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Description of key information

NOAEL (28 days repeated dose, Wistar): >= 1000 mg/kg bw (female rat); 300 mg/kg bw (male rat) due to effects on the spleen at 1000 mg/kg bw

Key value for chemical safety assessment

Additional information

n a repeated dose oral toxicity study in rats (Wistar, OECD TG 407), ethan-1,2 -diol, propoxylated was adimistered via gavage to 5 rats/sex/dose at 0, 100, 300, 1000 mg/kg bw for 4 weeks. Up to and including 1000 mg/kg bw no mortality occured. The behavior and clinical appearance of the rats were not influenced by the treatment up to and including 1000 mg/kg in both sexes. The body weight gain, the food and water intake were not affected up to and including 1000 mg/kg in males and females. The results from Functional Observational Battery (FOB) measurements in males and females receiving up to and including 1000 mg/kg bw did not differ from the control animals.Motor and Locomotor Activity(MA/LMA) tests did not indicate neurotoxicity up to and including 1000 mg/kg. No effects with toxiocological relevance in haematologyin both sexes up to and including 1000 mg/kg bw. No remarkable changes occurred in clinical chemical parameters in the blood up to and including 1000 mg/kg in males and females.Gross pathology revealed in the liver of some 1000 mg/kg males distinct lobulation, enlargement or swelling and accordingly an increase in liver weights.

Histopathologically these findings correlated with minimal to slight hepatocellular cytoplasmic change/hypertrophy in the males of the 1000 mg/kg bw dose group. In the absence of any other liver changes, this is not seen as an adverse effect but as an adaptive response.In the spleen increased germinal centers were present in the white pulp follicles of 1000 mg/kg males. A treatment-relation could not be excluded for this finding.

Based on these results the NOAEL was considered to be 1000 mg/kg bw and day for females and 300 mg/kg bw and day for males due to the microscopic changes in the spleen

"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 justification for the grouping of the new NLP polyols is given above. An earlier report (Illing and Barratt, 2009) set out proposals for the first group of NLP polyols. The conclusion was that no further testing would be required for these substances.

The new propoxylated NLP polyols are likely to be equally as non toxic as those previously examined, and therefore the arguments justifying no further testing for repeated dose (Illing and Barratt, 20010) toxicity apply equally to both the original group and the new group. Ethane-1,2-diol, propoxylated was specifically examined in a repeated dose study and found not to be an exception and not classifiable.

Given the large body of evidence, including long terms studies for core substances and repeating units, and the confirmation of the lack of toxicity in short term repeated dose studies on NLP polyols, there is no adequate justification for further animal testing, and, on grounds of animal welfare no further repeated dose toxicity should be undertaken."

(cited from Illing, H P A, Barratt, M D (2010). Grouping of Additional NLP ‘Polyols’ and their Toxicokinetics Assessments. Confidential report to the REACH Centrum July 2010)

 

Justification for classification or non-classification

The findings from repeated dose toxicity testing do not warrant classification according to EU criteria.