Registration Dossier

Administrative data

Description of key information

Skin: Irritating and classified according to CLP (1272/2008/EEC) and 67/548/EEC
Eye: Highly irritating and classified as Seriously eye damaging according to CLP (1272/2008/EEC) and 67/548/EEC

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:
key study
Study period:
1980
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study conducted in accordance with accepted test guidelines
Qualifier:
according to
Guideline:
other: FHSA (CFR 16 1500.41)
GLP compliance:
not specified
Species:
rabbit
Strain:
not specified
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Not reported
- Age at study initiation: Not reported
- Weight at study initiation: Not reported
- 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

IN-LIFE DATES: July 1980
Type of coverage:
occlusive
Preparation of test site:
other: Intact and abraded
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL

VEHICLE
- Not applicable
Duration of treatment / exposure:
24 hours
Observation period:
72 hours
Number of animals:
6
Details on study design:
TEST SITE
- Area of exposure: 1 inch x 1 inch square
- Type of wrap if used: Not reported

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Not reported

SCORING SYSTEM: Draize scale
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test, observations at 24 and 72 hours only
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2.5
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test, observations at 24 and 72 hours only
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.5
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test, observations at 24 and 72 hours only
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
2.5
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test, observations at 24 and 72 hours only
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
3
Max. score:
4
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test, observations at 24 and 72 hours only
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test, observations at 24 and 72 hours only
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test, observations at 24 and 72 hours only
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test, observations at 24 and 72 hours only
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.5
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test, observations at 24 and 72 hours only
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test, observations at 24 and 72 hours only
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test, observations at 24 and 72 hours only
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
3
Max. score:
3
Reversibility:
not fully reversible within: 72 hours
Remarks on result:
other: Intact skin
Remarks:
FHSA test, observations at 24 and 72 hours only

Animal

Response

24 hours

72 hours

Number

 

Intact

Abraded

Intact

Abraded

1

Erythema

2

2

2

2

 

Oedema

3

3

3

3

2

Erythema

2

2

3

3

 

Oedema

3

3

3

3

3

Erythema

2

2

3

3

 

Oedema

3

3

2

2

4

Erythema

2

2

3

3

 

Oedema

3

3

3

3

5

Erythema

4

2

2

2

 

Oedema

2

3

2

2

6

Erythema

3

3

3

3

 

Oedema

3

3

3

3

 

 

 

 

 

 

Primary Irritation Index:

5.3

Interpretation of results:
moderately irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
The substance is considered to be a moderate to severe irritant
Executive summary:

Skin irritation has been investigated following 24 hours exposure. Well-defined to moderate erythema and slight to moderate oedema was apparent and of sufficient severity for the substance to be regarded as a dermal irritant.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Link to relevant study records
Reference
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Screening study for suspected highly irritant substances. Some details on methods not available
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
no
Species:
rabbit
Strain:
other: Japanese white
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: No data
- Age at study initiation: No data
- Weight at study initiation: No data
- Housing: No data
- Diet (e.g. ad libitum): No data
- Water (e.g. ad libitum): No data
- Acclimation period: No data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): No data
Vehicle:
other: Undiluted and 10% in olive oil
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): Undiluted and 10% in olive oil
Duration of treatment / exposure:
Single exposure
Observation period (in vivo):
Up to 28 days
Number of animals or in vitro replicates:
3/group
Details on study design:
REMOVAL OF TEST SUBSTANCE
- Washing (if done): None

