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Description of key information

Skin sensitation (one topical induction, one topical challenge), (occlusive), female Dunkin-Hartley guinea pigs, OECD 406 (1981), = EEC B.6 (1984): Captan is skin sensitising category 1 with H 317 ´May Cause an allergic skin reaction’

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
6 August 1991 to 16 September 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 406 "Skin Sensitisation" - Magnusson and Kligman Maximisation Test referenced as according to EEC method B.6 published in the regulation 440/2008.
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
female
Details on test animals and environmental conditions:
- group of thirty (twenty treated and ten control) female guinea pigs of the Dunkin-Hartley strain
- Source: David Hall Ltd., Moston, Burton-on-Trent, Staffordshire, U.K.
- weight: 311 - 388 g
- age: eight to twelve weeks old
- free access to mains drinking water and food
- animal room temperature: 20 - 23°C- relative humidity: 52 - 61%
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
Intradermal Induction: 0.1% (w/v) in arachis oil B.P. Topical Induction: 50% (w/w) in arachis oil B.P. Topical Challenge: (w/w) in arachis oll B.P.
Day(s)/duration:
9 d
Adequacy of induction:
not specified
No.:
#1
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
Intradermal Induction: 0.1% (w/v) in arachis oil B.P. Topical Induction: 50% (w/w) in arachis oil B.P. Topical Challenge: (w/w) in arachis oll B.P.
Day(s)/duration:
21 d
Adequacy of challenge:
not specified
No. of animals per dose:
A group of thirty guinea pigs was used for the main study, twenty test and ten control. Control animals were treated in the same way as test animals, except that captan was excluded from the induction phases.
Details on study design:
For the intradermal induction phase, a row of three injections (0.1 mL) was made on each side of the midline of a shaved area of skin on the shoulder region: i) Freunds complete adjuvant (FCA) plus distilled water in a ratio of 1:1; ii) 0.1% captan (w/v) in arachis oil BP; iii) 0.1% captan (w/v) suspension in 1:1 preparation of FCA in distilled water. A topical induction of 50% captan (w/w) in arachis oil was applied to the same area after 7 days. The area was covered with an occlusive dressing which was held in place for 48 hours and the area examined after one and 24 hours.
Challenge controls:
A topical challenge of 0.1 to 0.2 mL 10% captan (w/w) in arachis oil was applied to the shorn flank on day 21. The area was covered with an occlusive dressing for 24 hours. The area was examined 24 and 48 hours after the removal of the challenge dressing. Control animals were treated in the same way, except that captan was excluded from the induction phases.
Positive control substance(s):
no
Key result
Reading:
other: Topical induction
Hours after challenge:
1
Group:
test chemical
Dose level:
50% captan w/w In arachis oil B.P.
No. with + reactions:
10
Total no. in group:
20
Clinical observations:
Scattered mild redness and moderate and diffuse redness were elicited. Bleeding, preventing accurate evaluation of erythema, was noted at three treatment sites. Residual test material on skin was commonly noted.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Topical induction. Hours after challenge: 1.0. Group: test group. Dose level: 50% captan w/w in arachis oil B.P. Total no. in groups: 20.0. Clinical observations: Scattered mild redness and moderate and diffuse redness were elicited. Bleeding, preventing accurate evaluation of erythema, was noted at three treatment sites. Residual test material on skin was commonly noted.
Key result
Reading:
other: Topical Induction
Hours after challenge:
24
Group:
test chemical
Dose level:
50% captan (w/w) in arachis oil B.P.
No. with + reactions:
16
Total no. in group:
20
Clinical observations:
Bleeding, preventing accurate evaluation of erythema, incidents of dried blood. Residual test material on skin was commonly noted.
Remarks on result:
other: see Remark
Remarks:
Reading: other: Topical induction. Hours after challenge: 24.0. Group: test group. Dose level: 50% captan (w/w) in arachis oil B.P. No with. + reactions: 16.0. Total no. in groups: 20.0. Clinical observations: Bleeding, preventing accurate evaluation of erythema, incidents of dried blood. Residual test material on skin was commonly noted.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.1 to 0.2 mL 10% captan (w/w) in arachis oil B.P.
No. with + reactions:
16
Total no. in group:
20
Clinical observations:
Isolated incidents of hardened light brown-coloured scab and small superficial scattered scabs and desquamation. Oedema. The reactions extended beyond treatment sites during the study.
Remarks on result:
other: see Remark
Remarks:
Reading: 1st reading. Hours after challenge: 24.0. Group: test group. Dose level: 0.1 to 0.2 mL 10% captan (w/w) in arachis oil B.P. No with. + reactions: 16.0. Total no. in groups: 20.0. Clinical observations: Isolated incidents of hardened light brown-coloured scab and small superficial scattered scabs and desquamatlon. Oedema. The reactions extended beyond treatment sites during the study.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.1 to 0.2 mL 10% captan (w/w) in arachis oil B.P.
No. with + reactions:
14
Total no. in group:
20
Clinical observations:
Isolated incidents of hardened light brown-coloured scab and small superficial scattered scabs and desquamation. Oedema. The reactions extended beyond treatment sites during the study.
Remarks on result:
other: see Remark
Remarks:
Reading: 2nd reading. Hours after challenge: 48.0. Group: test group. Dose level: 0.1 to 0.2 mL 10% captan (w/w) in arachis oil B.P.. No with. + reactions: 14.0. Total no. in groups: 20.0. Clinical observations: Isolated incidents of hardened light brown-coloured scab and small superficial scattered scabs and desquamation. Oedema. The reactions extended beyond treatment sites during the study..
Reading:
other: Topical induction, 1st and 2nd reading after challenge
Hours after challenge:
48
Group:
negative control
Dose level:
vehicle control: arachis oil
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
No adverse reactions
Remarks on result:
other: see Remark
Remarks:
Reading: other: Topical induction, 1st and 2nd reading after challenge. Hours after challenge: 48.0. Group: negative control. Dose level: vehicle control: arachis oil. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: No adverse reactions.
Reading:
other: Topical induction, 1st and 2nd reading after challenge
Hours after challenge:
48
Group:
test chemical
Dose level:
vehicle control: arachis oil
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
No adverse reactions
Remarks on result:
other: see Remark
Remarks:
Reading: other: Topical induction, 1st and 2nd reading after challenge. Hours after challenge: 48.0. Group: test group. Dose level: vehicle control: arachis oil. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: No adverse reactions.

