Registration Dossier

Administrative data

Description of key information

The test substance shows no indication of skin irritation.

The test substance is classified as irritating to the eyes.

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:
29 Oct 1985 to 3 Nov 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
equivalent or similar to guideline
Guideline:
other: Toxic Substances Control Act Draft Guidelines; Office of Toxic Substances; Office of Pesticides and Toxic Substances; United States Environmental Protection Agency; August 1982; Acute Exposure, Primary Dermal Irritation.
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of the test item (as cited in study report): Nickel dibutyldithiocarbamate
- Batch No.: 0131100 NF
- Appearance: Green, powder
Species:
rabbit
Strain:
New Zealand White
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Froxfield Rabbits, Petersfield, Hampshire, England
- Age at study initiation: 9-13 weeks
- Weight at study initiation: 1.9-3.1 kg
- Housing: The rabbits were individually housed in metal cages with perforated floors.
- Diet: SDS Standard Rabbit Diet, ad libitum
- Water: tap water, ad libitum

ENVIRONMENT
- Temperature (°C): 19
- Humidity (%): 30-70
- Air changes (per hr): 19
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
clipped
Vehicle:
unchanged (no vehicle)
Controls:
no
Amount / concentration applied:
A 0.5 g amount of the test substance was applied under a 2.5 cm square gauze pad moistened with 0.5 mL saline to two intact and two abraded skin sites on each animal.
Duration of treatment / exposure:
24 hours
Observation period:
5 day
Number of animals:
6 females
Details on study design:
TEST SITE
- Approximately 24 hours prior to application of the test substance, hair was removed with electric clippers from the dorso-lumbar region of each rabbit exposing an area of skin approximately 10 cm square.
- Immediately prior to application of the test substance, two areas of skin approximately 2.5 cm square on the right side of the spine were abraded using the tip of a scalpel blade to make minor incisions through the stratum corneum. These were not deep enough to disturb the dermis or cause bleeding. Two similar sites on the left side remained intact.
- The treatment sites were occluded with "Elastoplast" elastic adhesive dressing for approximately 24 hours. "Elizabethan collars" were placed on each animal in order to prevent the animal from disturbing the test sites. The animals were not restrained during thee exposure period and were returned to their cages.

REMOVAL OF TEST SUBSTANCE
At the end of the exposure period the semi-occlusive dressing and gauze pads were removed and the treatment sites wiped to remove any residual test substance.

OBERVATIONS AND SCORING
Examination of the treated skin sites was made approximately 30 minutes and 24, 48, 72 and 96 hours after removal of the patches.
Irritation parameter:
erythema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
edema score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritant / corrosive response data:
None of the animals showed any observable response to treatment throughout the 5-day observation period.
Interpretation of results:
GHS criteria not met
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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
GLP compliance:
not specified
Specific details on test material used for the study:
- Name of the test item (as cited in study report): Nickel dibutyldithiocarbamate
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
ENVIRONMENT
- Housing: The animals are caged individually and receive no hay or other extraneous material that might enter the eyes.
Vehicle:
unchanged (no vehicle)
Controls:
other: The untreated eye per animal served a control
Amount / concentration applied:
100 mg of the test substance is allowed to fall on the everted lower lid of one eye of each rabbit; the upper and lower eye lid are then carefully closed and subsequently held together for at least one second before releasing, to prevent loss of material.
Duration of treatment / exposure:
single application
Observation period (in vivo):
7 days
Number of animals or in vitro replicates:
6
Details on study design:
- The eyes are examined before testing and only those animals without observable eye defects were used.
- The eyes are not washed following instillation and the animals are released immediately.
- The eyes are examined at 24, 48, 72 hours and 7 days after instillation of the test material.
- Ocular reactions are read using a binocular magnifying glass.
Irritation parameter:
cornea opacity score
Basis:
animal: #1, #2, #5
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 7 days except for animal #2
Irritation parameter:
cornea opacity score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
cornea opacity score
Basis:
animal #4
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
cornea opacity score
Basis:
animal #6
Time point:
24/48/72 h
Score:
0.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
iris score
Basis:
animal: #1, #2, #3, #5
Time point:
24/48/72 h
Score:
1
Max. score:
2
Reversibility:
fully reversible within: 7 days except for animal #2
Irritation parameter:
iris score
Basis:
animal: #4, #6
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
animal: #1, #4
Time point:
24/48/72 h
Score:
1.33
Max. score:
3
Reversibility:
fully reversible within: 7 days except for animal #4
Irritation parameter:
conjunctivae score
Basis:
animal: #2, #3, #6
Time point:
24/48/72 h
Score:
1.67
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
conjunctivae score
Basis:
animal #5
Time point:
24/48/72 h
Score:
2
Max. score:
3
Reversibility:
not fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal: #1, #5
Time point:
24/48/72 h
Score:
2
Max. score:
4
Reversibility:
fully reversible within: 7 days
Irritation parameter:
chemosis score
Basis:
animal: #2, #6
Time point:
24/48/72 h
Score:
1.33
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Irritation parameter:
chemosis score
Basis:
animal #3
Time point:
24/48/72 h
Score:
1.67
Max. score:
4
Reversibility:
fully reversible within: 72 hours
Irritation parameter:
chemosis score
Basis:
animal #4
Time point:
24/48/72 h
Score:
1
Max. score:
4
Reversibility:
fully reversible within: 48 hours
Interpretation of results:
Category 2 (irritating to eyes) based on GHS criteria
Conclusions:
Irritating effects on the rabbit eye were reported in the key study (corneal opacity score ≥ 1 and iritis score ≥ 1). The study was limited by a reduced observation period (7 days in stead of 21 days), even though some effects were not fully reversed at day 7. Given that the supporting study shows no indication of eye irritation in rabbits, it is assumed that effects observed in the key study would have been fully reversed after 21 days after exposure. Therefore, the test substance is classified as irritating, but not corrosive.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Skin irritation / corrosion

