Registration Dossier

Administrative data

Description of key information

There are numerous acute oral and inhalation studies conducted in animals showing very low acute toxicity (LD 50’s in the region of 10,000 mg/kg or ppm).  Dermal data is less prevailant but again the LD 50 is in the region of 15,000 mg/kg.  A recent ATSDR review (2006) found lethal inhalation doses in humans to be in the region of 6000 to 20 000 ppm.  1,1,1-trichloroehtane can therefore be considered to be of no serious acute hazard.  However, it should be noted that in humans exposure  to 175 ppm for 3.5 hours results in reduced psychomotor abilities.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Dose descriptor:
LD50
10 300 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Dose descriptor:
LC50
14 250 mg/m³

Acute toxicity: via dermal route

Endpoint conclusion
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

1,1,1-trichloroethane is of low acute toxicity following oral (gavage) exposure.  The dog is the most sensitive species, having an LD50 of 750 mg/kg bwt, follwed by the rabbit with an LD50 or 5660 mg/kg bwt.  In the rat and mosue LD 50 values range from 9700 to 17148 mg/kg bwt. 

Summary of acute toxicity via the oral route

Author

Reliability

Species

sex

LD50

remarks

ISIS

IUCLID 4

Dog

 

750 mg/kg bw

 

ISIS

IUCLID 4

rabbit

 

5660 mg/kg bw

 

Janssen

IUCLID 4 (GLP)

rat

 

> 2000 mg/kg bw

 

Torkelson

3

rat

Male

14600 mg/kg bw

inhibited product

Male

12300 mg/kg bw

uninhibited product

Female

11000 mg/kg bw

inhibited product

Female

10300 mg/kg bw

uninhibited product

mouse

Female

9700 mg/kg bw

inhibited product

11240 mg/kg bw

uninhibited product

guinea pig

Male/Female

8600 mg/kg bw

inhibited product

Male

9470 mg/kg bw

uninhibited product

rabbit

Male/Female

10500 mg/kg bw

inhibited product

Female

10500mg/kg bw

uninhibited product

Bruckner

2

rat

Male

NOEL 4000 mg/kg bwt

 

ASTDR

2

mouse

Male

17148 mg/kg bwt

 

Female

12996 mg/kg bwt

 

The value for the dog is not cross referenced in any other reviews (eg ASTDR, WHO or RAIS) and is therefore not considered reliable.

Studies of animal mortality following acute inhalation exposure to 1,1,1-trichloroethane are numerous. Median lethal concentrations (LC50 values) have been calculated for rats and mice. For rats, LC50 values from 14250 to 38,000 ppm were reported. For mice, reported LC50 values ranged from 3,911 to 29492 ppm. Much of the variation in these data can be attributed to differences in the exposure duration (higher LC50 values were generally obtained in studies with short exposure periods).

Summary of acute toxicity via the inhalation route

Author

Reliability

Species

sex

LC50

remarks

ISIS

IUCLID 4

mouse

 

3911 ppm

2 hours

ISIS

IUCLID 4

rat

 

18000 ppm

4 hours

Siegel

IUCLID 4

rat

 

18400 ppm

4 minutes

Moser

IUCLID 4

mouse

Male

29492 ppm

10 minutes

Moser

IUCLID 4

mouse

Male

20616 ppm

30 minutes

Woolverton

IUCLID 4

mouse

Male

22241 ppm

30 minutes

Moser

IUCLID 4

mouse

18358 ppm

60 minutes

Gradiski

IUCLID 4

Mouse/rat

Female

13410 ppm

6 hours

Clark

IUCLID 4

rat

Male and female

38000 ppm

15 minutes

Adams

3

rat

Male and female

18000 ppm

3 hours

Adams

3

rat

Male and female

14250 ppm

7 hours

Clark

2

rat

Male and female

3.8 % in air (38000 ppm)

15 minutes

Clark

2

dog

 

0.7 % in air for cardiac changes

5 minutes

Inhalation exposure is the most likely route of exposure in man and the US Agency for Toxic Substances and Disease Registry (ATSDR) recently (July 2006) produced a full toxicological profile for 1,1,1-trichloroehtane.  In this review it is reported that the lethal concetraion of 1,1,1-trichlorethane in humans is between 6000 and 20000 ppm and that human death following exposure is usually attributed to either depression of the central nervous system, which results in respiratory arrest or sensitisation of the heart to epinephrine which results in severe cardiac arrhythmias.  Also reported in this review is the lowest-observed-adverse-effect level (LOAEL) of 175 ppm for reduced performance of psychomotor tests in a human study by Mackay et al. (1987). Individuals exposed to 175 or 350 ppm of 1,1,1-trichloroethane for 3.5 hours demonstrated impaired performance of psychomotor tests. This is supported by results of other human studies. Gamberale and Hultengren (1973) found psychophysiological test performance deficits in exposed individuals, although at a higher concentration than the LOAEL of 175 ppm identified by Mackay et al. (1987). Muttray et al. (1999, 2000) found EEG changes consistent with increased drowsiness and slight irritant nasal responses in volunteers exposed to 200 ppm. (ATSDR 2006).

Only limited data is available regarding the acute effects of dermal exposure to 1,1,1-trichloroethane and the volatile nature of the substance means that contact, unless covered, is likely to be brief.  Exposure in the rabbit suggests that 1,1,1-trichloroethane is only lethal at very high doses, the LD 50 being greater than 15,800 mg/kg

Summary of acute toxicity via the dermal route

Author

Reliability

Species

sex

LD50

remarks

Janssen

IUCLID 4 (GLP)

rat

> 2000 mg/kg bw

 

Torkelson

IUCLID 4

rabbit

 > 15800 mg/kg bw

 

A number of studies using the intraperitoneal route have also demonstrated relatively low acute toxicity, the LD50 being between 2000 to 5080 mg/kg bwt; although it should be noted that one limit study conducted at 2 mL/kg was associated with 4/5 deaths in the male rat group only.

Summary of acute toxicity via the intra peritoneal route

Author

Reliability

Species

sex

LD50

remarks

ISIS

IUCLID 4

dog

3100 mg/kg bw

 

ISIS

IUCLID 4

rat

3593 mg/kg bw

 

Gradiski

IUCLID 4

mouse

female

3700 mg/kg bw

 

Klassen

IUCLID 4

dog

Male

4140 mg/kg bw

 

mouse

male

5080 mg/kg bw

 

Lombard

1

rat

Male

2 ml/kg bw

 

female

> 2ml/kg bw

 

References

DAUGHERTY-MW; FORSYTH-CS
Toxicities Profiles - Toxicity Summary for 1,1,1-TRICHLOROETHANE
 RAIS
 Toxicological profile for 1,1,1-Trichloroethane.
ATSDR 2006
 1,1,1-Trichloroethane in drinking-water.
WHO 2003




Justification for classification or non-classification

GHS 1,1,1-trichloroethane is considered to come under hazard category 4 for acute toxicity.  This is based on the inhalation toxicity as the LD50 lies between 2500 to 20000 ppm (or 10 to 20 mg/l).