Registration Dossier

Administrative data

Link to relevant study record(s)

Description of key information

The available information suggests that 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol is absorbed via the oral route and distributed in the bloodstream at least to the liver, however the degree of absorption has not been quantified. The low vapour pressure indicates that the substance is non-volatile at room temperature and thus the exposure of the substances via inhalation route is unlikely. Considering its high water solubility, dermal absorption of 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol is expected to be limited as confirmed by the absence of systemic effects reported in the skin sensitisation study as well as in the acute dermal toxicity study performed on the analogue substance 2,2-Dimethyl-1,3-dioxolane-4-methanol. No information is available to assess metabolism or elimination. 

Key value for chemical safety assessment

Additional information

No specific toxicokinetic studies are available on 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol. The toxicokinetic assessment presented here is based on the physico-chemical properties of the test substance, scientific literature and the results of toxicity studies on the registered substance or its close analogue 2,2-dimethyl-1,3-dioxolane-4 -methanol (acute oral and dermal toxicity,in vitro genotoxicity studies and combined repeat dose study with reproductive/developmental screening).

Physicochemical Properties

 Properties relevant for assessment of toxicokinetic properties are:

 Molecular weight:      174.238 g/mol

Water solubility:       34.6 g/L

Log KOW:                 1.57

The vapour pressure of the test item at 20°C is 30+/- 2 Pa. The test item is considered as low volatile.

 

Absorption and Distribution

- Oral route:

2-isobutyl-2-methyl-1,3-dioxolane-4-methanol exhibits low acute toxicity by the oral route. In an acute oral toxicity study in the rat (Gemio dos Reis, 2011) its LD50 was reported to be greater than 2000 mg/kg bw. At necropsy, congestion was observed in the lung and the liver which indicate that some absorption from the gastrointestinal tract occurred. In a combined repeat dose toxicity with reproductive/developmental toxicity screening study (OECD 422) performed in the rat with the analogue 2,2-dimethyl-1,3-dioxolane-4-methanol (Chevalier, 2013), the only effects reported at the highest dose level of 1000 mg/kg bw/day were a significant increase in absolute and relative liver weight in males and an increase in absolute and relative kidney weight in females. In the absence of histological correlates, the effects in liver were considered of no toxicological relevance. However these minor variations in organ weight indicate that some absorption of 2,2-Dimethyl-1,3-dioxolane-4 -methanol from the gastrointestinal tract took place, with distribution via the bloodstream to the liver. It is not possible to deduce the extent of absorption from this study.

- Inhalation:

No data are available for inhalation route of exposure. However, the test substance is a liquid with a low volatility, as evidenced by its low vapour pressure. Therefore it can be considered that the absorption resulting from potential exposure by the inhalation route is limited.

- Dermal route:

The high water solubility of the registered substance tend to support a limited capacity of absorption through the skin. This is consistent with the absence of any signs of systemic toxicity and sensitization effects after cutaneous exposure to the registered substance in a Guinea Pig maximization study. There was also no evidence of systemic toxicity in the acute dermal toxicity study performed in rats with the analogue 2,2-Dimethyl-1,3-dioxolane-4 -methanol given at the dose of 2000 mg/kg bw.

 

Metabolism

Twoin vitrostudies assessed the potential genotoxicity of 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol both with and without auxiliary metabolic activation. An Ames test (R. C. Viana Silvino, 2011) gave negative results with no indication of cytotoxicity either with or without metabolic activation. A chromosome aberration test (R. Cardoso, 2015) showed no structural aberration and limited cytotoxicity in the presence or absence of metabolic activation. As such, these studies confirmed that 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol does not have genotoxic potential but did not provide any information on metabolism. Effects in the liver of males exposed to 1000 mg/kg bw/day were reported in the combined repeat dose toxicity with reproductive/developmental toxicity screening study in rat treated with the analogue 2,2-Dimethyl-1,3-dioxolane-4-methanol (Chevalier, 2013). This effect, together with the liver congestion reported in the acute oral toxicity study, suggest that these substances may be metabolized in this organ; however no studies to identify metabolites have been carried out.

Elimination

There is no information to indicate a route of excretion for 2-isobutyl-2-methyl-1,3-dioxolane-4-methanol but its high water suggests that excretion of unchanged parent substance and/or metabolites could occur by renal or biliary routes and that bioaccumulation is unlikely.