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Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1996-09-09 to 1996-10-20
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1996

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
adopted 17 July 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
According to the Reach Annex VIII, 8.3.2 column 2 the in vivo studies carried out before 10 May 2017 and that meet the requirements set out in Article 13(3), first subparagraph, and Article 13(4) shall be considered appropriate to address this standard information requirement. The non-LLNA study was conducted in 1996, according to GLP, and based on the performance and results it is considered suitable to cover the sensitisation endpoint.

Test material

Constituent 1
Chemical structure
Reference substance name:
-
EC Number:
424-210-0
EC Name:
-
Cas Number:
23911-85-5
Molecular formula:
C29 H24 O7
IUPAC Name:
2-benzoyl-5-[3-(4-benzoyl-3-hydroxyphenoxy)-2-hydroxypropoxy]phenol

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: David Hall Limited, Buftonon-Trent, Staffordshire, UK.
- Age at study initiation: 8 – 12 weeks old
- Weight at study initiation: males: 356 to 445 g
- Housing: in solid-floor polypropylene cages furnished with woodflakes
- Historical data: yes
- Diet (ad libitum): Guinea Pig FD1 Diet, special Diets services Limited, witham, Essex, uK)
- Water (ad libitum): yes, tap water

- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 22
- Humidity (%): 47 – 68
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: not specified

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
5% (w/v)
Day(s)/duration:
Day 1
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Route:
epicutaneous, occlusive
Vehicle:
arachis oil
Concentration / amount:
25% (w/w)
Day(s)/duration:
Day 7
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challengeopen allclose all
No.:
#1
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
10% (w/w)
Day(s)/duration:
Day 21
Adequacy of challenge:
highest non-irritant concentration
No.:
#2
Route:
intradermal and epicutaneous
Vehicle:
arachis oil
Concentration / amount:
5% (w/w)
Day(s)/duration:
Day 21
Adequacy of challenge:
other: one lower than the highest non-irritant concentration of the test material
No. of animals per dose:
Number of animals for selection of concentrations: 8
Number of animals in test group: 10
Number of animals in negative control group: 5
Details on study design:
RANGE FINDING TESTS:
1. Intradermal Induction: Four concentrations of test material were investigated (25%, 10%, 5% and 1% w/v in arachis oil BP). Injections were attempted in a total of four guinea pigs. A 25% preparation was considered to be impractical to dose satisfactorily. Therefore three guinea pigs received four 0.1 mL injections of only one concentration of test material. The degree of erythema at the injection sites was assessed approximately 24, 48 and 72 hours and 7 days after injection according to the Draize scale (see reference). The degree of oedema was not evaluated. Any evidence of systemic toxicity was also recorded. The highest concentration that caused only mild to moderate skin irritation, and which was well tolerated systemically, was selected for the intradermal induction stage of the main study.
2. Topical Induction: Two guinea pigs (intradermally injected with Freund's Complete Adjuvant ten days earlier) were treated with four preparations of the test material (25%, 10%, 5% and 2% w/v in arachis oil BP). Applications were made to the clipped flanks under occlusive dressings for an exposure period of 48 hours. The degree of erythema and oedema was evaluated approximately 1, 24 and 48 hours after dressing removal. The highest concentration producing only mild to moderate dermal irritation was selected for the topical induction stage of the main study.
3. Topical Challenge: Four preparations of the test material (25%, 10%, 5% and 2% w/v in arachis oil BP) were applied to the clipped flanks of two guinea pigs under occlusive dressings for an exposure period of 2+ hours. These guinea pigs did not form part of the main study but had been treated identically to the control animals of the main study, up to Day 14. The degree of erythema and oedema was evaluated approximately 1, 24 and 48 hours after dressing removal. The highest non-irritant concentration of the test material and one lower concentration were selected for the topical challenge stage of the main study.

