Amines, N-(C16-18 and C18-unsatd. alkyl)trimethylenedi-, dioleates

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.29 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):

6

Modified dose descriptor starting point:

NOAEC

Value:

1.76 mg/m³

Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for tallow-diamine in Tallow-diamine dioleate (see discussion) which is based upon cross-reading from the 90-day study on C12-14-Diamine resulting to a NOAEL of 0.4 mg/kgbw/d. This is then converted to the corresponding value for the dioleate salt of Tallow-diamine, resulting to a derived oral NOAEL for Tallow-diamine dioleate of about 1 mg/kg bw/day. (mw Tallow-diamine approx 310 (avg.), mw Tallow-diamine dioleate = 876 (avg.); 0.4 x 876/310 = 1.1 mg/kg bw/day) From this follows for the corrected 8 hr inhalation NOAEC for workers a NOAEL(1 mg/kg) * 1.76 mg/m3 = 1.76 mg/m3. No factor 2 route extrapolation from oral to inhalation. Due to very low vp (<< 0.0015 Pa as this is based on C12-14-diamine rather than de Tallow-diamine dioleate salt), significant exposure is only possible as aerosol. If any inhalation does occur, this can only be in the form of larger droplets, as the use does not include fine spraying. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route.

AF for dose response relationship:

1

Justification:

No specific concerns; starting point is NOAEL, effects at LOAEL are not severe and of local nature.

AF for differences in duration of exposure:

2

Justification:

Default assessment factor for sub-chronic to chronic.

AF for interspecies differences (allometric scaling):

1

Justification:

Already included in NOAEC calculation

AF for other interspecies differences:

1

Justification:

ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local and related to the route of exposure (see comments), the already applied allometric scaling already represents a worst case.

AF for intraspecies differences:

3

Justification:

ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intra-species differences for workers is 3 and not 5. As the effects for which the risk assessment is made is based on a local response following an non-specific mechanism with expected inherently relative low variation between individuals, no additional factor is needed to accommodate for possible high uncertainty between individuals on the basis of possible specific sensitivities.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

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:

0.04 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):

24

Modified dose descriptor starting point:

NOAEL

Value:

1 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for tallow-diamine in Tallow-diamine dioleate (see discussion) which is based upon cross-reading from the 90-day study on C12-14-Diamine resulting to a NOAEL of 0.4 mg/kgbw/d. This is then converted to the corresponding value for the dioleate salt of Tallow-diamine, resulting to a derived oral NOAEL for Tallow-diamine dioleate of about 1 mg/kg bw/day. (mw Tallow-diamine approx 310 (avg.), mw Tallow-diamine dioleate = 876 (avg.); 0.4 x 876/310 = 1.1 mg/kg bw/day) At this stage no data are available on dermal absorption. Tallow-diamine is not expected to easily pass the skin from the dioleate salt form, in view of its ionised form at physiological conditions. However, as this is not quantitatively evaluated, 100% dermal absorption is considered as worst case assumption.

AF for dose response relationship:

1

Justification:

No specific concerns. Effects at LOAEL are not severe and probably only of local nature.

AF for differences in duration of exposure:

2

Justification:

Default assessment factor for sub-chronic to chronic.

AF for interspecies differences (allometric scaling):

4

Justification:

Default factor for allometric scaling from rat to human.

AF for other interspecies differences:

1

Justification:

ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local related to the route of exposure, the applied allometric scaling already represents a worst case

AF for intraspecies differences:

3

Justification:

ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intra-species differences for workers is 3 and not 5. As the effects for which the risk assessment is made is based on a local response following an non-specific mechanism with expected inherently relative low variation between individuals, no additional factor is needed to accommodate for possible high uncertainty between individuals on the basis of possible specific sensitivities.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results within category.

AF for remaining uncertainties:

1

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)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

Tallow-diamine dioleate is a salt of tallow-diamine and oleic acid, in a molar ratio of 1:2. Absorption and subsequent possible toxicity follows the dissociation of the salt. The diamine structure is much more toxic than the oleic acid part, and therefore it is considered that toxicity profile of Tallow-diamine dioleate will be fully driven by its tallow-diamine content. This is supported by data from repeated dose studies performed on both the similar Oleyl-diamine dioleate and on Oleyl-diamine.

