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Toxicological information

Skin sensitisation

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Administrative data

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
no data on reliability check with positive control; more than 2-3 animals were used for primary irritation screen
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Justification for non-LLNA method:
The described guinea pig maximisation test according to OECD 406 was conducted in 1993 before the guidance for the LLNA (OECD429, first adopted in 2002) was available, and before the method was fully established and validated. And since the result of the guinea pig maximisation test is considered to be scientifically valid, the test was not repeated also taking into account exposure and animal welfare considerations.

Test material

Reference
Name:
Unnamed
Type:
Constituent

In vivo test system

Test animals

Species:
guinea pig
Strain:
other: Crl:(HA)BR VAF/Plus
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: males 5-6 weeks, females 6-7 weeks
- Weight at study initiation: males 278-399 g, females 334-450 g
- Housing: individually in suspended, stainless-steel mesh cages
- Diet: Agway Prolab Guinea Pig Diet certified pellets, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 5 days
- Animal supplier: Charles River Laboratories, Kingston, NY, USA

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-21
- Humidity (%): 50-58
- Photoperiod (hrs dark / hrs light): 12/12


IN-LIFE DATES: From: 10 Feb 1993 To: 26 Mar 1993

Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
water
Concentration / amount:
- intradermal induction: 0.1% in vehicle, 1.0% in 1:1 mixture (v/v) FCA/water
- epidermal induction: 75% in vehicle
- epidermal challenge: 75% in vehicle
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
water
Concentration / amount:
- intradermal induction: 0.1% in vehicle, 1.0% in 1:1 mixture (v/v) FCA/water
- epidermal induction: 75% in vehicle
- epidermal challenge: 75% in vehicle
No. of animals per dose:
20 test animals and 20 control animals
Details on study design:
RANGE FINDING TEST
A primary irritation screen was conducted to determine the concentrations for intradermal and epicutaneous induction as well as for challenge exposure.

Intradermal injection (4 animals): 0.1, 1.0, 3.0 and 5.0% test substance in water or 1:1 mixture (v/v) FCA/water
Four pairs of intradermal injections (0.1 mL each) were made on each side of the vertebral column of each of four guinea pigs assigned. Approximately 48 h after the intradermal injections, sites were evaluated. The highest concentration that did not produce ulceration or necrosis (0.1% test material in vehicle and 1.0% test material in 1:1 mixture (v/v) FCA/water) was utilized for the intradermal induction phase of the sensitisation study.

Topical application (4 animals): 9.5, 19, 38 and 75% in vehicle
Each of 4 guinea pigs received 0.5 mL of each of the four selected concentrations of the test substance by applying each test concentration to patches and securing them with an elastic wrap. Approximately 24 h after initiation of exposure, the wraps and patches were removed and residual test material wiped away. 24 hours after patch removal, the application sites were evaluated for signs of irritation using Draize scoring system.
The concentration that produced minimal irritation was used for the topical induction phase and the concentration that produced no irritation for the challenge exposure of the study.
No signs of irritation were evident for any of the test concentrations. Therefore, 75% was used for both the topical induction and for the challenge exposure.


MAIN STUDY
A. INDUCTION EXPOSURE
- No. of exposures: 2 (intradermal and epicutaneous, respectively)
- Exposure period: single injection (intradermal) and 48 h (epicutaneous)
- Test groups:
Intradermal (3 pairs of injections):
Injection 1: 0.1 mL test substance in water
Injection 2: 0.1 mL 1:1 mixture FCA/water
Injection 3: 0.1 mL test substance in a 1:1 mixture (v/v) FCA/water

Epicutaneous: 0.3 mL test substance in water

- Control group:
Intradermal (3 pairs of injections):
Injection 1: 0.1 mL water
Injection 2: 0.1 mL 1:1 mixture FCA/water
Injection 3: 0.1 mL water in a 1:1 mixture (v/v) FCA/water

Epicutaneous: 0.3 mL water

- Site: shoulder region (intradermal and epicutaneous)
- Frequency of applications: every 7 days
- Duration: Days 0-7
- Exposure period (epicutaneous induction): 48 h
- Concentrations: intradermal: 0.1% in water, 1% in 1:1 mixture (v/v) FCA/water; epicutaneous: 75%

B. CHALLENGE EXPOSURE
- No. of exposures: 1 (challenge)
- Day of challenge: 21 (challenge)
- Exposure period: 24 h
- Test groups: test substance and water only
- Control groups: test substance and water only
- Site: left flank (test substance) and right flank (water)
- Concentration: 75%
- Evaluation (hr after challenge): 48 and 72 h
Positive control substance(s):
no

Results and discussion

In vivo (non-LLNA)

Resultsopen allclose all
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
induction: 0.1 and 1%; challenge: 75 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no dermal responses
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. Dose level: induction: 0.1 and 1%; challenge: 75 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no dermal responses.
Key result
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
induction: 0.1 and 1%; challenge: 75 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no dermal responses
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: test group. Dose level: induction: 0.1 and 1%; challenge: 75 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no dermal responses.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
induction: 0%; challenge: 75 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no dermal responses
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. Dose level: induction: 0%; challenge: 75 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no dermal responses.
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
induction: 0%; challenge: 75 %
No. with + reactions:
0
Total no. in group:
20
Clinical observations:
no dermal responses
Remarks on result:
other: Reading: 2nd reading. . Hours after challenge: 48.0. Group: negative control. Dose level: induction: 0%; challenge: 75 %. No with. + reactions: 0.0. Total no. in groups: 20.0. Clinical observations: no dermal responses.
Group:
positive control
Remarks on result:
not measured/tested

Any other information on results incl. tables

The animals gained weight normally during the study.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this skin sensitisation study in the guinea pig TMT was not sensitising.