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Diss Factsheets

Administrative data

Description of key information

Skin Sensitisation, Maximization Test according to Magnusson and Kligman (Guinea pig, GLP, OECD TG 406, EU-Method B.6, OPPTS 870.2600): sensitising
[Bayer AG, Report No. PH-34678, 2006-11-23]


 

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records
Reference
Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Sep to Oct 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Version / remarks:
1992
Qualifier:
according to guideline
Guideline:
EU Method B.6 (Skin Sensitisation)
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2600 (Skin Sensitisation)
GLP compliance:
yes (incl. QA statement)
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
for global regulatory acceptance of this pharmaceutical intermediate an GPMT was required
Specific details on test material used for the study:
Batch BXR36DP
purity: 98.9%
Species:
guinea pig
Strain:
other: Crl:HA
Sex:
female
Route:
intradermal and epicutaneous
Vehicle:
other: Cremophor EL/sterile physiological saline solution 2% v/v
Concentration / amount:
Intradermal induction: 5 % (= 20 mg test substance/animal)
Topical induction: 50% (= 250 mg test substance/animal)
Day(s)/duration:
2d
Adequacy of induction:
highest concentration used causing mild-to-moderate skin irritation and well-tolerated systemically
No.:
#1
Route:
epicutaneous, semiocclusive
Vehicle:
other: Cremophor EL/sterile physiological saline solution 2% v/v
Concentration / amount:
50% (= 250 mg test substance/animal)
Day(s)/duration:
1d
Adequacy of challenge:
highest non-irritant concentration
No. of animals per dose:
control group. 10
test substance group: 20
range-finding group: 2
Details on study design:
Intradermal Induction: The dorsal region and the flanks of the guinea pigs were shorn one day prior to the application. Starting behind the nape of the neck, three injections each in a row were made on the left and the right side of the spinal column. The 1st and 2nd injections were made as contiguous as possible and the 3rd injections in a distance of about 2 cm from the 2nd. The volume applied per injection site was 0.1 ml.
The topical induction was performed one week after the intradermal induction. On the day prior to topical treatment, the test areas of the animals were shorn. Hypoallergenic patches (2x4 cm) were placed between and on the injection sites, covered with aluminum foil and held securely in place on the skin using a ORABAND® self-adhesive tape (Fa. Orafol). At the end of the 48-hour exposure period, the remaining test item was removed with sterile physicological saline solution and the treatment areas were visually assessed.
The challenge was performed three weeks after the intradermal induction. In the meantime, the test item concentrations for the challenge had been determined in a dose range-finding study using 2 guinea pigs that were treated during the inductions in the same manner as the control animals (see page 26). The dorsal region and the right flank of the animals were shorn one day prior to the challenge. During the challenge a hypoallergenic patch loaded with the 0.5% test item formulation was placed on the right flank (caudal) of the animals of the test item group and the control group and held securely in place on the skin with a ORABAND® self-adhesive tape for 24 hours. A patch loaded only with the vehicle was placed also on the right flank (cranial) as control. The volume applied in each case was 0.5 ml. At the end of the exposure period, the remaining test item was removed with physiological saline solution, and 21 hours later the skin of the animals was shorn in the zone of the challenge area.
Positive control substance(s):
no
Remarks:
alpha-Hexylzimtaldehyd used in a separate test for reliability of the method
Positive control results:
Reliability of the Method (Report PH-34587):
The Guinea Pig Maximization Test methodology was checked for reliability in a test on female guinea pigs using alpha-Hexylzimtaldehyd formulated in sterile physicological saline solution at the concentrations indicated below:
For the intradermal induction a 5% test item formulation was used, and for the topical induction a 25% formulation. After the challenge with a 12% test item formulation 100% of the test animals exhibited dermal reactions in the challenge treatment. There was no reddening of the skin to be observed on control group animals. The sensitivity as well as the reliability of the experimental technique is thus confirmed by this study.
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
positive control
Dose level:
12%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
skin reactions grade 1-3
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
positive control
Dose level:
12%
No. with + reactions:
8
Total no. in group:
10
Clinical observations:
skin reactions grade 1-3
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
Dose level:
50%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
skin reactions grade 1-2
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
Dose level:
40%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
test chemical
Dose level:
50%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
skin reactions grade 1-2
Remarks on result:
positive indication of skin sensitisation
Key result
Reading:
2nd reading
Hours after challenge:
72
Group:
negative control
Dose level:
50%
No. with + reactions:
0
Total no. in group:
10
Clinical observations:
none
Remarks on result:
no indication of skin sensitisation

Appearance and behaviour of the test substance group were not different from the control groups. At the end of the study, the mean body weight of the treatment group animals was in the same range than that of the control group animals.

After the intradermal induction the animals in the control group and the test item group showed strong effects up to encrustation at the injection sites of the first induction.

The incidence of skin reactions (number of animals exhibiting skin effects) following the challenge is summarized in the following table:

               Test substance group (20 animals)              Control group (10 animals)
         Test substance patch     Control patch        Test substance patch     Control patch
 Hours  48 72  total   48  72  48  72  total  48  72
 Challenge 50%  20 20  20  0  0  0  0  0  0  0 

The observed skin effects were grade 1 -2.

Interpretation of results:
Category 1B (indication of skin sensitising potential) based on GHS criteria
Conclusions:
skin-sensitization potential; hazard class H317 ; 100% of animals reacted positively after challenge with grade 1-2
Executive summary:

In a Guinea Pig Maximization Test (S)-Oxamin HCL was examined in female guinea pigs for its skin sensitizing properties. The intradermal induction was performed using a 5% test item concentration, and the topical induction was performed with a 50% test item concentration.


The test item was formulated in Cremophor EL/sterile physiological saline solution 2% v/v to yield a solution (5%-12%) or a suspension (25%-50%).


After the intradermal induction the animals in the control group and in the test item group showed strong effects up to encrustation at the injection sites of the first induction.


The challenge with the 50% test item concentration led to skin effects (grade 1-2) in 20 of 20 animals of the test item group (100%) and to no skin effects in the animals of the control group.


In summary, by comparing the results in the treatment group and in the control group under the conditions of the maximization test and with respect to the evaluation criteria the test item therefore exhibits a skin-sensitization potential.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (sensitising)
Additional information:

The Guinea Pig Maximization Test was performed on female guinea pigs according to OECD guideline 406 to determine wether the (S)-Oxamin Hydrochlorid exhibits skin-sensitizing properties. The study was conducted with the following test item concentrations:


intradermal induction: 5%


topical induction: 50%


challenge: 50%


The challenge led to skin effects (grade 1 -2) in all animals of the test item group and therefore, under the condition of the maximization test and with respect to the evaluation criteria (S)-Oxamin-Hydrochlorid exhibits a skin-sensitization potential.


 

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Based on the study results (S)-Oxamin Hydrochlorid has to be classified as Skin Sens. Cat. 1B (H317) according to Regulation (EC) No. 1272/2008 (CLP).

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