1,1,1-trichloroethane

Endpoint summary

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

Value:

10 300 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Dose descriptor:

LC50

Value:

14 250 mg/m³ air

Acute toxicity: via dermal route

Endpoint conclusion

Dose descriptor:

LD50

Value:

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).