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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:
88 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see discussion
Overall assessment factor (AF):
6
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
529 mg/m³
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:
25 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see discussion
Overall assessment factor (AF):
24
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
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 inhalative exposure was derived from the NOAEL value (300mg/kg bw/d) from a 90 d repeated dose oral study in rats (BASF SE 2017) using route-to-route extrapolation. No adverse effects were observed up to the limit dose of 1000 mg/kg bw/d for females whereas for males a NOAEL of 300mg/kg bw/d was derived based on slight effects. However, as a NOAEL value of 300 mg/kg bw/d in males is reflecting the highest value in repeated dose studies this value was used as a worst case assumption for risk assessment.

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 529 mg/m3/d.

Then the overall assessment factors were calculated based on recommendations given in ECETOC TR 86 (ECETOC, Feb 2003):

 

Assessment Factor for

Systemic effects

Intraspecies (worker)

3

Exposure duration (subchronic to chronic)

2

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

6

NAEC

529 mg/m3/d

DNEL

88 mg/m3/d

---

Thus, the DNEL for long-term exposure was calculated to be NAEC/AF = 88 mg/m3.

The substance has an extremely low vapour pressure (0.000000284 Pa at 20°C). Therefore inhalation exposure to the vapor is not expected as the vapor saturation concentration is below 0.01 µg/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 (300mg/kg bw/d) from a 90 d repeated dose oral study in rats (BASF SE 2017) using route-to-route extrapolation. No adverse effects were observed up to the limit dose of 1000 mg/kg bw/d for females whereas for males a NOAEL of 300mg/kg bw/d was derived based on slight effects. However, as a NOAEL value of 300 mg/kg bw/d in males is reflecting the highest value in repeated dose studies this value was used as a worst case assumption for risk assessment.

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 600 mg/kg bw/d.

Then the overall assessment factors were calculated based on recommendations given in ECETOC TR 86 (ECETOC, Feb 2003):

 

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

600 mg/kg bw/d

DNEL

25 mg/kg bw/d

 

Thus, the DNELs for long-term exposure were calculated to be NAEL/AF = 25 mg/kg bw/d.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
26 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see discussion
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
261 mg/m³
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:
15 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see discussion
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
600 mg/kg bw/day
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:
7.5 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
other: see discussion
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
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 (300mg/kg bw/d) from a 90 d repeated dose oral study in rats (BASF SE 2017) using route-to-route extrapolation. No adverse effects were observed up to the limit dose of 1000 mg/kg bw/d for females whereas for males a NOAEL of 300 mg/kg bw/d was derived based on slight effects. However, as a NOAEL value of 300 mg/kg bw/d in males is reflecting the highest value in repeated dose studies this value was used as a worst case assumption for risk assessment. 

Then the overall assessment factor was calculated based on the recommendations given in ECETOC TR 86 (ECETOC, Feb 2003):

Assessment Factor for

Systemic effects

Interspecies: allometric factor

4

Intraspecies (gen. population)

5

Exposure duration (subchronic to chronic)

2

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

40

NAEL

300 mg/kg bw/d

DNEL

7.5 mg/kg bw/d

Thus, the DNELs for long-term exposure were calculated to be NAEL/AF = 7.5 mg/kg bw/d.

 

Inhalation route:

The DNEL for long-term inhalative exposure was derived from the NOAEL value (300mg/kg bw/d) from a 90 d repeated dose oral study in rats (BASF SE 2017) using route-to-route extrapolation. No adverse effects were observed up to the limit dose of 1000 mg/kg bw/d for females whereas for males a NOAEL of 300 mg/kg bw/d was derived based on slight effects. However, as a NOAEL value of 300 mg/kg bw/d in males is reflecting the highest value in repeated dose studies this value was used as a worst case assumption for risk assessment.  

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. 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 261 mg/m3/d.

Then the overall assessment factor was calculated based on the recommendations given in ECETOC TR 86 (ECETOC, Feb 2003): 

Assessment Factor for

Systemic effects

Intraspecies (gen. population)

5

Exposure duration (subchronic to chronic)

2

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

10

NAEC

261 mg/m3

DNEL

26 mg/m3

 

Thus, the DNELs for long-term exposure were calculated to be NAEC/AF = 26 mg/m3.

The substance has an extremely low vapour pressure (0.000000284 Pa at 20°C). Therefore inhalation exposure to the vapor is not expected as the vapor saturation concentration is below 0.01 µg/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 (300mg/kg bw/d) from a 90 d repeated dose oral study in rats (BASF SE 2017) using route-to-route extrapolation. No adverse effects were observed up to the limit dose of 1000 mg/kg bw/d for females whereas for males a NOAEL of 300 mg/kg bw/d was derived based on slight effects. However, as a NOAEL value of 300 mg/kg bw/d in males is reflecting the highest value in repeated dose studies this value was used as a worst case assumption for risk assessment.   

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 general public for systemic effects was equal to 600 mg/kg bw/d.

 

Then the overall assessment factors were calculated based on recommendations given in ECETOC TR 86 (ECETOC, Feb 2003): 

Assessment Factor for

Systemic effects

Interspecies

4

Intraspecies (gen. population)

5

Exposure duration (subchronic to chronic)

2

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

40

NAEL

600 mg/kg bw/d

DNEL

15 mg/kg bw/d

 

Thus, the DNELs for long-term exposure were calculated to be NAEL/AF = 15 mg/kg bw/d.