polymeric zinc propylenebis(dithiocarbamate);propineb (ISO)

Endpoint summary

Description of key information

The test substance is not skin or eye irritating as shown in reliable in vivo skin and eye irritation studies.

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:

2010/03 to 2010/06

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

24th April 2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: Commission Regulation (EC) No. 440/2008, B.4

Version / remarks:

30 May 2008

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Remarks:

Esd:NZW

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 2 to 4 months old.
- Weight at study initiation: 2.8 to 3.2 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
- ventilation : approximately 12 cycles/hour of filtered, non-recycled air.

IN-LIFE DATES: 9 to 26 March 2010

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

A gauze pad moistened with purified water.

Controls:

yes

Amount / concentration applied:

Single dose of 500 mg

Duration of treatment / exposure:

The anterior left flank (application for 3 minutes), the anterior right flank (application for 1 hour) or the posterior right flank (application for 4 hours) of the animals. The day before treatment, both flanks of each animal were clipped using electric clippers and just before treatment, the skin of each animal was examined in order to check the absence of any signs of skin irritation. The test item was first evaluated on a single animal.

Doses of 500 mg of the test item in its original form were placed on a gauze pad moistened with purified water, which was then applied to an area of approximately 6 cm2 of the anterior left flank (application for 3 minutes), the anterior right flank (application for 1 hour) or the posterior right flank (application for 4 hours) of the animals. The gauze pad was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage. The untreated skin served as control. After removal of the dressing, any residual test item was wiped off by means of a dry or moistened cotton pad.

Observation period:

1, 24, 48, 72 hours, and observation period was extended up
to their complete reversibility (day 8).daily until day 8

Number of animals:

3

Details on study design:

Each animal was weighed at the beginning (before treatment) and at the end of the observation period. At the end of the observation period, the animals were not sacrificed. They were used subsequently for the evaluation of the ocular irritation potential on the same test item.

The skin was examined approximately 1 hour, 24, 48 and 72 hours after removal of the dressing. Since there were persistent irritation reactions at 72 hours, the observation period was extended up to their complete reversibility (day 8). The degree of erythema/eschar formation and oedema formation was recorded as specified by DRAIZE and any serious lesions or toxic effects other than dermal irritation were also recorded and fully described.

Each animal was weighed at the beginning (before treatment) and at the end of the observation
period. At the end of the observation period, the animals were not sacrificed. They were used
subsequently for the evaluation of the ocular irritation potential on the same test item.

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

4

Reversibility:

fully reversible within: day 4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

mean

Remarks:

out of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

Other effects:

Dryness of the skin was noted in 1/3 animals from day 4 until day 7.

Table one

Individual skin irritation scores for eryther according to the Draize scheme on the first animal

Duration of exposure	3 minutes		1 hour
	Erythema	Oedema	Erythema	Oedema
1 hour	0	0	2	0
24 hours	0	0	1 S	0
48 hours	0	0	1S	0
72 hours	0	0	1S	0
Mean score 24-72 hours	0	0	1	0
No positive response: mean scores < 2 = - Positive response      : mean scores ³ 2 = +

 

 

 

Table two

 

Individual and mean skin irritation scores after 4 hour exposure according the
Draize scheme

	Erythema and eschar			Oedema
Animal number (body weight in kg)	1 (2.8)	2 (3.0)	3 (3.2)	1 (2.8)	2 (3.0)	3 (3.2)
1 hour	2	1	2	0	0	1
24 hours	2	1	2	0	0	0
48 hours	2	1	1	0	0	0
72 hours	1S	0	0	0	0	0
120 hours	0	-	-	0	-	-
Mean score 24-72 hours	1.7	0.7	1.0	0	0	0
No positive response: mean scores < 2 = - Positive response      : mean scores ³ 2 = +

Interpretation of results:

GHS criteria not met

Conclusions:

The potential of the test item Propineb (AE F074263) to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 24th April 2002) and Commission Regulation (EC) (No. 440/2008, B.4, 30 May 2008) guidelines. A single dose of 500 mg of the test item in its original form was applied to the closely-clipped
skin of one flank. Under the experimental conditions of this study, the test item Propineb (AE F074263) was
slightly irritant when applied topically 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 Propineb does not trigger classification as irritating to the skin.

