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Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.59 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):
300
Modified dose descriptor starting point:
NOAEC
Value:
176 mg/m³
Explanation for the modification of the dose descriptor starting point:
According to ECHA REACH Guidance
AF for dose response relationship:
1
Justification:
According to ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
According to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
According to ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
According to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
According to ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
According to ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.33 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
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to ECHA REACH Guidance
AF for dose response relationship:
1
Justification:
According to ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
According to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
According to ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
According to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
According to ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
According to ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
40 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
Value:
2 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to ECHA REACH Guidance
AF for dose response relationship:
1
Justification:
According to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
According to ECHA REACH Guidance
AF for other interspecies differences:
10
Justification:
According to ECHA REACH Guidance
AF for intraspecies differences:
5
Justification:
According to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
According to ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
According to ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

DNEL Acute Short-term - dermal, systemic effects

Relevant dose descriptor for the endpoint concerned: dermal LD50 value of > 2000 mg/kg bw in rats

Assessment factors relating to the extrapolation procedure:

Interspecies: 10

Intraspecies: 5 (workers)

Additional safety factor: no (no systemic effects were seen at a dose level of 2000 mg/kg bw)

Overall assessment factor: 10 * 5 = 50

DNEL Acute Short-term - dermal, systemic effects: 2000 ÷ 50 = 40 mg/kg bw/d

DNEL Long-term – dermal, systemic effects

Relevant dose descriptor for the endpoint concerned: NOAEL of 100 mg MATMD/kg bw/d in male and female Wistar rats in a 28 d oral study

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 (allometric scaling) and 2.5 (remaining differences)

Intraspecies: 5 (workers)

Time extrapolation: 6 (subacute study)

Route to route extrapolation: 1 (oral to dermal)

Dose-response: no correction necessary

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 4 * 2.5 * 5 * 6 * 1 = 300

DNEL long-term– dermal, systemic effects: 100 mg/kg bw/d ÷ 300 = 0.33 mg/kg bw/d

DNEL Long-term–inhalation, systemic effects

Relevant dose descriptor for the endpoint concerned: NOAEL of 100 mg MATMD/kg bw/d in male and female Wistar rats in a 28 d oral study

Correction of starting point:

Bioavailability: complete absorption is assumed (no correction necessary)

Route of exposure (oral vs. inhalation exposure): complete absorption assumed (no correction necessary)

Differences in respiratory volumes: correction factor of 1.76

Overall correction factor: 1.76

Corrected starting point: 100 * 1.76 = 176 mg/m3

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 (allometric scaling) and 2.5 (remaining differences)

Intraspecies: 5 (workers)

Time extrapolation: 6 (subacute study)

Dose-response: no correction necessary

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 4 * 2.5 * 5 * 6 = 300

DNEL Long-term–inhalation, systemic effects: 176 mg/m3 ÷ 300 = 0.59 mg/m3

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.15 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):
600
Modified dose descriptor starting point:
NOAEC
Value:
87 mg/m³
Explanation for the modification of the dose descriptor starting point:
According to ECHA REACH Guidance
AF for dose response relationship:
1
Justification:
According to ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
According to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
According to ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
According to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
According to ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
According to ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 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
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to ECHA REACH Guidance
AF for dose response relationship:
1
Justification:
According to ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
According to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
According to ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
According to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
According to ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
According to ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
20 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
2 000
Explanation for the modification of the dose descriptor starting point:
According to ECHA REACH Guidance
AF for dose response relationship:
1
Justification:
According to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
According to ECHA REACH Guidance
AF for other interspecies differences:
10
Justification:
According to ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
According to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
According to ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
According to ECHA REACH Guidance

