Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.22 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
45
Modified dose descriptor starting point:
LOAEC
Value:
10.05 mg/m³
Explanation for the modification of the dose descriptor starting point:
conversion from the rat LOAEC of 20 mg/m3 and differences in daily exposure times
AF for dose response relationship:
3
Justification:
ECHA guidance for LOAEC to NOEAC extrapolation and effect seen in females only
AF for differences in duration of exposure:
2
Justification:
ECHA default, sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA default, included in the conversion
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
3
Justification:
based on ECETOC guidance for worker population and closed system use
AF for the quality of the whole database:
1
Justification:
ECHA default, dataset reliable and consistent
AF for remaining uncertainties:
1
Justification:
No other 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:
3.6 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):
90
Modified dose descriptor starting point:
NOAEL
Value:
320 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Dermal absorption was taken as 16 times lower than via oral route.
AF for dose response relationship:
1
Justification:
Clear dose response
AF for differences in duration of exposure:
3
Justification:
ECHA default, sub-chronic to chronic duration
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA default for human to rat extrapolation
AF for other interspecies differences:
2.5
Justification:
ECHA default
AF for intraspecies differences:
3
Justification:
based on ECETOC guidance for worker population and closed system use
AF for the quality of the whole database:
1
Justification:
ECHA default, dataset reliable and consistent
AF for remaining uncertainties:
1
Justification:
No other 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

 

Chronic, Systemic, Inhalation DNEL

The starting point for the calculation of the systemic, long term exposure DNEL is the 90-day inhalation study in rats, exposed 6h/d, 5d/week LOAEC of 20 mg/m3.

Dose Descriptor starting point for inhalation:     20mg/m3 * 6/8 * 0.67  = 10.05 mg/m3

The assessment factors chosen to convert this dose to a worker DNEL are as follows:

Dose response relationship - 3, LOAEC to NOAEC conversion default

Time Extrapolation – 2, Conversion from a sub chronic study to chronic default.

Other interspecies differences: 2.5, Default ECHA value.

Worker variability - 3, Based on ECETOC guidance and closed system use.

Additional uncertainty - 1, Absorption following inhalation is expected to be similar or greater in rats than in humans. No other uncertainties.

Total Assessment Factor = 45

Application of AF leads to a long-term systemic inhalation DNEL (worker) of 0.22 mg/m3

 

Chronic, systemic, Worker Dermal DNEL

The starting point for the long-term, systemic Dermal DNEL is the Oral combined repeated dose/reproductive screening study NOEL of 20 mg/kg bw/day.

In the summary of toxicokinetic properties of this substance it is indicated that the rate of absorption through the gut is far greater than the rate through the skin; 2,12 cm/h compared to 0.13 cm/h indicating a difference in bioavailability following dermal exposure compared to oral exposure. The rate of absorption through the gut is approximately 16 times greater than that through the skin. Therefore, it is considered that if penetration rate were the limiting factor then oral bioavailability would be 16 times greater than dermal. As such the starting point for Dermal DNEL derivation will be modified by a factor of 16.

Thus, the starting point for DNEL derivation is taken as 320 mg/kg bw/day

The assessment factors for extrapolating to a DNEL are as follows:

Allometric scaling: 4 (rat to man)

'Other differences': 2.5, ECHA default

Worker variability: 3, Based on the recent ECETOC guidance and closed system use.

Time extrapolation: 3, Conversion from a sub chronic study to chronic.

Quality of the database - 1 (the data are consistent and sufficient to conclude on a safe human level of exposure)

Total assessment factor: 90

Worker Dermal DNEL (systemic) = 320/60 = 3.6 mg/kg bw/day

 

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

There is no direct consumer exposure to this substance. Therefore, DNELs for inhalation and dermal exposure have not been calculated.

The possibility of indirect exposure via the environment is considered minimal since there are no intended releases of this material to the environment. Therefore, it was not considered necessary to calculate an oral DNEL for the general population.