Registration Dossier

Diss Factsheets

Administrative data

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study (EPA OPP 81-6)
Qualifier:
according to guideline
Guideline:
EPA OPP 81-6 (Skin Sensitisation)
Principles of method if other than guideline:
This study was also according to the method of Magnusson and Kligman (1970).
The objective of this investigation was to identify irritant test article concentrations suitable for the induction phase of the main study. In addition, a suitable non-irritant concentration of the test article, by the topical route of administration, was identified for the challenge application.
GLP compliance:
yes
Type of study:
guinea pig maximisation test
Species:
guinea pig
Strain:
Dunkin-Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Kleintierfarm Madoerin AG (CH4414 Fuellinsdorf, Switzerland)
- Age at study initiation: 8-9 week-old
- Weight at study initiation: males = 462-516g, females = 437-530g
- Housing: individually in Makrolon type-3 cages with standard softwood bedding.
- Diet (e.g. ad libitum): Pelleted standard Kliba 342, batch 25/85 and 26/85 guinea pig breeding/maintenance diet, ad libitum
- Water (e.g. ad libitum): Tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55+/-10
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 (music/light period)
Route:
intradermal and epicutaneous
Vehicle:
corn oil
Concentration / amount:
Induction : 1% with corn oil (intradermal + topical administrations).
Challenge : 1% with corn oil
Route:
epicutaneous, occlusive
Vehicle:
corn oil
Concentration / amount:
Induction : 1% with corn oil (intradermal + topical administrations).
Challenge : 1% with corn oil
No. of animals per dose:
Control group : 5 animals/sexe/dose
Treated group : 10 animals/sexe/dose
Details on study design:
RANGE FINDING TESTS: Intradermal injection (0.1 ml/site) were made into the clipped flank of 2 guinea-pigs at concentrations of 1, 0.5 and 0.1% of mITC in corn oil. The resulting dermal reactions were assessed 24 hours later. Topical application : patches of filter paper (2x2cm) were saturated with concentrations of 1, 0.5, 0.1% of MITC in corn oil, respectively as suspension and applied to the clipped and shaved flanks of each of 4 guinea pigs. The patches were covered by a strip of aluminium foil anf firmly secured by elastic plaster wrapped around the thunk and covered with impervious adhesive tape. The dressings were removed after an exposure period of 24 hours and the reaction sites were assessed for erythema and edema, on a numerical basis according to the scale described above. Further examination of the sites were performed 24 and 48h after removal of the dressing.

MAIN STUDY
A1. INDUCTION EXPOSURE No.1 (intradermal injection)
- No. of exposures: 1
- Animals received 3 pairs of intradermal injections :
1/Freuds complete adjuvant 50:50 with corn oil = control group
2/MITC diluted to 1% with corn oil = tested group (1)
3/MITC diluted to 1% with corn oil, amulsified in a 50:50 mixture of Freud's complete adjuvant = tested group (2)
- Site: dorsal skin from the scapular region (6x8cm)

A2. INDUCTION EXPOSURE No.2 (topical application) : one week after the injections.
- No. of exposures: 1
- Exposure period: 48 hours
- Site: dorsal skin from the scapular region
- Concentrations: patch was saturated with MITC (1%).
The patch were covered by aluminium foil and firmly secured by an elastic plaster wrapped around the thunk of the animal and secured with impervious adhesive tape.

B. CHALLENGE EXPOSURE : two weeks after the topical induction application.
- No. of exposures: 1
- Exposure period: 24 hours
-Treated group : with MITC
-Control group : vehicle alone
- Site: 5x5 cm area on the left flank of each animal
- Concentrations: 1% MITC (non-irritant concentration)
- Evaluation (hr after challenge): 24 and 48h

C. RECHALLENGE : two weeks after the first challenge.
The method was similar to that described for the first challenge with the exception that the right flanks of all the animals were used.
- Evaluation (hr after challenge): 24 and 48h

