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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.08 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:
other: NOEC
Value:
27.1 mg/m³
Explanation for the modification of the dose descriptor starting point:

Toxicokinetics data for rats indicate an bioavailability of 1,4-diamino-2-methoxymethyl-benzene sulfate by intravenous and oral routes. The route to route extrapolation from oral study to inhalation study could be used.

The oral bioavailability of 2-METHOXY-METHYL-P-PHENYLENEDIAMINE SULFATE, based on the AUC, was high and comparable to the AUC after i.v. administration. When calculated from the urine data from the mass balance groups, the oral bioavailability was 99% at 25 mg/kg bw and 84% at 100 mg/kg bw. The inhalation absorption was considered by default to be 100%.

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 1
AF for remaining uncertainties:
1
Justification:
not concerned
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
48.06 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):
12.5
Modified dose descriptor starting point:
other: MTD
Value:
600.7 mg/m³
Explanation for the modification of the dose descriptor starting point:

Toxicokinetics data for rats indicate an bioavailability of 1,4-diamino-2-methoxymethyl-benzene sulfate by intravenous and oral routes. The route to route extrapolation from oral study to inhalation study could be used.

The oral bioavailability of 2-METHOXY-METHYL-P-PHENYLENEDIAMINE SULFATE, based on the AUC, was high and comparable to the AUC after i.v. administration. When calculated from the urine data from the mass balance groups, the oral bioavailability was 99% at 25 mg/kg bw and 84% at 100 mg/kg bw. The inhalation absorption was considered by default to be 100%.

AF for dose response relationship:
1
Justification:
MTD is considered as relevant as a NOAEL
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:
defaut value
AF for intraspecies differences:
5
Justification:
default value for workers
AF for the quality of the whole database:
1
Justification:
reliability 1
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:
0.732 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):
100
Modified dose descriptor starting point:
other: NOEL
Value:
73.2 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Toxicokinetics data for rats indicate an bioavailability of 1,4-diamino-2-methoxymethyl-benzene sulfate by intravenous and oral routes. The route to route extrapolation from oral study to dermal study could be used.

The oral bioavailability of 2-METHOXY-METHYL-P-PHENYLENEDIAMINE SULFATE, based on the AUC, was high and comparable to the AUC after i.v. administration. When calculated from the urine data from the mass balance groups, the oral bioavailability was 99% at 25 mg/kg bw and 84% at 100 mg/kg bw. The inhalation absorption was considered by default to be 100%.

The average dermal absorption was low in the dermal dose groups, and was 2.0% (0.5 h exposure) at 24 mg/kg bw and 21% (24 hour exposure) at 100 mg/kg bw.

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 1
AF for remaining uncertainties:
1
Justification:
not concerned
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
71.7 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:
DNEL (Derived No Effect Level)
Value:
71.7 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:
EC 3 value acn 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:
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
high hazard (no threshold derived)

Additional information - 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

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