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Description of key information

According to the maximisation grading the test material showed a weak grade of skin-sensitising (contact allergenic) potential in albino guinea pigs.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

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Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Study period:
26th October 1992 - 3rd December 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
no
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
Results from a valid GMT study were already available.
Species:
guinea pig
Strain:
other: Pirbright White Strain (Tif: DHP)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production, 4332 Stein / Switzerland
- Age at study initiation:
- Weight at study initiation: 303 - 425 g
- Housing: Individually in Macrolon cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: NDA


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2 ºC
- Humidity (%): 30 - 70 %
- Air changes (per hr): NDA
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: 26th October 1992 To: December 3rd 1992
Route:
other: The induction was a two-stage operation. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later.
Vehicle:
other: peanut oil (intradermal); Vaseline (epidermal)
Concentration / amount:
Intradermal induction: 1 % in Oleum arachidis
Epidermal induction: 100 %
First epidermal challenge: 50 % in vaseline
Second epidermal challenge: 20 % in vaseline
Route:
epicutaneous, occlusive
Vehicle:
other: peanut oil (intradermal); Vaseline (epidermal)
Concentration / amount:
Intradermal induction: 1 % in Oleum arachidis
Epidermal induction: 100 %
First epidermal challenge: 50 % in vaseline
Second epidermal challenge: 20 % in vaseline
No. of animals per dose:
10 animals per sex per dose.
Details on study design:
RANGE FINDING TESTS:
The concentration for the intradermal injections was selected on account of the solubility of the test article in standard vehicles and its local and systemic tolerability in a pretest (data not reported).

MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2. First, intradermal injections (into the neck region); second, closed patch exposure over the injection sites one week later.
- Exposure period: One initial injection in week 1. 48 hour patch exposure in week 2.
- Test groups: 10 males 10 females. Three pairs of intradermal injections (0.1 ml per injection) were made simultaneously into the shaved neck of the guinea pigs as follows:
• adjuvant/saline mixture 1:1 (v/v)
• test article TK 10315/S in Oleum arachidis (w/v)
• test article TK 10315/S in the adjuvant/saline mixture (w/v)
- Control group: A group of 5 males and 5 females were treated with just adjuvant and vehicle.


B. CHALLENGE EXPOSURE
- No. of exposures: 2
- Day(s) of challenge: 24 hours per challenge. First performed in week 5, 2nd in week 6.
- Test groups: In the first challenge, the animals were tested on the flank with TK 10315/S in vaseline (w/w) and the vehicle alone (patch 2x2 cm; approx. 0.2 g paste per patch; occluded administration for 24 hours). Because reactions were observed in several animals of the control group a second challenge, using a lower concentration of the test article, was performed. The animals were tested on the flank with TK 10315/S in vaseline (w/w) and the vehicle alone (patch 2x2 cm; approx. 0.2 g paste per patch; occluded administration for 24 hours).
- Control group: During the challenge period the group was treated with the vehicle as well as with the test article to check the maximum subirritant concentration of the test article in adjuvant treated animals.
- Site: flank
- Evaluation (hr after challenge): 24 and 48 hours after removal of dressings.
Challenge controls:
Vehicle alone one of the flanks.
Positive control substance(s):
no
Positive control results:
N/A
Reading:
1st reading
Hours after challenge:
24
Group:
other: Vehicle control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
0.2g (50%)
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
Erythema and Oedema
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
0.2g (50%)
No. with + reactions:
18
Total no. in group:
20
Clinical observations:
Erythema and Oedema
Reading:
2nd reading
Hours after challenge:
48
Group:
other: Vehicle control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
0.2g (50%)
No. with + reactions:
6
Total no. in group:
10
Clinical observations:
Erythema and Oedema
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
0.2g (50%)
No. with + reactions:
18
Total no. in group:
20
Clinical observations:
Erythema and Oedema
Reading:
rechallenge
Hours after challenge:
24
Group:
other: Vehicle control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
24
Group:
negative control
Dose level:
0.04g (20%)
No. with + reactions:
2
Total no. in group:
10
Clinical observations:
Erythema and Oedema
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
Dose level:
0.04g (20%)
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
Erythema and Oedema
Reading:
rechallenge
Hours after challenge:
48
Group:
other: Vehicle control
Dose level:
0
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
48
Group:
negative control
Dose level:
0.04g (20%)
No. with + reactions:
0
Total no. in group:
10
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
Dose level:
0.04g (20%)
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
Erythema and Oedema
Interpretation of results:
other: negative with weakly sensitisation potential
Conclusions:
After the first challenge application 90% of the animals of the test group and 60% of the animals of the control group showed skin reactions 24 and 48 hours after removing the dressings. After a second challenge application, using a lower concentration of the test article, 20 and 0% of the animals of the control group and 0 and 10% of the animals of the test group showed skin reactions 24 and 48 hours after removing the dressings, respectively.

Frequency of observed skin reactions in control and test group are considered to indicate the absence of skin sensitisation.

TK 10315/S is, therefore, classified as a weak sensitiser in albino guinea pigs according to the grading of Magnusson and Kligman.
Executive summary:

A sensitisation test in albino guinea pigs was performed to determine the contact allergenic potency of TK 10315/S in albino guinea pigs.The test was conducted according to the OECD 406 guideline and to GLP standard.

10 % of the animals of the test group showed skin reactions by TK 10315/S under the experimental conditions employed. Since 2/10 animals of the control group also showed skin reactions observations made in the test group are considered to be of no toxicological relevance.

According to the maximisation grading TK 10315/S showed a weak grade of skin-sensitising (contact allergenic) potential in albino guinea pigs.

Endpoint:
skin sensitisation: in vitro
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
an in vitro skin sensitisation study does not need to be conducted because adequate data from an in vivo skin sensitisation study are available
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

A sensitisation test in albino guinea pigs was performed to determine the contact allergenic potency of the test material (a 70%/30% mixture of MOTE/DOTE)in albino guinea pigs.The test was conducted according to the OECD 406 guideline and to GLP standard.

10 % of the animals of the test group showed skin reactions by TK 10315/S under the experimental conditions employed. Since 2/10 animals of the control group also showed skin reactions observations made in the test group are considered to be of no toxicological relevance.

According to the maximisation grading the test material showed a weak grade of skin-sensitising (contact allergenic) potential in albino guinea pigs but did not conduct to classification.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to skin sensitisation.