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Administrative data

Description of key information

inhalation: LC50 (rat/mouse) > 19000 ppm (NTP, 1989)

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via inhalation route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April - May 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
fixed concentration procedure
Limit test:
yes
Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories (Portage, MI, USA)
- Age at study initiation: 9-10 weeks
- Housing: individually in stainless steel wire cages (Harford Metal Inc., Aberdeen, MD, USA)
- Diet: NIH 07 rat and mouse ration (Zeigler Bros., Inc., Gardners, PA, USA) available ad libitum during non-exposure periods
- Water: automatic watering system (Edstrom Industries, Waterford, WI, USA), available ad libitum
- Acclimation period: 26 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): exposure: 23.9 - 24.4 °C; non-exposure: 22.2 - 24.4 °C
- Humidity (%): exposure: 55 - 57%; non-exposure: 40 - 60%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: April 1980 To: 12 May 1980
Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: vapour generation system; the liquid to be vaporized was forced under pressure, at a metered rate, directly from the shipping container into a stainless steel boiler that was maintained at about 32 °C by a controlled-temperature water bath. The vapour was routed through a gas metering valve and a purge/expose valve into a pipe at the chamber inlet, where the vapour was mixed with dilution air entering the chamber.


Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
19000 ppm (50130 mg/m3)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed continually during exposure and then 3 times per day for 14 days; weighed initially
- Necropsy of survivors performed: no
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 19 000 ppm
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All mice survived.
Clinical signs:
other: No clinical signs of toxicity were seen.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Executive summary:

Groups of male and female mice (5/sex) were exposed by whole body inhalation for a single 4-hour exposure to air containing chloroethane at the target concentration of 19000 ppm (National Toxicology Program, 1989). Animals were weighed before exposure and were observed continually during exposure and then three times per day for 14 days. After 14 days, the animals were killed without a formal necropsy. All mice survived the 4-hour exposure to 19000 ppm chloroethane. No clinical signs of toxicity were seen.

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
April - May 1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given
Reason / purpose for cross-reference:
reference to same study
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
GLP compliance:
yes
Test type:
fixed concentration procedure
Limit test:
yes
Species:
rat
Strain:
other: F344/N
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories (Portage, MI, USA)
- Age at study initiation: 8-9 weeks
- Housing: individually in stainless steel wire cages (Harford Metal Inc., Aberdeen, MD, USA)
- Diet: NIH 07 rat and mouse ration (Zeigler Bros., Inc., Gardners, PA, USA) available ad libitum during non-exposure periods
- Water: automatic watering system (Edstrom Industries, Waterford, WI, USA), available ad libitum
- Acclimation period: 26 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): exposure: 23.9 - 24.4 °C; non-exposure: 22.2 - 24.4 °C
- Humidity (%): exposure: 55 - 57%; non-exposure: 40 - 60%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: April 1980 To: 12 May 1980
Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: vapour generation system; the liquid to be vaporized was forced under pressure, at a metered rate, directly from the shipping container into a stainless steel boiler that was maintained at about 32 °C by a controlled-temperature water bath. The vapour was routed through a gas metering valve and a purge/expose valve into a pipe at the chamber inlet, where the vapour was mixed with dilution air entering the chamber.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
4 h
Concentrations:
19000 ppm (50130 mg/m³)
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed continually during exposure and then 3 times per day for 14 days; weighed initially
- Necropsy of survivors performed: no
Key result
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 19 000 ppm
Based on:
test mat.
Exp. duration:
4 h
Mortality:
All rats survived.
Clinical signs:
other: No clinical signs of toxicity were seen.
Interpretation of results:
other: CLP/EU GHS criteria not met, no classification required according to Regulation (EC) No 1272/2008
Conclusions:
In the single 4-hour exposure studies, all rats survived at the sole concentration of 19000 ppm chloroethane. No clinical signs of toxicity were seen
Executive summary:

Groups of male and female rats (5/sex) were exposed by whole body inhalation for a single 4-hour exposure to air containing chloroethane at the target concentration of 19000 ppm (National Toxicology Program, 1989). Animals were weighed before exposure and were observed continually during exposure and then three times per day for 14 days. After 14 days, the animals were killed without a formal necropsy. All rats survived the 4-hour exposure to 19000 ppm chloroethane. No clinical signs of toxicity were seen.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
Value:
50 130 mg/m³
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 dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Inhalation is the only significant route of exposure since chloroethane is a gas.