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: topical 1; intradermal: 1
- Exposure period: not applicable for intradermal, topical: 48 h
- Test groups: 2 , for challenge concentrations 10% and 5% in arachis oil BP, both treated with 3 injections at induction phase:
a) Freund's complete Adjuvant plus distilled water in the ratio 1:1
b) a 5% w/v suspension of the test material in arachis oil BP
c) a 5% w/v suspension of the test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water

- Control group: 1 (vehicle group) treated with
a) Freund's complete Adjuvant plus distilled water in the ratio 1:1
b) arachis oil BP
c) a 5% w/v suspension of the test material in a 1:1 preparation of Freund's Complete Adjuvant plus distilled water

- Site: shoulder region
- Frequency of applications: Day 0: intradermal injections in a row, Day 7: topical application
- Duration: 9 days in total
- Concentrations: Intradermal: 5% w/v in Arachis oil BP, Topical Induction: 25% w/w in Arachis oil BP

B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day of challenge: Day 21
- Exposure period: 24 h
- Test groups: 2
- Control group: 1 (vehicle group)
- Site: right flank
- Concentrations: a) 10% (w/w) in Arachis oil BP; b) 5% (w/w) in Arachis oil
- Evaluation (hr after challenge): 24 and 48 h
Challenge controls:
To ensure that the maximum non-irritant concentration was used at challenge, the test material at a concentration of 5% w/w in arachis oil BP was similarly applied to a skin site on the left shorn flank
Positive control substance(s):
not specified

Results and discussion

Positive control results:
The strain used in this study record has been shown to produce satisfactory sensitisation responses using known positive sensitisers. As positive control trials have been conducted in the testing laboratory on a regular basis, no positive control has been evaluated in the presented test.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
-
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
not measured/tested
Remarks:
see "Positive control results"
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
-
No. with + reactions:
0
Total no. in group:
0
Remarks on result:
not measured/tested
Remarks:
see "Positive control results"
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
5%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
5%
No. with + reactions:
0
Total no. in group:
5
Remarks on result:
no indication of skin sensitisation

Any other information on results incl. tables

Maximum concentration not causing irritating effects in preliminary test: 5 %

Signs of irritation during induction:
Intradermal Induction: Erythema was noted at the intradermal induction sites of test group animals at the 24 and 48-hour observations. Very slight erythema was noted at the intradermal induction sites of all control group animals at the 24-hour observation and three control group animals at the 48-hour observation.

Topical Induction:
Very slight to well-defined erythema (8/10 animals) and incidents of very slight oedema (2/10 animals) were noted at the topical induction sites of test group animals at the 1-hour observation.

Evidence of sensitisation of each challenge concentration: None


 


Bodyweights: Bodyweight gains of guinea pigs in the test group, between Day 0 and Day 24, were comparable to those observed in the control group animals over the same period.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
FADEX He 1819 PK produced a 0% (0/10) sensitisation rate and was therefore classified as a non-sensitiser to guinea pig skin.
Executive summary:

A study was performed to assess the contact sensitisation potential of the test material FADEX He 1819 pK in the albino guinea pig. The study was performed in compliance with the OECD Guidelines for Testing of Chemicals No. 406 "Skin Sensitisation" (adopted 17 July 1992) and Method B6 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).


Ten test and five control animals were used for the main study. The bodyweight of each animal was recorded at the start and end of the study. Two main phases were involved in the main study; (a) an induction of a response and (b) a challenge of that response. Based on the results of sighting tests, the concentrations of test material for the induction and challenge phases were selected as follows:


lntradermal lnduction: 5% w/v in arachis oil BP


Topical lnduction:      25% w/w in arachis oil BP


Topical Challenge:     10% and 5% w/w in arachis oil BP


Approximately 24 and 48 hours after challenge dressing removal, the degree of erythema and oedema was quantified using the scale according to Draize (1977).


The test material produced a 0% (0/10) sensitisation rate and was classified as a non-sensitiser to guinea pig skin.