2,2-dimethyl-1,3-dioxolan-4-ylmethanol

Endpoint summary

Description of key information

The available information suggests that AUGEO SL 191 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. From its high water solubility, dermal absorption of AUGEO SL 191 is predicted to be low. No information is available to assess metabolism or elimination. 

Key value for chemical safety assessment

Bioaccumulation potential:

no bioaccumulation potential

Additional information

No specific toxicokinetic studies are available on AUGEO SL 191. The toxicokinetic assessment presented here is based on the physico-chemical properties of the test substance, scientific literature and the results of toxicity studies (acute oral, dermal, inhalation toxicity, in vitro and in vivo genotoxicity studies, combined repeat dose study with reproductive/developmental screening, sub-acute and sub-chronic toxicity studies by inhalation and prenatal developmental toxicity study).

 

Physicochemical Properties

 Properties relevant for assessment of toxicokinetic properties are:

 Molecular weight:      132.1577 g/mol

Water solubility:       172 g/L

Log KOW:                 0.3

The vapour pressure of the test item at 20°C is 34+/- 2 Pa. The test item is considered as low volatile.

 

Absorption and Distribution

- Oral route:

2,2-Dimethyl-1,3-dioxolane-4-methanol exhibits low acute toxicity by the oral route. In an acute oral toxicity study in the rat (Merck Index 2001) its LD50 was reported to be 7000 mg/kg bw. Therefore this product is expected to have no or very low acute toxic effects by the oral route. However no details were available on this study which was determined to be of reliability 4 (deaths and clinical signs of toxicity were not reported). It is not possible to determine from this study whether the low level of toxic effects was due to inherent low toxicity or to low absorption from the gastrointestinal tract.

In a combined repeat dose toxicity with reproductive/developmental toxicity screening study (OECD 422) in the rat (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.

- Dermal route:

There was no evidence of systemic toxicity in the acute dermal toxicity study in rats at the dose of 2000 mg/kg bw.

There were also no signs of toxicity and no sensitization effects after cutaneous exposure in a Guinea Pig maximization study.

However, the log Po/w of 0.3 and water solubility ( 172 g/L at 20°C) tend to support a limited capacity for absorption through the skin.

- Inhalation route:

There was no evidence of systemic toxicity in the acute inhalation toxicity study and in the 14-day and 90-day repeated dose toxicity study in rats at the dose of 5 mg/L air.

 

Metabolism

An in vitro study assessed the potential mutagenicity of 2,2-Dimethyl-1,3-dioxolane-4-methanol both with and without auxiliary metabolic activation. An Ames test (Camolesi, 2009) gave negative results with no indication of cytotoxicity either with or without metabolic activation. As such, this study confirmed that 2,2-Dimethyl-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 the rat (Chevalier, 2013). These effects suggest that 2,2-Dimethyl-1,3-dioxolane-4-methanol may be metabolized in this organ, however no studies to identify metabolites have been carried out. No systemic effects were reported in pregnant rats up to the oral dose of 1000 mg/kg bw in the prenatal developmental toxicity study (Oroszlány, 2018) nor in rats exposed by inhalation for up to 90 days to a test item concentration of up to 5 mg/L air (Toth, 2018).

 

Elimination

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