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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:
14.8 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):
50
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
739.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL from the OECD 422 of 300 mg/kgbw/d based on clinical signs observed in the high dose group.

The corrected 8 hr inhalation NOAEC for workers is NOAEL (300) * 1.76 *1.4* mg/m3 = 739.2 mg/m3.

- 1.76 : correction for differences in respiratory volume (workers) 

- 1.4 : for 7/5 correction for differences between human and experimental exposure condition (workers)

AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use a factor of 6, and a factor of 2 for a 90-day study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
1
Justification:
Already included in NOAEC calculation
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining differences
AF for intraspecies differences:
5
Justification:
Assessment factor of 5 for workers.
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
reliable data.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

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:
4.2 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):
200
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
840 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

DNEL derivation is based on a combined repeated dose toxicity study with the reproduction/developmental toxicity study by oral administration to rats (Salvador, 2019). The starting dose for DNEL calculation was a NOAEL of 300 mg/kg/day. Default absorption rates of 100 and 50% are assumed for the oral and dermal routes, respectively. The NOAEL (8h) derived for workers is :

300 x 2 x 1.4 = 840 mg/kg/day

- 2 : for 100/50. Default absorption rates of 100 and 50% are assumed for the oral and dermal routes, respectively

- 1.4 : correction for differences between human and experimental exposure condition (workers).

AF for dose response relationship:
1
Justification:
Default assessment (DNEL calculator). No specific concerns; starting point is NOAEL
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use a factor of 6, and a factor of 2 for a 90-day study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
4
Justification:
Default (DNEL calculator). Allometric scalling for oral to dermal.
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for remaining differences
AF for intraspecies differences:
5
Justification:
Assessment factor of 5 for workers.
AF for the quality of the whole database:
1
Justification:
Available data derived from valid studies showing consistent results.
AF for remaining uncertainties:
1
Justification:
Reliable data
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

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:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

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

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

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:
0.75 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):
400
Dose descriptor starting point:
NOAEL
Value:
100 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL from the OECD 422 of 300 mg/kgbw/day based on clinical signs observed in the high dose group. No correction factor should have to be applied.

AF for dose response relationship:
1
Justification:
No specific concerns; starting point is NOAEL.
AF for differences in duration of exposure:
4
Justification:
DNEL is based on an OECD 422 study. For an exposure of 28-day, ECHA recommends to use a factor of 6, and a factor of 2 for a 90-day study. In an OECD 422 study, rats were exposed approx. 6 weeks, thus a factor of 4 is appropriate.
AF for interspecies differences (allometric scaling):
4
Justification:
A defeult factor for allometric scaling is 4 for rat to human.
AF for other interspecies differences:
2.5
Justification:
A factor of 2.5 is applied for remaining differences
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Justification:
No additional factor.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population