1-chloro-4-(n-propoxy)-5-thioxanthen-10-one

Endpoint summary

Description of key information

Based on the guinea pigs study, 1-chlor-4-(n-propoxy)-5-thioxanthen-10-one is not considered as a skin sensitizer.

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:

September - October 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Type of study:

guinea pig maximisation test

Justification for non-LLNA method:

Study performed before the REACH regulation

Species:

guinea pig

Strain:

Dunkin-Hartley

Sex:

female

Details on test animals and environmental conditions:

TEST ANIMALS
- Source: D. Hall, Newchurch, Staffordshire, England.
- Age at study initiation: 6 to 7 weeks
- Weight at study initiation: 299 to 364 g
- Housing: in groups of ten
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: thirteen days prior to the allocation to the main study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21
- Humidity (%): 30-70
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

Route:

epicutaneous, open

Vehicle:

other: acetone

Concentration / amount:

60%

Route:

intradermal

Vehicle:

other: 5% acetone in Alembicol D

Concentration / amount:

7.5%

No.:

#1

Route:

epicutaneous, occlusive

Vehicle:

other: acetone

Concentration / amount:

60 and 30%

No. of animals per dose:

The animals on the main study were allocated into two groups 10 to control group and 20 to Test group.

An additional 6 animals of the same strain and supplier were used for preliminary investigations.

Details on study design:

Intradermal injections
A 4 x 6 cm area of dorsal skin on the scapular region of the guinea pig was clipped free of hair with electric clippers. Three pairs of interdermal injections were made into a 2 x 4 cm area within the clipped area. Injectables for the test animals were prepared as follows :
1 - Frend's complete adjuvant was diluted with an equal volume of water for irrigation
2 - CPTX, 7.5% w/w in 5% acetone in Alembicol D
3- CPTX, 7.5% w/w in a 50:50 mixture of Freund's complete adjuvant and 5% acetone in Alembicol D.

Topical application
The preliminary investigations indicated that the maximum practical concentration of the test substance for topical application (60% w/w) did not produce skin irritation. Therefore, six days after the injections, the same 4 x 6 cm interscapular area was clipped and shaved free of hair and the site was pre-treated by gentle rubbing with 0.2 ml per site of 10% w/w sodium lauryl sulphate in petrolatum. 24-h later a 2 x 4 cm patch of Whatman No.3 paper was saturated with approximately 0.4 ml of CPTX (60% in acetone). The patch was placed on the skin of the test animals and covered by a length of impermeable plastic adhesive tape. This in turn was firmly secured by elastic adhesive bandage wound round the torso of the animal and fiwed with Sleek impervious plastic adhesive tape. The dressing was left in place for 48 hours.

During the induction phase, the control animals were treated similarly to the test animals with the exception that the test substance was omitted from the intradermal injections and topical application.

Challenge
The control and test animals were challenged topically two weeks after the topical induction application using CPTX (60 and 30 % w/w in acetone).
Hair was removed by clipping and then shaving from an area on the left flank of each guinea-pig. A 2 x 2 cm patch of Whatman No.3 paper was saturated with approximately 0.2 ml of cPTX (60% in acetone) and applied to an antirior site on the flank. CPTX (30% in acetone) was applied in a similar manner to a posterior site. The patched were sealed to the flank for 24 hours under strips covered by adhesive wound round the trunk and secured with sleek.

Observations
The individual bodyweight for each animal were recorded at the start and finish of the main study.
All animals were observed daily for signs of ill health or toxicity.
The challenge sites were evaluated 24, 48 and 72 hours after removal of the patched.

Interpretation of results
Dermal reactions in the test animals elicited by the challenge application were compared with the findings simultaneously obtained in the control animals.
A test animal was considered to show positive evidence of delayed contact hypersensitivity if the observed dermal reaction at challenge was definitely more marked and/or persistent than the maximum reaction seen in animals of the control group.
If the dermal reaction seen in a test animal at challenge was slightly more marked and/or persistent than the maximum reaction seen in control animals, the result for that test animal was classified as inconclusive.
A test animal was considered to show no evidence of delayed contact hypersensitivity if the dermal reaction resulting from the challenge application was the same as, or less marked and/or persistent than the maximum reaction seen in animals of the control group.

Challenge controls:

no

Positive control substance(s):

yes

Remarks:

The sensitivity of the guinea-pig strain used is checked periodically at the laboratory with formalin, a known sensitizer.

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

n/a

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

7.5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

7.5%

No. with + reactions:

0

Total no. in group:

10

Remarks on result:

no indication of skin sensitisation

Reading:

1st reading

Hours after challenge:

24

Group:

positive control

Dose level:

0.1%

No. with + reactions:

10

Total no. in group:

10

Remarks on result:

positive indication of skin sensitisation

No signs of ill health or toxicity were recorded.

Intradermal injections : necrosis was recorded at sites receiving Frend's complete adjuvant in test and control animals. Slight irritation was seen in test animals at sites receiving 7.5 % CPTX.

Topical application: moderate erythema with yellow staining was observed in test animals following topical application with CPTX (60%). Slight erythema was seen in the controls.

Challenge : The bandage of one test animal did not remain in contact with the skin during the challenge application.  There were no dermal reactions seen in any of the remaining test of control animals.

 

Interpretation of results:

GHS criteria not met

Remarks:

Not skin sensitizer

Conclusions:

In this test performed with albino guinea pigs the test material did not produce evidence of skin sensitisation ( delayed contact hypersensitivity).

Executive summary:

A study was performed to assess the skin sensitisation potential of CPTX in the guinea-pig. The method followed the method of the test guideline OECD 406 and the method of magnuson and Kligman (1970).

Based on the results of a preliminary study and in compliance with guideline, the dose 7.5% w/w in 5% acetone in Alembicol D was used in intradermal injection, 60% w/w in acetone for topical application, and 30 et 60% in acetone for challenge application. Twenty test and ten control guinea pigs were used in this study.

The test substance did not produce evidence of skin sensitisation (delayed contact hypersensitivity) in test animals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not sensitising)

Additional information:

In vivo skin sensitisation study (1991).

A GPMT study was performed to assess the skin sensitisation potential of CPTX in the guinea-pig. The method followed the method of the test guideline OECD 406 and the method of Magnuson and Kligman (1970).

Based on the results of a preliminary study and in compliance with guideline, the dose 7.5% w/w in 5% acetone in Alembicol D was used in intradermal injection, 60% w/w in acetone for topical application, and 30 et 60% in acetone for challenge application. Twenty test and ten control guinea pigs were used in this study.

The test substance did not produce evidence of skin sensitisation (delayed contact hypersensitivity) in test animals.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Based on the available date, no classification for skin sensitisation is required for 1-chlor-4-(n-propoxy)-5-thioxanthen-10-one according to the Regulation EC n°1272/2008.