Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.7 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):
25
Dose descriptor starting point:
NOAEL
Value:
24 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
42.2 mg/m³
Explanation for the modification of the dose descriptor starting point:

ECHA guidance recommends that a factor of 2 be applied when doing route to route extrapolation for oral to inhalation exposure, recognizing higher absorption via the lungs. Based on available substance specific information, this additional assessment factor is not considered relevant in this particular case. The substance is handled as a liquid with a very low vapour pressure of 0.00073 Pa at 20 °C and inhalation is therefore unlikely and would have to be to an aerosol. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared to the oral route of administration. Allometric scaling is applied by taking account for the different breathing rates between rats and humans, as described in ECHA technical guidance the oral NOAEL in the rat mg/kg/day *1/0.38 * 6.7/10 = mg/m3 inhalation NOAEC for workers.

AF for dose response relationship:
1
Justification:
According to the ECHA guidance document Chapter R8, the default assessment factor is 1 when the starting point for the DNEL calculation is a NOAEL. In this particular case, the starting point used is a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor going from sub-chronic to chronic, according to ECHA guidance document Chapter R8, in Table R. 8-5 Assessment factors for duration extrapolation.
AF for interspecies differences (allometric scaling):
1
Justification:
No additional factor needed, as already included in the route to route extrapolation from the rat oral NOAEL to the equivalent human inhalation NOAEC. This is described in Example B. 3 Inhalatory exposure; oral N(L)OAEL rat in the ECHA guidance document Chapter R8.
AF for other interspecies differences:
2.5
Justification:
ECHA default factor as prescribed in the ECHA guidance document Chapter R8, Table R. 8-6 Default assessment factors.
AF for intraspecies differences:
5
Justification:
ECHA default factor as prescribed in the ECHA guidance document Chapter R8, Table R. 8-6 Default assessment factors.
AF for the quality of the whole database:
1
Justification:
Data used is based on testing of C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) in a Klimisch 1 validity OECD408 90-day repeat dose toxicity study. Also the other available Klimisch 1 validity studies on the substance, such as OECD 422 study and OECD 414 results in NOAEL values within the same range. According to ECHA guidance document Chapter R8, the default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
AF for remaining uncertainties:
1
Justification:
Possible uncertainties are already included in the assessment factors above, so a factor of 1 is applied.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium 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:
0.24 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):
100
Dose descriptor starting point:
NOAEL
Value:
24 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
24 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

ECHA guidance assumes that absorption for dermal exposure is the same as for oral exposure, which is a worst case assumption.

AF for dose response relationship:
1
Justification:
According to the ECHA guidance document Chapter R8, the default assessment factor is 1 when the starting point for the DNEL calculation is a NOAEL as is the case for the C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2).
AF for differences in duration of exposure:
2
Justification:
Default assessment factor going from sub-chronic to chronic, according to ECHA guidance document Chapter R8, in Table R. 8-5 Assessment factors for duration extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for allometric scaling between rat to human, according to ECHA guidance document Chapter R8, Table R. 8-3 Allometric scaling factors for different species as compared to humans.
AF for other interspecies differences:
2.5
Justification:
ECHA default factor as prescribed in the ECHA guidance document Chapter R8, Table R. 8-6 Default assessment factors.
AF for intraspecies differences:
5
Justification:
ECHA default factor as prescribed in the ECHA guidance document Chapter R8, Table R. 8-6 Default assessment factors.
AF for the quality of the whole database:
1
Justification:
Data used is based on testing of C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) in a Klimisch 1 validity OECD408 90-day repeat dose toxicity. Also the other available Klimisch 1 validity studies on the substance, such as OECD 422 study and OECD 414 results in NOAEL values within the same range. According to ECHA guidance document Chapter R8, the default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
AF for remaining uncertainties:
1
Justification:
Possible uncertainties are already included in the assessment factors above, so a factor of 1 is applied.
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

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

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:
0.4 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
Dose descriptor starting point:
NOAEL
Value:
24 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
20.8 mg/m³
Explanation for the modification of the dose descriptor starting point:

ECHA guidance recommends that a factor of 2 be applied when doing route to route extrapolation for oral to inhalation exposure, recognizing higher absorption via the lungs. Based on available substance specific information, this additional assessment factor is not considered relevant in this particular case. The substance is handled as a liquid with a very low vapour pressure of 0.00073 Pa at 20 °C and inhalation is therefore unlikely and would have to be to an aerosol. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared to the oral route of administration. Allometric scaling is applied by taking account for the different breathing rates between rats and humans, as described in ECHA technical guidance the oral NOAEL in the rat mg/kg/day *1/1.15 mg/m3 inhalation NOAEC for consumers.

