Registration Dossier

Administrative data

Description of key information

Skin and eye irritating properties of zinc bis(dibenzyldithiocarbamate) (ZBEC) were studied in two GLP-compliant guideline studies with rabbits. No signs of skin irritation were noted at any time observation points in the skin irritation study. Minor irritation of conjunctiva (redness, chemosis and/or discharge) was noted in rabbits eyes 1 hour post-instillation, which completely resolved within 48 hours. Based on these results, the substance is considered to be not irritating to skin and 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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 404 (Acute Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2500 (Acute Dermal Irritation)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan, Belton, Leics, England
- Age at study initiation: at least 6 weeks
- Weight at study initiation: at least 1.0 kg
- Housing: individually in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet (e.g. ad libitum): pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy, approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) was provided at least three times a week.
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18.8 -19.7
- Humidity (%): 46 - 77
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Preparation of test site:
other: clipped
Vehicle:
other: watery ethanol (50% v/v)
Controls:
not required
Amount / concentration applied:
TEST MATERIAL
- Amount applied (volume or weight with unit): 0.5 grams

VEHICLE
- Amount(s) applied (volume or weight with unit): 0.7 ml
- Concentration (if solution): 50% watery ethanol
Duration of treatment / exposure:
4 hours
Observation period:
72 hours
Number of animals:
3
Details on study design:
TEST SITE
- Area of exposure: 2x3 cm
- % coverage: 100
- Type of wrap if used: Micropore tape, which was wrapped around the abdomen and secured with Coban elastic bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with tap water
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize
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:
No skin irritation was caused by 4 hours exposure to Zinc dibenzyldithiocarbamate (Perkacit ZBEC pdr). There was no evidence of a corrosive effect on the skin. No staining of the treated skin by the test substance was observed and no test substance remnants were seen.
Other effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Qualifier:
according to
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
GLP compliance:
yes (incl. certificate)
Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Source: Harlan, Belton, Leics, England
- Age at study initiation: at least 6 weeks
- Weight at study initiation: at least 1.0 kg
- Housing: individually in labeled cages with perforated floors (Ebeco, Germany, dimensions 67 x 62 x 55 cm) and shelters (Ebeco, Germany, dimensions 40 x 32 x 23 cm).
- Diet (e.g. ad libitum): pelleted diet for rabbits (Global Diet 2030 from Harlan Teklad®, Mucedola, Milanese, Italy, approximately 100 grams per day. Hay (TecniLab-BMI BV, Someren, The Netherlands) was provided at least three times a week.
- Water: tap water, ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.0 - 19.7
- Humidity (%): 46 - 76
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
Vehicle:
unchanged (no vehicle)
Controls:
other: untreated eye served as a reference control
Amount / concentration applied:
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 39.9 mg (range 39.7 – 40.1 mg) (a volume of approximate 0.1 ml)
Duration of treatment / exposure:
Single instillation
Observation period (in vivo):
72 hours
Number of animals or in vitro replicates:
3
Details on study design:
SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE: fluorescein
Irritation parameter:
cornea opacity score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Irritation parameter:
iris score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
2
Irritation parameter:
conjunctivae score
Basis:
mean
Time point:
24/48/72 h
Score:
0.3
Max. score:
3
Reversibility:
fully reversible within: 48 hr
Irritation parameter:
chemosis score
Basis:
mean
Time point:
24/48/72 h
Score:
0
Max. score:
4
Reversibility:
fully reversible within: 24 hr
Irritant / corrosive response data:
Instillation of approximately 40 mg of Zinc dibenzyldithiocarbamate (Perkacit ZBEC pdr) (a volume of approximately 0.1 mL) into one eye of each of three rabbits resulted in irritation of the conjunctivae, which consisted of redness, chemosis and/or discharge. The irritation completely resolved within 48 hours. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage. There was no evidence of ocular corrosion. Remnants of the test substance were present in the eye of all animals on Day 1 and on the outside of the eyelids on Day 2 (all animals), Day 3 (two animals) and Day 4 (one animal). No staining of (peri) ocular tissues by the test substance was observed.
Other effects:
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occurred.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not irritating)

Respiratory irritation

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

Additional information

Skin and eye irritating properties of zinc bis(dibenzyldithiocarbamate) (ZBEC) were studied in two GLP-compliant guideline studies with rabbits (Notox B.V., 2010a and 2010b). In the skin irritation study, approximately 0.5 g of the test substance, moistened with 0.7 mL of watery ethanol (50%) was applied to clipped dorsal skin of 3 New Zealand White rabbits for 4 hours under semi-occlusive conditions. Animals were observed for 72 hours. No signs of irritation were noted at any time points, suggesting the that the substance is not irritating to rabbit skin.

In the eye irritation study, ca. 40 mg (ca. 0.1 ml) of the test substance were instilled in one eye of 3 New Zealand White rabbits. Immediately after the 24-hour observation, a solution of 2% fluorescein in water (adjusted to pH 7.0) was instilled into both eyes of each animal to quantitatively determine corneal epithelial damage. Minor irritation of the conjunctivae, which consisted of redness chemosis and/or discharge (average scores 1) was observed at 1 hour post-instillation. Redness persisted for 24 hours. The irritation completely resolved within 48 hours. No iridial irritation or corneal opacity was observed, and treatment of the eyes with 2% fluorescein 24 hours after test substance instillation revealed no corneal epithelial damage. Based on the results of the study, ZBEC was considered to be not irritating to rabbit eyes.

Justification for classification or non-classification

Based on the results of GLP-compliant guideline studies on skin and eye irritation, classification of zinc bis(dibenzyldithiocarbamate) (ZBEC) is not warranted in accordance with Directive 67/548/EEC and EU Classification, Labelling and Packaging of Substances and Mixtures (CLP) Regulation (EC) No. 1272/2008.