Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

Not a skin sensitiser in guinea-pigs studies:


1/ Korte & Kreim, 1981


2/ EU RAR / Brown et al., 1969.


3/ EU RAR / Du Pont de Nemours, 1971.

Key value for chemical safety assessment

Skin sensitisation

Link to relevant study records

Referenceopen allclose all

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
no guideline available
Principles of method if other than guideline:
A series of exposures was given to the male albino guinea-pigs over a three-week intervals; the first five guinea-pigs received nine topical applications of 0.05 mL varying concentrations (50% x 4, 75% x 5) in f.a.d. (13% guinea-pig fat in a 1:1 solution of acetone and dioxane) to clipped abraded skin, and the other five animals received four sacral intradermal injections of 0.1 mL 1% solution v/v of test material in DMP (dimethylphtalate). After a two-week rest period, the test animals were challenged for sensitization by applying 0.05 mL of 75% and 95% (v/v) concentrations to shaved intact shoulder skin. A group of 10 previously unexposed guinea-pigs received similar applications at the time of challenge to provide a direct comparison of the challenge reactions of skin of similar age.
GLP compliance:
no
Type of study:
not specified
Justification for non-LLNA method:
The study pre-dates LLNA method
Species:
guinea pig
Strain:
not specified
Remarks:
Albino
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: N/A
- Microbiological status of animals, when known: N/A
- Age at study initiation: N/A
- Weight at study initiation: 500 g
- Housing: N/A
- Diet (e.g. ad libitum): N/A
- Water (e.g. ad libitum): N/A
- Acclimation period: N/A
- Indication of any skin lesions: N/A

ENVIRONMENTAL CONDITIONS
- Temperature (°C): N/A
- Humidity (%): N/A
- Air changes (per hr): N/A
- Photoperiod (hrs dark / hrs light): N/A

- IN-LIFE DATES: N/A
Route:
other: epicutaneous, unknown (Group 1)
Vehicle:
other: f.a.d
Concentration / amount:
50% x 4, 75% x 5
Day(s)/duration:
9 days
Adequacy of induction:
not specified
Route:
other: intradermal (Group 2)
Vehicle:
other: DMP
Concentration / amount:
1% / 0.1 mL x 4 days
Day(s)/duration:
4 days
Adequacy of induction:
not specified
No.:
#1
Route:
other: epicutaneous, unknown (Group 1 + 2)
Vehicle:
other: f.a.d.
Concentration / amount:
75% / 0.05 mL
Day(s)/duration:
After a two-week rest period
Adequacy of challenge:
not specified
No.:
#1
Route:
other: epicutaneous, unknown (Group 1 + 2)
Vehicle:
other: f.a.d.
Concentration / amount:
95% / 0.05 mL
Day(s)/duration:
After a two-week rest period
Adequacy of challenge:
not specified
No. of animals per dose:
5 (Group 1) + 5 (Group 2)
Details on study design:
Cf. principles of method if other than guideline
Positive control substance(s):
no
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
95%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: all 10 animals showed irritant reactions
Key result
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
75%
No. with + reactions:
0
Total no. in group:
10
Remarks on result:
other: all 10 animals showed irritant reactions

Table 7.4.1/1: Reactions on intact Guinea Pig Skin


 
































 



Test animals



Control animals



Concentration (% in f.a.d.)



75%



95%



75%



95%



Primary irritation test – 24 hrs



4+, 6 neg.



4+, 6 neg.



-



-



Challenge test – 24 hrs



3+++, 7+++



4+++, 6++



3+++, 7++



3+++, 7++



 

Interpretation of results:
GHS criteria not met
Conclusions:
The test item did not cause skin sensitisation but produced irritation. 
Executive summary:

A series of exposures was given to the male albino guinea-pigs over a three-week intervals; the first five guinea-pigs received nine topical applications of 0.05 mL varying concentrations (50% x 4, 75% x 5) in f.a.d. (13% guinea-pig fat in a 1:1 solution of acetone and dioxane) to clipped abraded skin, and the other five animals received four sacral intradermal injections of 0.1 mL 1% solution v/v of test material in DMP (dimethylphtalate). After a two-week rest period, the test animals were challenged for sensitization by applying 0.05 mL of 75% and 95% (v/v) concentrations to shaved intact shoulder skin. A group of 10 previously unexposed guinea-pigs received similar applications at the time of challenge to provide a direct comparison of the challenge reactions of skin of similar age.


The test item did not cause skin sensitisation but produced irritation. 

Endpoint:
skin sensitisation
Type of information:
other: EU Risk Assessment
Adequacy of study:
other information
Reliability:
other: EU Risk Assessment
Rationale for reliability incl. deficiencies:
other: no reliability is given as this is a summary entry for the EU RAR
Principles of method if other than guideline:
EU Risk Assessment
GLP compliance:
not specified

EU Risk Assessment (2003):


 


Some studies on sensitisation are summarized in EU Risk Assessment.


Some of these studies were reliable studies with restrictions or reliability was not assignable because references were only cited as secondary literature.


 


In one study (Brown et al., 1969) guinea pigs were exposed subcutaneously and open epicutaneously to 0.1% w/v of 98% pure 1,2,4-TCB in light liquid paraffin to the shorn skin on the back of the guinea pigs on 3 days in each of three successive weeks. The animals then received no treatment for 10 days and a challenge dose of the same solution on the right flank and of solvent on the left flank on the eleventh day. Following the challenge the animals were examined at 1 hour, 24 hours and 48 hours for signs of sensitisation reaction. The test result was negative. The test was repeated with the same animals and also gave a negative result.


Tested in guinea pigs by Haskell Laboratories by applying 1,2,4-TCB either topically 9 times over a three week period, or by intradermal injection 4 times over the same period, and challenged by dermal application after a two-week rest period, the animals showed no sign of sensitisation (Du Pont de Nemours, 1971b). However (as described above under skin irritation) both treated and control animals showed signs of skin irritation after the challenge.

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
documentation insufficient for assessment
Qualifier:
equivalent or similar to guideline
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
Justification for non-LLNA method:
The GPMT was undertaken pre-introduction of the LLNA (adoption 2002).
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
Route:
intradermal and epicutaneous
Vehicle:
other: not specified
Concentration / amount:
see "Details on study design (traditional tests)"
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
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
Reading:
other: mean value of two readings
Hours after challenge:
72
Group:
test chemical
Dose level:
not reported
No. with + reactions:
2
Total no. in group:
20
Clinical observations:
not reported
Remarks on result:
other: Reading: other: mean value of two readings. . Hours after challenge: 72.0. Group: test group. Dose level: not reported. No with. + reactions: 2.0. Total no. in groups: 20.0.

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

Interpretation of results:
GHS criteria not met
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 GHS classification criteria.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available
Additional information:

Skin sensitisation:


A GPMT study performed according to OECD TG 406 resulted in < 10% sensitization rate (2/20 animals) (Korte and Greim, 1981). Two other assays reported also negative results (Brown et al., 1969 & Du Pont de Nemours, 1969).


According to the EU RAR, all the studies available suffer from various forms of deficiencies and as a result, the database for this effect is limited. However, these results indicate only a weak sensitisation potential and the classification of 1,2,4-TCB for skin sensitisation is not required.

Justification for classification or non-classification

Harmonised classification: 


The substance has no harmonised classification according to the Regulation (EC) No. 1272/2008 (CLP).


 


Self classification: 


Based on the available information no additional self-classification is proposed according to the CLP and the GHS.


No information is available regarding respiratory sensitisation.