Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.57 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):
216
Modified dose descriptor starting point:
LOAEC
Value:
263.16 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.26 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):
360
Modified dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Workers

Acute oral exposure

Chapter 8 of the reach TGD (Appendix R.8 -8) indicates that acute exposure DNEL values are not normally required.

 

Long-term inhalation, systemic

 

A 30-day repeat dose oral toxicity study gave a LOAEL of 100 mg/kg. Extrapolating from subchronic oral toxicity to chronic inhalation, the LOAEL first must be converted to mg/m3by dividing by a factor of 0.38, and then corrected for oral bioavailability (50%) by multiplying by a factor of 0.5. Further corrections are then necessary for 7-day experimental exposure to 5-day work week (1.4) and to adjusted for respiration for light work (0.67). ECETOC Assessment factors were applied, which consisted of LOAEL to NOAEL (3), subacute to chronic studies (6), for intraspecies (3), for interspecies (4), for a total of 216.

 

- Converting mg/kg to mg/m3= 100/0.38 = 263.16 mg/m3

- Correcting for oral bioavailability = 263.16*0.5 = 131.58 mg/m3

- Correcting for 7-day experimental exposure to 5-day work week, and light work= 131.58 mg/m3* (1.4) *(0.67) = 123.42 mg/m3

- Application of adjustment factors: 123.42 mg/m3/216 =0.57 mg/m3

 

Long-term dermal, systemic

 

A 30-day repeat dose oral toxicity study gave a LOAEL of 100 mg/kg. Extrapolating from subchronic oral toxicity to chronic dermal, the LOAEL first must be corrected for 7-day experimental exposure to 5-day work week (1.4) and to adjusted for respiration for light work (0.67). ECETOC Assessment factors were applied, which consisted of LOAEL to NOAEL (3), subacute to chronic studies (6), for intraspecies (5), for interspecies (4), for a total of 360.

 

- Correcting for 7-day experimental exposure to 5-day work week, and light work = 100 mg/kg*(1.4)*(0.67) = 93.8 mg/kg

- Application of adjustment factors: 93.8 mg/kg/360 =0.26 mg/kg

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 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):
360
Modified dose descriptor starting point:
LOAEC
Value:
86.96 mg/m³
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.28 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):
360
Modified dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.28 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):
360
Modified dose descriptor starting point:
LOAEL
Value:
100 mg/kg bw/day
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

General Population

Acute oral exposure

Chapter 8 of the reach TGD (Appendix R.8 -8) indicates that acute exposure DNEL values are not normally required.

Long-term inhalation, systemic

 

A 30-day repeat dose oral toxicity study gave a LOAEL of 100 mg/kg. Extrapolating from subchronic oral toxicity to chronic inhalation, the LOAEL first must be converted to mg/m3by dividing by a factor of 1.15, and then corrected for oral bioavailability (50%) by multiplying by a factor of 0.5. ECETOC Assessment factors were applied, which consisted of LOAEL to NOAEL (3), subacute to chronic studies (6), for intraspecies (5), for interspecies (4), for a total of 360.

   

 - Converting mg/kg to mg/m3= 100/1.15 = 86.96 mg/m3

- Correcting for oral bioavailability = 86.96*0.5 = 43.48 mg/m3

- Application of adjustment factors – 43.48 mg/m3/ 360 =0.12 mg/m3

 

Long-term dermal, systemic

 

A 30-day repeat dose oral toxicity study gave a LOAEL of 100 mg/kg.  ECETOC Assessment factors were applied, which consisted of LOAEL to NOAEL (3), subacute to chronic studies (6), for intraspecies (5), for interspecies (4), for a total of 360.

 

- Application of adjustment factors: 100 mg/kg/360 =0.28 mg/kg

 

Long-term oral, systemic

 

A 30-day repeat dose oral toxicity study gave a NOAEL of 100 mg/kg. ECETOC Assessment factors were applied, which consisted of LOAEL to NOAEL (3), subacute to chronic studies (6), for intraspecies (5), for interspecies (4), for a total of 360.

 

- Application of adjustment factors: 100 mg/kg/360 =0.28 mg/kg