2,4,6-trichloroaniline

Endpoint summary

Description of key information

The skin sensitization potential of target chemical 2,4,6-trichloroaniline (CAS No: 634-93-5)  was assessedin various experimental studies which were conducted on humans and guinea pigs for target chemical2,4,6-trichloroaniline (CAS No: 634-93-5) andits structurally similar read across substances.Based on the available data for the target and read across substances and applying the weight of evidence approach, it can be concluded that chemical 2,4,6-trichloroaniline (CAS No: 634-93-5)  is able to cause skin sensitization and thus can be considered as sensitizing. Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Skin sensitizer”.

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:

weight of evidence

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

secondary literature

Justification for type of information:

Data is from safety assessment report

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Skin sensitization study was conducted on guinea pigs for test chemical 2,4,6-trichloroaniline (CAS No: 634-93-5) to determine its sensitization potential.

GLP compliance:

not specified

Type of study:

not specified

Justification for non-LLNA method:

not specified

Specific details on test material used for the study:

- Name of test material (as cited in study report): 2,4,6-trichloroaniline
- Molecular formula: C6-H4-Cl3-N
- Molecular weight: 196.464 g/mol
- Smiles notation: c1(c(cc(Cl)cc1Cl)Cl)N
- InChl (if other than submission substance): 1S/C6H4Cl3N/c7-3-1-4(8)6(10)5(9)2-3/h1-2H,10H2
- Substance type: organic
- Physical state: Solid

Species:

guinea pig

Strain:

not specified

Sex:

not specified

Details on test animals and environmental conditions:

not specified

Route:

other: not specified

Route:

other: not specified

No. of animals per dose:

not specified

Details on study design:

not specified

Challenge controls:

not specified

Reading:

1st reading

Group:

test chemical

Dose level:

not specified

Clinical observations:

Moderate skin sensitization was observed in treated guinea pigs.

Remarks on result:

positive indication of skin sensitisation

Cellular proliferation data / Observations:

Moderate skin sensitization was observed in treated guinea pigs.

Interpretation of results:

other: sensitizing

Conclusions:

The test material 2,4,6-trichloroaniline (CAS No: 634-93-5) was considered to be sensitizing to the skin of guinea pigs.

Executive summary:

Skin sensitization study was conducted on guinea pigs for test chemical 2,4,6-trichloroaniline (CAS No: 634-93-5) to determine its sensitization potential.

 

When the guinea pigs were treated with test chemical, moderate skin sensitization was observed in treated guinea pigs.

 

Therefore the chemical 2,4,6-trichloroaniline (CAS No: 634-93-5) was considered to be sensitizing to the skin of guinea pigs.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (sensitising)

Additional information:

Skin sensitization:

Various studieshas been investigated for the test chemical2,4,6-trichloroaniline (CAS No: 634-93-5)to observe the potential for skin sensitization to a greater or lesser extent. The studies are based on in vivo experiments in guinea pigs and humans for target chemical2,4,6-trichloroaniline (CAS No: 634-93-5) and its structurally similar read across substanceswhich have beensummarized as below;

 

Skin sensitization study was reported by safety assessment report on guinea pigs for test chemical 2,4,6-trichloroaniline (CAS No: 634-93-5) to determine its sensitization potential. When the guinea pigs were treated with test chemical, moderate skin sensitization was observed in treated guinea pigs. Therefore the chemical 2,4,6-trichloroaniline (CAS No: 634-93-5) was considered to be sensitizing to the skin of guinea pigs.

 

Another Skin sensitization study was conducted for test chemical 2,4,6-trichloroaniline (CAS No: 634-93-5) on humans. The chemical have been suspected to cause skin sensitization in humans. Therefore the chemical 2,4,6-trichloroaniline (CAS No: 634-93-5) was considered to be sensitizing to the skin of humans.

 

The above results were supported by the Guinea pig maximization test conducted by authoratitave database on guinea pigs for similar read across chemical according to OECD Guide–line 406 "Skin Sensitization". The sample was formulated in propylene glycol. The induction concentrations were 2.5 % for the intradermal induction and 50 % for the topical induction. The first provocation was carried out with a 50 % 3,4-dichloroaniline solution. Effects on the skin were seen in all 20 animals of the test substance group and in 9 of 10 animals from the control group. As a result of the reaction in nearly all animals of the control group, the concentration of 50 % is to be regarded as irritative, and therefore a second provocation with concentrations of 5 % and 25% was carried out. The provocation concentration of 25% again produced irritative effects (effects on the skin in 19 of 20 animals of the test substance group, and in 8 of 10 animals from the control group), while the effects were only slight after 5 % (effects on the skin in 1 of 10 animals from the control group). The provocation concentration of 5 % caused effects on the skin in 14 of 20 animals of the test substance group. Therefore, on the basis of observed effects, the test chemical was considered to be sensitizing to the skin of guinea pigs.

 

The overall results were further supported by the Local Lymph Node Assay (LLNA) conducted by peer reviewed journal on Female CBA/Ca mice to assess the skin sensitization potential of test chemical. The LLNA was conducted on groups of CBA/Ca mice (8-12 weeks of age) by mean of topical application of chemical on the dorsum of both ears at a dose of 25µl of one of three concentrations (0.25%, 0.5% and 1.0%)of the test chemical. 5 days after the first topical application, all mice were injected iv with 250µl phosphate buffered saline (PBS) containing 20µCi of [³H]methyl thymidine (³HTdR) .The mice were killed 5 hr later and the draining auricular lymph nodes excised and pooled for each experimental group. A single cell suspension of lymph node cells (LNC) was prepared by gentle disaggregation through 200 mesh stainless steel gauze. Pooled LNC were pelleted by centrifugation at 190g for 10 min, washed twice with 10 ml PBS and resuspended in 3 ml 5% trichloroacetic acid (TCA). After incubation overnight at 4°C, the precipitate was recovered by centrifugation, resuspended in 1ml 5% TCA and transferred to 10 ml scintillation fluid. Incorporation of³HTdR was measured by p-scintillation counting.The proliferative response of LNC was expressed as mean radioactive disintegrations per minute per lymph node (dpm/node for each experimental group and as the ratio of³HTdR incorporation into LNC of test nodes relative to control nodes [test: control (T:C) ratio]. A chemical was regarded as a sensitizer in the LLNA if at least one concentration resulted in a T:C ratio of 3 or greater and the data were not incompatible with a biological dose response. The test: control (T:C) ratios were 11.2, 14.4 and 18.0 at concentration of 0.25%, 0.5% and 1.0% respectively. Since the resulted test: control (T:C) ratio was greater than 3 at each concentration, the test chemical was considered to be sensitizing in Local Lymph Node Assay (LLNA).

 

Based on the available data for the target and read across substances and applying the weight of evidence approach,it can be concluded that thechemical 2,4,6-trichloroaniline (CAS No: 634-93-5) is able to cause skin sensitization and considered as sensitizing to the skin.Comparing the above annotations with the criteria of CLP regulation, it can be classified under the category “Skin Sensitizer”.

Respiratory sensitisation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The skin sensitization potential of test substance 2,4,6-trichloroaniline (CAS No: 634-93-5) andits structurally similar read across substanceswere observed in various studies. From the results obtained from these studies it is concluded that the chemical 2,4,6-trichloroaniline (CAS No: 634-93-5) is likely to cause skin sensitization and hence can be classified as Skin Sensitizer.