systemic effects is set at 1000 mg/m3. Based on the observed increased in laryngeal squamous metaplasia, the LOAEC for local effects is set at 1000 mg/m3.

 

In a 13-week inhalation study in rats (0, 33, 165 or 660 mg/m3, actual concentrations 33, 167 and 662 mg/m3, 5d/week, 6h/d, MMAD <2 micrometres) no effects on mortality, clinical signs, body weight and food consumption, haematology, 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 set at ≥ 662 mg/m3. Based on the laryngeal squamous metaplasia at the high dose group, the NOAEC for local effects is set at 165 mg/m3.

Justification for classification or non-classification

Based on the results from the repeated dose toxicity studies, diglycerol is not classified according to CLP Regulation (EC) No. 1272/2008.