1,2-dichloroethane

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1951

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Cross-reference

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Vapor toxicity of ethylene dichloride determined by experiments on laboratory animals.

Author:

Spencer HC, Rowe VK, Adams EM, McCollister DD & Irish DD

Year:

1951

Bibliographic source:

J. Ind. Hyg. Occup. Med. 4: 482-493

Reference 2

Reference Type:

other: French Authority Report

Title:

Seuils de Toxicité aiguë 1,2-Dichloroéthane

Author:

Anonymous

Year:

2008

Bibliographic source:

Groupe d’Experts Toxicologues du Ministère de l’Ecologie, de l’Energie, du Développement Durable et de l’Aménagement du Territoire.

Report date:

2008

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

not specified

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

1,2-dichloroethane

EC Number:

203-458-1

EC Name:

1,2-dichloroethane

Cas Number:

107-06-2

Molecular formula:

C2H4Cl2

IUPAC Name:

1,2-dichloroethane

Details on test material:

1,2-dichloroethane used in the experimental work consisted of four individual samples of a commercial product, all purified by redistillation. The infrared-absorption spectra of these samples indicated purities of at least 99.7 %. The only impurity identified was trichloroethylene.

Test animals

Species:

rat

Strain:

other: albino rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

The albino rats were raised in this laboratory of stock originally obtained from Wistar Institute of Anatomy and Biology in 1938. They were maintained on a modified Sherman diet consisting of freshly ground whole wheat (55 %), dried whole milk (25 %), dried extracted liver (12 %), dried brewer's yeast (5 %), iodized table salt (2 %) and calcium carbonate (1 %).

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

A glass-walled chamber of about 160 L capacity was used. Two large copper tubes (closed with rubber stoppers) were soldered into the model top of the chamber so that rats could be introduced conveniently after a vapour concentration had been established. A constant air flow was maintained through the chamber, the lowest rate for any experiment being 15 L/min and the highest about 30 L/min. The desired vapour concentration was obtained by metering liquid 1,2-dichloroethane at a constant rate into the tube through which air entered the chamber, heat being applied at the point of vaporization as needed to effect complete volatilization.
The rats were introduced in groups of 5 to 12 within a period of 15 sec and were removed through the chamber door within a similar interval of time at the end of the exposure. It was shown by a continuously recording analyzer that the animals were introduced without appreciable alterations of the vapour concentration.

Analytical verification of test atmosphere concentrations:

yes

Remarks:

All vapour concentrations with animals in the chamber were checked repeatedly from time to time by combustion analyses; the results averaged better than 90 % of the calculated theroretical concentrations of 1,2-dichloroethane.

Duration of exposure:

>= 0.1 - <= 8 h

Concentrations:

200, 300, 600, 800, 1000, 1500, 3000, 12000 and 20000 ppm (corresponding to 823, 1234, 2468, 3290, 4113, 6169, 12339, 49354 and 82256 mg/m³) at various exposure times.

No. of animals per sex per dose:

between 10 and 54 rats

Control animals:

not specified

Details on study design:

All the rats were selected on the basis of general appearance and apparent good health, males and females being used in approximately equal numbers. Animals were observed as to their behavior, body weight changes, and time of death. Survivors were observed for two to three weeks, or until it was certain that they had fully recovery of weight.
Evidence of organ pathology: Special, additional groups of animals were killed at various intervals within the time-frame of 0.2-h to 20-h exposure to determine body weight, liver and kidney weight, blood parameters (urea nitrogen concentration, plasma prothrombin clotting time, serum phosphatase activity), liver lipids, and histopathological changes (liver, kidney, adrenals).

Statistics:

Statistics according to the method of Litchfield and Wilcoxon was performed.

Results and discussion

Preliminary study:

no data

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

7 758 mg/m³ air

95% CL:

7 485.38 - 8 061.15

Exp. duration:

4 h

Remarks on result:

other: corresponding to approx. 1886 ppm

Mortality:

Mortality occurred at different exposure concentrations and exposure times. For details see the section "Remarks on results including tables and figures".

Clinical signs:

other: Please refer to the section "Remarks on results including tables and figures".

