Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.94 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
18
Dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
52.89 mg/m³
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite.

Starting point: NOAEL of 30 mg/kg bw/day in a One Generation Reproduction Toxicity Study in rat.

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

           = 30 mg/kg bw/day * 1/0.38 m3/kg/8h * 100 /100 * 6.7 m3(8h)/10 m3(8h)

           = 30 mg/kg bw/day * 1/0.38 m3/kg/8h * 1 * 6.7 m3 (8h)/10 m3(8h)

= 30 /0.38 * 1* (6.7/10) = 52.89 mg/m3.

 

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

ABSoral-rat /ABSinhal-human= 100/100= 1, assuming no differences in inhalation absorption between rats and humans.

AF for dose response relationship:
1
Justification:
Value is a NOAEL
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
AF for intraspecies differences:
3
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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:
0.42 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
72
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:

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: 30 mg/kg bw/day x 100/100a= 30 mg/kg bw/day (a% oral/dermal absorption)

AF for dose response relationship:
1
Justification:
Value is a NOAEL
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
3
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

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:
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:
1.76 mg/m³
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
30
Dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
52.89 mg/m³
Explanation for the modification of the dose descriptor starting point:

Kinetics (metabolism, distribution and excretion) are considered to be similar for oral and inhalation intake in the absence of evidence of the opposite.

Starting point: NOAEL of 30 mg/kg bw/day in a One Generation Reproduction Toxicity Study in rat.

Conversion of an oral NOAEL into a corrected NOAEC:

The corrected inhalatory NOAEC (8 hours exposure/day) = oral NOAEL * 1/sRVrat * ABSoral-rat /ABSinhal-human * sRVhuman/wRV

= 30 mg/kg bw/day * 1/0.38 m3/kg/8h * 100 /100 * 6.7 m3 (8h)/10 m3 (8h)

= 30 mg/kg bw/day * 1/0.38 m3/kg/8h * 1 * 6.7 m3 (8h)/10 m3 (8h)

= 30 /0.38 * 1* (6.7/10) = 52.89 mg/m3.

 

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

ABSoral-rat /ABSinhal-human= 100/100= 1, assuming no differences in inhalation absorption between rats and humans.

Justification:
Value is a NOAEL
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
1
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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:
0.25 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
120
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:

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: 30 mg/kg bw/day x 100/100a= 30 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:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

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:
0.25 mg/kg bw/day
Most sensitive endpoint:
effect on fertility
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
120
Dose descriptor starting point:
NOAEL
Value:
30 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Value is a NOAE
AF for differences in duration of exposure:
6
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5 mg/kg bw/day
Most sensitive endpoint:
acute toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other:
Overall assessment factor (AF):
60
Dose descriptor starting point:
LOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

GST has harmonized classification for acute oral toxicity, cat. 4. The lower limit for this classification (300 mg/ kg bw) is considered a LOAEL.

AF for dose response relationship:
3
Justification:
Value is a LOAEL
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
1
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
AF for remaining uncertainties:
1

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population