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Administrative data

Description of key information

There are sufficient data to assess the acute toxicity of 3-methoxylbutyl acetate and it is considered to have low acute toxicity by oral, inhalation and dermal routes of exposure. 

Key value for chemical safety assessment

Additional information

Although there are no guideline acute toxicity studies available for 3-methoxybutyl acetate there is sufficient weight of evidence to conclude that the material is of low acute toxicity. 

The acute toxicity of 3-methoxybutyl acetate was first reported in the 1930’s. A series of tests investigated its acute and subacute toxicity in several animal species following, for example, inhalation and subcutaneous routes of exposure. Similar tests were conducted on 3-methoxybutan-1-ol which is likely to be the major proximate metabolite of 3-methoxybutyl acetate (see CSR Section 5.1) and results reported for 3-methoxybutan-1-ol are very similar to those for 3 -methoxybutyl acetate.  Although these tests are poorly reported by modern standards, comparable results have been reported in several species and following different routes of exposure and are also consistent with results of later guideline repeat dose studies for 3-methoxybutyl acetate.

In an early study, conducted and reported by Hoechst (1930), 5 groups of mice were exposed for 2 hours to concentrations of 3-methoxybutyl acetate ranging from about 47,500 to 285,000 mg/m3. Following exposure (2 hours) at 142,500 mg/m3 and at 190,000 mg/m3 one animal of three died during the overnight post exposure period. At the highest dose, all animals survived.

In contemporary experiments, various species including rats, cats and rabbits were exposed for 6 hours to 3 -methoxybutyl acetate saturated in air. In each study, no adverse clinical signs were reported, other than mild irritation. The concentration of 3-methoxybutyl acetate in these experiments was about 10,000 mg/m3.

Although these acute inhalation toxicity experiments are non-guideline studies, it appears that the LC50 (2 hour) for 3-methoxybutyl acetate is likely to be at least 95,000 mg/m3. In addition as exposure for 6 hours to other species such as cats and rabbits to a concentration of 10,000 mg/m3 were reported to produce, at worst, mild irritation, it seems likely that the LC50 (6 hour) is likely to be greater than 20,000 mg/m3.

Other early studies reported low acute and subacute toxicity following subcutaneous administration of 3-methoxybutyl acetate.  A 10% solution of 3 -methoxybutyl acetate in oil injected under the skin of one guinea pig as a single dose of 0.1 g/kg, and under the skin of another guinea pig on six consecutive days (same dose). The animals did not display any clinical symptoms and no abnormal findings were found in the urine. The same treatment also did not harm rats. In addition, a single dose of 0.5 g/kg and 1 g/kg did not cause any symptoms in rats. Therefore although there are no dermal acute toxicity studies available, the results of these subcutaneous injection studies (Hoechst AG, 1930) indicate that the dermal route is also likely to be characterised by low toxicity.

More recently in a guideline study 3-methoxybutyl acetate was administered to pregnant rats at limit dose (1000 mg/kg/d). In this prenatal developmental toxicity study, a group of 20 pregnant rats was dosed between days 7-16 of gestation with 1000 mg/kg, in sesame oil, orally by gavage. At 1000 mg/kg, 3-methoxybutyl acetate was neither maternally nor developmentally toxic.

This is consistent with results for oral acute toxicity studies with 3-methoxybutan-1-ol, the putative rapidly formed major metabolite of 3 -methoxybutyl acetate. In an acute oral study with male and female Wistar rats, 3-methoxybutan-1-ol was dosed orally, by gavage, at 2000 mg/kg in water. Animals were observed daily for a further 14 days and weighed at weekly intervals. On day 15, rats were killed and examined grossly. The LD50 of 3-methoxybutan-1-ol was reported to be >2000 mg/kg.

The diverse information above characterises a substance of low acute toxicity. By the inhalation route of exposure, although no guideline study is available, it is clear that the LC50 (4hr) is likely to be greater than 20,000 mg/m3. Similarly with oral gavage administration the lack of any toxic effects at 1000 mg/kg/d to pregnant rats indicates that the LD50 is clearly significantly greater. The low systemic toxicity profile indicated by these routes of exposure is also consistent with the lack of findings following subcutaneous injection of 1000 mg/kg to rats. Indeed the lack of effects reported following oral administration to pregnant rats, combined with the relatively high dose levels administered in inhalation studies without effect, supported by the lack of clinical signs from subcutaneous injection studies indicate that, as for 3-methoxybutan-1-ol (LD50 >2000 mg/kg), the oral LD50 is likely to significantly greater than 1000 mg/kg and probably similar to 3 -methoxybutan-1-ol.   Further acute toxicity investigations are considered scientifically unjustified.

Justification for classification or non-classification

According to criteria in Regulation (EC) No.1272/2008, 3 -methoxybutyl acetate is not classified for acute toxicity. There are sufficient data available for 3 -methoxybutyl acetate to conclude that the substance does not warrant classification for acute toxicity via oral, inhalation or dermal routes of exposure.