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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.164 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
75
Dose descriptor starting point:
LOAEL
Value:
30 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
12.34 mg/m³
Explanation for the modification of the dose descriptor starting point:

A long term study (>12 months) which can be used for assessment and derivation of a respective DNEL is not available. Furthermore, there are no quantitative data on inhalation absorption of m-toluidine. Therefore, the available OECD TG 422 study can be taken using oral application (MHLW 1995). The LOAEL for repeat dose toxicity was 30 mg/kg bw/day (UNEP 2003).

According to the ECHA guidance document R8 (Characterisation of dose [concentration]-response for human health) a factor 3 (When the starting point for the DNEL calculation is a LOAEL, it is suggested to use an assessment factor 3 (as minimum/majority of cases)) is used. Therfore the corrected human NOAEL/LOAEL = 1/3.

Bioavailability: animal experiment (oral) = 50% (default)

Bioavailability human route = 100% (default inhalation)

For the expose in animal study/exposure in humans a correction factor of 7/5 is used.

Corrected human LOAEC = 37 mg/m³ (30 x 1/0,38 x7/5 x50/100 x 6.7/10)

Corrected human NOAEC = 12.34 mg/m³

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
Sub-acute exposure to chronic exposure (defalut value ECHA)
AF for interspecies differences (allometric scaling):
1
Justification:
Rat versus human According to Table R8-4 in chapter R8 of EChA Guidance Document (Version 2.1, November 2012) the AF of 4 is already included in the route to route extrapolation (defalut value ECHA)
AF for other interspecies differences:
2.5
Justification:
(defalut value ECHA)
AF for intraspecies differences:
5
Justification:
Sub-acute exposure to chronic exposure (defalut value ECHA)
AF for the quality of the whole database:
1
Justification:
There are valid studies available for all required toxicological endpoints for that tonnage band
AF for remaining uncertainties:
1
Justification:
As the increased susceptibility of humans to methemoglobinemia is already considered by using factors for intraspecies and interspecies differences the remaining differences between worker and rats might be low and a factor of 1 justified.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.82 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.046 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
LOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
14 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In a study according to OECD TG 422 and GLP conditions male and female SD (Crj:CD) rats received 0, 30, 100, or 300 mg/kg bw/day m-toluidine by gavage (MHLW 1995). Hematological and biochemical analysis was conducted only for males. Compound related clinical signs were low locomotor activity and pale skin at 300 mg/kg bw. At the lowest dose of 30 mg/kg bw marginal deposit pigmentation and extramedullary hematopoiesis in the spleen were observed suggesting that a slight hemolysis occurred. Therefore, the dose of 30 mg/kg bw/day should be considered to be adverse effect level because of suggestive evidence of hemolytic anemia. LOAEL for repeat dose toxicity was 30 mg/kg bw/day (UNEP 2003).

According to the ECHA gueidance document R8 (Characterisation of dose [concentration]-response for human health) a factor 3 (When the starting point for the DNEL calculation is a LOAEL, it is suggested to use an assessment factor 3 (as minimum/majority of cases)) is used. Therfore the corrected human NOAEL/LOAEL = 1/3.

Bioavailability: animal experiment (oral) = 50% (default)

Bioavailability human route = 50% (default inhalation)

For the expose in animal study/exposure in humans a correction factor of 7/5 is used.

DNEL (systemic long term) = 0.046 mg/kg ( (14 / 300)

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic exposure (defalut value ECHA)
AF for interspecies differences (allometric scaling):
4
Justification:
rat versus human (defalut value ECHA)
AF for other interspecies differences:
2.5
Justification:
defalut value ECHA
AF for intraspecies differences:
5
Justification:
defalut value ECHA
AF for the quality of the whole database:
1
Justification:
There are valid studies available for all required toxicological endpoints for that tonnage band.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.23 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.029 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
150
Dose descriptor starting point:
LOAEC
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
4.34 mg/m³
Explanation for the modification of the dose descriptor starting point:

A long term study (>12 months) which can be used for assessment and derivation of a respective DNEL is not available. Furthermore, there are no quantitative data on inhalation absorption of m-toluidine. Therefore, the available OECD TG 422 study can be taken using oral application (MHLW 1995). The LOAEL for repeat dose toxicity was 30 mg/kg bw/day (UNEP 2003).

According to the ECHA gueidance document R8 (Characterisation of dose [concentration]-response for human health) a factor 3 (When the starting point for the DNEL calculation is a LOAEL, it is suggested to use an assessment factor 3 (as minimum/majority of cases)) is used. Therfore the corrected human NOAEL/LOAEL = 1/3.

