Reaction mass of bis(N-decyl-N,N-dimethyldecan-1-aminium) carbonate and N-decyl-N,N-dimethyldecan-1-aminium hydrogen carbonate

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.19 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):

3.2

Modified dose descriptor starting point:

NOAEC

Value:

7 mg/m³

Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation according to ECHA Guidance CSR R.8 (2010)

AF for dose response relationship:

1

Justification:

Default AF

AF for differences in duration of exposure:

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. Therefore, increasing exposure duration does not increase the incidence or severity of such adverse effects (ECHA guidance CSR R.8, 2010).

AF for interspecies differences (allometric scaling):

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. Since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (ECHA guidance CSR R.8, 2010).

AF for other interspecies differences:

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. No kinetic assessment factors are proposed for interspecies variability as the local toxicity caused by the test substance is the result of direct chemical reactivity and no kinetic processes are involved

AF for intraspecies differences:

3.2

Justification:

AF for potential intraspecies toxicodynamic effects

AF for the quality of the whole database:

1

Justification:

Good quality database

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties identified

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.19 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Modified dose descriptor starting point:

NOAEC

Value:

7 mg/m³

Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation according to ECHA Guidance CSR R.8 (2010)

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.75 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

3.2

Modified dose descriptor starting point:

NOAEL

Value:

12 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default AF

AF for differences in duration of exposure:

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. Therefore, increasing exposure duration does not increase the incidence or severity of such adverse effects (ECHA guidance CSR R.8, 2010).

AF for interspecies differences (allometric scaling):

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. Since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (ECHA guidance CSR R.8, 2010).

AF for other interspecies differences:

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. No kinetic assessment factors are proposed for interspecies variability as the local toxicity caused by the test substance is the result of direct chemical reactivity and no kinetic processes are involved

AF for intraspecies differences:

3.2

Justification:

AF for potential intraspecies toxicodynamic effects

AF for the quality of the whole database:

1

Justification:

Good quality database

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties identified

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

Value:

3.75 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.002 mg/cm²

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

6.4

Dose descriptor:

other: LOAEL

AF for dose response relationship:

2

Justification:

AF for extrapolation from a LOAEL

AF for differences in duration of exposure:

1

Justification:

The test substance is irritating/corrosive. Increasing exposure duration does not increase the incidence or severity of such adverse effects (ECHA guidance CSR R.8, 2010).

AF for interspecies differences (allometric scaling):

1

Justification:

The test substance is irritating/corrosive. Since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (ECHA guidance CSR R.8, 2010).

AF for other interspecies differences:

1

Justification:

The test substance is irritating/corrosive. No kinetic assessment factors are proposed for interspecies variability as the local toxicity caused by the test substance is the result of direct chemical reactivity and no kinetic processes are involved

AF for intraspecies differences:

3.2

Justification:

AF for potential intraspecies toxicodynamic effects

AF for the quality of the whole database:

1

Justification:

Good quality database

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties identified

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

Value:

0.002 mg/cm²

Most sensitive endpoint:

repeated dose toxicity

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

See discussion below.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.94 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):

3.2

Modified dose descriptor starting point:

NOAEC

Value:

3 mg/m³

Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation according to ECHA Guidance CSR R.8 (2010)

AF for dose response relationship:

1

Justification:

Default AF

AF for differences in duration of exposure:

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. Therefore, increasing exposure duration does not increase the incidence or severity of such adverse effects (ECHA guidance CSR R.8, 2010).

AF for interspecies differences (allometric scaling):

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. Since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (ECHA guidance CSR R.8, 2010).

AF for other interspecies differences:

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. No kinetic assessment factors are proposed for interspecies variability as the local toxicity caused by the test substance is the result of direct chemical reactivity and no kinetic processes are involved

AF for intraspecies differences:

3.2

Justification:

AF for potential intraspecies toxicodynamic effects

AF for the quality of the whole database:

1

Justification:

Good quality database

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties identified

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.94 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

Modified dose descriptor starting point:

NOAEC

Value:

3 mg/m³

Explanation for the modification of the dose descriptor starting point:

Route to route extrapolation according to ECHA Guidance CSR R.8 (2010)

Local effects

Long term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

Acute/short term exposure

Hazard assessment conclusion:

hazard unknown (no further information necessary)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

3.75 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

3.2

Modified dose descriptor starting point:

NOAEL

Value:

12 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default AF

AF for differences in duration of exposure:

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. Therefore, increasing exposure duration does not increase the incidence or severity of adverse effects (ECHA guidance CSR R.8, 2010).

AF for interspecies differences (allometric scaling):

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. Since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (ECHA guidance CSR R.8, 2010).

AF for other interspecies differences:

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. No kinetic assessment factors are proposed for interspecies variability as the local toxicity caused by the test substance is the result of direct chemical reactivity and no kinetic processes are involved

AF for intraspecies differences:

3.2

Justification:

AF for potential intraspecies toxicodynamic effects

AF for the quality of the whole database:

1

Justification:

Good quality database

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties identified

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

Value:

3.75 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Dermal

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.002 mg/cm²

Most sensitive endpoint:

skin irritation/corrosion

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

6.4

Dose descriptor:

other: NOAEL

AF for dose response relationship:

2

Justification:

AF for extrapolation from a LOAEL

AF for differences in duration of exposure:

1

Justification:

The test substance is irritating/corrosive. Therefore, increasing exposure duration does not increase the incidence or severity of such adverse effects (ECHA guidance CSR R.8, 2010).

