5-chloro-2-(4-chlorophenoxy)phenol;[DCPP]

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (non-LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

from 1998-11-16 to 1999-01-26

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study, GLP

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EU Method B.6 (Skin Sensitisation)

Version / remarks:

, 1996-07-30

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 406 (Skin Sensitisation)

Version / remarks:

, adopted on 1992-07-17

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

guinea pig maximisation test

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

429-290-0

EC Name:

-

Cas Number:

3380-30-1

Molecular formula:

C12 H8 Cl2 O2

IUPAC Name:

5-chloro-2-(4-chlorophenoxy)phenol

Details on test material:

- Name of test material (as cited in study report): FAT 80'220/A
- Physical state: pale beige solid, powder
- Analytical purity: >99 %
- Lot/batch No.: GRU 98
- Expiration date of the lot/batch: 2008-10-31
- Stability under test conditions: test item was stable in PEG 1 % for at least 10 days at room temperature
- Storage condition of test material: in the original container at room temperature (approx. 20°C) away from direct sunlight; the test item was stable under storage conditions.

In vivo test system

Test animals

Species:

guinea pig

Strain:

other: Ibm: GOHI; SPF-quality guinea pigs (synonym: Himalayan spotted)

Sex:

female

Details on test animals and environmental conditions:

ANIMALS
- Source: RCC Ltd, Biotechnology & Animal Breeding Division, Wolferstrasse 4, CH-4414 Füllins/ Switzerland
- Age at delivery: 4 - 6 weeks
- Body weight at beginning of acclimization period: 306-396 g
- Housing: individually, in Makrolon type 4-cages
- Diet: pelleted standard Natag Ecosan 845 25W4 guinea pig breeding/maintenance diet, ad libitum
- Water: tap water, ad libitum
- Acclimatization period : One week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22°C
- Humidity (%): 34-90 %
- Air changes (per hr): 10-15 air changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours dark/ 12 hours light

Study design: in vivo (non-LLNA)

Induction

Induction 1

Route:

intradermal and epicutaneous

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Induction 2

Concentration / amount:

Induction: 5 % in PEG 400 (intradermal) and 50 % in PEG 400 (epicutaneous)
Challenge: 50 % in PEG 400 (epicutaneous)

Challenge

Challenge 1

Route:

epicutaneous, occlusive

Vehicle:

polyethylene glycol

Remarks:

PEG 400

Challenge 2

Concentration / amount:

Induction: 5 % in PEG 400 (intradermal) and 50 % in PEG 400 (epicutaneous)
Challenge: 50 % in PEG 400 (epicutaneous)

No. of animals per dose:

Control group: 5 females
Test group 10 females

Details on study design:

RANGE FINDING TEST
A pretest for the identification of a maximally tolerated test item concentration for the induction phase and of the highest non-irritant concentration for the challenge phase in the main study was performed. The Pretest on intradermal application was done on one guinea pig with 1%, 3% and 5% DCPP in PEG 400. The pretest on topical application was conducted on 2 guinea pigs with 10%, 15%, 25% and 50% DCPP in PEG 400.
Intradermal injection of 5% Diclosan caused grade 1 edema/erythema, whereas topical application of 50% DCPP was not irritating.

MAIN STUDY
A. INDUCTION EXPOSURE
The intradermal induction was performed with a 5 % dilution of the test article in PEG 400 and in an emulsion of Freund's Complete Adjuvant (FCA) / physiological saline.
The epidermal induction was conducted under occlusion with the test article at 50 % in PEG 400.

B. CHALLENGE EXPOSURE
Two weeks after the epidermal induction application the challenge was completed by epidermal application of the test article at 50 % in PEG 400 under occlusive dressing. The animals of the control group were induced with PEG 400 and FCA/physiological saline and challenged similarly to those of the test group.

READING OF CHALLENGE REACTIONS
The challenge site was evaluated 24 and 48 hours after the removal of the patch. The readings were made under artificial fluorescent light (daylight spectrum). Redness constitutes the minimum criterion of an allergic reaction. Strongly sensitized animals display a vivid redness, associated with indurated swelling. The reactions were scored on the basis of the Draize score.

INTERPRETATION
The results obtained from test animals following the challenge applications were compared with the results seen in control animals. An allergic reaction was defined by visible reddening of the challenge site. If the dermal reactions of test animals following the challenge were more marked and/or persistent than those of the control animals, the animals were considered to show evidence of contact hypersensitivity. If the dermal reactions of test animals following the challenge were not clearly different from the reactions seen in the control group animals, the results for the test animals were considered "inconclusive".
The test animals were considered to show no evidence of contact hypersensitivity if the dermal reactions to the challenge application were identical to or less marked and/or persistent than the reactions observed in the control animals. By "maximizing" the exposure and enhancing allergenicity, some problems could arise, particularly in relation to specificity, especially the potential for false-positive reactions. An inflammatory response at challenge may not necessarily be due to allergenicity, but instead may be a false-positive irritant response caused by an inducing hyperirritability.

Positive control substance(s):

yes

Remarks:

2-mercaptobenzothiazole

Results and discussion

Positive control results:

The positive control, 2-mercaptobenzothiazole, elicited a positive response in 10/10 test animals.

In vivo (non-LLNA)

Results

Results 1

Reading:

1st reading

Hours after challenge:

24

Group:

negative control

Dose level:

0 % induction, 50 % challenge

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 0 % induction, 50 % challenge. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Results 2

Reading:

1st reading

Hours after challenge:

24

Group:

test chemical

Dose level:

5 % intradermal and 50 % epicutabeous induction, 50 % challenge

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 5 % intradermal and 50 % epicutabeous induction, 50 % challenge. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: none.

Results 3

Reading:

2nd reading

Hours after challenge:

48

Group:

negative control

Dose level:

0 % induction, 50 % challenge

No. with + reactions:

0

Total no. in group:

5

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 0 % induction, 50 % challenge. No with. + reactions: 0.0. Total no. in groups: 5.0. Clinical observations: none.

Results 4

Reading:

2nd reading

Hours after challenge:

48

Group:

test chemical

Dose level:

5 % intradermal and 50 % epicutabeous induction, 50 % challenge

No. with + reactions:

1

Total no. in group:

10

Clinical observations:

none

Remarks on result:

other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 5 % intradermal and 50 % epicutabeous induction, 50 % challenge. No with. + reactions: 1.0. Total no. in groups: 10.0. Clinical observations: none.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information