Registration Dossier

Administrative data

Description of key information

Dermal and ocular irritation studies have been conducted on four substances in the MDI category. In vivo studies on dermal and ocular irritation have been conducted on the substances with the EC numbers 406-530-2, 406-370-3, 445-760-8 and 406-690-3. No classifiable irritant responses were observed in any of the studies when applied to skin, indicating that these substances have no inherent irritant properties via hydrolysis or other chemical reactions.

For potential eye irritancy, the substances 406-690-3, 406-530-2 and 406-370-3 demonstrated no classifiable response according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System. The substance 445-760-8, however, was classified as an eye irritant since ocular reactions were observed in an in vivo study in the rabbit. Most effects were transient, but in one animal, the effects on the conjunctivae score (redness) and chemosis score were not fully reversed within the 21 day observation period. In the other animals, the observed effects were fully reversed within 21 days. However, in this study 100 mg of the substance (a white powder with a very poor water solubility of 4.38 µg/L) was put directly onto the eye (without vehicle) and no washing was applied. It was recorded that the material was still present in the eyes > 24 h after application. It is therefore most likely that the observed ocular effects were caused by mechanical irritation rather than inherent irritative properties of the material.

No data were identified relating to irritation of the respiratory tract. Given the results from the skin and eye irritation studies it is unlikely that MDI category members would cause significant respiratory irritation. The members of the MDI category are grease thickeners and although they were tested in the isolated form, they are only manufactured and marketed within the grease base where near stoichiometric quantities of starting materials are used to avoid the presence of excess isocyanate. Additionally, following the substance identification analysis conducted it is noted in all the study reports that no unreacted MDI starting material is present in the substances to be registered. Based on this information, it is considered that a respiratory classification is not required for any of the substances being registered in the MDI category.  

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
Qualifier:
according to
Guideline:
other: Annex V
GLP compliance:
yes
Species:
rabbit
Strain:
other: Japanese White
Type of coverage:
occlusive
Preparation of test site:
not specified
Vehicle:
other: Liquid paraffin
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg

VEHICLE
- Other: Liquid paraffin
Duration of treatment / exposure:
4 hours
Observation period:
Not reported
Number of animals:
6
Details on study design:
Conducted according to guideline and GLP
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: Timepoint not specified, standard timepoint assumed
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: Timepoint not specified, standard timepoint assumed
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: Timepoint not specified, standard timepoint assumed
Irritation parameter:
erythema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: Timepoint not specified, standard timepoint assumed
Irritation parameter:
erythema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: Timepoint not specified, standard timepoint assumed
Irritation parameter:
erythema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: Timepoint not specified, standard timepoint assumed
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: Timepoint not specified, standard timepoint assumed
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: Timepoint not specified, standard timepoint assumed
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: Timepoint not specified, standard timepoint assumed
Irritation parameter:
edema score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: Timepoint not specified, standard timepoint assumed
Irritation parameter:
edema score
Basis:
animal #5
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: Timepoint not specified, standard timepoint assumed
Irritation parameter:
edema score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0
Max. score:
0
Reversibility:
not specified
Remarks on result:
other: Timepoint not specified, standard timepoint assumed
Irritant / corrosive response data:
None reported
Other effects:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Edema and erythema scores were 0 for all animals. Therefore, the test item is not classified for skin irritation.
Executive summary:

The skin irritancy potential of the test item was assessed using 500 mg of the test item. The study was conducted according to a standard guideline using Japanese white rabbits. The mean and max edema and erythema scores were 0 for all animals. No other effects were observed. Therefore, the test item is not classified for skin irritation.

