Registration Dossier

Administrative data

Description of key information

ZMB2 is not irritating to the skin (Biosearch Inc, 1977) or to the eyes  (Biosearch Inc, 1977).

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
Study period:
June 1977 - May 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Conducted prior to GLP.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Principles of method if other than guideline:
The method employed in the testing, evaluation and the scoring of the results was similar to that described in Section 1500.41 - Hazardous Substances and Articles, Administration and Enforcement Regulations, Federal Register vol. 38, No. 187, P. 27019, 27 September 1973.
GLP compliance:
no
Remarks:
Prior to GLP.
Species:
rabbit
Strain:
not specified
Type of coverage:
occlusive
Preparation of test site:
shaved
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
0.5g
Duration of treatment / exposure:
24 hours.
Observation period:
72 hours.
Number of animals:
Six.
Details on study design:
The test material was used as supplied. A group of six albino rabbits were clipped over a wide area. One side of the rabbits back was allowed to remain intact. A 0.5 g portion of material was applied to the intact skin site. Gauze patches were then placed over the treated area and an impervious material was wrapped snugly around the trunks of the animals to hold the patch in place.

The wrapping was removed at the end of the 24 hour period and the treated areas were examined. Reading were also made after 72 hours.
Irritation parameter:
erythema score
Basis:
other: all animals
Time point:
other: 24 h
Score:
0
Max. score:
0
Irritation parameter:
erythema score
Basis:
other: all animals
Time point:
other: 72 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
other: all animals
Time point:
other: 24 h
Score:
0
Max. score:
0
Irritation parameter:
edema score
Basis:
other: all animals
Time point:
other: 72 h
Score:
0
Max. score:
0
Other effects:
No effects.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
0/6 animals showed evidence of skin irritation in the study, therefore, ZMB2 is not classified as an irritant.
Endpoint:
skin irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) 1907/2006 as amended: Annex VII, section 8.1.1: the skin corrosion: in vitro / ex vivo study does not need to be conducted based on existing data sufficient for classification and labelling being already available. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.2.2, October 2015) the study does not need to be conducted.
Endpoint:
skin irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Sufficient documentation and scientifically acceptable
Principles of method if other than guideline:
500 mg of the test substance were semi-occlusively applied once to the intact skin onto the inside of the ear of one male and one female young adult New Zealand White rabbit (3-4 kg) for an exposure period of 24 hours. Evaluation of skin irritation was made until day 7 according to Draize et al. (J.Pharmacol. Exp. Ther. 82, 377-390 (1944).
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Type of coverage:
semiocclusive
Preparation of test site:
other: application at the inside of the ear
Vehicle:
other: oil
Controls:
not required
Duration of treatment / exposure:
24 hours
Observation period:
7 days
Number of animals:
2 animals
Irritation parameter:
primary dermal irritation index (PDII)
Basis:
mean
Time point:
other: 1 h, 2 d, 7 d
Score:
0
Max. score:
8
Reversibility:
other: not applicable - score = 0 at any time point
Other effects:
no data

The test substance proved to be not irritating to the skin.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
500 mg of the test substance were semi-occlusively applied once to the intact skin onto the inside of the ear of one male and one female young adult New Zealand White rabbit (3 -4 kg) for an exposure period of 24 hours. Evaluation of skin irritation was made until day 7 according to Draize et al. (J. Pharmacol. Exp. Ther. 82, 377 -390 (1944)) The test substance proved to be not irritating to the skin.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Referenceopen allclose all

