Captan

Endpoint summary

Description of key information

1. Skin irritation (one single dose) study acute dermal irritation (semi-occlusive), rabbit, OECD 404 (1981) = EEC B.4 (1992): mean skin score < 2, primary irritation index of 0.5, classification is not required
2. Eye irritation (one single dose) study acute eye irritation, rabbit, OECD 405 (1987),method B.5 of Regulation (EC) No 440/2008; total score of ocular irritation: 43, captan is classified as irritating with the risk phrase ‘Causes serious eye damage’ (H318)

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:

7 August 1991 to 10 August 1991

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:

1981

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Physical state: white powder
- Purity: 90.5 %
- Batch number: 4102 L/7
- Date of arrival: 9 July 1991
- Storage conditions: room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- three New Zealand white rabbits
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- weight: 2.34 - 2.88 kg
- age: twelve to sixteen weeks old
- free access to mains drinking water and food
- animal room temperature: 20 - 23°C- relative humidity: 60 - 66%

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

no

Amount / concentration applied:

A quantity of 0.5 g of the test material, moistened with 0.5 ml of distilled water, was introduced under a 2.5 cm x 2,5 cm gauze patch and placed In position on the shorn skin.

Duration of treatment / exposure:

4 hours

Observation period:

One hour following the removal of the patches, and 1, 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored according to the scale from Draize J.H. (1959).

Number of animals:

three

Details on study design:

Captan was applied as a single 0.5 g dermal dose to three New Zealand White rabbits. The test substance, moistened with 0.5 mL distilled water was introduced under a 2.5 x 2.5 cm gauze patch onto shorn skin. After four hours the patch was removed and any residual test material removed. The areawas examined at 1, 24, 48 and 72 hours after the removal of the patch and scored according to Draize (1959).

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: 1 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: 1 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: 1 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 1 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 1 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

48 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 1 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

48 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

animal: #1, #2, #3

Time point:

other: 24/72 h

Score:

0.5

Max. score:

8

Reversibility:

fully reversible

Remarks on result:

probability of mild irritation

Irritation parameter:

edema score

Basis:

animal #1

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

4

Irritation parameter:

edema score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

4

The individual scores for erythema/eschar and oedema, are given in Table 7.3.1 -1. Very slight erythema was noted at all treated skin sites one and 24 hours after patch removal and at one treated skin site at the 48-hour observation. All treated skin sites appeared normal 72 hours after treatment.

 

Table 7.3.1 -1 Dermal irritation responses in rabbits: individual dermal responses

 

Animal No.			52	54	55	Mean scores
Draize grade after	1 h	O	0	0	01
		E	1	1	1
	24 h	O	0	0	0
		E	1	1	1
	48 h	O	0	0	0
		E	0	1	0
	72 h	O	0	0	0
		E	0	0	0
	mean^1	O	0	0	0
		E	0.33	0.66	0.33
Overall average means^1					O	0
					E	0.44

O = oedema.

E = erythema and eschar formation.

¹Mean for individual animals over three time points 24, 48 and 72 hours

for each lesion, calculated as mean score at (24 hours + 48 hours + 72 hours)/3.

Interpretation of results:

Category 3 (mild irritant) based on GHS criteria

Conclusions:

On the basis of the degree of skin reaction observed (mean skin irritation scores 24 to 72 hours after removal of test substance) and in accordance with the provisions of regulation 1272/2008, Annex I, 3.2, captan is not classified as irritating to rabbit skin.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 404 "Acute Dermal Irritation/Corrosion" referenced as EU method B.4 published in the regulation 440/2008.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight erythema. All treated skin sites appeared normal 72 hours after treatment.

The test material produced a primary irritation index of 0.5 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

15 August 1991

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:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Physical state: white powder- Purity: 90.5 %
- Batch number: 4102
- Date of arrival: 9 July 1991
- Storage conditions: room temperature

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- one female New Zealand white rabbit
- Source: David Percival Ltd., Moston, Sandbach, Cheshire, U.K.
- weight: 2.7 kg- age: approximately twelve to sixteen weeks old
- free access to mains drinking water and food
- animal room temperature: 20 - 23°C- humidity: 56%

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

A single dose of 82 mg (equivalent to 0.1 mL) captan (purity not specified in report; Batch no. 4102) was administered.

Duration of treatment / exposure:

5 hours

Observation period (in vivo):

Assessment of ocular damage was made at 1 and 5 hours

Number of animals or in vitro replicates:

one female

Details on study design:

Material and methods: A single dose of 82 mg (equivalent to 0.1 mL) captan (purity not specified in report; Batch no. 4102) was administered into the elevated lower lid of the right eye of one female New Zealand white rabbit. Immediately after administration of the test material, an assessment of the initial pain reaction was made. Assessment of ocular damage was made at 1 and 5 hours following administration according to Draize (1959).

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Assessment of ocular damage/irritation of the solid powder (test material) was made approximately 1 and 5 hours following treatment, according OECD 405 (1987), Method B.5 (Commission Directive 84/449/EEC) and Draize J.H. 1959.