Table 7.4.1-1 Magnusson Kligman maximisation study in the guinea pig: skin reactions of individual animals following topical induction with 50% w/w captan in arachis oil

Animal number

Skin reactions

1 hour

24 hours

1”

2

1

2

2 Rt

1

3

2 Rt

1 Bd

4

2 Rt

0

5

2 Rt

1 RtBd

6

2 Rt

0

7

1 Rt

0 Bd

8

Ta

0

9

1 Rt

0

10

1 Rt

0

11

1

0

12

?eBs

0 Bd

13

2 Rt

1 Rt

14

1 Rt

0 Bd

15

?eBs

0 Bd

16

2 Rt

1

17

1 Rt

1

18

?eBs

?eBd

19

Ta

1

20

1 Rt

1 RtBd

0 = no reaction; 1 = scattered mild redness; 2 = moderate and diffuse redness.

Rt = residual test material; Ta = test material adhered to treatment site preventing accurate evaluation of erythema;

?e = adverse reactions prevent accurate evaluation of erythema;

Bs = bleeding; Bd = dried blood.

Table 7.4.1-1 Magnusson Kligman maximisation study in the guinea pig: skin reactions of individual animals following topical challenge with 10% w/w captan in arachis oil

 

Animal number

Skin reactions (hours after removal of dressing)

24 h

48 h

Test

Vehicle

Test

Vehicle

1

2

0

?eD

0

2

2 R

0

2 Rd

0

3

2 R

0

1 R

0

4

?eWeSp

0

?eSt

0

5

?eWe

0

2 ROeSP

0

6

2 Oe

0

2 ROeSP

0

7

2 R

0

?eDR

0

8

2

0

1

0

9

1

0

0

0

10

1

0

0

0

11

2

0

1

0

12

?eDWeR

0

2 RD

0

13

2

0

1 RD

0

14

2 R

0

1 RD

0

15

2 R

0

2 R

0

16

2

0

1 R

0

17

1

0

1 D

0

18

2

0

1

0

19

?eDWe

0

2 SsD

0

20

1

0

1 D

0

0 = no reaction; 1 = scattered mild redness; 2 = moderate and diffuse redness.

R = extended reaction; ?e = adverse reactions prevent accurate evaluation of erythema;

We = well defined; erythema surrounding test site; Sp = hardened light brown coloured scab;

Oe = oedema extends ventrally below; treatment site; D = desquamation;

St = hardened dark brown/black coloured scab; Cr = superficial cracking of the epidermis;

Ss = small superficial scattered scabs.

Following challenge with the test material positive skin responses were noted in 16 and 14 animals after 24 and 48 hours, respectively. Adverse reactions prevented the accurate evaluation of erythema at test material sites in 4 of the 20 animals at 24 hours. At 48 hours, these reactions persisted in one animal and increased in severity in the other three animals. At no time were adverse reactions noted at the vehicle control sites in test animals or at any sites of control animals.

Interpretation of results:
Category 1 (skin sensitising) based on GHS criteria
Conclusions:
Under the conditions of the Magnusson Kligman test, captan produced a 100% sensitisation rate in the guinea pig and was considered as an extreme sensitiser. In accordance with the provisions of regulation 1272/2008, Annex I, 3.4 captan is classified as Skin Sens. category 1 with H317 ‘May cause an allergic skin reaction’
Executive summary:

A study was performed to assess the skin contact sensitisation potential of the test material in the albino guinea pig. The method used followed that described in the OECD Guidelines for Testing of Chemicals (1981) No. 406 "Skin Sensitisation" - Magnusson and Kligman Maximisation Test referenced as according to EEC method B.6 published in the regulation 440/2008. Twenty test and ten control animals were used for the main study. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows: Intradermal Induction: 0.1% (w/v) in arachis oil B.P. Topical Induction: 50% (w/w) in arachis oil B.P. Topical Challenge: 10 (w/w) in arachis oll B.P. The test material produced a 100% (20/20) sensitisation rate and in accordance with regulation 1272/2008, Annex I, 3.4 captan is classified as Skin Sens. category 1 with (H317) ´May cause an allergic skin reaction’

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

A study was performed according to OECD guideline 406 "Skin Sensitisation" by application of Magnusson and Kligman Maximisation Test on guinea pigs.

Twenty test and ten control animals were used for the main study. Captan test material produced a 100% (20/20) sensitisation rate and in accordance with regulation 1272/2008, Annex I, 3.4 captan is classified as skin sensitising category 1 with H317 ´May cause an allergic skin reaction´.

In accordance with guidance on information requirements and chemical safety assessment, part E, captan is classified with high hazard on skin exposure.


Skin sensitation (one topical induction, one topical challenge), (occlusive), female Dunkin-Hartley guinea pigs, OECD 406 (1981), = EEC B.6 (1984): Captan is skin sensitising category 1 with H 317 ´May Cause an allergic skin reaction’

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Captan is a skin sensitizer. In accordance with regulation 1272/2008, Annex I, 3.4 captan is classified as skin sensitising category 1 with H317 ´May cause an allergic skin reaction´.