Docosyltrimethylammonium methyl sulphate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.6 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):

30

Modified dose descriptor starting point:

NOAEC

Value:

17.6 mg/m³

Explanation for the modification of the dose descriptor starting point:

No data on toxicity of the submission substance after long-term inhalation available.

AF for dose response relationship:

1

Justification:

ECHA Guidance

AF for differences in duration of exposure:

3

Justification:

Longer-term repeated dose studies for analogue substances do not indicate lower NOAELs for similar effects.

AF for interspecies differences (allometric scaling):

1

Justification:

inhalation route, ECHA Guidance

AF for other interspecies differences:

1

Justification:

substance is considered to exert its effects directly, without the need for metabolism, through its surfactant properties which are unlikely to differ between species

AF for intraspecies differences:

5

Justification:

ECHA Guidance

AF for the quality of the whole database:

1

Justification:

ECHA Guidance

AF for remaining uncertainties:

2

Justification:

route-to-route extrapolation (oral to inhalation), ECHA Guidance

Acute/short term exposure

Hazard assessment conclusion:

low 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:

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):

60

Modified dose descriptor starting point:

NOAEL

Value:

200 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No adequate data for dermal exposure pathway. Oral abs. rat approx. 10%, dermal abs. humans <0.5%: 20 times lower

AF for dose response relationship:

1

Justification:

ECHA Guidance

AF for differences in duration of exposure:

3

Justification:

Longer-term repeated dose studies for analogue substances do not indicate lower NOAELs for similar effects.

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA Guidance

AF for other interspecies differences:

1

Justification:

substance is considered to exert its effects through its surfactant properties which are unlikely to differ between species

AF for intraspecies differences:

5

Justification:

ECHA Guidance

AF for the quality of the whole database:

1

Justification:

ECHA Guidance

AF for remaining uncertainties:

1

Justification:

ECHA Guidance

Acute/short term exposure

Hazard assessment conclusion:

low 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)

Additional information - workers

DNEL long-term exposure - systemic effects - dermal

No data on toxicity of the submission substance after long-term dermal exposure are available. Due to its low water solubility and highly ionic nature the substance will not be readily absorbed from the gastrointestinal tract or skin (see e.g. European Commission,Sanco/222/2000 rev. 7, 19 March 2004:Guidance Document on Dermal Absorption). As worst case consideration a DNEL "long-term dermal exposure - systemic effects" can be derived by route-to-route extrapolation of data after long-term oral exposure to the closely related substance Quaternary ammonium compounds, C20-22-alkyltrimethyl, chlorides, for which in a 28-day subacute oral study with rats a NOAEL of 10 mg/kg bw/d has been derived. This NOAEL is regarded as starting point for the derivation of the worker DNEL. Based on its ionic nature and the low water solubility it can be assumed that the dermal absorption and the oral absorption are small. Based on toxicokinetic data for structurally very similar substances, it can be assumed that the oral absorption in rats is approx. 10% and dermal absorption is <0.5%. Therefore, the corrected dermal NOAEL is obtained by multiplying the NOAEL with 20, resulting in 200 mg/kg/day.

An allometric scaling factor of 4 is applied for interspecies extrapolation. A factor 1 was used for remaining interspecies differences, because the substance is considered to exert its effects through its surfactant properties which are unlikely to differ between species.

A time extrapolation factor of 3 was used to account for possible differences in subacute to chronic exposure duration. This factor is lower than the default factor of 6 for subacute to chronic extrapolation, because several supporting long-term (subchronic or chronic) toxicity studies with analogue substances are available, which show that NOAELs for similar effects exerted by the analogue substances are similar or even higher after prolonged exposure.

 In the absence of any substance specific data a default factor of 5 is used for intraspecies extrapolation is applied, based on ECHA Guidance document on Information Requirements and CSA, R.8.

The resulting overall assessment factor is 60 (4 x 3 x 5). Based on these data a worker DNEL "long-term dermal exposure - systemic effects" of 3 mg/kg bw/day is derived for the submission substance.

DNEL long-term exposure - systemic effects - inhalation

 

No data on toxicity of the submission substance after long-term inhalation exposure are available. As worst case consideration a worker DNEL "long-term inhalation exposure - systemic effects" can be derived by route-to-route extrapolation of data after long-term oral exposure to the closely related substance Quaternary ammonium compounds, C20-22-alkyltrimethyl, chlorides, for which in a 28-day subacute oral study with rats a NOAEL of 10 mg/kg bw/d has been derived. This NOAEL is regarded as starting point for the derivation of the worker DNEL "long-term inhalation exposure - systemic effects". Based on its ionic nature and the low water solubility it is assumed that the oral absorption and the inhalation absorption are small and that absorption is similar for both routes of exposure and between species. As no experimental data are available, for the remaining uncertainty the default factor of 2 for oral-to-inhalation extrapolation will be applied. The corrected inhalatory NOAEC is obtained by multiplying the NOAEL with 1/0.38 m³/kg/day * 6.7 m³ / 10 m³ as 17.6 mg/m³.

A factor 1 was used for remaining interspecies differences, because the substance is considered to exert its effects directly, without the need for metabolism, through its surfactant properties which are unlikely to differ between species.

A time extrapolation factor of 3 was used to account for possible differences in subacute to chronic exposure duration. This factor is lower than the default factor of 6 for subacute to chronic extrapolation, because several supporting long-term (subchronic or chronic) toxicity studies with analogue substances are available, which show that NOAELs for similar effects exerted by the analogue substances are similar or even higher after prolonged exposure.

In the absence of any substance specific data a default factor of 5 is used for intraspecies extrapolation, based on ECHA Guidance document on Information Requirements and CSA R.8.

The resulting overall assessment factor is 30 (2 x 1 x 3 x 5). Based on these data a DNEL "long-term inhalation exposure “systemic effects" of 0.6 mg/m³ is derived for the subsmission substance.

Inhalation of the substance is not considered a potential route of exposure based on use patterns and the low vapour pressure and considering technical protection measures employed (partly use of closed systems, local exhaust ventilation).

 

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

With regard to consumer exposure, the submission substance is used only in cosmetic products. Therefore, derivation of DNELs, assessment of exposure and risk characterization are not required (ECHA guidance R8).