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Assessment of ocular damage/irritation of the solid powder (test material) was made approximately 1 and 5 hours following treatment, according OECD 405 (1987), Method B.5 (Commission Directive 84/449/EEC) and Draize J.H. 1959.

Irritation parameter:

conjunctivae score

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Assessment of ocular damage/irritation of the solid powder (test material) was made approximately 1 and 5 hours following treatment, according OECD 405 (1987), Method B.5 (Commission Directive 84/449/EEC) and Draize J.H. 1959.

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Assessment of ocular damage/irritation of the solid powder (test material) was made approximately 1 and 5 hours following treatment, according OECD 405 (1987), Method B.5 (Commission Directive 84/449/EEC) and Draize J.H. 1959.

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Remarks:

Assessment of ocular damage/irritation of the solid powder (test material) was made approximately 1 and 5 hours following treatment, according OECD 405 (1987), Method B.5 (Commission Directive 84/449/EEC) and Draize J.H. 1959.

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #1

Time point:

other: 5 h

Score:

43

Max. score:

80

Reversibility:

not reversible

Remarks on result:

probability of moderate irritation

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 1 h

Score:

0

Max. score:

80

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: 5 h

Score:

20

Max. score:

80

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 1 h

Score:

5

Max. score:

10

Reversibility:

not reversible

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: 5 h

Score:

5

Max. score:

10

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 1 h

Score:

16

Max. score:

20

Reversibility:

not reversible

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: 5 h

Score:

18

Max. score:

20

Reversibility:

not reversible

A dulling of the normal lustre of the corneal surface was noted in the treated eye one hour after treatment with areas of diffuse corneal opacity at the 5 hour observation. Iridial Inflammation was noted in the treated eye one and 5 hours after treatment. Severe conjunctival Irritation was noted in the treated eye one and 5 hours after treatment. Haemorrhage of the nictitating and conjunctival membranes was also noted in the treated eye at the 5 hour observation.

Table 7.3.2-1  Ocular irritation in the rabbit

Rabbit: female, number #1	IPR 2
		Draize grade:
Time after Treatment		1 h	5 h
Tissue	Signs
Cornea	E = Degree of Opacity	d	1
	F = Area of Opacity	4	4
Score (E x F) x 5		0	20
Iris	D = Iritis	1	1
Score (D x 5)		5	5
Conjunctiva	A = Redness	2	2^H
	B = Chemosis	3	4
	C = Discharge	3	3
Score (A + B + C) x 2		16	18
Total Score		21	43

IPR: Initial Pain Reaction

d: dulling of the normal lustre of the corneal surface

H: haemorrhage of the nictitating and conjunctival membranes

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

There was no evidence of recovery during the observation period following administration of the test substance since the study was terminated after 5 hours. In accordance the provisions of regulation 1272/2008, Annex I, 3.3 captan is classified as eye damaging category 1 with the hazard statement H318: Causes serious eye damage

Executive summary:

A study was performed to assess the irritancy potential of captan to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1987) No. 405 "Acute Eye Irritation/Corrosion" referenced as EEC method B.5 published in the regulation 440/2008. A single application of the test material to the non-irrigated eye of one rabbit produced areas of diffuse corneal opacity, iridial inflamm ation and severe conjunctival irritation. Other adverse ocular reactions noted were a dulling of the normal lustre of the corneal surface and haemorrhage of the nictitating and conjunctival membranes. The animal was killed for humane reasons immediately after the five hour observation in accordance with current U.K. Home Office guidelines. The test material produced a maximum total score of 43. There was no evidence of recovery during the observation period following administration of the test substance since the study was terminated after 5 hours. In accordance the provisions of regulation 1272/2008, Annex I, 3.3 captan is classified as eye damaging category 1 with the hazard statement H318: Causes serious eye damage

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irreversible damage)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The study according to OECD 404 on three rabbits produced very slight erythema. All treated skin sites appeared normal 72 hours after treatment. The test material produced a primary irritation index of 0.5 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

The study according to OECD 405 to the non-irrigated eye of one rabbit produced areas of diffuse corneal opacity, iridial inflammation and severe conjunctival irritation. Other adverse ocular reactions noted were a dulling of the normal lustre of the corneal surface and haemorrhage of the nictitating and conjunctival membranes. The test material produced a maximum total score of 43. There was no evidence of recovery during the observation period following administration of the test substance since the study was terminated after 5 hours. In accordance with regulation 1272/2008, Annex I, 3.3 captan is classified as eye damaging category 1 with the hazard statement H318: Causes serious eye damage

Effects on skin irritation/corrosion: slightly irritating

Effects on eye irritation: highly irritating

Justification for classification or non-classification

In a study on skin irritation the test material caused reversible slight erythema with a primary irritation index of 0.5 (mild irritant) not leading to classification according to EU regulation 1272/2008.

In eye irritation study there were severe effects on the eyes and no evidence of recovery during the observation period following administration of the test substance. In accordance with regulation 1272/2008, Annex I, 3.3 captan is classified as eye damaging category 1 with the hazard statement H318: Causes serious eye damage.