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Diss Factsheets

Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1993-11-01 to 1994-01-24
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study, used for read-across

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1994
Report date:
1994

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
Updated July 1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Version / remarks:
Updated July 1992, CJEC L383A 1992
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test

Test material

Constituent 1
Reference substance name:
Reference substance 002
Constituent 2
Chemical structure
Reference substance name:
1-(2-amino-3-methylbutyryl)pyrrolidine-2-carboxylic acid
EC Number:
416-950-8
EC Name:
1-(2-amino-3-methylbutyryl)pyrrolidine-2-carboxylic acid
Cas Number:
20488-27-1
Molecular formula:
C10H18N2O3
IUPAC Name:
1-(2-amino-3-methylbutyryl)-pyrrolid ine-2-carboxylic acid

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Albino, Hsd/Poc:DH
Sex:
female
Details on test animals and environmental conditions:
according to guideline

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
Sighting study: Dose levels were 10 %, 3 %, 1 5 and 0.3 %
Selected concentration for main study: 10 % for intradermal induction; after 1 week topical application 75 % w/v; 2 weeks after that for challange, topical application 75 % w/v and 30 % w/v
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
Sighting study: Dose levels were 10 %, 3 %, 1 5 and 0.3 %
Selected concentration for main study: 10 % for intradermal induction; after 1 week topical application 75 % w/v; 2 weeks after that for challange, topical application 75 % w/v and 30 % w/v
No. of animals per dose:
Sighting study: 2 or 4 animals per dose level and per stage of the study
Main study: 30 animals (of which 20 for the test substance and 10 for control)
Details on study design:
RANGE FINDING TESTS:
The dose level for each of the 3 stages of the study were determined by a sighting study in which groups of 2 or 4 guinea pigs were used and up to 4 dose levels were tested on each group of animals. The procedure was as follows:
i) intradermal injection (inducation): preparations of the test sample in deionised water were tested to determine the highest concentration, that could be well tolerated locally and systematically and was uitable for injecting through a needle.
ii) topical application (induction): a preparation of the test sample in deionised water were tested to determine the highest concentration which did not cause greater than a mild to moderate irritation response in animlas that had been injected with Freund's Complete Adjuvant at least 14 days previously.
iii) topical application (challange): preparations of the test sample in deionised water were tested to determine the highest concentration which did not produce irritation in animlas that had been injected with Freund's Complete Adjuvant at least 14 days previously.


MAIN STUDY
A. INDUCTION EXPOSURE
Inducation of test animals:
Intradermal induction injection: The hair was removed with a pair of veterinary clippers from an area of ca. 5 x 5 cm on the scapular region of each animal and a row of injections (0.05 - 0.1 ml each) was made on each side of the mid-line. The injections were:
i) Top: Freund's Complete Adjuvant plus deionised water in the ration 1 : 1
ii) Middle: a 10 5 w/v preparation of the test sample in deionised water
iii) Bottom: a 10 % w/v preparation of the test sample in a 1 : 1 preparation of Freund's Complete Adjuvant plus deionised water.

The injections were checked for any adverse effects for up to 1 day.

Topical induction application: One week later, the scapular area was clipped again and treated with a topical application of the test sample as a 75 % w/v preparation in deionised water. The preparation (0.2 - 0.3 ml) was applied on filtre paper (approximate size 4 x 2 cm) which was held in place by a piece of surgical tape. The tape was covered by a strip of adhesive bandage (apprximate size 20-30 x 5 cm) and secured by a piece of self-adhesive PVC tape. This occlusicve dressing was kept in place for approx. 48 hours.


B. CHALLENGE EXPOSURE
2 weeks after the topical inductions, an area, ca. 15 x 15 cm, on both flnaks of all the test and control animals, was clipped free of hair with a pair of veterinary clippers. An occlusive dressing was prepared which consisted of 2 pieces of filtre paper (approx. size 1 x 1.5-2 cm) stitched to a piece of rubber sheeting (approx. size 12 x 5 cm).
a 75 % w/v preparation of the test sample in deionised water (0.05 - 1 ml) was applied to one of the pieces of filtre paper and a 30 % w/v preparation in deionised water (0.05 - 1 ml) was applied to the second piece of filtre paper. The dressing was placed on to the guinea pig so that the 75 % w/v preparation wa son the left shron flank and the 30 % w/v preparation was on the right shorn flank. It was then covered with a strip of adhesive bandage (approximate size 25-40 x 7.5 cm) which was secured by a self-adhesive PVC tape.
After approx. 24 hours, the dressings were carefully cut, using blunt-tipped scissors, removed and discarded. The position of the pieces of filtre paper on the skin were identified using a black waterproof marker pen.
erythematous reactions were quantified and recorded using the four-point scale approx. 1 and 2 days after removal of the dressings. All animals were re-clipped prior to the 1 day reading.
Challenge controls:
Induction of the control animals:
Intradermal injections were administered using an identical procedure to that used for the test animals, except that the injections were:
i) Top: Freund's Complete Adjuvant plus deionised water in the ration 1 : 1
Middle: deionised water
Bottom: Freund's Complete Adjuvant plus deionised water in the ration 1 : 1
The topical applications followed the same procedure as for the test animals except that deionised water only was applied to the filtre paper.
Positive control substance(s):
yes
Remarks:
2-mercaptobenzothiazole

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 75 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
75 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 75 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
30 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: 30 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
30 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: 30 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
1st reading
Hours after challenge:
24
Group:
positive control
Dose level:
3 %
No. with + reactions:
18
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: positive control. Dose level: 3 %. No with. + reactions: 18.0. Total no. in groups: 20.0.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
75 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 75 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
75 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 75 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
30 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: 30 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
30 %
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: 30 %. No with. + reactions: 0.0. Total no. in groups: 10.0. Clinical observations: none.
Reading:
2nd reading
Hours after challenge:
48
Group:
positive control
Dose level:
3 %
No. with + reactions:
18
Total no. in group:
20
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: positive control. Dose level: 3 %. No with. + reactions: 18.0. Total no. in groups: 20.0.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
L-valyl-L-proline was tested for skin sensitisation. The substance was non-sensitising to the skin of guinea pigs.