Challenge controls:
Yes, control animals were treated with vehicle only.
Positive control substance(s):
not specified
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
No. with + reactions:
4
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 4.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
48
Group:
test chemical
No. with + reactions:
3
Total no. in group:
20
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 3.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
24
Group:
test chemical
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 24.0. Group: test group. No with. + reactions: 2.0. Total no. in groups: 20.0.
Reading:
rechallenge
Hours after challenge:
48
Group:
test chemical
No. with + reactions:
1
Total no. in group:
20
Remarks on result:
other: Reading: rechallenge. . Hours after challenge: 48.0. Group: test group. No with. + reactions: 1.0. Total no. in groups: 20.0.
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 24.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0.
Reading:
1st reading
Hours after challenge:
48
Group:
negative control
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: Reading: 1st reading. . Hours after challenge: 48.0. Group: negative control. No with. + reactions: 0.0. Total no. in groups: 10.0. 
After the first challenge application, the following positive results were observed in the animals treated with the test article:
- at the 24-hour reading: 4/20 (20%)
- at the 48-hour reading: 3/20 (15%)
After the second challenge application, the following positive results were observed in the animals treated with the test article:
- at the 24-hour reading: 2/20 (10%)
- at the 48-hour reading: 1/20 (5%)Animals in control group showed negative result (after 24h : 0/10, after 48h : 0/10).
No toxic symptoms were evident in the guinea pigs of either the control and test group.
There was no mortality.
Interpretation of results:
sensitising
Remarks:
Migrated information
Conclusions:
Trapex 40 is considered to possess a mild skin sensitization (contact allergenic) potential in albino guinea pigs.
Executive summary:

The purpose of this skin sensitization study was to assess the allergenic potential of Trapex 40 when administered to albino guinea pigs.

According to the procedures used in this experiment, slight differences between the test group and the vehicle-treated controls were evident after epidermal challenge application of Trapex 40. 

After the first challenge application, the following positive results were observed in the animals treated with the test article:
- at the 24-hour reading: 4/20 (20%)
- at the 48-hour reading: 3/20 (15%)
After the second challenge application, the following positive results were observed in the animals treated with the test article:
- at the 24-hour reading: 2/20 (10%)
- at the 48-hour reading: 1/20 (5%)Animals in control group showed negative result (after 24h : 0/10, after 48h : 0/10).
No toxic symptoms were evident in the guinea pigs of either the control and test group.
There was no mortality.

Trapex 40 is considered to possess a mild skin sensitization (contact allergenic) potential in albino guinea pigs.

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

In a guideline study, the sensitizing potential of methyl isothiocyanate (as a 40% formulation) was evaluated by intradermal injection and topical applications according to the guinea pig maximization test (Ullmann and Sachsse, 1986). The sensitization potential was evaluated after a 10-day induction period during which the animals were treated with the vehicle, or methyl isothiocyanate. On day 1, in presence of Freund's adjuvant 0.1 ml of methylisothiocyanate (40% formulation) at a concentration of 1% were administered by intradermal route, respectively. On day 8, methyl isothiocyanate (40% formulation) at 1% were applied by cutaneous route. After this induction period, a 14 days suspension of treatment is set. Then, a first challenge reaction was realised by applying methyl isothiocyanate (40% formulation) at 1% on the left flank of the abdomen, under occlusive patch for a 24 hours contact. A second challenge was performed two weeks later. Macroscopic skin reactions were evaluated 24, and 48 hours after patch removing. Erythema and oedema were scored according to a standardised scale (0-4). After the first challenge application, skin reactions were observed 4/20 and 3/20 animals at the 24- and 48-hour reading, respectively. After the second challenge application, 2/20 and 1/20 animals reacted positively at 24 and 48 hours, respectively. No toxic symptoms were evident in the guinea pigs of either the control and test group. There was no mortality. Under these experimental conditions, methyl isothiocyanate (40% formulation) was considered to possess a mild skin sensitizing potential in guinea pigs.


Migrated from Short description of key information:
Methyl isothiocyanate is a skin sensitizer.

Justification for selection of skin sensitisation endpoint:
Only one reliable study is available to evaluate the skin sensitisation potential of MITC.

Respiratory sensitisation

Endpoint conclusion
Additional information:
Migrated from Short description of key information:
No data available.

Justification for classification or non-classification

Mandatory classification and self classification:

- Regulation (EC) No 1272/2008 Annex VI Table 3.1

Skin Sens.1: H317, May cause allergic reaction.

- Regulation (EC) No 1272/2008 Annex VI Table 3.2 or Directive 67/548/EEC

Xi, R43: May cause sensitization by skin contact