SCORING SYSTEM: Draize scale

TOOL USED TO ASSESS SCORE: fluorescein staining to aid assessment of corneal opacity
Irritation parameter:
cornea opacity score
Basis:
animal #1
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 28 days
Remarks on result:
other: Undiluted substance
Irritation parameter:
cornea opacity score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
not fully reversible within: 28 days
Remarks on result:
other: Undiluted substance
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
not fully reversible within: 28 days
Remarks on result:
other: Undiluted substance
Irritation parameter:
iris score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Undiluted substance
Irritation parameter:
iris score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Undiluted substance
Irritation parameter:
iris score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0.7
Max. score:
1
Reversibility:
fully reversible within: 24 days
Remarks on result:
other: Undiluted substance
Irritation parameter:
conjunctivae score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.3
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Undiluted substance
Irritation parameter:
conjunctivae score
Basis:
animal #2
Time point:
24/48/72 h
Score:
2
Max. score:
2
Reversibility:
fully reversible within: 14 days
Remarks on result:
other: Undiluted substance
Irritation parameter:
conjunctivae score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2.3
Max. score:
3
Reversibility:
fully reversible within: 25 days
Remarks on result:
other: Undiluted substance
Irritation parameter:
chemosis score
Basis:
animal #1
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 15 days
Remarks on result:
other: Undiluted substance
Irritation parameter:
chemosis score
Basis:
animal #2
Time point:
24/48/72 h
Score:
1.7
Max. score:
3
Reversibility:
fully reversible within: 17 days
Remarks on result:
other: Undiluted substance
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
fully reversible within: 17 days
Remarks on result:
other: Undiluted substance

Undiluted substance – Corneal effects noted in at least one animal within 3 hours of exposure, increasing to a maximum after 6 days. Some recovery apparent after 13 days but full reversibility not apparent within 28 days. Iris effects first noted 48 hours after exposure with full recovery apparent within 24 days. Marked chemosis observed within 1 hour of exposure, reaching a maximum (score) after 2 hours. Severity of response decreased with time and recovery apparent 17 days after exposure. Conjunctival reaction noted in at least one animal within 1 hour of exposure, response reaching its greatest after 24 hours. Full recovery occurred within 25 days.

 

10% concentration in olive oil – Corneal effects noted in at least one animal within 3 hours of exposure, increasing in incidence/severity to its highest level 5 days after exposure. Full recovery apparent after 11 days. Iris effects first noted 24 hours after exposure with full recovery not apparent within 28 days. Marked chemosis observed within 1 hour of exposure, reaching a near maximum (score) after 2 hours. Severity of response decreased with time and recovery apparent 9 days after exposure. Conjunctival reaction noted in at least one animal within 1 hour of exposure, response reaching its greatest after 72 hours. Full recovery occurred within 11 days.

Interpretation of results:
Category 1 (irreversible effects on the eye)
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The undiluted substance is highly irritating to the eye with effects not fully reversible within 28 days of exposure
Executive summary:

Eye irritation has been assessed in the rabbit using methods essentially similar to those described by OECD/EU test guidelines. The severity of response and lack of full reversibility was such that the substance was judged to be highly irritating/corrosive to the eye.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin:

In a number of primary dermal irritation studies on the substance, rabbits were dermally exposed to 0.5 mL for 24 hours. In general, well defined erythema and slight to moderate oedema were observed. Taking the test conditions into account, in particular the 24 hour exposure period compared with 4 hours of current test methods (described in OECD TG 404), the severity of response suggests that the substance should be classified and labelled as a dermal irritant according to CLP (1272/2008/EEC), and according to 67/548/EEC (DSD).

 

Eye:

In a number of primary eye irritation studies , 0.1 mL of the substance was instilled into the conjunctival sac of the eye of rabbits. Significant and marked responses to treatment were noted, of sufficient severity to require the substance to be classified as seriously eye damaging according to CLP (1272/2008/EC).


Justification for selection of skin irritation / corrosion endpoint:
Best documented study available

Justification for selection of eye irritation endpoint:
Best documented study available

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

Skin:

Based on the results of the presented in the skin irritation studies the test substance should be classified and labelled according to Regulation 1272/2008/EC (CLP) and Directive 67/548/EEC (DSD).

Eyes:

Based on the results of the available eye irritation studies, tetrahydromethylphthalic anhydride (MTHPA) was classified as eye damaging category 1 with labelling of H318: causes serious eye damage according to CLP (1272/2008/EC) and as seriously eye damaging (Xi, R41) according to 67/548/EEC.