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:
weight of evidence
Study period:
From March 19, 1991 to April 25, 1991
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Type of study:
Buehler test
Justification for non-LLNA method:
The study was conducted before the requirement for LLNA testing came into force.

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Remarks:
clear, colourless, density 1.15 g/mL
Details on test material:
sol. 58.23 % (50.2 % TLA) and
sol. 20.23 % (17.57 % TLA)
solvent: aqua ad iniectabilia

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Pirbright white
Sex:
male/female
Details on test animals and environmental conditions:
Animals
Substrain: Bor: DHPW (SPF)
Source: Firma Winkelmann, Versuchstierzucht, Gartenstr. 27, 4799 Borchen
Acclimatisation period: at least 5 days
Animal selection: random
Animal identification: with colored markings; cage labelled with sex, date of study initiation, project no.
Weight range at study initiation: 307 - 400 g

Husbandry
Housing: collective housing up to a maximum of 5 animals per cage (Macrolon type IV)
Illumination: artificial lighting (120 lux) from 7.00 a.m. - 7.00 p.m.
Temperature: 22±3 °C
Relative humidity: 30 - 70 %
Measurement: with thermohygrometer twice daily

Study design: in vivo (non-LLNA)

Induction
Route:
epicutaneous, occlusive
Vehicle:
unchanged (no vehicle)
Concentration / amount:
undiluted
Day(s)/duration:
6 hours
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
Challenge
No.:
#20
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
58.2 % and 20.2 %
Day(s)/duration:
6 hours
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
Pilot study: 4 (two males and two females)
Main study: 20 animals (10 animals per treatment group)
Details on study design:
Pilot study (range finding):
A range finding test was conducted in two males and two females in order to determine the highest concentration of the test substance which did not produce excessive inflammation. Using Hill-Top Chambers (Hill Top, USA) secured with rubber dental dam (4D Rubber Co., Ltd., UK), the test substance was applied in four different concentrations to discrete areas of clipped skin on the back of each animal. The animals were then immobilized in metal restrainers for 6 h, after which time the patches were removed and the animals returned to their cages. Skin reactions were recorded 24 h and 48 h after patch removal.

Main study

Induction procedure:
Only test group was subject to an induction procedure. The test substance was applied undiluted to an area of clipped skin in the left anterior quadrant of the back of each animal. Method of application and duration of exposure were the same as in the pilot study. Dermal irritation was assessed 24 h after patch removal.
This procedure was repeated on the same site once weekly for a total of three 6-h exposures. After the last induction exposure all animals remained untreated for 2 weeks prior to challenge.

Challenge procedure:
Both test and control groups were subjected to a challenge exposure with the test substance. The latter was applied in concentrations of 58.23 % and 20.38 % to clipped areas of skin in the left posterior quadrant (58.23 %, induction area a) and in the right anterior quadrant (20.38 %, induction area b) of the back of each animal. Method of application and duration of exposure were the same as in the pilot study.
18 - 22 h after patch removal all animals were depilated with "Nair" roll-on (Carter Products, Inc., New York). Allergic responses were evaluated 24 h and 48 h after the end of the exposure period.
Challenge controls:
10 animals
Positive control substance(s):
yes
Remarks:
2.4 dinitrochlorobenzene (extreme sensitizer) and benzocaine (moderate sensitizer)

Results and discussion

Positive control results:
The reaction to the positive control substances 2.4 dinitrochlorobenzene (extreme sensitizer) and benzocaine (moderate sensitizer) is tested periodically. The last test with an acceptable leval of response to each of these substances was perfonned in April, 1991.

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
test substance 58.2% (a.i.)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test group
Dose level:
test substance 20.2% (a.i.)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
test substance 58.2 % (a.i.)
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
positive indication of skin sensitisation
Remarks:
sensitisation rate 5 %
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test group
Dose level:
test substance 20.2 % (a.i.)
No. with + reactions:
0
Total no. in group:
20
Remarks on result:
no indication of skin sensitisation
Remarks:
sensitisation rate 0 %
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
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:
positive control
Remarks on result:
other: Positive controls have been periodically tested by CRO

Any other information on results incl. tables

Pilot study:

58.23 %: partly very faint, nonconfluent erythema

55, 40, 20.38 %: no skin reactions

Main study:

The Sensitization rate of induction area a: (58.23 % a.i.) 48 h was 5 %.

The Sensitization rate of induction area b: (20.38 % a.i.) 48 h was 0 %.

According to the OECD guideline for testing of chemicals (OECD 406, May 12, 1981), test substance 50.2 % may be classified as a weak sensitizer, and test substance 17.57 % may be classified as a non-sensitizer.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the study conditions, test substance at 58.23% gave a positive response in 5% of the animals. There was no positive sensitisation response at treatment with the test substance at 20.38%.
Executive summary:

A study was conducted to determine the potential skin sensitising properties of the test substance (Ammonium 2-mercaptopropionate) in a solution at 58.23% (a.i.) and at 20.38% (a.i.) in the guinea pig sensitisation test (Buehler) according to OECD Guideline 406, in compliance with GLP. Twenty test and ten control animals were used. Initially a 6 h induction exposure to the test substance was performed in the test group once weekly for three weeks. Two weeks later both test and control groups were subjected to a single 6 h challenge exposure with the test substance. Allergic responses to the challenge procedure were evaluated 24 and 48 h after the challenge. Under the study conditions, test substance at 58.23% gave a positive response in 5% of the animals. There was no positive sensitisation response at treatment with the test substance at 20.38% (Kaufmann, 1999).