Registration Dossier

Administrative data

Description of key information

Limited data are available for skin- and eye irritation. Most studies lacking detailed information on individual animal data. Based on a weight of evidence, it had been concluded:

- skin irritation:  not irritating  for the rabbit, weight of evidence; studies Duprat (1976), Roudabush (1965), Anderson (1986)

- eye irritation:   not irritating for the rabbit (OECD TG 405); study Duprat (1976), Scholz (1967)

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records
Reference
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: A scientifically sound study, but no individual data, limited methodological information.
Qualifier:
no guideline followed
Principles of method if other than guideline:
- application of CTC and other chlorinated solvents to the skin of rabbits
- at day 3 histologic examinations of the treated skin regions
- a non-discribed ranking system for skin lesions (differentiating between erythema and edema) was used to classify the skin lesions macroscopically
GLP compliance:
no
Species:
rabbit
Strain:
other: New Zealand
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: not reported
- Age at study initiation: not reported
- Weight at study initiation: 2.4 - 3.0 Kg
- Housing: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light):not reported

Type of coverage:
not specified
Preparation of test site:
not specified
Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): very likely 0.5 mL (methods not detailed, only referenced to other publication)
- Concentration (if solution): unclear
- Purity > 99.5 %


VEHICLE
- not reported
Duration of treatment / exposure:
24 h
Observation period:
72 h, observations at 24, 48 and 72 h post treatment
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure:
- % coverage:
- Type of wrap if used:


REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure:


SCORING SYSTEM: Draize scoring system
Irritation parameter:
other: I.I.C.P (very likely: primary skin irritation index)
Basis:
mean
Time point:
other: 24 and 72 h
Score:
4.2
Reversibility:
fully reversible within: 2 weeks or less
Irritation parameter:
erythema score
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
edema score
Time point:
24/48/72 h
Remarks on result:
not determinable

- the authors classify the skin irritation potency of CTC as medium in ranking comprising the stages: non irritating, almost non irritating, medium irritant and severely irritant.

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The present publication (Duprat 1976) states CTC to be medium irritating to the skin of rabbits after single application.
Executive summary:

Individual data from different time points of observation are not presented, so a clear classification according to OECD GHS is not possible.

The publication is a survey report on the irritative potential of different chlorinated solvents. Rabbits were dermaly exposed with CTC (and other solvents) and the skin reaction was observed macroscopically as well as microscopically and scored by an undisclosed scoring system (very likely the Draize score system). Observation periods and dosing also remains unclear.

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

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Scientifically sound study, but no individual data, limited methodological information
Qualifier:
no guideline followed
Principles of method if other than guideline:
The system of eye irritation scoring by Kay and Calandra (John H. Kay , Joseph C. Calandra , Interpretation of eye irritation tests (1962), Journal of Cosmetic Science, Vol. 13, No. 6, pp. 281-290) was used to classify the skin lesions macroscopically
GLP compliance:
no
Species:
rabbit
Strain:
other: New Zealand
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: not reported
- Age at study initiation: not reported
- Weight at study initiation: 2.4 - 3.0 Kg
- Housing: not reported
- Diet (e.g. ad libitum): not reported
- Water (e.g. ad libitum): not reported
- Acclimation period: not reported


ENVIRONMENTAL CONDITIONS
- Temperature (°C): not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light):not reported

Vehicle:
not specified
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 100 %


VEHICLE
- not applicable
Duration of treatment / exposure:
single application, no wash out
Observation period (in vivo):
7 d
Number of animals or in vitro replicates:
6
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): not reported



SCORING SYSTEM: Draize Scoring (see "Any other information on materials and Methods")


TOOL USED TO ASSESS SCORE: not reported
Irritation parameter:
other: irritation score as defined by Kay and Calandra (1962)
Basis:
mean
Time point:
other: unclear
Score:
5
Reversibility:
fully reversible within: 2 weeks
Irritation parameter:
cornea opacity score
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
iris score
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
conjunctivae score
Time point:
24/48/72 h
Remarks on result:
not determinable
Irritation parameter:
chemosis score
Time point:
24/48/72 h
Remarks on result:
not determinable

- according to Kay and Calandra (1962) a score of 5 is equivalent with minimally irritating

Interpretation of results:
slightly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The present publication (Duprat 1976) states CTC to be minimally irritating to the eye of rabbits after single application.
Executive summary:

The publication is a survey report on the irritative potential of different chlorinated solvents. Rabbits were ocular exposed with CTC (and other solvents) and the reaction of the eye was observed macroscopically as well as microscopically and scored by the scoring system of Kay and Calandra (1962). Individual data from different time points of observation are not presented. The effects are reported to be reversible within 1 to 2 weeks.

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

Respiratory irritation

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

Additional information

Skin irritation:

All studies are survey studies lack detailed information on individual animal data for CTC. All studies stated a slight or moderate irritating potential of CTC based on primary irritation indices with the exception of Anderson 1986 that uses an unevaluated scoring system. Therefore the evaluation of the key parameter is based on a weight of evidence approach concerning the findings in the studies of Duprat (1976), Anderson (1986) and Roudabush (1964). In all of these studies, the exposure duration was 24 hours, therefore much longer than the exposure duration of 4 hours described in the OECD 404 guideline. The coverage was not reported in the Duprat study and was under occlusive system in Roudabush studies. No species differences were obvious comparing rabbits and guinea pigs. It seems reasonable that an irritating or corrosive action of CTC would have led to much higher primary irritation indices than those reported in the study reports. Even authors stated a slight to moderate irritating potential for CTC, the exposure conditions were very different from those required in the OECD 404 guideline. Moreover, in a skin sensitization test (LLNA) recently performed (Rokh, 2010), CTC did not induce any local reaction at the highest tested concentration (100%).

Eye irritation:

The evaluation of the key parameter is based on a weight of evidence approach ( Duprat 1976; Scholz 1967; Olson 1956). Duprat, Scholz and Olson state mild irritation reaction of the rabbit eye after treatment with CTC, but the reported data and the information on methods (including doses) is very limited. Duprat reported a recovery period of 1 to 2 weeks, while Scholz reports recovery within 48 h. Olson reports a recovery period of one week.

Respiratory irritation:

No data

Justification for classification or non-classification

-Skin irritation: based on the weight of evidence from the present studies, it can be concluded that carbon tetrachloride is not irritating to skin, since the effects on skin were mostly slight to moderate irritation, for 24 hours exposure. It is to note that due to the vapour pressure, CTC will evaporate quickly from the skin in case of open contact.

Moreover, a recent skin sensitization test shown that CTC did not induce local signs of irritation at the highest concentration (100 %). Therefore there is no reason to classify CTC according to EU Regulation (EC) N0. 1272/2008 (CLP) and according to EU directive 67/548/EEC.

-Eye irritation: based on the weight of evidence approach it can be concluded that carbon tetrachloride is not irritating to eyes, as it is suggested by the study results. Slight to moderate eye irritation was seen after the application of CTC to the rabbit eye. Therefore no classification is considered to be required for CTC according to EU Regulation (EC) N0. 1272/2008 (CLP) and according to EU directive 67/548/EEC.

-Repiratory irritation: no information is available. No classification is proposed.