Registration Dossier

Administrative data

Description of key information

Tetrachloroethylene is irritating to skin and eyes, but not to the respiratory tract. 

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation / corrosion, other
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1990
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, GLP status not reported, available as unpublished report, fully adequate for assessment
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
GLP compliance:
not specified
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS- Source: ENKI-Konijnenfarm, Someren, The Netherlands- Weight at study initiation: 2.5 - 3.0 kg- Housing: individually, suspended, galvanized cages, fitted with a wire-mesh floor and front. - Diet: ad libitum- Water: ad libitum- Acclimatization period: 6 daysENVIRONMENTAL CONDITIONS- Temperature (°C): 18 +/- 3- Humidity (%): >40- Air changes (per hr): 10 - Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
other: stabilized with ionol
Controls:
not required
Amount / concentration applied:
TEST MATERIAL- Amount(s) applied (volume or weight with unit): 0.5 ml- Concentration (if solution): 10 mg/l
Duration of treatment / exposure:
4 hours
Observation period:
at 1, 24, 48, 72 hours, 9 and 16 days after the 4 hour expsoure period
Number of animals:
Experiment 1 (tetrachloroethylene tested individually): 3Experiment 2 (tetrachloroethylene examined simultaneously with three other solvents on separate skin areas): 3
Details on study design:
TEST SITE- Area of exposure: 1 inch x 1 inch- Type of wrap if used: patches fixed to the application sites by means of adhesive tape and the entire trunk of each rabbit was wrapped with an impervious material. REMOVAL OF TEST SUBSTANCE- Washing (if done): with lukewarm water and soap- Time after start of exposure: 4 hoursSCORING SYSTEM:Method of Draize et al. (1944)
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours after the application
Score:
4
Max. score:
4
Reversibility:
other: at day 16, the mean score was 1.3
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours, 9 and 16 days after the application
Score:
1.7
Max. score:
4
Reversibility:
other: at day 16, the mean score was 0.7
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other: The primary Irritation Index was calculated by combining the scores for erythema/eschar formation and oedema
Time point:
other: 24, 48 and 72 hours after application
Score:
5.7
Remarks on result:
other: Experiment 1 (tetrachloroethylene tested individually): 3
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: 24, 48, 72 hours after the application
Score:
4
Max. score:
4
Reversibility:
other: at day 16, the mean score was 0.7. After five weeks all effects had cleared completely.
Remarks on result:
other: tetrachloroethylene examined simultaneously with three other solvents on separate skin areas
Irritation parameter:
edema score
Basis:
mean
Time point:
other: 1, 24, 48, 72 hours, 9 and 16 days after the application
Score:
1.9
Max. score:
4
Reversibility:
other: at day 16, the mean score was 0.3. After five weeks all effects had cleared completely.
Remarks on result:
other: tetrachloroethylene examined simultaneously with three other solvents on separate skin areas
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
other: The primary Irritation Index was calculated by combining the scores for erythema/eschar formation and oedema
Time point:
other: 24, 48 and 72 hours after application
Score:
5.9
Remarks on result:
other: Experiment 2 tetrachloroethylene examined simultaneously with three other solvents on separate skin areas
Irritant / corrosive response data:
Experiment 1:Generally the following skin reactions were observed at one or more observation time points, up to 72 hours after treatment: well-defined erythema, very slight or slight oedema, very slight ischemic necrosis (not after 4 hours) and very slight incrustation (after 72 hours only).After 9 days well-defined erythema, very slight oedema and moderate scaliness (in all three rabbits) and very slight incrustation (in two rabbits) were reported.After 16 days very slight or well-defined erythema (in all three rabbits) and slight oedema (in one rabbit) were observed.Experiment 2:Generally the following skin reactions were observed at one or more observation time points, up to 72 hours after treatment: well-defined or moderate erythema, very slight or slight oedema, very slight ischemic necrosis (not after 4 hours) and slight scaliness or slight incrustation (mainly after 72 hours).After 9 days well-defined erythema, very slight or slight oedema (in all three rabbits), slight or severe scaliness (in two rabbits) and moderate incrustation (in one rabbit) were reported.After 16 days very slight or well-defined erythema (in all three rabbits), very slight oedema (in two rabbits) and decreased hair growth (in one rabbit) were observed.After five weeks all effects had cleared completely.
Interpretation of results:
Category 2 (irritant) based on GHS criteria
Conclusions:
According to CLP criteria (mean value of ≥2,3 - ≤4,0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal) the substance shall be classified as Skin Irrit. Category 2, H315: causes skin irritation.
Executive summary:

