Reaction products of fatty acids, tall oil and fatty acids, C18 unsaturated, trimers and fatty acids, C18 unsaturated, dimers with (9Z)-octadec-9-en-1-amine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.75 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:

22.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

Since the substance contains only 49% of oleylamine, which is beliefed to be responsible for any toxic effects of the substance and from which the NOAEL was derived, the NOAEL was divided by 0.49. The resulting NOAEL was converted to an inhalatory NOAEC according to the following formula. Absorption via the oral route was considered to be less effective by a factor of 2 as a worst case assumption. NOAEC = NOAEL / resp. volume (rat) x (resp. volume (human) / resp. volume (human, light activity)) x (absorption (oral) / absorption (inhal.)) = 25.5mg/kg b.w. / 0.38m³/kg b.w. x 0.67 x 0.5.

AF for dose response relationship:

1

Justification:

NOAEL was used as starting point

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

Already considered during route to route extrapolation.

AF for other interspecies differences:

1

Justification:

Effects observed in the repeated dose study were due to local irritation / inflammation and subsequent stress. No interspecies differences are expected for these parameters.

AF for intraspecies differences:

5

Justification:

default factor for workers

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

The NOAEL is based on body weight loss most likely as a consequence of severe GI tract irritation. This was the most sensitive effect observed for the "Amine-part" of the test substance, but might only be observed to a lesser extend with the salt itself. Using this value is thus already considered a worst case approach and no further factor seems justified.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

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:

0.43 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):

120

Modified dose descriptor starting point:

NOAEL

Value:

51 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

As discussed in the toxicokinetic assessment, 50% absorption is assumed for dermal compared to oral uptake, because of the high log Pow and high molecular weight, and based on the data available for the two ions. Since the substance contains only 49% of oleylamine, which is beliefed to be responsible for any toxic effects of the substance and from which the NOAEL was derived, the NOAEL was divided by 0.49.

AF for dose response relationship:

1

Justification:

NOAEL was used as starting point

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic exposure.

AF for interspecies differences (allometric scaling):

4

Justification:

This factor describes the differences in metabolic rate between rats and humans based on body weight.

AF for other interspecies differences:

1

Justification:

Effects observed in the repeated dose study were due to local irritation / inflammation and subsequent stress. No interspecies differences are expected for these parameters.

AF for intraspecies differences:

5

Justification:

default factor for workers

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

The NOAEL is based on body weight loss most likely as a consequence of severe GI tract irritation. This was the most sensitive effect observed for the "Amine-part" of the test substance, but might only be observed to a lesser extend with the salt itself. Using this value is thus already considered a worst case approach and no further factor seems justified.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

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:

no hazard identified

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.37 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):

60

Modified dose descriptor starting point:

NOAEC

Value:

22.5 mg/m³

Explanation for the modification of the dose descriptor starting point:

Since the substance contains only 49% of oleylamine, which is beliefed to be responsible for any toxic effects of the substance and from which the NOAEL was derived, the NOAEL was divided by 0.49. The resulting NOAEL was converted to an inhalatory NOAEC according to the following formula. Absorption via the oral route was considered to be less effective by a factor of 2 as a worst case assumption. NOAEC = NOAEL / resp. volume (rat) x (resp. volume (human) / resp. volume (human, light activity)) x (absorption (oral) / absorption (inhal.)) = 25.5mg/kg b.w. / 0.38m³/kg b.w. x 0.67 x 0.5.

AF for dose response relationship:

1

Justification:

NOAEL was used as starting point

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic exposure.

AF for interspecies differences (allometric scaling):

1

Justification:

Already considered during route to route extrapolation.

AF for other interspecies differences:

1

Justification:

Effects observed in the repeated dose study were due to local irritation / inflammation and subsequent stress. No interspecies differences are expected for these parameters.