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.17 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
Modified dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to ECHA REACH Guidance
AF for dose response relationship:
1
Justification:
According to ECHA REACH Guidance
AF for differences in duration of exposure:
6
Justification:
According to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
4
Justification:
According to ECHA REACH Guidance
AF for other interspecies differences:
2.5
Justification:
According to ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
According to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
According to ECHA REACH Guidance
AF for remaining uncertainties:
1
Justification:
According to ECHA REACH Guidance
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.1 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 000
Modified dose descriptor starting point:
NOAEL
Value:
1 100 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
According to ECHA REACH Guidance
AF for dose response relationship:
1
Justification:
According to ECHA REACH Guidance
AF for interspecies differences (allometric scaling):
1
Justification:
According to ECHA REACH Guidance
AF for other interspecies differences:
10
Justification:
According to ECHA REACH Guidance
AF for intraspecies differences:
10
Justification:
According to ECHA REACH Guidance
AF for the quality of the whole database:
1
Justification:
According to ECHA REACH Guidance
AF for remaining uncertainties:
10
Justification:
According to ECHA REACH Guidance

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

DNEL Acute Short-term - dermal, systemic effects

Relevant dose descriptor for the endpoint concerned: dermal LD50 value of > 2000 mg/kg bw in rats

Assessment factors relating to the extrapolation procedure:

Interspecies: 10

Intraspecies: 10

Additional safety factor: no (no systemic effects were seen at a dose level of 2000 mg/kg bw)

Overall assessment factor: 10 * 10 = 100

DNEL Acute Short-term - dermal, systemic effects: 2000 ÷ 100 = 20 mg/kg bw/d

DNEL Acute Short-term - oral, systemic effects

Relevant dose descriptor for the endpoint concerned: oral LD50 value of ca. 1100 mg/kg bw in rats

Assessment factors relating to the extrapolation procedure:

Interspecies: 10

Intraspecies: 10

Additional safety factor: 10 (LD50 to NOAEL)

Overall assessment factor: 10 * 10 * 10 = 1000

DNEL Acute Short-term - oral, systemic effects: 1100 ÷ 1000 = 1.1 mg/kg bw/d

DNEL Long-term – dermal, systemic effects

Relevant dose descriptor for the endpoint concerned: NOAEL of 100 mg MATMD/kg bw/d in male and female Wistar rats in a 28 d oral study

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 (allometric scaling) and 2.5 (remaining differences)

Intraspecies: 10 (general population)

Time extrapolation: 6 (subacute study)

Route to route extrapolation: 1 (oral to dermal)

Dose-response: no correction necessary

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 4 *2.5 * 10 * 6 * 1 = 600

DNEL long-term– dermal, systemic effects: 100 mg/kg bw/d ÷ 600 = 0.17 mg/kg bw/d

DNEL Long-term–inhalation, systemic effects

Relevant dose descriptor for the endpoint concerned: NOAEL of 100 mg MATMD/kg bw/d in male and female Wistar rats in a 28 d oral study

Correction of starting point:

Bioavailability: complete absorption is assumed (no correction necessary)

Route of exposure (oral vs. inhalation exposure): complete absorption assumed (no correction necessary)

Differences in respiratory volumes: correction factor of 0.87

Overall correction factor: 0.87

Corrected starting point: 100 * 0.87 = 87 mg/m3

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 (allometric scaling) and 2.5 (remaining differences)

Intraspecies: 10 (general population)

Time extrapolation: 6 (subacute study)

Dose-response: no correction necessary

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 4 * 2.5 * 10 * 6 = 600

DNEL Long-term–inhalation, systemic effects: 87 mg/m3 ÷ 600 = 0.15 mg/m3

DNEL Long-term - oral, systemic effects

Relevant dose descriptor for the endpoint concerned: NOAEL of 100 mg MATMD/kg bw/d in male and female Wistar rats in a 28 d oral study

Correction of starting point:

Bioavailability: complete absorption is assumed (no correction necessary)

Route of exposure: similar to general population (no correction necessary)

Exposure conditions: oral uptake via food in humans compared to application via diet (no correction necessary)

Assessment factors relating to the extrapolation procedure:

Interspecies: 4 (allometric scaling) and 2.5 (remaining differences)

Intraspecies: 10 (general population)

Time extrapolation: 6 (subacute study)

Dose-response: no correction necessary

Quality of whole database: sufficient (no correction necessary)

Overall assessment factor: 4 * 2.5 * 10 * 6 = 600

DNEL long-term– oral, systemic effects: 100 mg/kg bw/d ÷ 600 = 0.17 mg/kg bw/d