Bis(hydroxyethyl)methyloleylammonium chloride

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.88 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:

25 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

22.04 mg/m³

Explanation for the modification of the dose descriptor starting point:

In accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health" (Figure R. 8-3) the oral - inhalation (route to route) dose descriptor modification is calculated as follows :-

NOAEC (workers) = NOAEL (oral) x [1 / sRVrat] x [ABSoral-rat / ABSinh-human] x [sRVhuman / wRV]

 

where :-

ABS = Absorption

sRV = Standard Respiratory Volume

           (sRV [rat], 8 hours = 0.38 m3 / kg bw)

           (sRV [human], 8 hours = 6.7 m3 / person)

wRV = Worker Respiratory Volume

            (wRV, 8 hours, = 10 m3 / person)

Therefore :-

NOAEC (workers) = NOAEL x [1/0.38] x [0.5 x 1] x 6.7 / 10

the "0.5 / 1" factor is added since the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", section R.8.4.2 b) under "Ad 2" (5th paragraph) states :-

"It is proposed, thus, in the absence of route-specific information on the starting route, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) in the case of oral-to inhalation extrapolation. The inclusion of this factor 2 means for example that 50% (instead of 100%) absorption is assumed for oral absorption, and 100% for inhalation.".

Therefore for the route to route modification the NOAEL from the OECD 422 study in section 7.5 is 25 mg/kg bw/ day

NOAEC (workers) = 25 x [1/0.38] x [0.5 x 1] x 6.7 / 10

NOAEC (workers) = 22.04 mg/m3

AF for dose response relationship:

1

Justification:

Default assessment factor for dose response relationship specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for differences in duration of exposure:

2

Justification:

Subacute to sub-chronic default assessment factor in accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health"; Table R. 8-5.

AF for interspecies differences (allometric scaling):

1

Justification:

For inhalation, DNELs allometric scaling is not usually applied.

AF for other interspecies differences:

2.5

Justification:

Default assessment factor for interspecies "remaining differences" specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for intraspecies differences:

5

Justification:

Default assessment factor for intraspecies specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for the quality of the whole database:

1

Justification:

Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown but no further hazard information necessary as no exposure expected

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.25 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:

25 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

25 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", section R.8.4.2 b) under "Ad 2" (7th paragraph) states :-

On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation.

DNEL (Long term systemic [workers]) = NOAEL / AF (differences in duration of exposure [3]) x AF (interspecies differences [allometric scaling {4}]) x (other interspecies differences [2.5]) x AF (intraspecies differences [5])

DNEL (Long term systemic [workers]) = 25 / 2 x 4 x 2.5 x 5

DNEL (Long term systemic [workers]) = 25 / 100 = 0.25 mg/kg bw / d

AF for dose response relationship:

1

Justification:

Default assessment factor for dose response relationship specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for differences in duration of exposure:

2

Justification:

Subacute to sub-chronic default assessment factor in accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health"; Table R. 8-5.

AF for interspecies differences (allometric scaling):

4

Justification:

Default allometric scaling factor for rats compared to humans specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-3

AF for other interspecies differences:

2.5

Justification:

Default assessment factor for interspecies "remaining differences" specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for intraspecies differences:

5

Justification:

Default assessment factor for intraspecies specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for the quality of the whole database:

1

Justification:

Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.15 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):

75

Dose descriptor starting point:

NOAEL

Value:

25 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

10.87 mg/m³

Explanation for the modification of the dose descriptor starting point:

In accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health" (Figure R. 8-3) the oral - inhalation (route to route) dose descriptor modification is calculated as follows :-

NOAEC (general population) = NOAEL (oral) x [1 / sRVrat] x [ABSoral-rat / ABSinh-rat] x [ABSinh-rat / ABSinh-human]

 

where :-

ABS = Absorption

sRV = Standard Respiratory Volume

           (sRV [rat], 24 hours = 1.15 m3 / kg bw)

Therefore :-

NOAEC (general population) = NOAEL x [1 / 1.15] x [0.5 x 1]

the "0.5 / 1" factor is added since the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", section R.8.4.2 b) under "Ad 2" (5th paragraph) states :-

"It is proposed, thus, in the absence of route-specific information on the starting route, to include a default factor of 2 (i.e. the absorption percentage for the starting route is half that of the end route) in the case of oral-toinhalation extrapolation. The inclusion of this factor 2 means for example that 50% (instead of 100%) absorption is assumed for oral absorption, and 100% for inhalation.".

Therefore for the route to route modification the NOAEL from the OECD 422 study in section 7.5 is 25 mg/kg bw/ day

NOAEC (general po[pulation = 25 x [1 / 1.15] x [0.5 x 1]

NOAEC (general population) = 10.87 mg/m3

AF for dose response relationship:

1

Justification:

Default assessment factor for dose response relationship specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for differences in duration of exposure:

3

Justification:

Subacute to sub-chronic default assessment factor in accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health"; Table R. 8-5.

AF for interspecies differences (allometric scaling):

1

Justification:

For inhalation, DNELs allometric scaling is not usually applied

AF for other interspecies differences:

2.5

Justification:

Default assessment factor for interspecies "remaining differences" specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for intraspecies differences:

10

Justification:

Default assessment factor for intraspecies specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for the quality of the whole database:

1

Justification:

Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

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:

0.083 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

Dose descriptor starting point:

NOAEL

Value:

25 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

25 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", section R.8.4.2 b) under "Ad 2" (7th paragraph) states :-

On the assumption that, in general, dermal absorption will not be higher than oral absorption, no default factor (i.e. factor 1) should be introduced when performing oral-to-dermal extrapolation.

AF for dose response relationship:

1

Justification:

Default assessment factor for dose response relationship specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for differences in duration of exposure:

3

Justification:

Subacute to sub-chronic default assessment factor in accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health"; Table R. 8-5.

AF for interspecies differences (allometric scaling):

4

Justification:

Default allometric scaling factor for rats compared to humans specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-3

AF for other interspecies differences:

2.5

Justification:

Default assessment factor for interspecies "remaining differences" specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for intraspecies differences:

10

Justification:

Default assessment factor for intraspecies specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for the quality of the whole database:

1

Justification:

Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

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:

0.083 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

Dose descriptor starting point:

NOAEL

Value:

25 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default assessment factor for dose response relationship specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for differences in duration of exposure:

3

Justification:

Subacute to sub-chronic default assessment factor in accordance with ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health"; Table R. 8-5.

AF for interspecies differences (allometric scaling):

4

Justification:

Default allometric scaling factor for rats compared to humans specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-3

AF for other interspecies differences:

2.5

Justification:

Default assessment factor for interspecies "remaining differences" specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for intraspecies differences:

10

Justification:

Default assessment factor for intraspecies specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

AF for the quality of the whole database:

1

Justification:

Default assessment factor for the quality of the whole database specified in the ECHA "Guidance on information requirements and chemical safety assessment - Chapter R. 8 : Characterisation [concentration] - response for human health", Table R. 8-6

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:

high hazard (no threshold derived)