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Description of key information

Key studies with rabbits do not show an irritation of the substance to skin or eye.

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:
2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
Species and strain: Rabbits, New Zealand White.Supplier: Charles River Deutschland GmbH, D-97633 Sulzfeld.Number and sex: 3 females.Body weights (at the start and at the termination of the study): 2.1-2.3 and 2.3-2.5 kgHygiene: Optimal hygienic conditions.Room temperature: Average of 20.3 °C (continuous control and recording).Relative humidity: Average of 58.0 % (continuous control and recording).Light: Artificial light from 6 a.m. to 6 p.m.Cages: Individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 79 cm x 59 cm bottom area, 38 cm height.Feed: Altromin 2123 maintenance diet for rabbits, rich in crude fiber, ad libitum. Analysis of the feed for ingredients and contaminants is performed randomly by Altromin, D-32791 Lage, Germany.Hay-briquettes (supplied by SSNIFF, D-59494 Soest) are offered additionally as a dietary supplement.Water: Tap water from an automatic watering system, ad libitum.Environmental Enrichment: Aspen wood boards during acclimatisation and observation period. Exception: boards were withdrawn during the exposure.Acclimatisation: 5 days (1 animal) and 12 days (2 animals).Identification: Individual labelling with felt-tipped pen on an ear pinna and cage labels.Sacrifice of animals: The animals were killed by inhalation of 80 % CO2 + 20 % air.
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
water
Controls:
not required
Amount / concentration applied:
Samples with approximately 0.5 g of the test substance were moistened with 1.0 mL deionised water and were placed on gauze patches in a size of about 2.5 cm x 2.5 cm and were applied to the test sites.
Duration of treatment / exposure:
4 hours.
Observation period:
72 hours. Examination at 1, 24, 48 and 72 hours after the patch removal.
Number of animals:
3
Irritation parameter:
erythema score
Basis:
animal: each
Time point:
other: 1, 24, 48 and 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
edema score
Basis:
animal: each
Time point:
other: 1, 24, 48 and 72 h
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Other effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.

All areas treated with the test substance and all control areas were normal before the application and at each observation time.

Interpretation of results:
not irritating
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Adipic acid dihydrazide is not irritating to skin.
Executive summary:

The possible irritation or corrosion by the test substance following a single application to the intact skin of rabbits was determined applying the OECD and the EU-methods. Results:

Test sites, exposed for 3 minutes and 1 hour (one animal):

- No adverse skin reactions were noted immediately after the patch removal.

Test sites, exposed for 4 hours (three animals):

- Erythema/Eschars: Not affected.

- Oedema: Not affected.

Adipic acid dihydrazide is not irritating to skin.

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:
key study
Study period:
2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study with GLP.
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
GLP compliance:
yes
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Supplier: Charles River Deutschland GmbH, D-97633 Sulzfeld.Number and sex: 3 females.Body weights (at the start and at the termination of the study): 1.9-2.4 and 2.1-2.6 kgHygiene: Optimal hygienic conditions.Room temperature: Average of 19.6 °C (continuous control and recording).Relative humidity: Average of 66.3 % (continuous control and recording).Light: Artificial light from 6 a.m. to 6 p.m.Cages: Individual caging in metal wire cages, Ehret GmbH, D-79312 Emmendingen, type KK 016R, 79 cm x 59 cm bottom area, 38 cm height.Feed: Altromin 2123 maintenance diet for rabbits, rich in crude fiber, ad libitum. Analysis of the feed for ingredients and contaminants is performed randomly by Altromin, D-32791 Lage, Germany.Hay-briquettes (supplied by SSNIFF, D-59494 Soest) are offered additionally as a dietary supplement.Water: Tap water from an automatic watering system, ad libitum.Environmental Enrichment: Aspen wood boards during acclimatisation and observation period. Exception: boards were withdrawn during the exposure.Acclimatisation: 5 days (1 animal) and 12 days (2 animals).Identification: Individual labelling with felt-tipped pen on an ear pinna and cage labels.Sacrifice of animals: The animals were killed by inhalation of 80 % CO2 + 20 % air.
Vehicle:
unchanged (no vehicle)
Controls:
not required
Amount / concentration applied:
The weighed amounts of the individual doses were 60, 60 and 61 mg.
Duration of treatment / exposure:
The approximate equivalent of 0.1 mL of the test substance was administered per animal into the conjunctival sacs of the right eyes by gently pulling the lower lids away from the eyeballs for instillation. The eyes were held closed for about one second to prevent a loss of test substance.The left eyes remained untreated and served as a control.
Observation period (in vivo):
Both eyes of the animals were examined within 24 hours before the instillation and approximately 1, 24, 48 and 72 hours p.a.
Number of animals or in vitro replicates:
3
Details on study design:
Prior to starting the eye irritation/corrosion study the pH-value of the test substance was determined. Firstly, the test substance was given to one animal. As no evidence for a serious damage to the eye of this animal was found during the initial 72 hour observation period (no corrosive effect), the test substance was administered to the other two animals subsequently.
Irritation parameter:
cornea opacity score
Basis:
animal: each
Time point:
other: 24 hours before the instillation and ca. 1, 24, 48 and 72 hours p.a.
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
iris score
Basis:
animal: each
Time point:
other: 24 hours before the instillation and ca. 1, 24, 48 and 72 hours p.a.
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
conjunctivae score
Basis:
animal: each
Time point:
other: 24 hours before the instillation and ca. 1, 24, 48 and 72 hours p.a.
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Irritation parameter:
chemosis score
Basis:
animal: each
Time point:
other: 24 hours before the instillation and ca. 1, 24, 48 and 72 hours p.a.
Score:
0
Max. score:
0
Reversibility:
other: not applicable
Other effects:
No signs of systemic toxicity were observed in the animals during the test period and no mortality occurred.

The untreated eyes ("control eyes") were normal at each observation time. The eyes, treated with the test substance ("test eyes") were normal before the instillation and at each observation time.

Interpretation of results:
not irritating
Remarks:
Migrated informationCriteria used for interpretation of results: EU
Conclusions:
Adipic acid dihydrazide is not irritating to eyes.
Executive summary:

The possible irritation by the test substance following a single application to the intact eyes of rabbits was determined applying the OECD and the EU-methods.

Results: Cornea, iris, conjunctiva and chemosis were not affected by the test substance.

Adipic acid dihydrazide is not irritating to eyes.

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

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for selection of skin irritation / corrosion endpoint:
Key study.

Justification for selection of eye irritation endpoint:
Key study.

Justification for classification or non-classification

There are no indications to support a classification of the substance as being irritant to skin or eye.

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