Executive summary:

The potential of the test item Propineb (AE F074263) to induce skin irritation was evaluated in rabbits according to OECD (No. 404, 24th April 2002) and Commission Regulation (EC) (No. 440/2008, B.4, 30 May 2008) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice
Regulations.

 

The test item was first applied for periods of 3 minutes, 1 hour and 4 hours to a single male New Zealand White rabbit. Since the test item was neither severely irritant nor corrosive on this first animal, it was then applied sequentially for 4 hours to two other animals.
A single dose of 500 mg of the test item in its original form was applied to the closely-clipped skin of one flank.

 

The test item was held in contact with the skin by means of a semi occlusive dressing. Cutaneous reactions were observed approximately 1 hour, 24, 48 and 72 hours after removal of the dressing and then daily until reversibility of cutaneous reactions (day 8). The mean values of the scores for erythema and edema 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).

After a 3-minute exposure (one animal) No cutaneous reactions were observed. After a 1-hour exposure (one animal) A very slight or well-defined erythema was noted from day 1 until day 4. Dryness of the skin was observed from day 2 until day 7. After a 4-hour exposure (three animals) A very slight or well-defined erythema was noted in all animals from day 1 until day 3 (two animals) or day 4 (one animal). A very slight edema was noted in another animal on day 1. Dryness of the skin was noted in 1/3 animals from day 4 until day 7. Mean scores over 24, 48 and 72 hours for each animal were 1.7, 0.7 and 1.0 for erythema and 0.0, 0.0 and 0.0 for edema.

Under the experimental conditions of this study, the test item Propineb (AE F074263) was slightly irritant when applied topically 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 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:

2010/03/19 to 2010/04/09

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

2002

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

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.

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.

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 96 hours

Irritation parameter:

chemosis score

Basis:

mean

Time point:

48 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

mean

Time point:

72 h

Score:

0

Max. score:

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

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

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

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

72 h

Score:

0.3

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

48 h

Score:

0.7

Max. score:

4

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24 h

Score:

2

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

2

Irritation parameter:

cornea opacity score

Basis:

mean

Remarks:

of 3 animals

Time point:

24/48/72 h

Score:

0

Max. score:

4

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

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.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A key skin irritation study according to OECD 404 and GLP is available (M-370061-01-1). Doses of 500 mg of the test item in its original form were placed on a gauze pad moistened with purified water, which was then applied to an area of approximately 6 cm2 of the anterior left flank (application for 3 minutes), the anterior right flank (application for 1 hour) or the posterior right flank (application for 4 hours) of the animals. The gauze pad was held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage.

After a 3-minute exposure (first animal): no cutaneous reactions were observed.

After a 1-hour exposure (first animal): a very slight or well-defined erythema (grade 1 or 2) was noted from day 1 until day 4. Mean score for erythema between 24 and 72 hours: 1. Dryness of the skin was observed from day 2 until day 7.

After a 4-hour exposure (three animals): a very slight or well-defined erythema (grade 1 or 2) was noted in all animals from day 1 until day 3 (two animals) or day 4 (one animal). A very slight edema (grade 1) was noted in another animal on day 1. Dryness of the skin was noted in 1/3 animals from day 4 until day 7. Mean scores over 24, 48 and 72 hours for each animal were 1.7, 0.7 and 1.0 for erythema and 0.0, 0.0 and 0.0 for edema, respectively.

A key eye irritation study according to OECD 404 and GLP is available (M-370060-01-1). 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 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). A slight or moderate chemosis (grade 1 or 2) 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 (grades 1 to 3) 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 (grade 1) 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.

Justification for classification or non-classification

The available data on skin and eye irritation do not meet the criteria for classification according to Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.