Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
5 August and 5 September 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: done under GLP and OECD method

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guidelineopen allclose all
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Qualifier:
equivalent or similar to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Principles of method if other than guideline:
The first study was conducted with 5 control and I 0 test animals between 12 September and l3 October 1995 (Huntingdon Lite Sciences repmt No PFZ 681/952756/S S). In this first study two of the ten test animals gave a positive response and the remaining eight animals gave negative responses. It was considered that a further five control and ten test animals should be tested to confirm this negative result. The second study was conducted between 5 August and 5 September 1997
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Chemical structure
Reference substance name:
2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)benzoic acid
EC Number:
424-110-7
EC Name:
2-ethoxy-5-(4-methyl-1-piperazinylsulfonyl)benzoic acid
Cas Number:
194602-23-8
Molecular formula:
C14 H20 N2 O5 S
IUPAC Name:
2-Ethoxy-5-(4-methyl-1- piperazinylsulphonyl)-benzoic acid
Test material form:
solid: crystalline
Details on test material:
Appearence: Off-white crystalline solid
Expiry : February l 998
Purity: 99.6% excluding organic solvents
Date received : 19 May 1995

In vivo test system

Test animals

Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male
Details on test animals and environmental conditions:
At the start of the study the animals were in the weight range of 278 to 379 grams and were 4-7 weeks old. Animals were acclimatised for 5 days prior to the study. Free access to mains drinking water and food (vitamin C enriched guinea-pig diet (Harlan Teklad 9600 FD2 SQC))was allowed throughout the study. The temperature and relative humidity were set to achieve limits of 25C and 67% respectively. Air exchange was maintained at approximately 15 air changes per hour and lighting was controlled by means of a time switch to give 12 hours of artificial light (0700 - 1900 hours) in each 24 hours period

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
other: intradermal injections & topical application
Vehicle:
water
Concentration / amount:
Based on the results of the preliminary investigations. the following concentrations of UK-143- l 08 were
selected:
Induction intradermal injection - 7.5% w/v in water for irrigation
This was the highest concentration that caused irritation but did not adversely affect the animals Induction topical application - 60% w/v in distilled water
Topical challenge - 60 and 30% w/v in distilled \water
Challengeopen allclose all
Route:
other: topical application
Vehicle:
water
Concentration / amount:
Based on the results of the preliminary investigations. the following concentrations of UK-143- l 08 were
selected:
Induction intradermal injection - 7.5% w/v in water for irrigation
This was the highest concentration that caused irritation but did not adversely affect the animals Induction topical application - 60% w/v in distilled water
Topical challenge - 60 and 30% w/v in distilled \water
No. of animals per dose:
No Data (20 test animals in total)
Details on study design:
Main study
The procedure may be considered in two parts, Induction and Challenge.
1. Induction

Induction intradermal injections - test animals

A 40 x 60 mm area of dorsal skin on the scapular region of the guinea-pig was clipped free of hair with electric clippers .

injections for the test animals were prepared as follows:

I . Freund, s complete adjuvant** was diluted with an equal volume of water for irrigation(Ph.Eur.) .
2. UK-143J08, 7.5% w/v in water for irrigation.
3. UK-143, 108_ 7.5% w/v in a 50 : 50 of Freund 's compare adjuvarit and water for irrigation.
**Difeo Laboratories . Detroit . Michigan , U.SA.

Challenge - control and test animals

The control and test animals were challenged topically two weeks after the topical induction application using UK- l 43 , 108, 60 and 30% w/v in distilled water.

Hair was removed by clipping and then shaving from an area on the left flank of each guinea-pig A 20 x 20 mm patch of Whatman No . 3 paper was saturated with approximately 0.2 ml of UK-143,108 . 60% w/v in distilled water and applied to an anterior site on the flank UK-
143.l 08, 30% w/v in distilled water was applied in a similar manner to a posterior site. The
patches were scaled to the flank for 24 hours under strips of ''Blenderm" covered by
"Elastoplast ' wound round the trunk and secured with 'Sleek"

Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
No. with + reactions:
2
Total no. in group:
30
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 2.0. Total no. in groups: 30.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
No. with + reactions:
2
Total no. in group:
30
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 2.0. Total no. in groups: 30.0.

Any other information on results incl. tables

INDUCTION

Intradermal injections

Necrosis was recorded at sites receiving Frcund's Complete Adjuvant in test and control animals.

Slight irritation was seen in test animals at sites receiving UK-143,108, 7.3% wiv in water for irrigation

and no irritation was ohscrved in control animals receiving water for irrigation.

Topical application

Sight enothema was observed ir test. animals following topical application with UK-143,108, 60% w/v

in distilled water.Slight erythema was seen in the control guinea-pigs.

CHALLENGE

There were no dermal reactions seen in eighteen of the twenty test animals or in the control animals, therefore these eighteen test animals gave negative responses. Dermal reactions were observed for two of the test animals, therefore these gave positive responses.

Applicant's summary and conclusion

Interpretation of results:
not sensitising
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In this study, 11K-143.108 did not produce evidence of skin sensitisation (delayed contact hypersensitivity) in eighteen of the twenty test animals. The remaining two animals gave positive responses.
Overall, evidence of skin sensitisation was seen in 10% of the animals and UK-143,108 is not considered to be a sensitiser.