Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.037 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):
12.5
Dose descriptor starting point:
NOAEL
Value:
0.26 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
0.46 mg/m³
Explanation for the modification of the dose descriptor starting point:

In the absence of repeated dose inhalation toxicity data, the NOEL from the 2-year combined chronic toxicity and carcinogenicity study in rat (0.26 mg/kg bw/day) can be taken as a starting point for deriving a DNELlong-term, workers, inhalation. The value must first be corrected for route differences as described in REACH guidance document R.8 of May 2008 (‘Characterisation of dose (concentration)-response for human health’): NOAEC corr = (NOAEL oral/sRVrat) X (sRV human/wRVhuman) X (ABSoral-rat/ABSinh-human) = (0.26/0.38) x (6.7/10) x (100/100) = 0.46 mg/m3. The absorption values are based on the toxicokinetic evaluation presented in Section 5.1.

AF for dose response relationship:
1
Justification:
Starting point is a NOAEL
AF for differences in duration of exposure:
1
Justification:
Chronic study
AF for interspecies differences (allometric scaling):
1
Justification:
Rat to human - not required; already accounted during route to route extrapolation from oral to inhalation
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
5
Justification:
Workers
AF for the quality of the whole database:
1
Justification:
Good quality complete database
AF for remaining uncertainties:
1
Justification:
No major remaining uncertainties
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:
0.83 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Dermal
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
300
Dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Not required as the starting point is an NOEL from a 21-d dermal study in rats

AF for dose response relationship:
1
Justification:
Starting point is a NOEL
AF for differences in duration of exposure:
6
Justification:
Sub-acute to chronic study
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
Remaining differences
AF for intraspecies differences:
5
Justification:
Workers
AF for the quality of the whole database:
1
Justification:
Good quality complete database
AF for remaining uncertainties:
1
Justification:
No major remaining uncertainties
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:
no hazard identified

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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population