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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:
23.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC TR 110 (ECETOC, Oct 2010) and ECHA guideline
Overall assessment factor (AF):
6
Dose descriptor starting point:
NOAEL
Value:
80 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
141 mg/m³
Explanation for the modification of the dose descriptor starting point:
see discussion below
AF for dose response relationship:
1
Justification:
see discussion below
AF for differences in duration of exposure:
2
Justification:
see discussion below
AF for interspecies differences (allometric scaling):
1
Justification:
see discussion below
AF for other interspecies differences:
1
Justification:
see discussion below
AF for intraspecies differences:
3
Justification:
see discussion below
AF for the quality of the whole database:
1
Justification:
see discussion below
AF for remaining uncertainties:
1
Justification:
see discussion below
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:
6.7 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC TR 110 (ECETOC, Oct 2010) and ECHA guideline
Overall assessment factor (AF):
24
Dose descriptor starting point:
NOAEL
Value:
80 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
160 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
see discussion below
AF for dose response relationship:
1
Justification:
see discussion below
AF for differences in duration of exposure:
2
Justification:
see discussion below
AF for interspecies differences (allometric scaling):
4
Justification:
see discussion below
AF for other interspecies differences:
1
Justification:
see discussion below
AF for intraspecies differences:
3
Justification:
see discussion below
AF for the quality of the whole database:
1
Justification:
see discussion below
AF for remaining uncertainties:
1
Justification:
see discussion below
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

DNEL derivation for Worker:

 

Inhalation route:

The DNEL for long-term exposure following vapor inhalation was derived from the NOAEL value from a oral rat OECD 408 study (90d repeated oral dose gavage; ERBC 2020) using route-to-route extrapolation. The exposure period was at least 90 days with additional recovery groups. The respective NOAEL for systemic effects was 80 mg/kg bw/d based on effects in liver (adaptive) and kidney as well as severe clinical signs and deaths at higher dosages

This value which was taken as relevant dose descriptor for long-term toxicity was modified in order to get the correct starting point for DNEL derivation:

According to RIP R.8 (ECHA, May 2008, Example R.8 -1, p. 65), the oral rat NOAEL was converted into the NAEC corrected for human inhalation-exposure conditions [1/standard Respiratory Volume (rat) for 8 h exposure, respiratory volume adapted for a worker with light activity] by multiplying with the corresponding factors (x 1/0.38 x 0.67). A default correction factor of 1 was used for Absorption (oral-rat)/Absorption (inhalation-human). The resulting corrected NAEC-worker (8h) for systemic effects was equal to 141 mg/m3/d.

 

Then the overall assessment factors were calculated based on recommendations given in ECETOC TR 110 (ECETOC, Oct 2010) and based on ECHA guideline:

 

Assessment Factor for

Systemic effects

Intraspecies

3

Exposure duration

2

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

6

NAEC

141 mg/m3/d

DNEL

23.5 mg/m3/d

Thus, the DNEL for long-term exposure was calculated to be NAEC/AF = 23.5 mg/m3.

 

Further the substance has an extremely low vapor pressure (< 0.000000978 hPa at 25°C). Therefore inhalation exposure to the vapor is not expected as the vapor saturation concentration is below 0.0136 mg/m3. This concentration is well below the DNEL calculated by route-to-route extrapolation.

 

 

Dermal route:

The DNEL for long-term dermal exposure following dermal contact was derived from the NOAEL value from a oral rat OECD 408 study (90d repeated oral dose gavage; ERBC 2020) using route-to-route extrapolation. The exposure period was at least 90 days with additional recovery groups. The respective NOAEL for systemic effects was 80 mg/kg bw/d based on effects in liver (adaptive) and kidney as well as severe clinical signs and deaths at higher dosages.

 

This value which was taken as relevant dose descriptor for long-term toxicity was modified in order to get the correct starting point for DNEL derivation:

According to RIP R.8 (ECHA, May 2008, p. 69), the oral rat NOAEL was converted into the NAEL corrected for human dermal exposure conditions by applying the factor for Absorption (oral-rat)/Absorption (dermal-human). A default correction factor of 2 was used for Absorption (oral-rat)/Absorption (dermal-human) as a very low dermal absorption potential is assumed. The resulting corrected NAEL-worker for systemic effects was equal to 160 mg/kg bw/d.

 

Then the overall assessment factors were calculated based on recommendations given in ECETOC TR 110 (ECETOC, Oct 2010) and based on ECHA guideline:

 

Assessment Factor for

Systemic effects

Interspecies: allometric factor

4

Intraspecies

3

Exposure duration

2

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

24

NAEL

160 mg/kg bw/d

DNEL

6.7 mg/kg bw/d

 

