Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
11 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):
25
Modified dose descriptor starting point:
NOAEC
Value:
264 mg/m³
Explanation for the modification of the dose descriptor starting point:

Corrected inhalation NOAEC from oral NOAEL of 150 mg/kg/day. Assume ABSoral-rat/ABSinh-human is equal (1)   =150 mg/kg bw/day x (1/0.38m3/kg bw/day) x (1.0) x (6.7m3/10m3) = 264 mg/m3 inhalation dose descriptor.

AF for dose response relationship:
1
Justification:
Based on REACH guidance
AF for differences in duration of exposure:
2
Justification:
Based on REACH guidance
AF for interspecies differences (allometric scaling):
1
Justification:
Based on REACH guidance
AF for other interspecies differences:
2.5
Justification:
Based on REACH guidance
AF for intraspecies differences:
5
Justification:
Based on REACH guidance
AF for the quality of the whole database:
1
Justification:
Based on REACH guidance
AF for remaining uncertainties:
1
Justification:
Based on REACH guidance
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:
15 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):
100
Modified dose descriptor starting point:
NOAEL
Value:
1 500 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

A systemic NOAEL of 150 mg/kg/day is based on the 90-day oral rat gavage study (OECD 408).   Oral absorption rat — oral/dermal absorption human: Assume 10% dermal absorption.  Therefore, 150 mg/kg bw/day/0.1 = 1500 mg/kg bw/day dermal dose descriptor.  

AF for dose response relationship:
1
Justification:
REACH guidance
AF for differences in duration of exposure:
2
Justification:
REACH guidance
AF for interspecies differences (allometric scaling):
4
Justification:
REACH guidance
AF for other interspecies differences:
2.5
Justification:
REACH guidance
AF for intraspecies differences:
5
Justification:
REACH guidance
AF for the quality of the whole database:
1
Justification:
REACH guidance
AF for remaining uncertainties:
1
Justification:
REACH guidance
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
acute toxicity
Route of original study:
Dermal
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Systemic Dermal DNEL Worker

A systemic NOAEL of 150 mg/kg/day is based on the 90-day oral rat gavage study (OECD 408).

 

Oral absorption rat — oral/dermal absorption human: Assume 10% dermal absorption based on molecular weight of 290.4, a log Pow of 7.34, water solubility of 131 μg/l and calculated vapor pressure of 0.00951 mm Hg (1.268 Pa) at 25 °C. Dermal absorption is unlikely due to the low water solubility and high partition coefficient.

 

= 150 mg/kg bw/day/0.1

= 1500 mg/kg bw/day dermal dose descriptor

Correction for interspecies differences (apply factor for allometric scaling 4 for rat x 2.5 for additional factors):10

= 1500 mg/kg bw/day/10

= 150 mg/kg bw/day

Correction for intraspecies differences: 5

= 150 mg/kg bw/day/5

= 30 mg/kg bw/day

Correction for duration between 90-day sub-chronic to chronic: 2

= 30 mg/kg bw/day/2

= 15 mg/kg bw/day

Correction for dose-response: 1

= 15 mg/kg bw/day/1

= 15 mg/kg bw/day

Correction of whole database: 1 due to quality of study

= 15 mg/kg bw/day/1

= 15 mg/kg bw/day (DNEL dermal-worker-systemic)

based on an overall AF of 100

 

 

Systemic Inhalation DNEL Workers

A systemic NOAEL of 150 mg/kg/day is based on the 90-day oral rat gavage study (OECD 408).

 

Corrected inhalation NOAEC from oral NOAEL

oral NOAEL x (1/sRVrat)x(ABSoral-rat/ABSinh-human)x(sRVhuman/wRV)

 

Assume ABSoral-rat/ABSinh-human is equal (1)

 

=150 mg/kg bw/day x (1/0.38m3/kg bw/day) x (1.0) x (6.7m3/10m3)

= 264 mg/m3inhalation dose descriptor

 

[: Absorption; sRV: standard Respiratory Volume; wRV: worker Respiratory Volume]

 

Correction for interspecies differences: 2.5

= 264 mg/m3/ 2.5

= 106 mg/m3

Correction for intraspecies differences: 5

= 106 mg/m3/ 5

= 21 mg/m3

Correction for duration between sub-chronic to chronic: 2

= 21 rng/m3/2

= 11 mg/m3

Correction for dose-response: 1

= 11 mg/m3/1

=11 mg/m3

Correction of whole database: 1 due to quality of study

= 11 mg/m3/1

= 11 mg/m3(DNELinhalation-worker-systemic)

based on an overall AF of 25.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected

Additional information - General Population