[2-[[2-cyano-3-[4-[ethylbenzylamino]phenyl]-1-oxoallyl]oxy]ethyl]trimethylammonium chloride

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

70 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:

600 mg/kg bw/day

Modified dose descriptor starting point:

NOAEC

Value:

5 250 mg/m³

Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation taking into account that oral and inhalation absorption are set at 50 and 10%, respectively. The starting dose for the derivation of the inhalation DNEL is 600 mg/kg bw (highest dose tested in the oral study according to OECD 422). At this dose level no corrosive effects of the substance were reported.

The NOAEC for inhalation exposure has been calculated according to the following formula:

NOAEL * abs oral/abs inhal / allometric scaling factor * 70 kg / 10 m3= 600*5/4 * 70/10 = 5250 mg/m3

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

subacute to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

this factor has been taken into account in the derivation of the starting NOAEC

AF for other interspecies differences:

2.5

Justification:

default

AF for intraspecies differences:

5

Justification:

workere exposure

AF for the quality of the whole database:

1

Justification:

based on guideline study under GLP

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low 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:

1 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:

600 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation taking into account that oral and dermal absorption are set at 50 and 100%, respectively. The starting dose for the derivation of the dermal DNEL is 600 mg/kg bw (highest dose tested in the oral study according to OECD 422). At this dose level no corrosive effects of the substance were reported.

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

subacute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

species tested is the rat

AF for other interspecies differences:

2.5

Justification:

default value

AF for intraspecies differences:

5

Justification:

worker exposure

AF for the quality of the whole database:

1

Justification:

based on guideline study under GLP

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

Exposure to the substance as registered is expected during manufacturing, formulation and coloring of paper (batch and sizing). In other life stages the substance is incorporated in the paper matrix. During paper coloring the substance, which is a basic dye, reacts with the acid groups present on paper fibres to produce, by salt formation, very stable lakes* that are insoluble in water. During this process only the chromophore will be part of this reaction, while other components (like acetic acid), that may contribute to the corrosiveness of the substance, remain in the paper sludge.

* a lake is formed by precipitating a dye with an inert binder

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:

DNEL (Derived No Effect Level)

Value:

0.5 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):

600

Dose descriptor starting point:

NOAEL

Value:

600 mg/kg bw/day

Modified dose descriptor starting point:

NOAEL

Value:

300 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation taking into account that oral and dermal absorption are set at 50 and 100%, respectively. The starting dose for the derivation of the dermal DNEL is 600 mg/kg bw (highest dose tested in the oral study according to OECD 422). At this dose level no corrosive effects of the substance were reported.

Although corrosion could be of influence on dermal absorption, this is not applicable for consumer exposure because the substance (chromophore) is incorporated in the paper matrix. Therefore the derived DNEL is considered a worst case.

AF for dose response relationship:

1

AF for differences in duration of exposure:

6

Justification:

subacute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

The species tested is the rat

AF for other interspecies differences:

2.5

Justification:

default value

AF for intraspecies differences:

10

Justification:

consumer exposure

AF for the quality of the whole database:

1

Justification:

Based on guidelines study under GLP

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Justification:

not applicable

AF for the quality of the whole database:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic 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:

DNEL (Derived No Effect Level)

Value:

35 mg/kg bw/day

Most sensitive endpoint:

acute toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

100

Dose descriptor starting point:

other: LD50/NOAEL

Value:

3 500 mg/kg bw/day

AF for interspecies differences (allometric scaling):

4

Justification:

study in rat

AF for other interspecies differences:

2.5

Justification:

default value

AF for intraspecies differences:

10

Justification:

consumer exposure

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

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

Additional information - General Population

During paper coloring the substance, which is an acid dye, is precipitated on the fibres by interference of fixing agents, which form a linkage between the cationic-treated fibres and the dyestuff molecules. During this process only the chromophore will react while other components (like acetic acid) that may contribute to the corrosiveness of the substance, remain in the paper sludge. Therefore for consumer exposure to the substance incorporated in the paper matrix, corrosiveness will not be taken into account.