Body weight:

In special groups of animals (exposure causing 99.9, 50 or 0.01 % death), reported signs of exposure mediated toxicity were decreased body weights.

Gross pathology:

In special groups of animals (exposure causing 99.9, 50 or 0.01 % death), reported signs of exposure mediated toxicity were increased liver and kidney weights and slight parenchymatous degeneration to severe haemorrhagic necrosis (kidney, liver, adrenals), congestion (kidney, liver, adrenals, lungs) and oedema (kidney, lungs), increase in blood urea nitrogen concentration, plasma prothrombin clotting time, liver lipids, decrease in serum phospatase activity.

Other findings:

none

Any other information on results incl. tables

The 4-h LC50 corresponded to approx. 1886 ppm (approx. 7758.5 mg/m³) and was derived from the data by Standard Probit analysis (please refer to "Seuils de Toxicité aiguë 1,2-Dichloroéthane from Groupe d’Experts Toxicologues du Ministère de l’Ecologie, de l’Energie, du Développement Durable et de l’Aménagement du Territoire" dated 2008-12-03).

With 22000 ppm (approx. 90420 mg/m³), death occurred within 24 min after deep anaesthesia by depression of the central nervous system. At 12000 ppm and lower concentrations this depressant action resulted in varying degrees of "drunkenness".

In special groups of animals (exposure causing 99.9, 50 or 0.01 % death), reported signs of exposure mediated toxicity were decreased body weights, increased liver and kidney weights and slight parenchymatous degeneration to severe haemorrhagic necrosis (kidney, liver, adrenals), congestion (kidney, liver, adrenals, lungs) and oedema (kidney, lungs), increase in blood urea nitrogen concentration, plasma prothrombin clotting time, liver lipids, decrease in serum phospatase activity.

The following concentrations and exposure times were not lethal:

300 ppm (approx. 1200 mg/m³) after 7 h (20 animals)

600 ppm (approx. 2400 mg/m³) after 5 h (20 animals)

1500 ppm (approx. 6100 mg/m³) after 2 h (10 animals)

3000 ppm (approx. 12100 mg/m³) after 0.5 h (22 animals)

20000 ppm (approx. 81000 mg/m³) after 0.1 h (10 animals)

The following concentrations were void of adverse effects:

200 ppm (approx. 800 mg/m³) for 7 h

300 ppm (approx. 1200 mg/m³) for 3 h (but effects at 5.5 h)

1000 ppm (approx 4000 mg/m³) for 1.5 h (but effects at 3 h).

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The 4-h LC50 in rats derived by Standard Probit analysis was 1886 ppm (approx. 7758 mg/m³).

Executive summary:

In an acute inhalation toxicity study, groups of young adult albino rats (10-54/dose, approximately equal numbers of males and females) were whole body exposed to 1,2 -dichloroethane for 0.1 to 8 hours at concentrations of 200, 300, 600, 800, 1000, 1500, 3000, 12000 or 20000 ppm (corresponding to 823, 1234, 2468, 3290, 4113, 6169, 12339, 49354 and 82256 mg/m³). Animals then were observed for 2 to 3 weeks. At 20000 ppm, death occurred within 24 min after deep anaesthesia by depression of the central nervous system. At 12000 ppm and lower concentrations this depressant action resulted in varying degrees of "drunkenness". According to authors, deaths tended to occur at three different time intervals and in such a manner as to suggest three separate toxic actions of fatal degree:

1. At very high concentrations (e.g. 20000 ppm), deaths occurred due to depression and paralysis of CNS functions.

2. At all vapour concentrations causing death, a large proportion died rather suddenly and quietly a few hours after termination of exposure, showing marked cyanosis, reduced body temperature, stupor or coma and failing respiration. The character and sudden development of this response suggested "shock" or cardiovascular collapse.

3. All other deaths occurred delayed over a period of 2 to 7 days with progressive loss of body weight and other evidence of toxic effects, suggesting organ failure, probably due to kidney lesions.

The 4 -h LC50 derived by Standard Probit analysis in this acute inhalation study in rats was 1886 ppm (approx. 7758 mg/m³).

1,2 -dichloroethane is of low acute oral toxicity based on the LC50 (4 hours) in male and female albino rats.