polymeric zinc propylenebis(dithiocarbamate);propineb (ISO)

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2010/03/19 to 2010/04/09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Commission Regulation (EC) No. 440/2008, B.5

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

polymeric zinc 1,2-propylenebis(dithiocarbamate)

EC Number:

620-365-5

Cas Number:

9016-72-2

IUPAC Name:

polymeric zinc 1,2-propylenebis(dithiocarbamate)

Test material form:

solid

Remarks:

Powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Age at study initiation: 2 to 4 months old.
- Weight at study initiation: 3.2 to 3.4 kg.
- Housing: The animals were housed individually in Pajon cages (50 cm x 57 cm x 75 cm).
- Diet: 110 Pelleted diet, ad libitum.
- Water: tap water, ad libitum.
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature: 18 ± 3 °C
- Humidity: 30-70 %
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: 26 March to April 10 2010.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes

Amount / concentration applied:

100 mg

Duration of treatment / exposure:

A single dose of 100 mg of the test item in its original form was introduced into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lower and upper eyelids were held together for about one second to avoid any loss of test item. The eyes were not rinsed after administration of the test item

Observation period (in vivo):

1, 24, 48 and 72 hours, 5 days

Number of animals or in vitro replicates:

3 animals

Details on study design:

Just before treatment, the eyes of each animal were examined in order to check the absence of any signs of ocular irritation, ocular defects or pre-existing corneal injury. The test item, propineb, was first administered to a single animal. Since the test item was not severely irritant on this first animal, it was then evaluated sequentially on two other animals. A single dose of 100 mg of the test item, propineb, in its original form was introduced into the conjunctival sac of the left eye after gently pulling the lower lid away from the eyeball. The lower and upper eyelids were held together for about one second to avoid any loss of test item. The right eye, which remained untreated, served as control.

The eyes were not rinsed after administration of the test item. The eyes were examined approximately 1 hour, 24, 48 and 72 hours after administration of the test item. Since there were persistent ocular reactions at 72 hours, the observation period was extended up to their complete reversibility (day 5). Conjunctival reactions, iritis and corneal opacification were evaluated daily for each animal.

For the evaluation of corneal opacification (presence or absence, affected area), the eyes were examined under a UV lamp after instillation of one or two drops of 0.5% sodium fluorescein solution (a clear fluorescence is visible in the areas of opacification). This evaluation was performed on day 2 and repeated thereafter whenever necessary. The degree of ocular lesions was recorded as specified by DRAIZE and any serious lesions or toxic effects other than ocular lesions were also recorded and fully described. Each animal was weighed at the beginning (before treatment) and at the end of the observation period.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 96 hours

Results 2

Irritation parameter:

chemosis score

Basis:

mean

Time point:

48 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Results 3

Irritation parameter:

chemosis score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

4

Results 4

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

3

Reversibility:

fully reversible within: 96 hours

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Results 7

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

72 h

Score:

0.3

Max. score:

4

Results 8

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

48 h

Score:

0.7

Max. score:

4

Results 9

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

2

Max. score:

4

Results 10

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Results 11

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Any other information on results incl. tables

Table one

 

Eye irritation scores according to the Draize scheme

	Cornea			Iris			Conjunctiva-redness			Conjunctiva-chemosis
Animal number (body weight in kg)	972 (3.2)	970 (3.2)	971 (3.4)	972 (3.2)	970 (3.2)	971 (3.4)	972 (3.2)	970 (3.2)	971 (3.4)	972 (3.2)	970 (3.2)	971 (3.4)
Time of observation
1 hour	0	0	0	1	0	0	3	2	3	2	2	2
24 hours	0	0	0	0	0	0	2	2	1	1	2	0
48 hours	0	0	0	0	0	0	2	0	0	1	0	0
72 hours	0	0	0	0	0	0	2	0	0	1	0	0
120 hours	0	0	0	0	0	0	0	0	0	0	0	0
Mean scores 24-72 hours	0.0	0.0	0.0	0.0	0.0	0.0	2.0	0.7	0.3	1.0	0.7	0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item was administered to induce ocular irritation was evaluated in rabbits according to OECD (No. 405, 24th April 2002) and Commission Regulation (EC) (No. 440/2008, B.5, 30 May 2008) guidelines. A single dose of 100 mg of the test item in its original form was introduced into the left conjunctival sac. The right eye was not treated and served as control. Under the experimental conditions of the study, the test item was slightly irritating when administered by ocular route to rabbits. According to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations) on the approximation of the laws, regulations and administrative provisions relating to the classification, packaging and labeling of dangerous substances, the test item propineb should not be classified as irritating to the eyes

Executive summary:

The potential of the test item, Propineb, to induce ocular irritation was evaluated in rabbits according to OECD (No. 405, 24th April 2002) and Commission Regulation (EC) (No. 440/2008, B.5, 30 May 2008) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations.

The test item was first administered to a single male New Zealand White rabbit. Since the test item was not severely irritant on this first animal, it was then evaluated sequentially in two other animals. A single dose of 100 mg of the test item in its original form was introduced into the left conjunctival sac. The right eye was not treated and served as control. The eyes were not rinsed after administration of the test item.

Ocular reactions were observed approximately 1 hour, 24, 48 and 72 hours after the administration and then daily until reversibility of the ocular reactions (day 5). The mean values of the scores for chemosis, redness of the conjunctiva, iris lesions and corneal opacity were calculated for each animal. The interpretation of results was carried out according to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations).

A slight or moderate chemosis was noted from day 1 in all animals, persisting until day 2 in one animal and until 4 in another one. A slight to severe redness of the conjunctiva was observed in all animals on days 1 and 2, persisting in one of them until day 4. A clear discharge was noted on day 1 in all animals, persisting in two of them on day 2. An iritis was noted in 1/3 animals on day 1.

Mean scores calculated for each animal over 24, 48 and 72 hours were 1.0, 0.7 and 0.0 for chemosis, 2.0, 0.7 and 0.3 for redness of the conjunctiva, 0.0, 0.0 and 0.0 for iris lesions and 0.0, 0.0 and 0.0 for corneal opacity. Under the experimental conditions of the study, the test item Propineb was slightly irritant when administered by ocular route to rabbits. However, according to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations), the test item should not be classified as irritating to the eyes.