Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
53 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
DNEL value:
1 325 mg/m³
Explanation for the modification of the dose descriptor starting point:
NOAEC converted to starting point for DNEL derivation as follows: (2650 x 6hr/8hr x 6.7m3/10m3) = 1325 mg/m3
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
chronic study used as starting point
AF for interspecies differences (allometric scaling):
1
Justification:
not relevant for inhalation DNEL based on inhalation study
AF for other interspecies differences:
2.5
Justification:
ECHA
AF for intraspecies differences:
5
Justification:
ECHA
AF for the quality of the whole database:
1
AF for remaining uncertainties:
2
Justification:
use of read across addressed with additional uncertainty factor
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:
7.7 mg/kg bw/day
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):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
769 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
assume 100% bioavailability via both inhalation and dermal routes. Use conversion of 0.29 m3/kg bw to convert inhalation dose to systemic dose.
AF for dose response relationship:
1
AF for differences in duration of exposure:
1
Justification:
Chronic study used as starting point
AF for interspecies differences (allometric scaling):
4
Justification:
rat study - ECHA factor
AF for other interspecies differences:
2.5
Justification:
ECHA
AF for intraspecies differences:
5
Justification:
ECHA
AF for the quality of the whole database:
1
Justification:
ECAH
AF for remaining uncertainties:
2
Justification:
Additional factor of 2 used to address residual uncertainty associated with the use of read across.
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

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Starting point for the DNEL calculations is the Inhalation 2 year study in rats.

The NOAEC from this study is taken as 2650 mg/m3 (following molar conversion from MIBK to DIBC)

Bioavailability: 100% is assumed for all 3 routes.

This is likely an over estimate however the physical chemical properties (log Kow, water sol, MW, vapour pressure, absence of charge) indicate that this substance would be bioavailable via all three routes. It is likely that oral availability is higher and that although bioavailable via dermal route, the rate of absorption would be lower than inhalation and oral such that there would be kinetic differences that may modify the toxicity (dermal being less toxic).

An additional assessment factor of 2 has been utilised in deriving the DNELs due to the use of read across. This factor is not being used because of a suspicion that the read across is not 100% reliable. Rather, it is being used to address the uncertainty in associated with the trend in toxicity across the group of substances.

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

No consumer Exposure