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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:
0.98 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
12
Dose descriptor starting point:
NOAEL
Value:
6.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
11.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

Starting point: NOAEL of 6.7 mg/kg bw/day in a 100-day repeated dose toxicity study in rat (performed with substance analogue).

Conversion of an oral NOAEL into a corrected NOAEC:

For workers (8h exposure/day), the corrected inhalatory NOAEC = oral NOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human * sRVhuman/wRV

= 6.7 * 1/0.38 m3/kg/8h * ABSoral-rat /ABSinhal-human * 6.7 m3 (8h)/10 m3 (8h)

= 6.7 * 1/0.38 m3/kg/8h * 1 * 6.7 m3 (8h)/10 m3 (8h)

= 6.7 /0.38 * 1* (6.7/10) = 11.8 mg/m3.

 

With ABS: Absorption, sRV: Standard Respiratory Volume; wRV: Worker Respiratory Volume;

ABSoral-rat /ABSinhal-human= 10/10= 1, assuming no differences in inhalation absorption between rats and humans.

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
2
Justification:
From sub-chronic to chronic worker
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
3
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
2
Justification:
Reliable study used; study has been performed with analogue
AF for remaining uncertainties:
1
Justification:
No remaining differences
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:
140 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
48
Dose descriptor starting point:
NOAEL
Value:
6.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
6.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Correction dermal NOAEL: 6.7 x 10/10a = 6.7 mg/kg bw/day a % oral/dermal absorption

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
3
Justification:
Difference in sensitivity among workers
AF for the quality of the whole database:
2
Justification:
Reliable study used; study has been performed with analogue
AF for remaining uncertainties:
1
Justification:
No remaining differences
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:
DNEL (Derived No Effect Level)
Value:
0.29 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
20
Dose descriptor starting point:
NOAEC
Value:
6.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
5.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

For the general population (24h exposure/day), the corrected inhalatory NOAEC = oral NOAEC * 1/sRVrat * ABSoral-rat /ABSinhal-human

= 6.7 * 1/1.15 m3/kg * ABSoral-rat /ABSinhal-human

= 6.7 * 1/1.15 m3/kg * 1 = 5.8 mg/m3

With ABS: Absorption, sRV: Standard Respiratory Volume; ABSoral-rat /ABSinhal-human= 10/10= 1, assuming no differences in inhalation absorption between rats and humans.

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic study to chronic exposure public.
AF for interspecies differences (allometric scaling):
1
Justification:
No correction for caloric demand for inhalation; is included in dose descriptor starting point
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
5
Justification:
Difference in sensitivity within population
AF for the quality of the whole database:
2
Justification:
Reliable study used; study has been performed with analogue
AF for remaining uncertainties:
1
Justification:
No 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

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
84 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
80
Dose descriptor starting point:
NOAEL
Value:
6.7 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
6.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and dermal intake in the absence of evidence of the opposite. Correction dermal NOAEL: 6.7 x 10/10a = 6.7 mg/kg bw/daya % oral/dermal absorption

AF for dose response relationship:
1
Justification:
Value is NOAEL
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic study to chronic exposure public
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
No remaining differences
AF for intraspecies differences:
5
Justification:
Difference in sensitivity among general population
AF for the quality of the whole database:
2
Justification:
Reliable study used, study has been performed with analogue
AF for remaining uncertainties:
1
Justification:
No 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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
84 µg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC guidance (Technical Report No. 110, October 2010)
Overall assessment factor (AF):
80
Dose descriptor starting point:
NOAEL
Value:
6.7 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Not relevant, oral study was used.

AF for dose response relationship:
1
Justification:
value is NOAEL
AF for differences in duration of exposure:
2
Justification:
Extrapolation from sub-chronic study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Correction for caloric demand from rat to human
AF for other interspecies differences:
1
Justification:
no remaining differences
AF for intraspecies differences:
5
Justification:
Difference in sensitivity among general population
AF for the quality of the whole database:
2
Justification:
Reliable study used; study has been performed with analogue
AF for remaining uncertainties:
1
Justification:
No remaining uncertainties
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