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Administrative data

Description of key information

NOAEL for systemic toxicity = 1000 mg/kg bw/day for males since the observed effects in males are not relevant for human risk assessment. 
NOEL for systemic toxicity = 1000 mg/kg bw/day for females based on the absence of significant effects related to test item on females (data obtained on the analogue substance 2,2-dimethyl-1,3-dioxolane-4-methanol)

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
Study duration:
subacute
Species:
rat
Quality of whole database:
Recent GLP study conducted on the analogue substance 2,2-dimethyl-1,3-dioxolane-4-methanol according to OECD Guideline 422 without any major deviation (Klimisch score = 2).

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

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

Mode of Action Analysis / Human Relevance Framework

Additional information

The toxicity following repeated exposures of 2 -isobutyl-2 -methyl-1,3 -dioxolane-4 -methanol was determined by a read-across approach using the analogue substance 2,2-dimethyl-1,3-dioxolane-4 -methanol.

The repeated dose toxicity study of 2,2-dimethyl-1,3-dioxolane-4 -methanol is summarized below:

In a Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test conducted according to OECD Guideline 422 and in compliance with GLP, 2,2-Dimethyl-1,3-dioxolane-4-methanol diluted in Phosphate Buffer Saline solution was administered daily by oral gavage to male and female Sprague-Dawley rats (10/sex/dose), for 2 weeks before mating, during mating and (for females) throughout gestation and until day 5 post-partum, at dose-levels of 250, 500 or 1000 mg/kg bw/day. A control group was treated with Phosphate Buffer Saline solution.

No test item-related deaths or clinical signs were noted in any group and sex. No toxicologically relevant effects on mean body weight, mean food consumption, mean Functional Observation Battery and motor activity data and mean clinical pathology parameters in any group and sex. The increase in the absolute and relative liver weights recorded in males given 1000 mg/kg bw/day was considered not to be adverse in view of the slight magnitude of the changes and the absence of microscopic correlates. None of the macroscopic findings were attributed to the test item administration. At histopathology, tubular hyaline droplets in the kidneys (consistent with rat-specific alpha-2u-globulin) were seen with increased incidence and severity in males treated at 1000 mg/kg bw/day compared to controls (presence of dense eosinophilic droplets in proximal tubular epithelium). This finding was not observed at 250 or 500 mg/kg bw/day. These kidney effects were considered to be related to alpha-2u globulin nephropathy and of no relevance to humans. There were no toxicologically relevant effects on mean mating, fertility and delivery data in any group. There were no test item-related effects on pups by day 5 post partum (viability, clinical signs, sex ratio, macroscopic post-mortem findings).

 

Under the test conditions, the No Observed Adverse Effect Level (NOAEL) for systemic toxicity was considered to be 1000 mg/kg bw/day in rats (based on findings in the kidneys of males).

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
Only one study available

Justification for classification or non-classification

Under the test conditions, the No Observed Adverse Effect Level (NOAEL) for systemic toxicity obtained in an OECD 422 study performed on the analogue substance 2,2-dimethyl-1,3-dioxolane-4 -methanol was considered to be the highest dose tested in rats based on findings in the kidneys of males (i.e. 1000 mg/kg bw/day which is >300 mg/kg bw/day); as these effects are considered not relevant to humans therefore no target organ was identified. Thus, by analogy, 2 -isobutyl-2 -methyl-1,3-dioxolane-4-methanol does not need to be classified for repeated dose toxicity according to the Regulation (EC) No. 1272-2008 (CLP) and according to the Directive 67/548/EEC.