AF for interspecies differences (allometric scaling):

1

Justification:

The test substance is irritating/corrosive. Since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (ECHA guidance CSR R.8, 2010).

AF for other interspecies differences:

1

Justification:

The test substance is irritating/corrosive. No kinetic assessment factors are proposed for interspecies variability as the local toxicity caused by the test substance is the result of direct chemical reactivity and no kinetic processes are involved

AF for intraspecies differences:

3.2

Justification:

AF for potential intraspecies toxicodynamic effects

AF for the quality of the whole database:

1

Justification:

Good quality database

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties identified

Acute/short term exposure

Hazard assessment conclusion:

no DNEL required: short term exposure controlled by conditions for long-term

Value:

0.002 mg/cm²

Most sensitive endpoint:

skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.31 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):

3.2

Modified dose descriptor starting point:

NOAEL

Value:

1 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default AF

AF for differences in duration of exposure:

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. Therefore, increasing exposure duration does not increase the incidence or severity of adverse effects (ECHA guidance CSR R.8, 2010).

AF for interspecies differences (allometric scaling):

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. Since local effects are independent of the basal metabolic rate, allometric scaling should not be applied (ECHA guidance CSR R.8, 2010).

AF for other interspecies differences:

1

Justification:

Systemic effects are secondary to local irritation/corrosion caused by the test substance. No kinetic assessment factors are proposed for interspecies variability as the local toxicity caused by the test substance is the result of direct chemical reactivity and no kinetic processes are involved

AF for intraspecies differences:

3.2

Justification:

AF for potential intraspecies toxicodynamic effects

AF for the quality of the whole database:

1

Justification:

Good quality database

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties identified

Acute/short term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.31 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - General Population

Oral repeated dose studies have been conducted using the structurally-related substance Didecyldimethylammonium chloride (DDAC) in rats, mice and dogs. The read-across between DDACarbonate and DDAC is justified. Further to the repeated dose toxicity studies two developmental toxicity studies using DDAC are available. The NOAEL for maternal toxicity revealed in the key developmental study was determined to be 1.0 mg/kg bw/day. The observed adverse effects at higher concentrations were considered to be either the result of or a consequence of local irritation. This worst-case NOAEL is used for oral DNEL derivation.

A standard dermal sub-chronic repeated dose toxicity study is available using the structural analog DDAC. The systemic NOAEL of 12 mg AI/kg bw/day was used for systemic DNEL derivation. The LOAEC of 0.01 mg/cm2/day based on slight and reversible local toxicity effects is used for DNEL derivation. The results for local toxicity observed are supported by a non-standard repeated exposure toxicity test using DDACarbonate (21-Day Repeated Dose Dermal Irritation Study in Female Rats).

No studies assessing the effect of inhalation exposure are available. However, further data are not required as appropriate risk mitigation measures can be employed to prevent inhalation exposure. Route-to-route extrapolation was carried out for risk assessment purposes.

A standard study on skin irritation was carried out. The study was conducted to assess the potential of a 50 % active ingredient formulation of the test material to cause irritation after one topical application to the skin of a New Zealand White male rabbit for four hours. The test item was considered to be corrosive in this skin irritation test. Therefore, testing for eye irritation was waived.

Toxicity of DDACarbonate and the structural analog DDAC are characterized by severe irritation and primary tissue damage by corrosion at the site of application (e.g. skin and gastrointestinal tract) in all species and via all exposure routes tested. Systemic effects are secondary to primary local effects observed. No data are available to assess the relative sensitivities of humans to these local effects compared to experimental animals.

No kinetic assessment factors are proposed for interspecies variability in deriving the DNEL-values, because the local toxicity caused by DDACarbonate is the result of direct chemical reactivity and no kinetic processes are involved (ECHA Guideline CSR R.8, 2010). Similarly, no dynamic interspecies assessment factors are proposed as humans are not considered to be more susceptible to the local effects on the skin and the gastrointestinal tract compared to animals.

DDACarbonate is a cationic surfactant type active substance that reacts directly with the cell walls of microorganisms. This mode of action is most likely to be the underlying mechanism of the observed local toxicity of DDAC/DDACarbonate in mammals. Hence, it is considered that the local toxicity of DDACarbonate is the result of the direct interaction of DDACarbonate with the external membranes of the skin and gastrointestinal tract. In addition it is not considered necessary to include a toxicokinetic factor to account for intraspecies variability because the local effects observed in the animals exposed to DDAC/DDACarbonate do not involve kinetic and metabolic processes. In line with previous assessments only, a toxicodynamic assessment factor of 3.2 for intraspecies variability is proposed (UK MSCA (2012) Assessment Report for the Inclusion of Active Substances in Annex I to Directive 98/8/EC).