D-Glucitol, propoxylated

Endpoint summary

Description of key information

NOAEL (28 days repeated dose, Wistar): ≥ 1000 mg/kg bw.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Additional information

Result 'read across' from study on 2,2’,2’’ nitrilotriethanol, propoxylated as permitted by Annex XI para 1.5, based on the justification in the report from Paul Illing Consultancy Services Ltd. and Marlin Consultancy (Illing and Barratt, 2007). The report identifies that 2,2’,2’’-nitrilotriethanol, propoxylated is the most bioavailable of the NLP polyols linked by an ether group, and that the lack of systemic toxicity seen for it, and for both the components (Glucitol and propane-1,2-diol) of Glucitol, propoxylated should be considered representative of the lack of toxicity of the ether-linked NLP polyol. Thus, an animal welfare grounds this test should not be undertaken on D-Glucitol, propoxylated. For further details concerning the grouping, consult Illing and Barratt, 2009 and 2009 attached in Section 13.

In a repeated dose oral toxicity study in rats (Wistar, OECD TG 407), 2,2',2" -Nitrilotriethanol, propoxylated was administered via gavage to 5 rats/sex/dose at 0, 100, 300, 1000 mg/kg bw for 4 weeks. No death was observed in either sex. No clinical effects were observed in both sexes of all dose groups. There was no effect observed upon haematological, clinical biochemistry or macroscopic examination at any dose. Based on these results the NOAEL was considered to be ≥ 1000 mg/kg bw/day. If at all the slight changes in thyroids of females at 1000 mg/kg were related to the treatment, they are regarded as an indirect and adaptive effect.

The need for further testing for individual NLP polyols under the REACH Regulation can be significantly modified if arrangements for grouping into categories and ‘read across’, based on the principles in Annex XI can be used. The justifications and the proposed categories are set out in Part 1 of Barratt and Illing (2009). 'Read across' based on (a) the same bond linking the core moiety and the repeating unit moiety (b) molecular weight distributions. Glucitol listed in Annex 4 of the regulation. Experimental data on core substances, repeating units, selected polyols within the category and 'read across' based on bioavailabilities indicates that the propoxylated substances in this category are not classifiable in respect of their repeated dose toxicity. This categorisation for read across has also been used to justify read across for tests required by Annex VII and VIII. There is sufficient available information for an adequate hazard characterisation and a chemical safety assessment. In view of this ‘weight of evidence’ approach and the need to consider animal welfare, no further testing is proposed.

As stated above, there is sufficient information from a qualitative and quantitative understanding of the toxicological properties of the core substance (glucitol is listed on Annex IV of the REACH Regulation) and the repeating unit, propane-1,2-diol. D-glucitol enters endogenous carbohydrate metabolism and is converted metabolically to fructose (Illing and Barratt, 2009 and 2009; see Section 13). Repeated exposure of rats to propylene glycol (propane-1,2 -diol) in drinking water or fed did not result in adverse effects at levels up to 10% in water (estimated at about 10 g/kg bw/d for 140 days) or 5% in feed (dosage reported as 2.5 g/kg bw/d for two years) (Illing and Barratt, 2009 and 2009; see Section 13).

 

Justification for classification or non-classification

On the basis of read across the substance does not meet the criteria for classification.