Thus, the DNELs for long-term exposure were calculated to be NAEL/AF = 6.7 mg/kg bw/d.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC TR 110 (ECETOC, Oct 2010) and ECHA guideline
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEL
Value:
80 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
69.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
see discussion below
AF for dose response relationship:
1
Justification:
see discussion below
AF for differences in duration of exposure:
2
Justification:
see discussion below
AF for interspecies differences (allometric scaling):
1
Justification:
see discussion below
AF for other interspecies differences:
1
Justification:
see discussion below
AF for intraspecies differences:
5
Justification:
see discussion below
AF for the quality of the whole database:
1
Justification:
see discussion below
AF for remaining uncertainties:
1
Justification:
see discussion below
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:
4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC TR 110 (ECETOC, Oct 2010) and ECHA guideline
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
80 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
160 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
see discussion below
AF for dose response relationship:
1
Justification:
see discussion below
AF for differences in duration of exposure:
2
Justification:
see discussion below
AF for interspecies differences (allometric scaling):
4
Justification:
see discussion below
AF for other interspecies differences:
1
Justification:
see discussion below
AF for intraspecies differences:
5
Justification:
see discussion below
AF for the quality of the whole database:
1
Justification:
see discussion below
AF for remaining uncertainties:
1
Justification:
see discussion below
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:
2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: ECETOC TR 110 (ECETOC, Oct 2010) and ECHA guideline
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
80 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
80 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
see discussion below
AF for dose response relationship:
1
Justification:
see discussion below
AF for differences in duration of exposure:
2
Justification:
see discussion below
AF for interspecies differences (allometric scaling):
4
Justification:
see discussion below
AF for other interspecies differences:
1
Justification:
see discussion below
AF for intraspecies differences:
5
Justification:
see discussion below
AF for the quality of the whole database:
1
Justification:
see discussion below
AF for remaining uncertainties:
1
Justification:
see discussion below
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

DNEL derivation for General population:

 

Oral route:

The DNEL for long-term oral exposure was derived from the NOAEL value from a oral rat OECD 408 study (90d repeated oral dose gavage; ERBC 2020) using route-to-route extrapolation. The exposure period was at least 90 days with additional recovery groups. The respective NOAEL for systemic effects was 80 mg/kg bw/d based on effects in liver (adaptive) and kidney as well as severe clinical signs and deaths at higher dosages

As oral rat to oral human is extrapolated and know information on different oral absorption is available the correction factor used is 1 for the route-to-route conversion.  

Then the overall assessment factors were calculated based on recommendations given in ECETOC TR 110 (ECETOC, Oct 2010) and based on ECHA guideline:

 

Assessment Factor for

Systemic effects

Interspecies: allometric factor

4

Intraspecies

5

Exposure duration

2

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

40

NAEL

80 mg/kg bw/d

DNEL

2 mg/kg bw/d

 

Thus, the DNELs for long-term exposure were calculated to be NAEL/AF = 2 mg/kg bw/d.

 

Inhalation route:

The DNEL for long-term exposure following vapor inhalation was derived from the NOAEL value from a oral rat OECD 408 study (90d repeated oral dose gavage; ERBC 2020) using route-to-route extrapolation. The exposure period was at least 90 days with additional recovery groups. The respective NOAEL for systemic effects was 80 mg/kg bw/d based on effects in liver (adaptive) and kidney as well as severe clinical signs and deaths at higher dosages

This value which was taken as relevant dose descriptor for long-term toxicity and was modified in order to get the correct starting point for DNEL derivation:

According to RIP R.8 (ECHA, May 2008, Example R.8 -1, p. 64), the oral rat NOAEL was converted into the NAEC corrected for human inhalation-exposure conditions of consumers (dividing by a factor of 1.15 m3/kg bw). The resulting corrected NAEC-worker (24h) for systemic effects was equal to 69.6 mg/m3/d. 

Then the overall assessment factors were calculated based on recommendations given in ECETOC TR 110 (ECETOC, Oct 2010) and based on ECHA guideline:

 

Assessment Factor for

Systemic effects

Intraspecies

5

Exposure duration

2

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

10

NAEC

69.6 mg/m3

DNEL

7 mg/m3

 

Thus, the DNELs for long-term exposure were calculated to be NAEC/AF = 7 mg/m3.

Further the substance has an extremely low vapor pressure (< 0.000000978 hPa at 25°C). Therefore inhalation exposure to the vapor is not expected as the vapor saturation concentration is below 0.0136 mg/m3. This concentration is well below the DNEL calculated by route-to-route extrapolation.

 

Dermal route:

The DNEL for long-term dermal exposure was derived from the NOAEL value from a oral rat OECD 408 study (90d repeated oral dose gavage; ERBC 2020) using route-to-route extrapolation. The exposure period was at least 90 days with additional recovery groups. The respective NOAEL for systemic effects was 80 mg/kg bw/d based on effects in liver (adaptive) and kidney as well as severe clinical signs and deaths at higher dosages

This value which was taken as relevant dose descriptor for long-term toxicity was modified in order to get the correct starting point for DNEL derivation:

According to RIP R.8 (ECHA, May 2008, p. 69), the oral rat NOAEL was converted into the NAEL corrected for human dermal-exposure conditions by applying factor for Absorption (oral-rat) /Absorption (dermal-human). A default factor of 2 was used for Absorption (oral-rat)/Absorption (dermal-human) as a very low dermal absorption potential is assumed.

The resulting corrected NAEL worker for systemic effects was equal to 160 mg/kg bw/d.

Then the overall assessment factors were calculated based on recommendations given in ECETOC TR 110 (ECETOC, Oct 2010) and based on ECHA guideline:

 

Assessment Factor for

Systemic effects

Interspecies

4

Intraspecies

5

Exposure duration

2

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

40

NAEL

160 mg/kg bw/d

DNEL

4 mg/kg bw/d

 

Thus, the DNELs for long-term exposure were calculated to be NAEL/AF = 4 mg/kg bw/d.