Registration Dossier

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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

There is no sensitisation study available for nitrotoluene (CAS 1321-12-6), but a read-across can be made from 4-nitrotoluene (CAS 99-99-0).

4-nitrotoluene is not sensitizing to the skin of guinea pigs in the Buehler test.

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:
key study
Study period:
1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study with acceptable restrictions
Qualifier:
according to guideline
Guideline:
OECD Guideline 406 (Skin Sensitisation)
Deviations:
yes
Remarks:
No data about GLP compliance; analytical purity not reported
GLP compliance:
not specified
Type of study:
Buehler test
Justification for non-LLNA method:
The LLNA method was not established yet by the time the study was conducted.
Specific details on test material used for the study:
- Name of test material (as cited in study report): 4-nitrotoluene
- Analytical purity: not reported
Species:
guinea pig
Strain:
Hartley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Age at study initiation: not reported. Young adult animals were used
- Weight at study initiation: 326-521 grams
- Housing: animals were individually housed in wire mesh suspension cages
- Diet (e.g. ad libitum): diet ad libitum during acclimatization and test period
- Water (e.g. ad libitum): tap water ad libitum during acclimatization and test period
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18°-26°
- Humidity (%): 30-70%
- Photoperiod (hrs dark / hrs light): 12 hrs light/12 hrs dark cycle


Route:
other: epicutaneous, chamber
Vehicle:
other: acetone
Concentration / amount:
see details on study design
Route:
other: epicutaneous, chamber
Vehicle:
other: acetone
Concentration / amount:
see details on study design
No. of animals per dose:
20
Details on study design:
RANGE FINDING TESTS: Irritation screening (Pilot)
The irritation potential of the test material at levels of 50%, 25%, 10%, 5%, 2.5%, 1%, 0.5% and 0.25% was evaluated in 2 groups of 4 animals each. 4 levels of the test material were evaluated per animal such that each animal in a given pilot group was exposed to the same levels. Dilutions of the test material were formulated w/v in acetone.
On the day prior to test material exposure the hair was removed from each of the animals' backs. A 0.3 ml quantity of each test preparation was applied into a 25 mm chamber which was applied to the clipped surface of the animals in restrainers and occluded with rubber dental dam pulled out and fastened to the bottom of the restrainer with clips. The day following the irritation exposure all animals were depilated and scored.


MAIN STUDY
A. INDUCTION EXPOSURE
Induction Phase

The left shoulder (site 1) of each test animal was clipped the day before exposure. The animals were restrained and a 0.3 ml quantity of the test preparation was applied as previously described. The procedure was repeated at the same site once a week for the next 2 weeks for a total of 3 approximate 6-hour exposures. After the last induction exposure, the animals were left untreated for approximately 2 weeks (13 days) before primary challenge.
50% w/v concentration of 4-nitrotoluene in acetone was chosen for use at induction


B. CHALLENGE EXPOSURE
Primary Challenge Phase

The test animals were again exposed in the challenge phase. In addition 10 naive animals which had never been exposed to the test material were concurrently treated with the same test material concentration. The same exposure procedure was used as for the "Induction Phase" but the chambers were applied to a skin side that had not been exposed previously. Each animal received one patch of the test material using site 2.
10% w/v concentration of 4-nitrotoluene in acetone was chosen for use at
primary challenge
Positive control substance(s):
yes
Remarks:
1-Chloro-2,4-Dinitrobenzene, alpha-Hexylcinnamaldehyde
Positive control results:
Historical positive control data
1-Chloro-2,4-dinitrobenzene, incidences-mean score:
0.1% in acetone: 10/10-11.7 (24 hrs), 10/10-1.4 (48 hrs)
alpha-Hexylcinnamaldehyd, techn. = 85 %, incidences-mean score:
5 % in acetone: 10/10-1.1 (24 hrs), 7/10-0.9 (48 hrs)
2.5 % in acetone: 7/10-0.9 (24 hrs), 4/10-0.8 (48 hrs)
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
10/10 females with slight, patchy erythema, 10/10 males with slight, patchy erythema: numerical mean score : 0.5
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
11
Total no. in group:
20
Clinical observations:
5/10 females with slight, patchy erythema, 5/10 females with no reaction, 6/10 males with slight, patchy erythema, 4/10 males with no reaction: numerical mean score 0.3
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
5/5 females, 5/5 males : with slight, patchy erythema, numerical mean score, 0.5
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
3/5 females with slight patchy erythema, 2/5 females with no reactions, 2/5 males with slight patchy erythema, 3/5 males with no reaction: numerical mean score 0.3

Based on these results an assessment by comparison of responses in the test group to that of the corresponding control group was carried out. Since the Buehler test showed the same effects in the test group and the control group, 4-nitrotoluene was evaluated as not sensitizing to the skin of guinea pigs.

