polymeric zinc propylenebis(dithiocarbamate);propineb (ISO)

Skin irritation / corrosion

Administrative data

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

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 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

24th April 2002

Deviations:

no

Test guideline 2

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)

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

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

Test system

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.

Results and discussion

In vivo

Results

Results 1

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

Results 2

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

Results 3

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 4

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.

Any other information on results incl. tables

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 = +

Applicant's summary and conclusion

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.