Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
8.82 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):
50
Modified dose descriptor starting point:
NOAEC
Value:
440.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL for the systemic toxicity was 1000 mg/kg bw per day in the key study (OECD 422). Step 1) Relevant dose-descriptor: NOAEL, rat, systemic toxicity = 1000 mg/kg bw per day Step 2) Modification of starting point - Conversion into inhalation NOAEC (in mg/m³) by using an 8-hour respiratory volume for the rat: 0.38 m³/kg bw - Correction for activity driven differences of respiratory volumes in workers compared to workers in rest: 6.7 m³/10 m³ - Correction for inhalation to oral absorption: no factor is added. Justification: the test substance is expected to have a low volatility - No difference in oral and inhalation absorption is expected between rats and human. NOAEC corrected = 1000*1/0.38*6.7/10 = 1763.2 mg/m³

As the key study was performed with the registered substance at about 25%, the NOAEL value was corrected.

=> NOAEC corrected for registered substance = 440.8 mg/m3

AF for dose response relationship:
1
Justification:
NOAEL available
AF for differences in duration of exposure:
4
Justification:
subchronic (about 54 days) to chronic = 4
AF for interspecies differences (allometric scaling):
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
1
Justification:
Klimich 1, GLP study
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.25 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):
200
Modified dose descriptor starting point:
NOAEL
Value:
250 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The NOAEL for the systemic toxicity was 1000 mg/kg bw per day in the key study (OECD 422). Step 1) Relevant dose-descriptor: NOAEL, rat = 1000 mg/kg bw per day Step 2) Modification of starting point Correcting for dermal to oral absorption: factor of 1 is used. As no dermal penetration study is available, 100% absorption will be considered as a worst case. No difference in oral and dermal absorption is expected between rats and human. Corrected dermal NOAEL: 1000 mg/kg-day x 100%/100% = 1000 mg/kg-day.

As the key study was performed with the registered substance diluted at about 25%, the NOAEL value was corrected

=> NOAEL corrected for dermal route for the registered substance = 250 mg/kg bw/d

AF for dose response relationship:
1
Justification:
NOAEL available
AF for differences in duration of exposure:
4
Justification:
subchronic (about 54 days) to chronic = 4
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
Justification:
workers
AF for the quality of the whole database:
1
Justification:
GLP study, K1
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population