Registration Dossier

Administrative data

Description of key information

Ethyl acetate has a low order of toxicity in animals following single oral, dermal, or inhalation exposure.  

ACUTE ORAL toxicity LD50 values (mg/kg):

rat: 5620, 6100, 10200. rabbit: 4934, 7650.  mouse: 4100

ACUTE INHALATION toxicity values (mg/l)

rat: LC50: >22.5 (6hr), 200 (1hr), >18 (3-4hr)

mouse: LD100 ~8.8, 44

ACUTE DERMAL

rabbit: >20g/kg

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
Value:
4 934 mg/kg bw

Additional information

In a recent, well-conducted dose range study, all exposed rats survived inhaled concentrations up to 6000 ppm (22.5 mg/l) for 6 hours. . The main symptoms seen following acute exposure are those typical of substances which cause central nervous system depression, including loss of voluntary movement and sedation at concentrations of 11.25mg/l and above. In a 4-hour acute inhalation study, the LC50 was between 29.3 mg/L (LC0) and 58.6 mg/L (LC100). Examples of other acute inhalation LC50 values are 44 mg/L after 3 hours, 33.5 mg/L after 2 hrs, and 200 mg/L after 1 hour of exposure; these studies however, reported limited information and thus, could not be verified.

A dermal LD50 of >20,000 mg/kg was determined for rabbits (Smyth et al., 1962).

The lowest reported oral LD50 s are 10,170 mg/kg (rat) and 4,934 mg/kg (rabbit). Rabbits were administered ethyl acetate via oral gavage. The narcotic dose at which 50% exhibited loss of voluntary movements and stupor was 4493 mg/kg-bw. Additional symptoms included disappearance of corneal reflexes, shortness of breath, involuntary eye movements and slowed heart rates at some doses. The second lowest available value is selected for the key parameter as the lowest value (mouse) is from a study that cannot be confirmed as reliable. The difference between these values is relatively small and likely to be within statistical error. A weight of evidence approach is used across two studies, both of which have some shortcomings but combined, along with the supporting data, provide sufficient evidence to conclude that this substance is of low acute oral toxicity.

There are few reports available which document the effects of acute high-level exposure to ethyl acetate alone in humans. There is a case report of a worker who died following accidental inhalation exposure in an enclosed space to vapor from a lacquer containing 80% ethyl acetate. The other constituents of the lacquer were not identified. The worker was reported to have hyperaemia of the upper respiratory tract. A recent study reported a fatal workplace accident involving acute intoxication by ethyl acetate. See Section 7.10.3 for details.

 

Justification for classification or non-classification

No classification for acute toxicity is proposed based on reliable animal data. Neither the oral, dermal or inhalation LC50/LD50 values reach the thresholds under directive 67/548 or regulation 1272/2008 that would require classification.

The available evidence does suggest that acute narcotic effects can be produced from the inhalation of ethyl acetate vapours at concentrations below 20mg/l. A classification of R67 is therefore warranted. Under GHS, a classification for single exposure STOT category 3 (H336) is warranted.