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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:
1.76 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):
150
Dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
264.47 mg/m³
Explanation for the modification of the dose descriptor starting point:

A modification of the dose descriptor starting point (oral to inhalation) was conducted. It is assumed as a worst case assumption that the oral absorption rate is 50% of that of the inhalation absorption.

The corrected dose descriptor (NOAEC) for inhalation was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.

The conversion of an oral rat NOAEL into a corrected inhalatory NOAEC to assess human inhalatory exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for workers (in the case of 8 hour exposure/day).

Default parameters for rats and humans (for 8 hour exposure) were used for the modification of starting point under the allometric scaling principle as given in Table R. 8-2 of the above ECHA guidance.

Conversion of an oral rate N(L)OAEL into a correct inhalatory N(L)OAEC to assess human inhalatory exposure:

For workers (in case of 8h exposure/day):

Corrected inhalatory N(L)OAEC = oral N(L)OAEL x (1 / sRVrat) x (ABSoral-rat / ABSinh-human) x (sRVhuman / wRV)

Corrected inhalatory N(L)OAEC= 300 mg/kg bw/day x (1 / 0.38 m3/kg/d) x (0.5) x (6.7 m3(8h) / 10 m3(8h)) = 264.47 mg/m3

Where:

ABS: Absorption

sRV: standard Respiratory Volume

wRV: worker Respiratory Volume (light activity)

Default parametrs:

sRVrat (8 h): 0.38m3/kg bw

sRVhuman (8 h): 6.7 m3/ person

wRV (8 h): 10 m3/ person

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL the default assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
Default for subacute to chronic studies (OECD 422 study assessed as subacute study as most conservative value)
AF for interspecies differences (allometric scaling):
1
Justification:
AF for allometric scaling not required as the differences in allometry (respiration rate and rate to human body sizes) were considered in the conversion from oral to inhalation starting point.
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
Default AF for worker population
AF for the quality of the whole database:
1
Justification:
Quality of data considered to be reliable.
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been applied as the OECD 422 study (providing the repeat dose toxicity data) has been read-across from a structurally similar analogue substance. An additional AF has been considered applicable based on any minor potential differences between the substances.
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:
0.63 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):
600
Dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
375 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A skin absorption model (Shen et al., 2014) was used to predict a skin absorption of ≤ 40 % for the substance.

Absorption via the inhalation route is assumed to be 100% as a worst case assumption, whereas absorption via the oral route is assumed to be 50%. Therefore, an additional factor of 1.25 (50/40) is used for correction, assuming 50% absorption via the oral route of the original study.

 

Modified dose descriptor starting point = 300 x (50/40) = 375 mg/kg bw/day

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL the default assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
Default for subacute to chronic studies (OECD 422 study assessed as subacute study as most conservative value).
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for allometric scaling based on rats
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences.
AF for intraspecies differences:
5
Justification:
Default AF for worker population
AF for the quality of the whole database:
1
Justification:
Quality of data considered to be reliable
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been applied as the OECD 422 study (providing the repeat dose toxicity data) has been read-across from a structurally similar analogue substance. An additional AF has been considered applicable based on any minor potential differences between the substances.
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:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.43 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):
300
Dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
130.43 mg/m³
Explanation for the modification of the dose descriptor starting point:

A modification of the dose descriptor starting point (oral to inhalation) was conducted. It is assumed as a worst case assumption that the oral absorption rate is 50% of that of the inhalation absorption.

The corrected dose descriptor (NOAEC) for inhalation was calculated in accordance with the ECHA Guidance on information requirements and chemical safety assessment, Chapter R.8: Characterisation of dose [concentration]-response for human health.

The conversion of an oral rat NOAEL into a corrected inhalatory NOAEC to assess human inhalatory exposure was performed using the modification of starting point equation as given in Figure R. 8-3 (see below) for general population (in the case of 24 hour exposure/day).

Default parameters for rats and humans (for 24 hour exposure) were used for the modification of starting point under the allometric scaling principle as given in Table R. 8-2 of the above ECHA guidance.

Conversion of an oral rate N(L)OAEL into a correct inhalatory N(L)OAEC to assess human inhalatory exposure:

For general population (in case of 24h exposure/day):

Corrected inhalatory N(L)OAEC = oral N(L)OAEL x (1 / sRVrat) x (ABSoral-rat / ABSinh-human)

Corrected inhalatory N(L)OAEC= 300 mg/kg bw/day x (1 / 1.15 m3/kg/d) x (0.5) = 130.43 mg/m3

Where:

ABS: Absorption

sRV: standard Respiratory Volume

wRV: worker Respiratory Volume (light activity)

Default parametrs:

sRVrat (24 h): 1.15m3/kg bw

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL the default assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
Default for subacute to chronic studies (OECD 422 study assessed as subacute study as most conservative value)
AF for interspecies differences (allometric scaling):
1
Justification:
AF for allometric scaling not required as the differences in allometry (respiration rate and rate to human body sizes) were considered in the conversion from oral to inhalation starting point.
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences.
AF for intraspecies differences:
10
Justification:
Default AF for general population
AF for the quality of the whole database:
1
Justification:
Quality of data considered to be reliable.
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been applied as the OECD 422 study (providing the repeat dose toxicity data) has been read-across from a structurally similar analogue substance. An additional AF has been considered applicable based on any minor potential differences between the substances.
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:
0.31 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):
1 200
Dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
375 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A skin absorption model (Shen et al., 2014) was used to predict a skin absorption of ≤ 40 % for the substance.

Absorption via the inhalation route is assumed to be 100% as a worst case assumption, whereas absorption via the oral route is assumed to be 50%. Therefore, an additional factor of 1.25 (50/40) is used for correction, assuming 50% absorption via the oral route of the original study.

 

Modified dose descriptor starting point = 300 x (50/40) = 375 mg/kg bw/day

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL the default assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
Default for subacute to chronic studies (OECD 422 study assessed as subacute study as most conservative value)
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for allometric scaling based on rats
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default AF for general population.
AF for the quality of the whole database:
1
Justification:
Quality of data considered to be reliable
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been applied as the OECD 422 study (providing the repeat dose toxicity data) has been read-across from a structurally similar analogue substance. An additional AF has been considered applicable based on any minor potential differences between the substances.
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:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
1 200
Dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Route of exposure is the same as route of original study.

AF for dose response relationship:
1
Justification:
When the starting point for the DNEL calculation is a NOAEL the default assessment factor is 1.
AF for differences in duration of exposure:
6
Justification:
Default for subacute to chronic studies (OECD 422 study assessed as subacute study as most conservative value)
AF for interspecies differences (allometric scaling):
4
Justification:
Default AF for allometric scaling based on rats
AF for other interspecies differences:
2.5
Justification:
Default AF for remaining interspecies differences
AF for intraspecies differences:
10
Justification:
Default AF for general population.
AF for the quality of the whole database:
1
Justification:
Quality of data considered to be reliable
AF for remaining uncertainties:
2
Justification:
An additional AF of 2 has been applied as the OECD 422 study (providing the repeat dose toxicity data) has been read-across from a structurally similar analogue substance. An additional AF has been considered applicable based on any minor potential differences between the substances.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population