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
May 1977 - June 1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Conducted prior to GLP.
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
not applicable
Principles of method if other than guideline:
The methods employed in the testing, evaluation and in the grading of the test material are those described in Section 1500.42 - Hazardous Substances and Articles, Administration and Enforcement Regulations, Federal Register, Vol. 38, No. 187, P. 27019, 27 September 1973.
GLP compliance:
no
Remarks:
Conducted prior to GLP.
Species:
rabbit
Strain:
not specified
Vehicle:
unchanged (no vehicle)
Controls:
other: Left eye remained untreated.
Amount / concentration applied:
0.1 g
Duration of treatment / exposure:
The test material was not washed from the eyes.
Observation period (in vivo):
7 days.
Number of animals or in vitro replicates:
Six.
Details on study design:
0.1 g of the experimental material was instilled into the right eyes of the test animals while the other eyes remained untreated to serve as controls. The test material was not washed from the eyes.
The treated eyes were examined at 1, 24, 48 and 72 hours and 5 and 7 days following instillation of the test material into the eyes.
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 24 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
0
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
other: 7 d
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 24 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
0
Irritation parameter:
iris score
Basis:
mean
Time point:
other: 7 d
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 24
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
0
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
other: 7 d
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 24 h
Score:
0
Max. score:
1
Reversibility:
fully reversible within: 48 h
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
0
Irritation parameter:
chemosis score
Basis:
mean
Time point:
other: 7 d
Score:
0
Max. score:
0
Irritation parameter:
other: Discharge
Basis:
mean
Time point:
other: 24 h
Score:
1
Max. score:
1
Reversibility:
fully reversible within: 72 hrs
Irritation parameter:
other: Discharge
Basis:
mean
Time point:
other: 72 h
Score:
0
Max. score:
0
Irritation parameter:
other: Discharge
Basis:
mean
Time point:
other: 7 d
Score:
0
Max. score:
0
Other effects:
No effects.
Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
0/6 animals showed evidence of occular irritation in the study, therefore, ZMB2 is not classified as an irritant.
Endpoint:
eye irritation: in vitro / ex vivo
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available
Justification for type of information:
JUSTIFICATION FOR DATA WAIVING
In accordance with REACH Regulation (EC) 1907/2006 as amended: Annex VII, section 8.2.1: the skin corrosion: in vitro / ex vivo study does not need to be conducted based on existing data sufficient for classification and labelling being already available. According to ECHA Guidance on Information Requirements and Chemical Safety Assessment (Chapter R.7a: Endpoint Specific Guidance, R.7.2.2, October 2015) the study does not need to be conducted.
Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Sufficient documentation and scientifically acceptable
Principles of method if other than guideline:
A dose of 50 mg of the test substance was administered into one eye of one male and one female adult New Zealand White rabbit (3-4 kg) for an exposure period of 24 hours. Then the treated eyes were rinsed with sterile water. The contralateral eye remained untreated and served as a control. The eyes were examined and the grade of the ocular reaction was recorded until day 7 according to Draize et al. (J. Pharmacol. Exp. Ther. 82, 377-390 (1944)).
GLP compliance:
no
Species:
rabbit
Strain:
New Zealand White
Vehicle:
unchanged (no vehicle)
Controls:
not required
Duration of treatment / exposure:
1 day
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
2 animals
Irritation parameter:
overall irritation score
Basis:
mean
Time point:
other: 1 h, 24 h, 2 d, 7 d
Score:
0
Max. score:
13
Reversibility:
other: not applicable - score=0 at any time point

The test substance proved to be not irritating to the eye.

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
A dose of 50 mg of the test substance was administered into one eye of one male and one female adult New Zealand White rabbit (3-4 kg) for an exposure period of 24 hours. Then the treated eyes were rinsed with sterile water. The contralateral eye remained untreated and served as a control. The eyes were examined and the grade of the ocular reaction was recorded until day 7 according to Draize et al. (J. Pharmacol. Exp. Ther. 82, 377-390 (1944)).
The test substance proved to be not irritating to the eye.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation

In vivo

Key study:

ZMB2 is considered not irritating to the skin based on the following results:

erythema score: at 24, and 72 hours = 0,

edema score: at 24, and 72 hours = 0 (Biosearch Inc, 1977).

Supporting study:

500 mg of ZMB2 weas semi-occlusively applied once to the intact skin onto the inside of the ear of one male and one female young adult New Zealand White rabbit for an exposure period of 24 hours. Evaluation of skin irritation was made until day 7. The test substance proved to be not irritating to the skin (Bayer, 1979).

Justification for selection of skin irritation / corrosion endpoint:
This study was conducted according to a method equilavent or similar to OECD 404 using rabbits.

In vitro

An in vitro study was not required due to the availability of adequate in vivo skin irritation data.

Eye irritation

In vivo

Key study:

ZMB2 is considered not irritating to the eyes based on the following results:

cornea score: at 24, 72 hours and 7 days = 0

iris score: at 24, 72 hours, and 7 days = 0

conjunctivae score: at 24 hours = 1, fully reversable within 48 hours

chemosis score: at 24, 72 hours and 7 days = 0

Discharge score: at 24 hours = 1, fully reversible within 48 hours (Biosearch Inc, 1977).

Supporting study:

50 mg of ZMB2 was administered into one eye of one male and one female adult New Zealand White rabbit for an exposure period of 24 hours. Then the treated eyes were rinsed with sterile water. The contralateral eye remained untreated and served as a control. The eyes were examined and the grade of the ocular reaction was recorded until day 7. The test substance proved to be not irritating to the eye (Bayer, 1979).


Justification for selection of eye irritation endpoint:
This study was conducted according to a method equilavent or similar to OECD 405 using rabbits.

In vitro

An in vitro study was not required due to the availability of adequate in vivo eye irritation data.

Justification for classification or non-classification

Skin irritation

Out of 6 animals 0 showed a mean score of >2.3 for erythema or edema, therefore, according to Regulation EC No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, ZMB2 is not classified.

Eye irritation

Out of 6 animals 0 showed a mean score of >1 for the cornea, 0 showed a mean score of >1 for the iris and 0 showed a mean score of >2 for conjunctiva erythema or swelling, therefore, according to Regulation EC No. 1272/2008 on classification, labelling and packaging (CLP) of substances and mixtures, ZMB2 is not classified.