Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Dose descriptor starting point:
NOAEC
Value:
500 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
251 mg/m³
Explanation for the modification of the dose descriptor starting point:

Data available from an inhalation 90-days repeated dose toxicity study in rats shows a NOAEC of 500 mg/m3. This NOAEC being the lowest from the repeated dose studies available (90-days inhalation toxicity study and prenatal developmental study) is used as a dose descriptor starting point. No route-to-route extrapolation was necessary.

Conversion of an inhalatory rat N(L)OAEC into a corrected inhalatory N(L)OAEC in case of differences between experimental and human exposure conditions

The dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (5 m3/kg for 6hours exposure of workers). For workers the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor derives from the inhalative volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity). No correction for bioavailability via the inhalation route is made as 100% absorption is assumed.

AF for dose response relationship:
1
Justification:
Default assessment factor from ECHA Guidance document R8
AF for differences in duration of exposure:
2
Justification:
Default assessment factor used for subchronic to chronic; ECHA Guidance R8; Table R.8-6
AF for interspecies differences (allometric scaling):
1
Justification:
Assessment factor not used for inhalation route; no allometric scaling required; cf. ECHA Guidance R8
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for workers ECHA Guidance R8; Table R.8-6
AF for intraspecies differences:
5
Justification:
Default assessment factor ECHA Guidance R8; Table R.8-6
AF for the quality of the whole database:
1
Justification:
Default assessment factor as no systemic effects at the top dose in a subchronic GLP guideline study
AF for remaining uncertainties:
1
Justification:
Default assessment factor, no further uncertainties identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
6.1 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: MAK value: is the maximum permissible concentration of isobutylamine in the air at the workplace which does not affect worker health with repeated and long-term exposure, 8 hours a day, but assuming an average weekly working time of 40 hours.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
15 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: Maximum permissible short-term concentration of isobutylamine in the air at the workplace which, according to current knowledge, does not normally affect worker health or cause unreasonable nuisance even with short-term exposure. Derived from MAK value.

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.43 mg/kg bw/day
Most sensitive endpoint:
skin irritation/corrosion
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
100
Dose descriptor starting point:
NOAEC
Value:
500 mg/m³
Modified dose descriptor starting point:
NOAEL
Value:
143 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

Data available from an inhalation 90-days repeated dose toxicity study in rats shows a NOAEC of 500 mg/m3. This NOAEC being the lowest from the repeated dose studies available (90-days inhalation toxicity study and prenatal developmental study) is used as a dose descriptor starting point.

Conversion of an inhalatory rat N(L)OAEC into a corrected inhalatory N(L)OAEC in case of differences between experimental and human exposure conditions.

The dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat(6.7 m3/kg for 8 hours exposure of workers). Additional correction difference between human and experimental exposures conditions for workers was done (0.75). As the expsoure in the inhalation study is 6h/day whereas it is 8h/day for the workplace.

AF for dose response relationship:
1
Justification:
Default assessment factor from ECHA Guidance document R8
AF for differences in duration of exposure:
2
Justification:
Default assessment factor used for subchronic to chronic; ECHA Guidance R8; Table R.8-6
AF for interspecies differences (allometric scaling):
1
Justification:
Default assessment factor from ECHA Guidance document R8
AF for other interspecies differences:
2.5
Justification:
Default assessment factor for workers ECHA Guidance R8; Table R.8-6
AF for intraspecies differences:
5
Justification:
Default assessment factor ECHA Guidance R8; Table R.8-6
AF for the quality of the whole database:
1
Justification:
Default assessment factor as no systemic effects at the top dose in a subchronic GLP guideline study
AF for remaining uncertainties:
1
Justification:
Default assessment factor from ECHA Guidance document R8
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
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:
no hazard identified
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:
no hazard identified
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