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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:
19.59 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
9
Modified dose descriptor starting point:
NOAEC
Explanation for the modification of the dose descriptor starting point:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
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:
5.56 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
36
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
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 combined repeated dose/ reproduction toxicity screening oral study in rats (RTC/ Rohm and Haas 2004) using route-to-route extrapolation. The exposure period was at least 43 days. The respective NOAEL for systemic effects was 100 mg/kg bw/d based on decreased body weight, food consumption, increased liver weights and microscopic liver changes.

 

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 176.3 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

3

Exposure duration

3*

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

9

NAEC

176.3 mg/m3/d

DNEL

19.59 mg/m3/d

 * The exposure period of the relevant study was at least 43 days (between the tresholds for subacute and subchronic studies, i.e. 28 and 90 days, respectively). ECHA and ECETOC recommended AFs of 2 and 6 for the extrapolation from subacute and subchronic to chronic study durations, respectively. Escher et al. (2009) calculated AFs of 2.0 and 3.4 for the respective extrapolations for inhalation studies and AFs of 1.3 and 3.0 for oral studies. Here, an AF of 3 was assessed as appropiate AF for the adaption of the exposure duration to chronic exposure.

---

Thus, the DNEL for long-term exposure was calculated to be NAEC/AF = 19.59 mg/m3.

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 vapor inhalation was derived from the NOAEL value from a combined repeated dose/ reproduction toxicity screening oral study in rats (RTC/ Rohm and Haas 2004) using route-to-route extrapolation. The exposure period was at least 43 days. The respective NOAEL for systemic effects was 100 mg/kg bw/d based on decreased body weight, food consumption, increased liver weights and microscopic liver changes.

 

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 200 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

3 (see explanation above)

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

36

NAEL

200 mg/kg bw/d

DNEL

5.56 mg/kg bw/d

 

Thus, the DNELs for long-term exposure were calculated to be NAEL/AF = 5.56 mg/kg bw/d.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.8 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
15
Modified dose descriptor starting point:
NOAEC
Explanation for the modification of the dose descriptor starting point:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
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:
3.33 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
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:
1.67 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
60
Modified dose descriptor starting point:
NOAEL
Explanation for the modification of the dose descriptor starting point:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
Justification:
see discussion below
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 combined repeated dose/ reproduction toxicity screening oral study in rats (RTC/ Rohm and Haas 2004) using route-to-route extrapolation. The exposure period was at least 43 days. The respective NOAEL for systemic effects was 100 mg/kg bw/d based on decreased body weight, food consumption, increased liver weights and microscopic liver changes.

 

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

5

Exposure duration

3 (see workers DNEL discussion for explanation)

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

60

NAEL

100 mg/kg bw/d

DNEL

1.67 mg/kg bw/d

Thus, the DNELs for long-term exposure were calculated to be NAEL/AF = 1.67 mg/kg bw/d.

 

Inhalation route:

The DNEL for long-term exposure following vapor inhalation was derived from the NOAEL value from a combined repeated dose/ reproduction toxicity screening oral study in rats (RTC/ Rohm and Haas 2004) using route-to-route extrapolation. The exposure period was at least 43 days. The respective NOAEL for systemic effects was 100 mg/kg bw/d based on decreased body weight, food consumption, increased liver weights and microscopic liver changes.

  

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:

 

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 87 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

5

Exposure duration

3

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

15

NAEC

87 mg/m3

DNEL

5.80 mg/m3

 

Thus, the DNELs for long-term exposure were calculated to be NAEC/AF = 5.80 mg/m3.

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 combined repeated dose/ reproduction toxicity screening oral study in rats (RTC/ Rohm and Haas 2004) using route-to-route extrapolation. The exposure period was at least 43 days. The respective NOAEL for systemic effects was 100 mg/kg bw/d based on decreased body weight, food consumption, increased liver weights and microscopic liver changes.

 

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 200 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

5

Exposure duration

3 (see workers DNEL discussion for explanation)

Dose-response

1

Quality of whole database

1

Overall assessment factor (AF)

60

NAEL

200 mg/kg bw/d

DNEL

3.33 mg/kg bw/d

 

Thus, the DNELs for long-term exposure were calculated to be NAEL/AF = 3.33 mg/kg bw/d.