In an acute inhalation toxicity study similar to OECD guideline 403 groups of F344/N-rats (5/sex) and B6C3F1 mice (5/sex) were exposed by whole body inhalation 4 hours to air containing chloroethane vapour at the target concentration of 19000 ppm (NTP, 1989). No deaths occurred in both species followed by a fourteen days observation period. No clinical signs of toxicity were observed. Thus, the LC50 was considered to be greater than 19000 ppm.

Although testing was not performed up to 20000 ppm, a classification is not considered necessary because in these two studies, no signs of toxicity were seen after exposure to 19000 ppm and it is therefore considered unlikely that a mortality rate of 50% would occur at 20000 ppm. Futhermore, concentrations of 20000 ppm were tested in fully reliable repeated dose toxicity studies in rabbits (OECD 414) and rats (DRF OECD 443). In these studies no or only a very low incidence of mortalities were noted at 20000 ppm.

A series of acute inhalation studies point out a narcotic effect in several species of animals at high concentrations of chloroethane. Anaesthetic concentrations are 52240 ppm for mice (Lazarew, 1929), 35000-40000 ppm for dogs (Henderson, 1930) and cats and 12300 – 18650 ppm for guinea pigs (Lehmann and Flury, 1938). The anaesthetic property is attributed to physical interaction of the entire lipophilic molecule and biological membranes.

 

In additions, chloroethane was observed to have cardiovascular effects. Bush et al. (1952) anaesthesized male Beagle dogs with chloroethane and took electrocardiographic tracings. A twofold effect on the heart was observed: (1) an inhibition due to vagal stimulation, which was observed early in the course of anaesthesia and (2) a direct depression of the cardiac tissues. The vagal inhibition was prevented by premedication with anticholinergic drugs (atropine or scopolamine).

 

Several reports of human exposure experience, including poisoning incidents with chloroethane have been published.

In humans narcosis occurring at very high concentrations was the basis of historic use as a surgical anesthetic (Clayton and Clayton, 1994). The anaesthetic concentration in humans has been estimated to be 4% (Lawson, 1965). Due to its cardiotoxicity (vagal inhibition) when inhaled in high concentrations, chloroethane was later abandoned as an anaesthetic. Deaths that occurred under anaesthesia were due mainly to very high chloroethane concentrations, which caused primary respiratory depression (Bush et al., 1952; Henderson and Kennedy, 1930; Dobkin and Byles, 1971).

 

Davidson (1926) exposed volunteers to 1.3-3.6% chloroethane vapour in air. After exposure to 1.3% for 21 minutes no adverse effects were observed. Decreased reaction times were seen with exposure to concentrations of 2.5%, whereas exposure to 3.36% led to noncoordination, unconsciousness and cyanosis within minutes.

 

References:

BUA (Beratergremium für umweltrelevante Altstoffe) (1991) Chloroethane. Stoffbericht 60 (April 1991), S. Hirzel Verlag Stuttgart

Clayton, G.D. and Clayton, F.E. (1994) Patty’ Industrial Hygiene and Toxicology. Vol II Part E.: John Wiley and Sons, Inc. pp 4082-4087 (as cited in OECD SIDS, Chloroethane, 2006)

Davidson, B.M. (1926) Studies on intoxication. V. The action of ethyl chloride. J. Pharmacol. Exp. Ther. 26, 37-42 (as cited in IARC, 1991)

Henderson, V.E. (1930) Anaesthetic toxicity. Arch. Int. Pharmacodyn. Ther. 38, 150-165 (as cited in BUA Report 60, Chloroethane, 1991)

IARC 1991, Monogr. Eval. Carcinog.Risks Hum. 52, 315-335

Lawson, J:I:M (1965). Ethyl chloride.Br. J. Anaest.37:667-670 (as cited in IARC 1991)

Lazarew, N.W. (1929) Über die narkotische Wirkungskraft der Dämpfe der Chlorderivate des Methans, des Äthans und des Äthylens. Naunyn-Schmiedebergs Arch. Exp.Pharmakol. Pathol. 141, 19-24 (as cited in BUA Report 60, Chloroethane, 1991)

Lehmann, K.B. and Flury, F. (1938) Toxikologie und Hygiene der technischen Lösungsmittel, Julius Springer Verlag, S. 119 (as cited in BUA Report 60, Chloroethane, 1991)

Justification for classification or non-classification

The data is conclusive but not sufficient for classification to CLP (1272/2008/EC).