Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.27 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):
25
Modified dose descriptor starting point:
NOAEC
DNEL value:
6.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

According to the toxicokinetic data for Sprague-Dawley rats, that indicate oral availability of toluene-2,5-diamine at 10 mg/kg bw to be 69%.

The route to route extrapolation from oral study to inhalation study could be used. This is also the consideration of SCCS evaluation.

AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
default value for extrapolation subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Extrapolation from oral to inhalation route (example B3 of guidance R8)
AF for other interspecies differences:
2.5
Justification:
R8 ECHA guidance
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
1
Justification:
reliability 2 because data on 2,5-toulene diamine sulphate
AF for remaining uncertainties:
1
Justification:
not concerned
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1 mg/m³
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
125
Modified dose descriptor starting point:
other: LOAEL
DNEL value:
130 mg/m³
Explanation for the modification of the dose descriptor starting point:

According to toxicokinetic data for Sprague-Dawley rats, that indicate oral availability of toluene-2,5-diamine at 10 mg/kg bw to be 69%.

The route to route extrapolation from oral study to inhalation study could be used. This is also the consideration of SCCS evaluation.

AF for dose response relationship:
10
Justification:
the LOAEL taken from the acute oral toxicity is related to lethality as most severe effect
AF for interspecies differences (allometric scaling):
1
Justification:
Extrapolation from oral to inhalation route (example B3 of guidance R8)
AF for other interspecies differences:
2.5
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
1
Justification:
reliability 2 because data on 2,5-toulene diamine sulphate
AF for remaining uncertainties:
1
Justification:
not concerned

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.759 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):
250
Modified dose descriptor starting point:
NOAEL
DNEL value:
189.75 mg/kg bw/day
AF for dose response relationship:
1
Justification:
default value
AF for differences in duration of exposure:
2
Justification:
default value for extrapolation subchronic to chronic
AF for interspecies differences (allometric scaling):
2.5
Justification:
default value
AF for other interspecies differences:
4
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value for worker
AF for the quality of the whole database:
1
Justification:
reliability 2 because data on 2,5-toulene diamine sulphate
AF for remaining uncertainties:
2.5
Justification:
uncertainty in bioavailability on skin between analogue 2,5-toulene diamine sulphate and 2,5-toulene diamine
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
2.84 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
15
Dose descriptor:
other: EC3
AF for dose response relationship:
3
Justification:
EC3 value can be considered as LOAEL for induction (R8 guidance document) maximum factor
AF for differences in duration of exposure:
1
Justification:
not concerned
AF for interspecies differences (allometric scaling):
1
Justification:
not concerned
AF for other interspecies differences:
1
Justification:
default value
AF for intraspecies differences:
5
Justification:
default value for worker
AF for the quality of the whole database:
1
Justification:
reliability 1
AF for remaining uncertainties:
1
Justification:
not concerned
Acute/short term exposure
Hazard assessment conclusion:
other toxicological threshold
Value:
2.84 µg/cm²
Most sensitive endpoint:
sensitisation (skin)
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
15
Dose descriptor starting point:
other: EC3
AF for dose response relationship:
3
Justification:
EC3 value can be considered as LOAEL for induction (R8 guidance document) maximum factor
AF for interspecies differences (allometric scaling):
1
Justification:
not concerned
AF for other interspecies differences:
1
Justification:
not concerned
AF for intraspecies differences:
5
Justification:
default value for worker
AF for the quality of the whole database:
1
Justification:
reliability 1
AF for remaining uncertainties:
1
Justification:
not concerned

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - workers

The substance has been shown inin vitroandin vivostudy to be severely irritant for the eyes and classified H318 according to CLP criteria. H318: Causes serious eye damage. Discussion No DNEL could be derived but qualitative approach is recommended. According to irritant effect on the eyes, risk management measures should be considered for workers.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown (no further information necessary)

Additional information - General Population