A skin irritation in rabbits is avaialble according to OECD guideline No. 404 and conducted under GLP (Van Beek, 1990). Two groups of 3 New Zealand White rabbits were treated with a substance of > 99.95 % purity stabilized with ionol (concentration 10 mg/l). 0.5 ml of the test material was applied as an occlusive coverage on a shaved skin for 4 hours. After exposure the test material was washed up with a warm water and soap. Skin reactions were scored by the method of Draize (1944) at 1, 24, 48, 72 hours, 9 and 16 days after the exposure. Well-defined erythema was observed 24, 48, 72 hours after the application (mean score “4”) which was not fully reversed at day 16. Other skin reactions (oedema – mean score 1.7-1.9, ischemic necrosis, incrustation, scaliness) were from slight to moderate at different time points. According to CLP criteria (mean value of ≥2,3 - ≤4,0 for erythema/eschar or for oedema in at least 2 of 3 tested animals from gradings at 24, 48 and 72 hours after patch removal) the substance shall be classified as Skin Irrit. Category 2, H315: causes skin irritation.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Additional information

There is convincing evidence from observations in humans (Redmond and Schappert, 1987; Morgan, 1969; Ling and Lindsay, 1971; Meyer, 1973; Hake and Stewart, 1977; Metz et al, 1982; Stewart and Dodd, 1964) and a good-quality animal study (van Beek, 1990) that tetrachloroethylene is irritating (but not corrosive) to the skin.

 

Slight and transient eye irritation which developed within the first two hours of exposure and subsided before the end of the 7-hour exposure has been reported by human volunteers at about 100 ppm, 690 mg/m3 (Stewart et al., 1970). In a rabbit study instillation of liquid tetrachloroethylene produced only minimal effects. Based on the fact that this substance is a skin irritant and given the mild findings from animal data and human observations, it is concluded that tetrachloroethylene should be considered as irritating to the eyes. This is supported by the fact that trichloroethylene, dichloroethylene and methyl chloride are all irritating to eyes.

 

Mild nasal irritation was reported by volunteers exposed at 216 ppm (1490 mg/m3) for 2 hours but not at 106 ppm (731 mg/m3) for 1 hour (Rowe et al., 1952) and at 100 ppm (690 mg/m3) for 7 hours (Stewart et al., 1970). Given the very mild and transient nature of the nasal irritation reported in the two human volunteer studies available and the complete absence of signs of respiratory tract irritation in animals, tetrachloroethylene is not considered to be a respiratory tract irritant.


Justification for selection of skin irritation / corrosion endpoint:
Guideline study, GLP status not reported, available as unpublished report, fully adequate for assessment

Justification for selection of eye irritation endpoint:
In accordance with section 1.1 and 1.2 of REACH Annex XI, further testing does not appear scientifically necessary. The available animal study (limited reported, not performed in accordance with currently regulatory guidelines) in combination with the human data on eye irritation (see section 7.10) are considered sufficient to cover the endpoint eye irritation.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the available human and animal data, according to Directive 67/548/EEC criteria, tetrachloroethylene has to be classified as irritating to skin and eyes (Xi; R36 /R38). According to EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008, the substance should be classified as Skin corrosion/irritation Cat.2; H315 and as an Eye corrosion/irritation Cat. 2; H319.

The available data do not warrant classification for respiratory tract irritation according to EU Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.