Interpretation of results:
GHS criteria not met
Conclusions:
4-Nitrotoluene was not sensitizing to the skin of guinea pigs in the Buehler test.
Executive summary:

A Buehler test performed with 20 guinea pigs according to OECD TG 406 with deviations (No data about GLP compliance; analytical purity not reported) did not reveal any skin sensitization. Induction was performed by dermal application of a 50 % solution in acetone and a 10 % solution was used for challenge. Concurrent control guinea pigs were treated with acetone alone. Animals treated with 1-chloro-2,4-dinitrobenzene (10/10 positive at 24 and 48 hrs), or alpha hexylcinnamaldehyde (10/10 positive at 24 hrs, 7/10 at 48 hrs) served as positive controls.

4-Nitrotoluene was not sensitizing to the skin of guinea pigs in the Buehler test.

 

Endpoint:
skin sensitisation: in vivo (non-LLNA)
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
There is no experimental test data available for nitrotoluene (CAS 1321-12-6), but a read-across can be made from its components. Nitrotoluene (CAS 1321-12-6) is a mixture of mainly 4-nitrotoluene (CAS 99-99-0) and/or 2-nitrotoluene (CAS 88-72-2). In addition, the mixture is containing small amounts of 3-nitrotoluene (CAS 99-08-1). A wealth of data is existing for the hazard assessment of 2- and 4-nitrotoluene, which can be used for the classification of nitrotoluene (CAS 1321-12-6). Key data and classification are derived from the isomer with the most critical hazard identified for each specific end point. The available experimental test data are considered reliable and suitable for the classification of nitrotoluene (CAS 1321-12-6) under Regulation 1272/2008.
Reason / purpose for cross-reference:
read-across source
Reading:
1st reading
Hours after challenge:
24
Group:
test chemical
Dose level:
10%
No. with + reactions:
20
Total no. in group:
20
Clinical observations:
10/10 females with slight, patchy erythema, 10/10 males with slight, patchy erythema: numerical mean score: 0.5
Reading:
2nd reading
Hours after challenge:
48
Group:
test chemical
Dose level:
10%
No. with + reactions:
11
Total no. in group:
20
Clinical observations:
5/10 females with slight, patchy erythema, 5/10 females with no reaction, 6/10 males with slight, patchy erythema, 4/10 males with no reaction: numerical mean score 0.3
Reading:
1st reading
Hours after challenge:
24
Group:
negative control
Dose level:
10%
No. with + reactions:
10
Total no. in group:
10
Clinical observations:
5/5 females, 5/5 males: with slight, patchy erythema, numerical mean score, 0.5
Reading:
2nd reading
Hours after challenge:
48
Group:
negative control
Dose level:
10%
No. with + reactions:
5
Total no. in group:
10
Clinical observations:
3/5 females with slight patchy erythema, 2/5 females with no reactions, 2/5 males with slight patchy erythema, 3/5 males with no reaction: numerical mean score 0.3
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (not sensitising)
Additional information:

Mononitrotoluene is a mixture of mainly 4-nitrotoluene (CAS 99-99-0) and/or 2-nitrotoluene (CAS 88-72-2). In addition the mixture is containing small amounts of 3-nitrotoluene (CAS 99-08-1). A wealth of data is existing for the hazard assessment of 2- and 4-nitrotoluene. Key data and classification is derived from the isomer with the most critical hazard identified for each specific end point. For completeness key data of the other isomer is added as supporting information.

Regarding sensitization only one study is available for 4-nitrotoluene which is applied forclassification purposes of Mononitrotoluene.

A Buehler test performed with 20 guinea pigs according to OECD TG 406 did not reveal any skin sensitization for 4 -NT (Chemfirst Inc., 1998). Induction was performed by dermal application of a 50 % solution in acetone and a 10 % solution was used for challenge. Concurrent control guinea pigs were treated with acetone alone. Animals treated with 1-chloro-2,4-dinitrobenzene (10/10 positive at 24 and 48 hrs), or alpha-hexylcinnamaldehyde (10/10 positive at 24 hrs, 7/10 at 48 hrs) served as positive controls.

Respiratory sensitisation

Endpoint conclusion
Endpoint conclusion:
no study available

Justification for classification or non-classification

Classification, Labelling, and Packaging Regulation (EC) No. 1272/2008

The available experimental test data are reliable and suitable for classification purposes under Regulation 1272/2008. There is no sensitisation study available for nitrotoluene (CAS 1321-12-6), but a read-across can be made from 4-nitrotoluene (CAS 99-99-0). 4-nitrotoluene is not sensitizing to the skin of guinea pigs in the Buehler test.

Therefore, nitrotoluene (CAS 1321-12-6) is not considered to be classified for sensitisation under Regulation (EC) No. 1272/2008, as amended for the thirteenth time in Regulation (EC) No. 2018/1480.