Oleyl-diamine is almost identical to Tallow-diamine and cross-reading from the available data on Oleyl-diamine to Tallow-diamine is therefore applied.

For further evaluation of toxicity of Tallow-diamine dioleate, including reproduction toxicity, therefore cross-reading can be done to the data available on Oleyl-diamine. For DNEL setting use is made of thesub-chronic90-daystudiesin ratbased on read-across from C12-14-diamine, which related tothe shorteralkylchain-lengthcan be regarded to be the worst case representative for the group of alkyl-diamines with longer chain lengths such as Oleyl-diamine and Tallow-diamine.The NAOEL of 0.4 mg/kg for C12-14-diamine is therefore taken as starting point for the NOAEL value for Tallow-diamine, which then is converted to the corresponding value for the dioleate salt of Tallow-diamine.

(mw Tallow-diamine is approx. 310 (avg.), mw Tallow-diamine dioleate is 876 (avg.); 0.4 x 876/310 = 1.1 mg/kg bw/day)

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.07 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):

14

Modified dose descriptor starting point:

NOAEC

Value:

0.87 mg/m³

Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for tallow-diamine in Tallow-diamine dioleate (see discussion) which is based upon cross-reading from the 90-day study on C12-14-Diamine resulting to a NOAEL of 0.4 mg/kgbw/d. This is then converted to the corresponding value for the dioleate salt of Tallow-diamine, resulting to a derived oral NOAEL for Tallow-diamine dioleate of about 1 mg/kg bw/day. (mw Tallow-diamine approx 310 (avg.), mw Tallow-diamine dioleate = 876 (avg.); 0.4 x 876/310 = 1.1 mg/kg bw/day) The corrected 8 hr inhalation NOAEC for consumers is NOAEL(1 mg/kg) * 1/1.15 mg/m3 = 0,87 mg/m3. No factor 2 route extrapolation from oral to inhalation. Due to very low vp (<< 0.0015 Pa as this is based on C12-14-diamine rather than de Tallow-diamine dioleate salt), significant exposure is only possible as aerosol. If any inhalation does occur, this can only be in the form of larger droplets, as the use does not include fine spraying. Droplets will deposit mainly on upper airways, and will be subsequently swallowed following mucociliary transportation to pharynx. This results to no principal difference in absorption compared oral route.

AF for dose response relationship:

1

Justification:

No specific concerns; starting point is NOAEL, effects at LOAEL are not severe and of local nature.

AF for differences in duration of exposure:

2

Justification:

Default assessment factor for sub-chronic to chronic

AF for interspecies differences (allometric scaling):

1

Justification:

Already included in NOAEC calculation

AF for other interspecies differences:

1

Justification:

ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local and related to the route of exposure (see comments), the already applied allometric scaling already represents a worst case.

AF for intraspecies differences:

7

Justification:

ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for general public is 5 and not 10, In this case the factor 7 is used to accommodate for the possible high uncertainty between individuals as the effects for which the risk assessment is made possibly includes a local response.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

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:

0.018 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):

56

Modified dose descriptor starting point:

NOAEL

Value:

1 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for tallow-diamine in Tallow-diamine dioleate (see discussion) which is based upon cross-reading from the 90-day study on C12-14-Diamine resulting to a NOAEL of 0.4 mg/kgbw/d. This is then converted to the corresponding value for the dioleate salt of Tallow-diamine, resulting to a derived oral NOAEL for Tallow-diamine dioleate of about 1 mg/kg bw/day. (mw Tallow-diamine approx 310 (avg.), mw Tallow-diamine dioleate = 876 (avg.); 0.4 x 876/310 = 1.1 mg/kg bw/day) At this stage no data are available on dermal absorption. Tallow-diamine is not expected to easily pass the skin from the dioleate salt form, in view of its ionised form at physiological conditions. However, as this is not quantitatively evaluated, 100% dermal absorption is considered as worst case assumption.

AF for dose response relationship:

1

Justification:

No specific concerns. Effects at LOAEL are not severe and probably only of local nature.

