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Administrative data

Workers - Hazard via inhalation route

Systemic effects

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

Oral rat systemic NOAEL of 30 mg/kg bw derived for developmental toxicity in a study similar to OECD TG 421 (Nemec, 1995) served as the starting point for the DNEL derivation. The NOAEL was converted into inhalatory NOAEC by using the default respiratory volume for rats (8 h), assuming 50% absorption by oral route and 100% absorption by inhalation route (default procedure in case of oral-to-inhalation extrapolation). The NOAEC is additionally corrected by a factor of 1.4 to account for differences in exposure conditions (5 days/week for workers and 7 days for week for animals in the test).

corrected NOAEC = 30 mg/kg bw/d / 0.38 m3/kg bw * (6.7 m3/d / 10 m3/d) * 1.4 / (100% / 50%) = 37.03 mg/m3

AF for dose response relationship:
1
Justification:
default, NOAEL is used as starting point
AF for differences in duration of exposure:
6
Justification:
default for subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
already regarded by deriving a corrected NOAEC
AF for other interspecies differences:
2.5
Justification:
default for remaining interspecies differences
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
2
Justification:
due to read-across
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No DNEL for acute toxicity is needed, because the systemic toxicity of the substance is low; the substance is not toxic by ingestion. The oral LD50-values of the analogue substances are > 3000 mg/kg bw. Therefore, no DNEL for acute / short term exposure via the inhalatory route should be derived. The long-term DNELs are sufficient to ensure that acute effects do not occur, provided high-peak acute exposure can be avoided.

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:
70 µg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
600
Dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
42 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

It is assumed, that the dermal absorption will not be higher than the oral absorption (ECHA's Guidance R.8, v2.1, Nov 2012). Therefore, the NOAEL obtained via the oral route is regarded as a worst-case staring point to determine the dermal DNEL. This NOAEL is corrected by a factor of 1.4 to account for differences in exposure conditions (5 days/week for workers and 7 days for week for animals in the test).

30 mg/kg bw/day * 1.4 = 42 mg/kg bw/day

AF for dose response relationship:
1
Justification:
default, starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
default for subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat to human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
default for workers
AF for the quality of the whole database:
2
Justification:
due to read-across
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No DNEL for acute toxicity is needed, because the systemic toxicity of the substance is low; the substance is not toxic by ingestion. The oral LD50-values of the analogue substances are > 3000 mg/kg bw. Therefore, no DNEL for acute / short term exposure via the dermal route should be derived. The long-term DNELs are sufficient to ensure that acute effects do not occur, provided high-peak acute exposure can be avoided.

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
43 µg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
13 mg/m³
Explanation for the modification of the dose descriptor starting point:

Oral rat systemic NOAEL of 30 mg/kg bw from a study similar to OECD TG 421 for developmental toxicity (Nemec 1995) served as the starting point for the DNEL derivation. The NOAEL was converted into inhalatory NOAEC by using the default respiratory volume for rats (24 h), assuming 50% absorption by oral route and 100% absorption by inhalation route (default procedure in case of oral-to-inhalation extrapolation).

corrected NOAEC = 30 mg/kg bw/d / 1.15 m3/kg bw / (100 % / 50 %) = 13.04 mg/m3

AF for dose response relationship:
1
Justification:
default, NOAEL is used as starting point
AF for differences in duration of exposure:
6
Justification:
default for subacute to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
already regarded by deriving a corrected NOAEC
AF for other interspecies differences:
2.5
Justification:
default for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
2
Justification:
due to read-across
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No DNEL for acute toxicity is needed, because the systemic toxicity of the substance is low; the substance is not toxic by ingestion. The oral LD50-values of the analogue substances are > 3000 mg/kg bw. Therefore, no DNEL for acute / short term exposure via the inhalatory route should be derived. The long-term DNELs are sufficient to ensure that acute effects do not occur, provided high-peak acute exposure can be avoided.

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:
25 µg/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):
1 200
Dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

It is assumed, that the dermal absorption will not be higher than the oral absorption (ECHA's Guidance R.8, v2.1, Nov 2012). Therefore, the NOAEL obtained via the oral route is regarded as a worst-case starting point to determine the dermal DNEL.

AF for dose response relationship:
1
Justification:
default, starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
default for subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat to human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
2
Justification:
due to read-across
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No DNEL for acute toxicity is needed, because the systemic toxicity of the substance is low; the substance is not toxic by ingestion. The oral LD50-values of the analogue substances are > 3000 mg/kg bw. Therefore, no DNEL for acute / short term exposure via the dermal route should be derived. The long-term DNELs are sufficient to ensure that acute effects do not occur, provided high-peak acute exposure can be avoided.

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
25 µg/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):
1 200
Dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

It is assumed, that the oral absorption in human will not be higher than the oral absorption in rats. Therefore, the NOAEL of 30 mg/kg bw obtained in a study similar to OECD TG 421 via the oral route (Nemec 1995) is regarded as a starting point to determine the oral DNEL.

AF for dose response relationship:
1
Justification:
default, starting point is a NOAEL
AF for differences in duration of exposure:
6
Justification:
default for subacute to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
default for rat to human
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default for general population
AF for the quality of the whole database:
2
Justification:
due to read-across
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information
Explanation for the modification of the dose descriptor starting point:

No DNEL for acute toxicity is needed, because the systemic toxicity of the substance is low; the substance is not toxic by ingestion. The oral LD50-values of the analogue substances are > 3000 mg/kg bw. Therefore, no DNEL for acute / short term exposure via the oral route should be derived. The long-term DNELs are sufficient to ensure that acute effects do not occur, provided high-peak acute exposure can be avoided.

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population