In a pre-GLP study similar to OECD TG 404, skin irritation was assessed with six New-Zealand rabbits. The intact skin (clipped) of the animals were exposed to 0.5 g of the test substance on an area of 2.5 cm² under a gauze pad (semi-occlusive) moistened with 0.5 ml saline for 24 hours. Examination was made approximately 30 minutes and 24, 48, 72, 96 hours after exposure.

Based on the average erythema and oedema scores, the substance is considered to be not irritating to skin.

In a pre-GLP study similar to OECD TG 404, skin irritation was assessed with twelve New-Zealand rabbits (six on intact skin and six on abraded skin). Animals were exposed to 0.5 g of the test substance on an area of ca. 2.5 cm² for 24 hours. Examinations were made 24 and 72 hours after the start of the exposure. Only in one animal, very slight erythema was observed. Based on the average erythema and oedema scores, the substance is considered to be not irritating to skin.

Eye irritation

In a pre-GLP acute toxicity study similar to OECD 405, eye irritation was assessed with six New Zealand rabbits. Animals were exposed to 100 mg of the test substance. Eyelids were held together for one second before releasing. The eyes were not rinsed afterwards. The untreated eye served as a control. Eyes were examined 1 hour and 1, 2, 3, 4 and 7 days after instillation and scored according to the Draize scale. 24 hours after the test substance had been brought into the eyes, the following effects were observed: slight to moderate corneal opacity, slight iritis, moderate redness of the conjunctivae and swelling with eye lids half closed. Ocular lesions recovered partly over the following days. At Day 7, the following effects were observed: Very slight corneal opacity in two rabbits, slight iritis in one rabbit, and slight conjunctivitis in five rabbits. Under the conditions of the test, the test substance was considered irritating to the eyes.

In a pre-GLP acute toxicity study similar to OECD 405, eye irritation was assessed with six New Zealand rabbits. Animals were exposed to 65 mg of the test substance. Eyelids were held together for one second before releasing. The eyes were not rinsed afterwards. The untreated eye served as a control. Eyes were examined 1 hour and 1, 2, 3, 4 and 7 days after instillation and scored according to the Draize scale. Two animals gave a positive response. Redness of the conjunctivae was observed in two animals one day after instillation. Transient mild conjunctival reactions were seen in three animals. All eyes were normal one to three days after instillation. Under the conditions of the test, the test substance was not considered irritating to eyes.

Justification for classification or non-classification

Based on the results of the available studies, classification for skin irritation is not warranted in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008.

Based on a worst-case approach, the test substance has to be classified as Eye Irrit. 2: H319: Causes serious eye irritation in accordance with EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation No. (EC) 1272/2008. Irritating effects on the rabbit eye were reported in the key study (corneal opacity score ≥ 1 and iritis score ≥ 1). The study was limited by a reduced observation period (7 days in stead of 21 days), even though some effects were not fully reversed at day 7. Given that the supporting study shows no indication of eye irritation in rabbits, it is assumed that effects observed in the key study would have been fully reversed after 21 days after exposure. Therefore, the test substance is classified as irritating, but not corrosive.