Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.7 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):
75
Modified dose descriptor starting point:
LOAEC
Value:
204 mg/m³
AF for dose response relationship:
3
Justification:
The starting point for the 90-day inhalation study is a LOAEC. The severity of the kidney nephropathy was minimal-mild (compared to minimal in controls). Therefore, a factor of 3 is also considered appropriate to account for the associated uncertainty.
AF for differences in duration of exposure:
2
Justification:
A default factor of 2 will be applied to extrapolate to long-term exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
Since we are deriving an inhalation DNEL, no allometric scaling is necessary
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
5
Justification:
There are no data to quantify the variability in susceptibility to the effects of long-term exposure to tertiary butyl alcohol in the human population. The default value of 5 for workers will therefore be used to take account of intraspecies variability
AF for the quality of the whole database:
1
Justification:
The quality of the database is adequate. The information comes from an NTP 90-day inhalation study. The results of which are supported by the effects observed in other studies.
AF for remaining uncertainties:
1
Justification:
default.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
214 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):
12.5
Modified dose descriptor starting point:
NOAEC
Value:
2 677 mg/m³
AF for dose response relationship:
1
Justification:
The starting point is a NOAEC. A factor for uncertainties is not considered necessary
AF for interspecies differences (allometric scaling):
1
Justification:
There are no data for tertiary butyl alcohol to quantify other differences between animals and humans that could affect interspecies extrapolation. On this basis the default value of 2.5 to account for other species difference will be applied.
AF for other interspecies differences:
2.5
Justification:
Since the dose descriptor was derived from an inhalation study and is being used to derive an inhalation DNEL, no allometric scaling is necessary.
AF for intraspecies differences:
5
Justification:
There are no data to quantify the variability in susceptibility to the effects of long-term exposure to tertiary butyl alcohol in the human population. The default value of 5 for workers will therefore be used to take account of intraspecies variability
AF for the quality of the whole database:
1
Justification:
The quality of the database is adequate. The information comes from an NTP 18-day inhalation study. The results of which are supported by effects observed in other studies. This consistency provides confidence in the reliability of these studies. It is not necessary to apply a factor to take account of deficiencies in the quality of the database.
AF for remaining uncertainties:
1
Justification:
default

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
5.5 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):
150
Modified dose descriptor starting point:
LOAEL
Value:
818 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The oral chronic study in rats was selected for worker long-term dermal DNEL derivation. To convert the oral value to dermal, a route-to-route extrapolation is required. The equations used were obtained from ECHA’s Practical Guide 14; Table 2, page 38.  The dermal N(L)OAEL = oral N(L)OAEL*(Absoral/Absdermal)).  Using data from the chronic study in rats: 90*(1/0.38) *0.67*(11/60) = 818 mg/kg bw/day (LOAEC).

AF for dose response relationship:
3
Justification:
The starting point for the chronic oral study is a LOAEL, based on a 15% bodyweight reduction
AF for differences in duration of exposure:
1
Justification:
Chronic study. No factor is required as exposure is already long-term
AF for interspecies differences (allometric scaling):
4
Justification:
For the oral study in the rat, an allometric scaling factor of 4 is required to take account of differences in basal metabolic rates between rats and humans.
AF for other interspecies differences:
2.5
Justification:
There are no data for tertiary butyl alcohol to quantify other differences between animals and humans that could affect interspecies extrapolation. On this basis the default value of 2.5 to account for other species difference will be applied.
AF for intraspecies differences:
5
Justification:
There are no data to quantify the variability in susceptibility to the effects of long-term exposure to tertiary butyl alcohol in the human population. The default value of 5 for workers will therefore be used to take account of intraspecies variability
AF for the quality of the whole database:
1
Justification:
The quality of the database is adequate.
AF for remaining uncertainties:
1
Justification:
default
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:
no hazard identified