AF for dose response relationship:
1
Justification:
According to the ECHA guidance document Chapter R8, the default assessment factor is 1 when the starting point for the DNEL calculation is a NOAEL. In this particular case, the starting point used is a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor going from sub-chronic to chronic, according to ECHA guidance document Chapter R8, in Table R. 8-5 Assessment factors for duration extrapolation.
AF for interspecies differences (allometric scaling):
1
Justification:
No additional factor needed, as already included in the route to route extrapolation from the rat oral NOAEL to the equivalent human inhalation NOAEC. This is described in Example B. 3 Inhalatory exposure; oral N(L)OAEL rat in the ECHA guidance document Chapter R8.
AF for other interspecies differences:
2.5
Justification:
ECHA default factor as prescribed in the ECHA guidance document Chapter R8, Table R. 8-6 Default assessment factors.
AF for intraspecies differences:
10
Justification:
ECHA default factor as prescribed in the ECHA guidance document Chapter R8, Table R. 8-6 Default assessment factors.
AF for the quality of the whole database:
1
Justification:
Data used is based on testing of C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) in a Klimisch 1 validity OECD408 90-day repeat dose toxicity study. Also the other available Klimisch 1 validity studies on the substance, such as OECD 422 study and OECD 414 results in NOAEL values within the same range. According to ECHA guidance document Chapter R8, the default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
AF for remaining uncertainties:
1
Justification:
Possible uncertainties are already included in the assessment factors above, so a factor of 1 is applied.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
medium 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:
0.12 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
Dose descriptor starting point:
NOAEL
Value:
24 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

ECHA guidance assumes that absorption for dermal exposure is the same as for oral exposure, which is a worst case assumption.

AF for dose response relationship:
1
Justification:
According to the ECHA guidance document Chapter R8, the default assessment factor is 1 when the starting point for the DNEL calculation is a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor going from sub-chronic to chronic, according to ECHA guidance document Chapter R8, in Table R. 8-5 Assessment factors for duration extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for allometric scaling between rat to human, according to ECHA guidance document Chapter R8, Table R. 8-3 Allometric scaling factors for different species as compared to humans.
AF for other interspecies differences:
2.5
Justification:
ECHA default factor as prescribed in the ECHA guidance document Chapter R8, Table R. 8-6 Default assessment factors.
AF for intraspecies differences:
10
Justification:
ECHA default factor as prescribed in the ECHA guidance document Chapter R8, Table R. 8-6 Default assessment factors.
AF for the quality of the whole database:
1
Justification:
Data used is based on testing of C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) in a Klimisch 1 validity OECD408 90-day repeat dose toxicity. Also the other available Klimisch 1 validity studies on the substance, such as OECD 422 study and OECD 414 results in NOAEL values within the same range. According to ECHA guidance document Chapter R8, the default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
AF for remaining uncertainties:
1
Justification:
Possible uncertainties are already included in the assessment factors above, so a factor of 1 is applied.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

Local effects

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

General Population - Hazard via oral route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.12 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
Dose descriptor starting point:
NOAEL
Value:
24 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL is derived from a NOAEL in an OECD408 90-day Repeated dose toxicity feed study, so no route to route extrapolation is needed.

AF for dose response relationship:
1
Justification:
According to the ECHA guidance document Chapter R8, the default assessment factor is 1 when the starting point for the DNEL calculation is a NOAEL.
AF for differences in duration of exposure:
2
Justification:
Default assessment factor going from sub-chronic to chronic, according to ECHA guidance document Chapter R8, in Table R. 8-5 Assessment factors for duration extrapolation.
AF for interspecies differences (allometric scaling):
4
Justification:
Default assessment factor for allometric scaling between rat to human, according to ECHA guidance document Chapter R8, Table R. 8-3 Allometric scaling factors for different species as compared to humans.
AF for other interspecies differences:
2.5
Justification:
ECHA default factor as prescribed in the ECHA guidance document Chapter R8, Table R. 8-6 Default assessment factors.
AF for intraspecies differences:
10
Justification:
ECHA default factor as prescribed in the ECHA guidance document Chapter R8, Table R. 8-6 Default assessment factors.
AF for the quality of the whole database:
1
Justification:
Data used is based on testing of C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) in a Klimisch 1 validity OECD408 90-day repeat dose toxicity. Also the other available Klimisch 1 validity studies on the substance, such as OECD 422 study and OECD 414 results in NOAEL values within the same range. According to ECHA guidance document Chapter R8, the default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
AF for remaining uncertainties:
1
Justification:
Possible uncertainties are already included in the assessment factors above, so a factor of 1 is applied.
Acute/short term exposure
Hazard assessment conclusion:
medium hazard (no threshold derived)
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population