Registration Dossier

Administrative data

Description of key information

The available oral and dermal LD50 values and the inhalation LC50 values are all above the classification cut-offs. In the rat, an inhalation 4-hour LC50 value of 12000 ppm and oral LD50 values of 5400 to 7200 mg/kg bw are reported. For the dermal route there are no human data and little animal data; in rabbits the dermal LD50 exceeds 2000 mg/kg bw.
The main toxic effect associated with acute inhalation exposure (humans and animals) is CNS depression.
Based on the available data, at a concentration of 30 ppm (161 mg/m3) for 15 minutes no adverse health effects are to be expected in humans.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline study, some restrictions in reporting, nevertheless acceptable for assessment
Principles of method if other than guideline:
Dose range-finding study for determination of dose levels in a 8-week subchronic study
GLP compliance:
no
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Osborne-Mendel
Sex:
male
Details on test animals and environmental conditions:
The study report only specifies the details on test animals and environmental conditions for the chronic study with trichloroethylene also performed by the NCI.
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Groups of 2 animals each were administered a single dose of trichloroethylene in corn oil by gavage by oral intubation and observed for 14 days.
Doses:
Ten dosages were used: 100, 178, 316, 562, 1000, 1420, 3160, 5620, 10000, and 17800 mg/kg.
No. of animals per sex per dose:
2
Control animals:
yes
Details on study design:
Single-dose range-finding studies were conducted with male rats to determine the highest dose to be used in the 8-week subchronic study:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Not reported
- Necropsy of survivors performed: Not reported
- Other examinations performed: Not reported
Statistics:
Not reported.
Sex:
male
Dose descriptor:
other: lowest dose causing death
Effect level:
5 620 mg/kg bw
Mortality:
No mortality was observed below a single dose of 5620 mg/kg bw.
Clinical signs:
Not reported.
Body weight:
Not reported.
Gross pathology:
Not reported.
Other findings:
Not reported.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
5 400 mg/kg bw
Quality of whole database:
good

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP, non-guideline study, some restrictions in reporting, nevertheless acceptable for assessment.
Principles of method if other than guideline:
Determination of the LC50
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: NMRI:O(SD) Sprague-Dawley derived
Sex:
male
Details on test animals and environmental conditions:
No details were reported.
Route of administration:
inhalation
Type of inhalation exposure:
not specified
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Vapor of TCE was obtained in high concentrations by passing air through a large fritted gas absorber containing the material and then collected in a metallized plastic bag. All exposures were conducted under a fume hood. The animals were exposed for 4 hours and then returned to their individual cages for a 2-week observation period. No food or water was provided during the exposure.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Gas chromatography equipped with a hydrogen flame ionisation detector. The chromatograph was equipped with an automatic valve which permitted sampling every 5 min during the exposure periods.
Duration of exposure:
4 h
Concentrations:
6750, 8000 and 14700 ppm.
No. of animals per sex per dose:
16
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
- Other examinations performed: no data
Statistics:
Not reported.
Sex:
male
Dose descriptor:
LC50
Effect level:
12 500 ppm
Exp. duration:
4 h
Remarks on result:
other: Estimated by the method of Miller and Tainter (1944)
Mortality:
Mortality rate:
6750 ppm: 2/16
8000 ppm: 3/16
14700 ppm: 10/16

All deaths occurred during exposure.
Clinical signs:
other: Not reported.
Body weight:
Not reported.
Gross pathology:
Not reported.
Other findings:
Not reported.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LC50
Value:
64 500 mg/m³
Quality of whole database:
good

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Additional information

In the rat, an inhalation 4-hour LC50 value of 12000 ppm and oral LD50 values of 5400 to 7200 mg/kg are reported. For the dermal route there are no human data and little animal data; in rabbits the dermal LD50 exceeds 2000 mg/kg.

The main toxic effect associated with acute inhalation exposure is CNS depression in humans and animals. Exposure to very high concentrations causes narcosis; extensive experience in the use of trichloroethylene as an anaesthetic at concentrations of 5000 to 10000 ppm has demonstrated that recovery from narcosis is usually complete. Studies in human volunteers have shown that the NOAEL for CNS depression is about 300 ppm, for exposures of up to eight hours. CNS depression can also occur in humans following oral ingestion of doses of about 450 mg/kg and above. In animals the main signs of toxicity observed were also those typical of CNS depression.

Single exposures of rats (pre-treated with enzyme inducers) and rabbits to trichloroethylene at atmospheric concentrations of > 6000 ppm for one hour can cause cardiac hyperreactivity to catecholamine stimulation. Cardiac sensitisation was not seen in rabbits exposed to 2000 ppm of trichloroethylene for one hour. The observed effects were potentiated in rabbits pre-treated with ethanol. Similar effects also occurred in dogs exposed for short periods to trichloroethylene at concentrations > 5000 ppm.

Regarding acute inhalation exposure, the STEL (15 min) as derived by the SCOEL will be used as a DNEL. The argumentation for the STEL is as follows: as high TCE peak exposures have been described as being critical in the development of human renal cell cancer, a STEL can provide additional protection against potentially hazardous over-exposures. Considering a mean TCE exposure level of 32 ppm reported in the study of Green et al. (2004), a STEL of 30 ppm (164 mg/m3) is proposed, in order to ensure an adequate safety margin to potentially nephrotoxic exposure situations. This limit value is also considered sufficient to prevent CNS depression (the effect based on which trichloroethylene is labelled with R67).


Justification for selection of acute toxicity – oral endpoint
reliable study

Justification for selection of acute toxicity – inhalation endpoint
reliable study

Justification for classification or non-classification

Based on the oral and dermal LD50 and inhalation LC50 values, classification for acute toxicity is not warranted according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.

Based on the acute effects on the CNS, trichloroethylene should be labelled with R67 according to Directive 67/548/EEC (Vapours may cause drowsiness and dizziness). According to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, trichloroethylene should be classified for Specific Target Organ toxicity – Single exposure, Cat. 3 (H336).