Bioavailability: animal experiment (oral) = 50% (default)

Bioavailability human route = 100% (default inhalation)

Corrected human LOAEC = 13.04 mg/m³ (30 x 1/1,15 x 50/100)

Corrected human NOAEC = 4.34 mg/m³

DNEL (systemic long term) = 0.029 mg/m³ (4.34 / 150)

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic exposure (defalut value ECHA)
AF for interspecies differences (allometric scaling):
1
Justification:
Rat versus human: According to Table R8-4 in chapter R8 of EChA Guidance Document (Version 2.1, November 2012) the AF of 4 is already included in the route to route extrapolation (defalut value ECHA).
AF for other interspecies differences:
2.5
Justification:
defalut value ECHA
AF for intraspecies differences:
10
Justification:
defalut value ECHA
AF for the quality of the whole database:
1
Justification:
There are valid studies available for all required toxicological endpoints for that tonnage band
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.145 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.016 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
LOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In a study according to OECD TG 422 and GLP conditions male and female SD (Crj:CD) rats received 0, 30, 100, or 300 mg/kg bw/day m-toluidine by gavage (MHLW 1995). Hematological and biochemical analysis was conducted only for males. Compound related clinical signs were low locomotor activity and pale skin at 300 mg/kg bw. At the lowest dose of 30 mg/kg bw marginal deposit pigmentation and extramedullary hematopoiesis in the spleen were observed suggesting that a slight hemolysis occurred. Therefore, the dose of 30 mg/kg bw/day should be considered to be adverse effect level because of suggestive evidence of hemolytic anemia. LOAEL for repeat dose toxicity was 30 mg/kg bw/day (UNEP 2003).

According to the ECHA gueidance document R8 (Characterisation of dose [concentration]-response for human health) a factor 3 (When the starting point for the DNEL calculation is a LOAEL, it is suggested to use an assessment factor 3 (as minimum/majority of cases)) is used. Therfore the corrected human NOAEL/LOAEL = 1/3.

Bioavailability: animal experiment (oral) = 50% (default)

Bioavailability human route = 50% (default inhalation)

DNEL (systemic long term) = 0.016 mg/kg (10 / 600)

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
sub-acute to chronic exposure (defalut value ECHA)
AF for interspecies differences (allometric scaling):
4
Justification:
defalut value ECHA
AF for other interspecies differences:
2.5
Justification:
defalut value ECHA
AF for intraspecies differences:
10
Justification:
defalut value ECHA
AF for the quality of the whole database:
1
Justification:
There are studies available for all required toxicological endpoints for that tonnage band
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.016 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
LOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In a study according to OECD TG 422 and GLP conditions male and female SD (Crj:CD) rats received 0, 30, 100, or 300 mg/kg bw/day m-toluidine by gavage (MHLW 1995). Hematological and biochemical analysis was conducted only for males. Compound related clinical signs were low locomotor activity and pale skin at 300 mg/kg bw. At the lowest dose of 30 mg/kg bw marginal deposit pigmentation and extramedullary hematopoiesis in the spleen were observed suggesting that a slight hemolysis occurred. Therefore, the dose of 30 mg/kg bw/day should be considered to be adverse effect level because of suggestive evidence of hemolytic anemia. LOAEL for repeat dose toxicity was 30 mg/kg bw/day (UNEP 2003).

According to the ECHA guidance document R8 (Characterisation of dose [concentration]-response for human health) a factor 3 (When the starting point for the DNEL calculation is a LOAEL, it is suggested to use an assessment factor 3 (as minimum/majority of cases)) is used. Therfore the corrected human NOAEL/LOAEL = 1/3.

Bioavailability: animal experiment (oral) = 50% (default)

Bioavailability human route = 50% (default inhalation)

DNEL (systemic long term) = 0.016 mg/kg (10 / 600)

AF for dose response relationship:
1
AF for differences in duration of exposure:
6
Justification:
sub-acute to chornic exposure (defalut value ECHA)
AF for interspecies differences (allometric scaling):
4
Justification:
rat versus human (defalut value ECHA)
AF for other interspecies differences:
2.5
Justification:
defalut value ECHA
AF for intraspecies differences:
10
Justification:
defalut value ECHA
AF for the quality of the whole database:
1
Justification:
There are valid studies available for all required toxicological endpoints for that tonnage band.
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.08 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
DNEL extrapolated from long term DNEL

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population