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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
7.6 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
190 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEC for long-term inhalation is based on the dietary NOAEL of 30 mg/kg bw/day for dogs in a 90-day study with the analogue N-(n-octyl)-2-pyrrolidinone. Correction for molecular weight is 1.28. Extrapolation formula: corrected oral NOAEL for dog in mg/kg bw/d : 38.5/AS (1.4) * 70 (kg bw)/ 10 (m³/person/day)= 193 mg/m³
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
AF for sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
5
Justification:
Default
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
14 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
12.5
Modified dose descriptor starting point:
other: NOAEL
Value:
176 mg/m³
Explanation for the modification of the dose descriptor starting point:
Extrapolation formula: NOAEL inhalation human= NOAEL oral: 100 mg/kg / 0.38 m³/kg bw x 0.67
AF for dose response relationship:
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1

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)
Most sensitive endpoint:
skin irritation/corrosion
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.1 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
35
Modified dose descriptor starting point:
NOAEL
Value:
38.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
NOAEL is based on the dietary NOAEL of 30 mg/kg bw/day for dogs in a 90-day study with the analogue N-(n-octyl)-2-pyrrolidinone. Absorption through skin is considered as being equal to absorption after oral uptake. Correction for molecular weight is 1.28.
AF for dose response relationship:
1
Justification:
At the LOAEL of 90 mg/kg bw/day only minor effects were observed in the dog study.
AF for differences in duration of exposure:
2
Justification:
AF for sub-chronic to chronic.
AF for interspecies differences (allometric scaling):
1.4
Justification:
dog-human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
4 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Extrapolation formula: NOAEL dermal acute = NOAEL oral: 100 mg/kg x 0.5 (sub-acute to acute), suggesting absorption by skin is equal to absorption after oral uptake.
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
5
AF for the quality of the whole database:
1

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:
high hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.9 mg/m³
Most sensitive endpoint:
repeated dose toxicity
DNEL related information
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
96.5 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEC for long-term inhalation is based on the dietary NOAEL of 30 mg/kg bw/day for dogs in a 90-day study with the analogue N-(n-octyl)-2-pyrrolidinone. Correction for molecular weight is 1.28. Extrapolation formula: corrected oral NOAEL for dog in mg/kg bw/d : 38.5/AS (1.4) * 70 (kg bw)/ 20 (m³/person/day)= 96.5 mg/m³
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
sub-chronic to chronic
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.5 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
88 mg/m³
Explanation for the modification of the dose descriptor starting point:
Extrapolation formula: NOAEC inhalation human= NOAEL oral: 100 mg/kg / 0.38 m³/kg bw x 0.335
AF for dose response relationship:
1
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1

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:
DNEL (Derived No Effect Level)
Value:
0.55 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
70
Modified dose descriptor starting point:
NOAEL
Value:
38.5 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
The dermal NOAEL is based on the dietary NOAEL of 30 mg/kg bw/day for dogs in a 90-day study with the analogue N-(n-octyl)-2-pyrrolidinone. Absorption through skin is considered as being equal to absorption after oral uptake. Correction for molecular weight is 1.28.
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1.4
Justification:
dog to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Extrapolation formula: NOAEL dermal acute = NOAEL oral: 100 mg/kg x 0.5 (sub-acute to acute), suggesting absorption by skin is equal to absorption after oral uptake.
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1

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:
DNEL (Derived No Effect Level)
Value:
0.55 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
70
Modified dose descriptor starting point:
NOAEL
Value:
38.5 mg/kg bw/day
AF for dose response relationship:
1
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1.4
Justification:
dog to human
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2 mg/kg bw/day
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
Oral
DNEL related information
Overall assessment factor (AF):
100
Modified dose descriptor starting point:
NOAEL
Value:
200 mg/kg bw/day
AF for dose response relationship:
1
AF for interspecies differences (allometric scaling):
4
AF for other interspecies differences:
2.5
AF for intraspecies differences:
10
AF for the quality of the whole database:
1

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - General Population

Based on available date, the most relevant reproducible effect, liver related changes in dogs, was identified as the basis for establishing the long-term DNELs. The NOEL for repeated exposure of rats in the 28 -day study was used for estimation of the acute DNELs. These data are more conservative than those identified in association with local and/or acute effects. The route-to-route extrapolation of DNELs is performed according to the ECHA Guidance Document R.8, Characterization of Dose [Concentration]-Response for Human Health dated November 2012.