Registration Dossier

Toxicological information

Skin sensitisation

Currently viewing:

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: Comparable to guideline study with acceptable restrictons

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Ûberprüfung der durchführbarkeit von Prüfungsvorschriften und der Aussagekraft der Grundprüfung des E Chem G
Author:
Korte F and Greim H
Year:
1981
Bibliographic source:
Umweltforschungsplan des Umweltministeriums des Innern, Chemikalien, Forschungsbericht 107 04 006/01. 172
Reference Type:
secondary source
Title:
European Union Risk Assessment Report - 1,2,4-Trichlorobenzene
Author:
European Commission - European Chemicals Bureau
Year:
2003
Bibliographic source:
Office for Official Publications of the European Communities

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
No GLP. No information about negative control group, and concentration of 1,2,4-TCB. Occlusive bandage during epicutaneous exposure. Detailed results are not reported.
GLP compliance:
no
Remarks:
GLP was not mandatory at the time of the study
Type of study:
guinea pig maximisation test

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): 1,2,4-trichlorobenzene
- Analytical purity: 98%

In vivo test system

Test animals

Species:
guinea pig
Strain:
Pirbright-Hartley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Lippische Versuchstierzucht, HAGEMANN GmbH & Co., D-4923 Extertal 1, Germany
- Age at study initiation: 21-28 days
- Weight at study initiation: 250-300g
- Housing: Makrolon- cage (type III)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 1.0 °C
- Humidity (%): 60% ± 5%
- Photoperiod (hrs dark / hrs light): 12 hrs dark /12 hrs light



Study design: in vivo (non-LLNA)

Inductionopen allclose all
Route:
intradermal and epicutaneous
Vehicle:
other: not specified
Concentration / amount:
see "Details on study design (traditional tests)"
Challengeopen allclose all
Route:
epicutaneous, occlusive
Vehicle:
other: not specified
Concentration / amount:
see "Details on study design (traditional tests)"
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS:
To test the sensitization potential of 1,2,4-trichlorobenzene the maximization procedure was conducted. For this, a preliminary test was conducted on 2-3 animals to delineate any irritating properties of the test substance. The aim was to determine the doses so that, by intradermal administration they arise a skin irritation, by percutaneous application provoke any irritation to the skin.
MAIN STUDY
A. INDUCTION EXPOSURE
INTRADERMAL INJECTIONS: The hair was removed from the back of the animals without injuring the skin. Then an intradermal administration of 0.1 mL of the test substance in an appropriate concentration (0.5-10%) and in appropriate solvent was performed. In addition, the test substance was intradermally applied at the same final concentration and in a mixture of FREUND `S (Bacto Adjuvant, Complete Freund, Fa. Difco Laboratories, Detroit, Michigan, USA) complete Adjuvant, and the solvent (0.1 mL, in the ratio 1 +1). Finally a treatment with intradermal FREUND`S complete Adjuvant plus solvent (0.1 mL in proportion 1+1) was performed.
The first evaluation (induction exposure, nonspecific irritation) of the skin reaction was made 1 hour after the intradermal injection of the substance, and the second 24 hours.

TOPICAL APPLICATION: To assess a possible local skin reaction a patch test procedure was conducted in the following week (7 days after the first application) on the back of the same animals.
Therefore, 2 mL of 20% preparation of the test substance was applied on an approximately 30 cm² of plastic film, covered by a rubberised bandage and attached between the front and hind limbs on the intact and shaved skin of the back of animals. The gauze-patch remained on the skin fixed for 48 hours. 24 hours after removing the patch the 3rd assessment of skin reaction was performed.

B. CHALLENGE EXPOSURE
In order to evaluate the possible sensitizing properties of 1,2,4-trichlorobenzene, a further dermal treatment (patch test procedure as described above) was conducted 2 weeks after the percutaneous exposure on both flanks of animals.
The piece of tissue with the test substance was placed on the left flank, the one with the vehicle on the right flank.
The fourth assessment of the skin reaction was performed 24 hours after the removal of the patches. Changes, provoked by the bandage, were by that time faded away. The fifth assessment was made after 48 hours after the removal of the patch.

Challenge controls:
no data
Positive control substance(s):
yes
Remarks:
5000IE/0.1 mL Penicillin G-Na

Results and discussion

Positive control results:
20 animals were used as positive control group in the main test. The degree of sensitization was V, so that in this control experiment Penicillin G-Na was classified as extreme

In vivo (non-LLNA)

Results
Reading:
other: mean value of two readings
Hours after challenge:
72
Group:
test group
Dose level:
not reported
No. with + reactions:
2
Total no. in group:
20
Remarks on result:
other: Reading:

Any other information on results incl. tables

1,2,4-TCB resulted in a positive reaction in <10% of the animals. Detailed test results are not available.

Applicant's summary and conclusion

Interpretation of results:
other: classification for skin sensitization is not required according to the EU classification criteria
Executive summary:

Korte & Greim (1981)

 

A guinea-pig maximisation study according to OECD TG 406 with deviations ( No GLP. No information on any negative control group, or the concentration of 1,2,4-TCB. Occlusive bandage during epicutaneous exposure. Detailed results are not reported). In general, substances were tested in this study at concentrations of 0.5-10%.

1,2,4-TCB resulted in a positive reaction in <10% of the animals.

These results indicate only a weak sensitisation potential and the classification of 1,2,4-TCB for skin sensitisation is not required according to the EU classification criteria.