Reaction mass of ethane-1,2-diol and 2-hydroxyethyl formate and ethylene diformate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

publication

Title:

The single dose toxicity of some glycols and derivatives.

Author:

Smyth H.F. Jr., Seaton J. and Fischer L.

Year:

1941

Bibliographic source:

Journal of Industrial Hygiene and Toxicology 23, 259 - 268

Materials and methods

Principles of method if other than guideline:

Single oral administration by stomach tube in male rats.

GLP compliance:

no

Test type:

standard acute method

Test material

Test material information

Constituent 1

Reference substance name:

Ethylene diformate

EC Number:

211-077-7

EC Name:

Ethylene diformate

Cas Number:

629-15-2

Molecular formula:

C4H6O4

IUPAC Name:

ethane-1,2-diyl diformate

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 90-120 g
- Diet: Purina chows, supplemented by fresh vegetables
- Water: ad libitum

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% aqueous "Tergitol" penetrant 7 (sodium sulfate of heptadecyl alcohols)

Details on oral exposure:

DOSAGE PREPARATION: The test material was handled as temporary dispersion in 1% aqueous sodium sulfate of heptadecanol (trademarked "Tergitol" penetrant 7).

MAXIMUM DOSE VOLUME APPLIED: Individual dose levels were not reported for any of the substances tested including the test substance considered herein. According to the authors, the highest dose level which could safely be hold at one time by the animal was just over 10% of the animal’s bodyweight, corresponding to approx. 50 g/kg bw, when a substance was administered as a 50% solution. This is equivalent to a dose volume of 100 mL/kg bw.
Multiple doses were tested. It was reported that in most cases 10 animals were dosed to determine the toxicity of a particular dosage and enough dosages were given to include those at which no mortality occurred and those at which all tested animals died.
The test substance was administered as a 5% dispersion in 1% aqueous sodium sulfate of heptadecanol (trademarked "Tergitol" penetrant 7) and based on the information above and the resulting LD50 value, the dose volume of 100 mL/kg bw cannot have been exceeded. It is therefore assumed that the maximum dose volume applied was 100 mL/kg bw corresponding to a maximum dose level of 5000 mg/kg bw.

Doses:

Multiple dose levels, presumably up to 5000 mg/kg bw/d

No. of animals per sex per dose:

ca. 10 animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Statistics:

The data were calculated by the method of probits, described by Bliss C.I. (1935. The calculation of the dosage-mortality curve. Ann. Appl. Biol. 22:134-167).

Results and discussion

Effect levels

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

1 510 mg/kg bw

Based on:

test mat.

95% CL:

>= 1 280 - <= 1 780

Mortality:

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.

Clinical signs:

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

Gross pathology:

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.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 is 1510 mg/kg bw in male rats.

Executive summary:

The acute oral toxicity of ethylene diformate was tested by single gavage application to rats. The LD₅₀ determined after the 14 -day observation period was 1510 mg/kg bw (95% CL: 1280 -1780 mg/kg bw)