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Key value for chemical safety assessment

Effects on fertility

Effect on fertility: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
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).
Effect on fertility: via inhalation route
Endpoint conclusion:
no study available
Effect on fertility: via dermal route
Endpoint conclusion:
no study available
Additional information

The toxicity to reproduction 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 toxicity study to reproduction 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 condition, the dose-level of 1000 mg/kg/day was considered to be the No Observed Effect Level (NOEL) for reproductive performance (mating and fertility).

Short description of key information:
NOEL for reproductive toxicity = 1000 mg/kg bw/day based on no adverse effects on fertility (data obtained on the analogue substance 2,2-dimethyl-1,3-dioxolan-4-ymethanol).

Justification for selection of Effect on fertility via oral route:
Only one study available for this endpoint

Effects on developmental toxicity

Description of key information
NOEL for developmental toxicity = 1000 mg/kg bw/day based on no adverse effects on post-natal development of offspring (data obtained on the analogue substance 2,2-dimethyl-1,3-dioxolane-4-methanol).
Effect on developmental toxicity: via oral route
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
1 000 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
GLP study conducted on the analogue substance 2,2-dimethyl-1,3-dioxolane-4-methanol according to OECD Guideline 422 without any deviation (Klimisch score = 2).
Effect on developmental toxicity: via inhalation route
Endpoint conclusion:
no study available
Effect on developmental toxicity: via dermal route
Endpoint conclusion:
no study available
Additional information

The developmental toxicity 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 reproduction/developmental toxicity screening 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 condition, the dose-level of 1000 mg/kg/day was considered to be the No Observed Effect Level (NOEL) for toxic effects on progeny.

Justification for selection of Effect on developmental toxicity: via oral route:
Only one study available for this endpoint

Justification for classification or non-classification

In a GLP combined repeated dose toxicity and reproduction / developmental toxicity screening test conducted on the analogue substance

2,2-Dimethyl-1,3-dioxolane-4-methanol

according to OECD guideline 422, no adverse signs of toxicity to reproduction (mating performance, fertility and post-natal development of offspring) were observed and therefore, by analogy, 2 -isobutyl-2 -methyl-1,3-dioxolane-4-methanol is not classified for reproduction and for developmental toxicity according to the Regulation (EC) N° 1272 -2008 (CLP) and the Directive 67/548/EEC.