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Description of key information

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
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with acceptable restrictions
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.
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

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
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
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
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.

The animals gained weight normally during the study.

Animal supplier: Charles River Laboratories, Kingston, NY, USA

Interpretation of results:
GHS criteria not met
Remarks:
Migrated information
Conclusions:
Under the conditions of this skin sensitisation study in the guinea pig TMT was not sensitising.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Skin

TMT was examined for its skin sensitisation potential in a Guinea Pig Maximisation test (GPMT) which was conducted under GLP according to OECD Guideline 406 adopted in 1981 (93-0164-FGT).

A pilot study was performed to evaluate irritating effects after intradermal and topical application. Concentrations of 0.1%, 1%, 3% and 5% of TMT 55 each in water and in a 1:1 mixture (v/v) FCA/water were used in the primary irritation screen. The highest concentration that did not produce ulceration and/or necrosis was determined to be 0.1% in water and 1% in a 1:1 mixture (v/v) FCA/water. Moreover concentrations of 9.5%, 19%, 38% and 75% in water were selected to determine the topical dermal irritation threshold concentration of TMT 55. No signs of irritation were evident for any of these concentrations after a 24 h exposure period.

Therefore, in the main study 20 Crl:(HA)BR VAF/Plus guinea pigs received an intradermal application of 0.1% test material in water and 1% test material in a 1:1 mixture (v/v) FCA/water for induction at day 0 of the experimental period. A control group with 20 animals were treated with water and adjuvance only. On day 7 occlusive patches with 75% of the test substance were applied on the same site of the test animals for 48 h for topical induction, the control group were treated with water only. On day 21 test and control animals were challenged with 75% test material by occluded patch for 24 h on the right flank. 24 h and 48 h after removing the patches, no dermal reactions were recorded. Thus it is concluded, that based on the results of this GPMT test TMT 55 is not skin sensitising. This negative result on skin sensitisation can be transferred to anhydrous TMT.

 


Migrated from Short description of key information:
skin sensitisation (OECD 406, GPMT): not classified (no positive reactions were observed for TMT 55)

Justification for selection of skin sensitisation endpoint:
There is only one study available.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:
Migrated from Short description of key information:
no data available

Justification for selection of respiratory sensitisation endpoint:
Study not required according to Annex VII - X of Regulation (EC) No 1907/2006.

Justification for classification or non-classification

The available data on skin sensitisation of TMT do not meet the criteria for classification according to Regulation (EC) 1272/2008 or Directive 67/548/EEC, and are therefore conclusive but not sufficient for classification.