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:
DNEL (Derived No Effect Level)
Value:
0.5 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):
150
Modified dose descriptor starting point:
LOAEC
Value:
72.5 mg/m³
AF for dose response relationship:
3
Justification:
The starting point for the 90-day inhalation study is a LOAEC. The severity of the kidney nephropathy was minimal-mild (compared to minimal in controls). Therefore, a factor of 3 is also considered appropriate to account for the associated uncertainty.
AF for differences in duration of exposure:
2
Justification:
A default factor of 2 was applied to extrapolate to long-term exposure.
AF for interspecies differences (allometric scaling):
1
Justification:
Since we are deriving an inhalation DNEL, no allometric scaling is necessary.
AF for other interspecies differences:
2.5
Justification:
There are no data for tertiary butyl alcohol to quantify other differences between animals and humans that could affect interspecies extrapolation. On this basis the default value of 2.5 to account for other species difference will be applied.
AF for intraspecies differences:
10
Justification:
The default factor of 10 for consumers was used.
AF for the quality of the whole database:
1
Justification:
The quality of the database is adequate. The information comes from an NTP 90-day inhalation study. The results of which are supported by the effects observed in other studies.
AF for remaining uncertainties:
1
Justification:
default
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
159.8 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
Modified dose descriptor starting point:
NOAEC
Value:
3 995 mg/m³
AF for dose response relationship:
1
Justification:
The starting point is a NOAEC. A factor for uncertainties is not considered necessary.
AF for interspecies differences (allometric scaling):
1
Justification:
Since the dose descriptor was derived from an inhalation study and is being used to derive an inhalation DNEL, no allometric scaling is necessary.
AF for other interspecies differences:
2.5
Justification:
default
AF for intraspecies differences:
10
Justification:
default
AF for the quality of the whole database:
1
Justification:
The quality of the database is adequate. The information comes from an NTP 18-day inhalation study. The results of which are supported by the effects observed in other studies. This consistency provides confidence in the reliability of these studies. It is not necessary to apply a factor to take account of deficiencies in the quality of the database.
AF for remaining uncertainties:
1
Justification:
default

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.7 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):
300
Modified dose descriptor starting point:
LOAEL
Value:
818 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The oral chronic study in rats was selected for general population long-term dermal DNEL derivation. To convert the oral value to dermal, a route-to-route extrapolation is required. The equations used were obtained from ECHA’s Practical Guide 14; Table 2, page 38.  The dermal N(L)OAEL = oral N(L)OAEL*(Absoral/Absdermal)).  Using data from the chronic study in rats: 90*(1/0.38) *0.67*(11/60) = 818 mg/kg bw/day (LOAEC)

AF for dose response relationship:
3
Justification:
The starting point for the chronic oral study is a LOAEC, based on a 15% bodyweight reduction. Default factor for LOAEC to NOAEC used.
AF for differences in duration of exposure:
1
Justification:
Chronic study. No factor is required as exposure is already long-term
AF for interspecies differences (allometric scaling):
4
Justification:
For the oral study in the rat, an allometric scaling factor of 4 is required to take account of differences in basal metabolic rates between rats and humans.
AF for other interspecies differences:
2.5
Justification:
There are no data for tertiary butyl alcohol to quantify other differences between animals and humans that could affect interspecies extrapolation. On this basis the default value of 2.5 to account for other species difference will be applied.
AF for intraspecies differences:
10
Justification:
The default factor of 10 for consumers was used
AF for the quality of the whole database:
1
Justification:
The quality of the database is adequate.
AF for remaining uncertainties:
1
Justification:
default.
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:
no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.3 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):
300
Modified dose descriptor starting point:
LOAEL
Value:
90
AF for dose response relationship:
3
Justification:
The starting point for the chronic oral study is a LOAEC, based on a 15% bodyweight reduction.
AF for differences in duration of exposure:
1
Justification:
Chronic study. No factor is required as exposure is already long-term.
AF for interspecies differences (allometric scaling):
4
Justification:
For the oral study in the rat, an allometric scaling factor of 4 is required to take account of differences in basal metabolic rates between rats and humans.
AF for other interspecies differences:
2.5
Justification:
There are no data for tertiary butyl alcohol to quantify other differences between animals and humans that could affect interspecies extrapolation. On this basis the default value of 2.5 to account for other species difference will be applied.
AF for intraspecies differences:
10
Justification:
The default factor of 10 for consumers was used.
AF for the quality of the whole database:
1
Justification:
The quality of the database is adequate.
AF for remaining uncertainties:
1
Justification:
default.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

General population-DNEL for infrequent use for inhalation route, systemic effects:    13.8 mg/m3(assumptions: not more than10 days/year, 24 hours/day, ECHA Guidance R.15)