AF for differences in duration of exposure:

2

Justification:

Default assessment factor for sub-chronic to chronic.

AF for interspecies differences (allometric scaling):

4

Justification:

Default factor for allometric scaling from rat to human.

AF for other interspecies differences:

1

Justification:

ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local related to the route of exposure, the applied allometric scaling already represents a worst case.

AF for intraspecies differences:

7

Justification:

ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for general public is 5 and not 10, In this case the factor 7 is used to accommodate for the possible high uncertainty between individuals as the effects for which the risk assessment is made possibly includes a local response.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Justification:

Cross-reading to more extended studies on diamines does also not indicate additional concerns to be considered.

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)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

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:

0.018 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):

56

Modified dose descriptor starting point:

NOAEL

Value:

1 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

Starting point is the NOAEL for tallow-diamine in Tallow-diamine dioleate (see discussion) which is based upon cross-reading from the 90-day study on C12-14-Diamine resulting to a NOAEL of 0.4 mg/kgbw/d. This is then converted to the corresponding value for the dioleate salt of Tallow-diamine, resulting to a derived oral NOAEL for Tallow-diamine dioleate of about 1 mg/kg bw/day. (mw Tallow-diamine approx 310 (avg.), mw Tallow-diamine dioleate = 876 (avg.); 0.4 x 876/310 = 1.1 mg/kg bw/day) No route to route extrapolation required as is based on oral route.

AF for dose response relationship:

1

Justification:

No specific concerns; starting point is NOAEL, effects at LOAEL are not severe and of local nature.

AF for differences in duration of exposure:

2

Justification:

Default assessment factor for sub-chronic to chronic.

AF for interspecies differences (allometric scaling):

4

Justification:

Default factor for allometric scaling from rat to human.

AF for other interspecies differences:

1

Justification:

ECETOC reported in 2010 after an extensive review that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied. As effects are interpreted as being local related to the route of exposure, the applied allometric scaling already represents a worst case.

AF for intraspecies differences:

7

Justification:

ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for general public is 5 and not 10, In this case the factor 7 is used to accommodate for the possible high uncertainty between individuals as the effects for which the risk assessment is made possibly includes a local response.

AF for the quality of the whole database:

1

Justification:

Available data derived from valid studies showing consistent results within category.

AF for remaining uncertainties:

1

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - General Population

Exposure of the general population to Tallow-diamine dioleate salt based on the uses indicated in this dossier includes the use as ingredient in paints (at low concentration) with possible exposure via the paints as well as indirect exposures via the environment. Therefore DNELs are derived for systemic, long-term exposures for all routes. The concentrations of Tallow-diamine dioleate in the applications of use are low, and therefore no DNELs for short term exposures and local effects are derived.

 

Tallow-diamine dioleate is a salt of tallow-diamine and oleic acid, in a molar ratio of 1:2. Absorption and subsequent possible toxicity follows from the dissociation of the salt. The diamine structure is much more toxic than the oleic acid part, and therefore it is considered that toxicity profile of Tallow-diamine dioleate will be fully driven by its tallow-diamine content. This is supported by data from repeated dose studies performed on both the similar Oleyl-diamine dioleate and on Oleyl-diamine.

Oleyl-diamine is almost identical to Tallow-diamine and cross-reading from the available data on Oleyl-diamine to Tallow-diamine is therefore applied.

For further evaluation of toxicity of Tallow-diamine dioleate, including reproduction toxicity, therefore cross-reading can be done to the data available on Oleyl-diamine. For DNEL setting use is made of thesub-chronic90-daystudiesin ratbased on read-across from C12-14-diamine, which related tothe shorteralkylchain-lengthcan be regarded to be the worst case representative for the group of alkyl-diamines with longer chain lengths such as Oleyl-diamine and Tallow-diamine.The NAOEL of 0.4 mg/kg for C12-14-diamine is therefore taken as starting point for the NOAEL value for Tallow-diamine, which then is converted to the corresponding value for the dioleate salt of Tallow-diamine.

(mw Tallow-diamine is approx. 310 (avg.), mw Tallow-diamine dioleate is 876 (avg.); 0.4 x 876/310 = 1.1 mg/kg bw/day)