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Description of key information

Oral: LD50 (guinea pig, m/f) = 390 mg/kg bw (lowest dose descriptor available)
Inhalation: LC50 (rat, m/f) > 5.05 mg/L

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
390 mg/kg bw
Quality of whole database:
The available information comprises adequate, reliable (Klimisch score 2) and consistent studies, and is thus sufficient to fulfil the standard information requirements set out in Annex VII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1), and is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral

The acute oral toxicity of Ethylene diformate (and further glycol derivatives) was investigated in two early studies conducted in rats and guinea pigs (Smyth, 1941). Groups of ca. 10 animals (male rats and male and female guinea pigs) were given the test substance as a 5% dispersion in 1% aqueous "Tergitol" penetrant 7 (sodium sulfate of heptadecyl alcohols) by single oral gavage. The dose levels administered were not explicitly reported, but it can be assumed that the maximum dose level was in the order of 5000 mg/kg bw. The observation period following administration was up to 14 days.

Mortality data were summarised for all substances tested. Therefore, no substance specific data were reported. According to the authors, most deaths occurred within the first 48 h post-dose, but all deaths within 14 days post-administration were taken into account for calculation of LD50 values.

The test substance was tested along with other glycol esters. For this substance group, (near) fatal doses caused no narcosis but various degrees of sluggish depressed function.

Gross pathology findings were summarised for all substances tested. According to the authors, all doses caused some degree of irritation of the digestive tract. The primary target organ was the kidney; blood in urine and free blood beneath the capsule were seen at the highest dosages. The liver was less affected, but orange or reddish bile was often observed. Glycol esters were reported to produce livers of bright eosin colour.

The calculated oral LD50 values for male rats and male/female guinea pigs were 1510 and 390 mg/kg bw, respectively. The substance is therefore considered to be harmful if swallowed.

Inhalation

The acute inhalation toxicity of Ethylene diformate was evaluated in a study performed according to OECD guideline 403 under GLP conditions (Griffiths, 2012). A group of 10 male and female RccHan:WIST rats were nose-only exposed to 5.05 mg/L (analytical concentration) for 4 h. The animals were observed for a period of 14 days following administration.

No mortality occurred. During exposure increased respiratory rate and hunched posture were observed; however, all animals recovered during Days 3 to 4 after exposure. Hunched posture, pilo-erection, red-brown staining around the eyes and snout were seen in animals for short periods on removal from the chamber following the exposure period. Wet fur is commonly recorded both during and for a short period after exposure. These observations were thus considered to be associated with the restraint procedure and not indicative of toxicity. Necropsy and body weight development revealed no substance-related adverse findings.

Therefore, the LC50 for male and female rats was greater than 5.05 mg/L, and the substance is considered to be not toxic after acute exposure by inhalation.

Dermal

This information is not available.

The substance fulfils the criteria for classification as skin corrosive (Category 1B) according to Regulation (EC) No 1272/2008. Therefore, an acute dermal toxicity study does not need to be conducted in accordance with Column 2 of Annex VIII, Section 8.5, of Regulation (EC) No 1907/2006.

Conclusions for acute toxicity

The available data on the acute toxicity of Ethylene diformate comprise studies by the oral and inhalation routes. The substance has been tested for acute oral toxicity in rats (males) and guinea pigs (males and females) resulting in oral LD50 values of 1510 and 390 mg/kg bw, respectively. In an acute toxicity study in male and female rats exposed by inhalation, the LC50 was estimated to be greater than 5.05 mg/L (analytical concentration).

The substance is therefore considered to be harmful if swallowed but not toxic by inhalation.

Information on the acute dermal toxicity of Ethylene diformate is not available. The substance is, however, classified for skin corrosion (Category 1B) and therefore, an acute dermal toxicity study does not need to be conducted.


Justification for selection of acute toxicity – oral endpoint
The selected study is the most adequate and reliable study with the lowest dose descriptor.

Justification for selection of acute toxicity – inhalation endpoint
There is only one study available.

Justification for classification or non-classification

The available data on the acute oral toxicity of Ethylene diformate meet the classification criteria for Acute toxicity Category 4 (H302: Harmful if swallowed) according to Regulation (EC) 1272/2008 and for R22 (Harmful if swallowed) according to Directive 67/548/EEC.

The available data on the acute toxicity by inhalation of Ethylene diformate do not meet the classification criteria according to Regulation (EC) 1272/2008 or according to Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.

There are no data available on acute dermal toxicity.