The study is a GLP compliant, guideline study and is acceptable with restrictions for evaluation of this endpoint.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
Qualifier:
according to
Guideline:
other: Annex V
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
not specified
Vehicle:
water
Remarks:
Milli-Q water
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): Not reported
- Concentration (if solution): 500 mg
Duration of treatment / exposure:
4 hours
Observation period:
Not reported
Number of animals:
3
Details on study design:
Conducted according to guideline and GLP
Irritation parameter:
erythema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
mean
Time point:
72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
72 h
Score:
0
Irritant / corrosive response data:
Any changes observed were fully reversible within 1 day
Other effects:
Slight erythema was noted in one animal after removal of dressing.
Interpretation of results:
GHS criteria not met
Conclusions:
Mean edema and erythema scores after 24, 48 and 72 hours were 0 for all animals. Therefore, the test item is not classified for skin irritation.
Executive summary:

The skin irritancy potential of the test item was assessed with New Zealand White rabbits according to a standard guideline. 500 mg of the test item was applied to 3 rabbits and the exposure period was 4 hours. The edema and erythema scores after 24, 48 and 72 hours were 0 for all animals. Slight erythema was noted in one animal after removal of dressing. Any changes observed were fully reversible within 1 day. Therefore, the test item is not classified for skin irritation.

 

The study is a GLP compliant, guideline study and is acceptable with restrictions for evaluation of this endpoint.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
Qualifier:
according to
Guideline:
other: Annex V
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
not specified
Vehicle:
other:
Remarks:
Substance moistened with water
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
Duration of treatment / exposure:
4 hours
Observation period:
Not reported
Number of animals:
3
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
Mean Score 1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
Mean Score 2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
Mean Score 3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
Mean Score 1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
Mean Score 2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
Mean Score 3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Irritant / corrosive response data:
None reported
Other effects:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Mean and maximum edema and erythema scores were 0 for all animals at all timepoints assessed. Therefore, the test item is not classified for skin irritation.
Executive summary:

The skin irritancy potential of the test item was assessed in a study conducted according to EU Annex V guidelines. 500 mg of test item was applied to 3 New Zealand White rabbits. The mean and maximum edema and erythema scores were 0 for all animals. No other effects were observed. Therefore, the test item is not classified for skin irritation.

The study is a GLP compliant, guideline study and is acceptable with restrictions for evaluation of this endpoint.

Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study without detailed documentation
Remarks:
This study is included in a NONS registration and therefore has been evaluated by a relevant competent authority and is considered to be reliable.
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
not specified
Vehicle:
unchanged (no vehicle)
Remarks:
Substance wetted with reverse osmosis purified water
Controls:
not specified
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 500 mg
Duration of treatment / exposure:
4 hours
Observation period:
Not reported
Number of animals:
3
Details on study design:
Conducted according to guideline and GLP
Irritation parameter:
erythema score
Basis:
animal #1
Remarks:
Mean Score 1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #2
Remarks:
Mean Score 2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
animal #3
Remarks:
Mean Score 3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
erythema score
Basis:
mean
Time point:
other: Not reported
Score:
0
Irritation parameter:
edema score
Basis:
animal #1
Remarks:
Mean Score 1
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #2
Remarks:
Mean Score 2
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
animal #3
Remarks:
Mean Score 3
Time point:
24/48/72 h
Score:
0
Irritation parameter:
edema score
Basis:
mean
Time point:
other: Not reported
Score:
0
Irritant / corrosive response data:
None reported
Other effects:
None
Interpretation of results:
GHS criteria not met
Conclusions:
Mean and maximum edema and erythema scores were 0 for all animals at all timepoints assessed. Therefore, the test item is not classified for skin irritation.
Executive summary:

The skin irritancy potential of the test item was assessed with a 500 mg application to New Zealand White rabbits in a study conducted according to according to a OECD 404 and EU B4 guidelines. The mean and maximum edema and erythema scores were 0 for all animals. No other effects were observed. Therefore, the test item is not classified for skin irritation.

The study is a GLP compliant, guideline study and is acceptable with restrictions for evaluation of this endpoint.

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

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

The category members are not classified as irritant to skin as the in vivo rabbit studies on all but one MDI category members were negative. The one substance with EC number 445-760-8 that was reported as positive for eye irritation was tested without a vehicle. The insoluble powder was reported to be present >24 h after application to the eye and the observed effects (redness and chemosis which had not fully reversed during the study in a single animal) are most likely due to mechanical rather than chemical irritation.

As a consequence, the overall weight of evidence leads to the conclusion that the PU thickeners of the MDI category are not eye irritants according to the Classification, Labelling and Packaging Regulation or the Globally Harmonised Classification System.