AF for intraspecies differences:

10

Justification:

default factor for consumers

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

The NOAEL is based on body weight loss most likely as a consequence of severe GI tract irritation. This was the most sensitive effect observed for the "Amine-part" of the test substance, but might only be observed to a lesser extend with the salt itself. Using this value is thus already considered a worst case approach and no further factor seems justified.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

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

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.21 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):

240

Modified dose descriptor starting point:

NOAEL

Value:

51 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

As discussed in the toxicokinetic assessment, 50% absorption is assumed for dermal compared to oral uptake, because of the high log Pow and high molecular weight, and based on the data available for the two ions. Since the substance contains only 49% of oleylamine, which is beliefed to be responsible for any toxic effects of the substance and from which the NOAEL was derived, the NOAEL was divided by 0.49.

AF for dose response relationship:

1

Justification:

NOAEL was used as starting point

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic exposure.

AF for interspecies differences (allometric scaling):

4

Justification:

This factor describes the differences in metabolic rate between rats and humans based on body weight.

AF for other interspecies differences:

1

Justification:

Effects observed in the repeated dose study were due to local irritation / inflammation and subsequent stress. No interspecies differences are expected for these parameters.

AF for intraspecies differences:

10

Justification:

default factor for consumers

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

The NOAEL is based on body weight loss most likely as a consequence of severe GI tract irritation. This was the most sensitive effect observed for the "Amine-part" of the test substance, but might only be observed to a lesser extend with the salt itself. Using this value is thus already considered a worst case approach and no further factor seems justified.

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

11.3 µg/cm²

Most sensitive endpoint:

sensitisation (skin)

DNEL related information

Overall assessment factor (AF):

10

Dose descriptor:

other: EC1.6 (µg/cm²)

AF for other interspecies differences:

10

Justification:

It is recognized that a general DNEL must take into account that the threshold for skin sensitization varies between individuals. This may be due to differences in parameters such as genetic effects, sensitive subpopulations, inherent barrier function, age, gender, and ethnicity (Api et al., 2008). The barrier function of the skin may be compromised which in turn may lead to a greater susceptibility of the individual. At the same time the barrier function is thought to be very similar from infancy to adulthood. The influence of the genetic setting is not well understood, however, may be plausible in the light of the immunological effect under consideration. The term sensitive subpopulations refer mostly to individuals who have previously been sensitized to other substances which may increase the susceptibility to further sensitisers (Api et al., 2006, Api et al., 2008). Overall, an assessment factor of 10 for intraspecies differences is applied to adequately address the combined influence of these effects. References: - Api AM, Basketter DA, Cadby PA, Cano M-F, Graham E, Gerberick F, Griem P, McNamee P, Ryan CA, Safford B (2006). Dermal Sensitization Quantitative Risk Assessment (QRA) for fragrance ingredients. Technical dossier. March 15, 2006 (revised May 2006). - Api AM, Basketter, DA, Cadby PA, Cano M-F, Ellis G, Gerberick GF, Griem P, McNamee PM, Ryan CA, Safford R (2008). Dermal sensitization quantitative risk assessment (QRA) for fragrance ingredients. Reg Toxicol Pharmacol 52: 3-23.

Acute/short term exposure

Hazard assessment conclusion:

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

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.11 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):

240

Modified dose descriptor starting point:

NOAEL

Value:

25.5 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No route to route extrapolation required. Since the substance contains only 49% of oleylamine, which is beliefed to be responsible for any toxic effects of the substance and from which the NOAEL was derived, the NOAEL was divided by 0.49.

AF for dose response relationship:

1

Justification:

NOAEL was used as starting point

AF for differences in duration of exposure:

6

Justification:

extrapolation from sub-acute to chronic exposure.

AF for interspecies differences (allometric scaling):

4

Justification:

This factor describes the differences in metabolic rate between rats and humans based on body weight.

AF for other interspecies differences:

1

Justification:

Effects observed in the repeated dose study were due to local irritation / inflammation and subsequent stress. No interspecies differences are expected for these parameters.

AF for intraspecies differences:

10

Justification:

default factor for consumers

AF for the quality of the whole database:

1

Justification:

GLP guideline study

AF for remaining uncertainties:

1

Justification:

The NOAEL is based on body weight loss most likely as a consequence of severe GI tract irritation. This was the most sensitive effect observed for the "Amine-part" of the test substance, but might only be observed to a lesser extend with the salt itself. Using this value is thus already considered a worst case approach and no further factor seems justified.

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified