Overbased reaction products of distilled tall oil and magnesium hydroxide’

Toxicological Summary

Workers - Hazard via inhalation 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:

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

DNEL related information

Local 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:

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

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

2.83 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

300

Modified dose descriptor starting point:

NOAEL

Value:

849 mg/kg bw/day

AF for dose response relationship:

1

Justification:

default AF

AF for differences in duration of exposure:

6

Justification:

sub-acute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

default for rat

AF for other interspecies differences:

2.5

Justification:

default for remaining differences

AF for intraspecies differences:

5

Justification:

default for workers

AF for the quality of the whole database:

1

Justification:

default AF

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - workers

Acute Toxicity

A DNEL for acute toxicity need only be derived if an acute hazard leading to classification for acute toxicity (e. g. under CLP[A1]) has been identified and there is a potential for high peak exposures. If no hazard has been identified, then a DNEL for acute toxicity is unnecessary as the long-term DNEL will be sufficient to ensure that adverse effects do not occur. Distilled tall oil, magnesium salts are not classified for acute toxicity and are not irritant (eye, skin or respiratory tract) and therefore no acute DNELs (systemic or local) have been calculated.

 

Long-term Systemic Toxicity

Distilled tall oil, magnesium salts is a complex reaction product formed by reacting magnesium hydroxide with distilled tall oil. It has the generic structure RCOO—Mg—OOCR, with the R groups being derived from the distilled tall oil. Distilled tall oil is a UVCB substance derived from natural sources and typical analysis shows it comprises a mixture of unsaturated fatty acids – primarily C18 (~70%) and mixed rosin acids (~30%).

Repeat dose systemic toxicity data are available for a lithium salt of C18 unsaturated fatty acids and also gum rosin. As the R groups are derived from distilled oil, the ratio of unsaturated C18 and rosin acids R groups in the molecule are likely to be proportional to the levels found in the parent distilled tall oil. The NOAEL value used as the starting point for systemic DNEL derivation is calculated proportionally, to give an estimated DNEL.

The NOAEL value is derived from a combined dermal repeat dose/reproductive toxicity screening study in rats on (Thorsrud, 2011) and an oral reproductive toxicity screening study in rats (Inveresk Research, 2003).

Based on the above calculation, a NOAEL of 849 mg/kg bw/d was derived ((70% x 1089.75 mg/kg bw/d) + (30% x 288 mg/kg bw/d)).

Dermal DNEL (systemic)

Dose descriptor

The calculated NOAEL of 849 mg/kg bw/d will be used as the starting point.

Modification of dose descriptor

100% absorption after ingestion and 100% after skin contact are assumed.

Assessment factors (ECHA Guidance Chapter R8, Table R8-6, November 2012

Long-term DNEL Assessment Factors (Dermal)
Assessment Factor	Worker
Interspecies	2.5 (for systemic effects)   4 (Allometric scaling for rats)
Intraspecies	5 (for worker)
Exposure duration	6 (subacute to chronic)
Issues related to dose-response	1
Issues related to dose-response	1
Overall AF	300

 

DNEL Worker long-term dermal-systemic = 849 / 300 = 2.83 mg/kg bw/day

General Population - Hazard via inhalation 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:

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

DNEL related information

Local 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:

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

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.415 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

600

Modified dose descriptor starting point:

NOAEL

Value:

849 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default AF

AF for differences in duration of exposure:

6

Justification:

For sub-acute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

Default for rat

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

10

Justification:

Default for general population

AF for the quality of the whole database:

1

Justification:

default AF

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

1.415 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

DNEL related information

DNEL derivation method:

ECHA REACH Guidance

Overall assessment factor (AF):

600

Modified dose descriptor starting point:

NOAEL

Value:

849 mg/kg bw/day

AF for dose response relationship:

1

Justification:

Default AF

AF for differences in duration of exposure:

6

Justification:

Sub-acute to chronic

AF for interspecies differences (allometric scaling):

4

Justification:

Default for rat

AF for other interspecies differences:

2.5

Justification:

Default AF

AF for intraspecies differences:

10

Justification:

Default for general population

AF for the quality of the whole database:

1

Justification:

Default AF

Acute/short term exposure

Hazard assessment conclusion:

no-threshold effect and/or no dose-response information available

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

low hazard (no threshold derived)

Additional information - General Population

Acute Toxicity

A DNEL for acute toxicity need only be derived if an acute hazard leading to classification for acute toxicity (under CLP [A1]) has been identified and there is a potential for high peak exposures. If no hazard has been identified then a DNEL for acute toxicity is unnecessary as the long-term DNEL will be sufficient to ensure that adverse effects do not occur. Distilled tall oil, magnesium salts are not classified for acute toxicity and are not irritant (eye, skin or respiratory tract) and therefore no acute DNELs (systemic or local) have been calculated.

 

Long-term Systemic Toxicity

Distilled tall oil, magnesium salts is complex reaction product formed by reacting magnesium hydroxide with distilled tall oil. It has the generic structure RCOO—Mg—OOCR, with the R groups being derived from the distilled tall oil. Distilled tall oil is a UVCB substance derived from natural sources and typical analysis shows it comprises a mixture of unsaturated fatty acids – primarily C18 (~70%) and mixed rosin acids (~30%).

Repeat dose systemic toxicity data are available for a lithium salt of C18 unsaturated fatty acids and also gum rosin. As the R groups are derived from distilled tall oil, the ratio of unsaturated C18 and rosin acids R groups in the molecule is likely to be proportional to the levels found in the parent distilled tall oil. The NOAEL value used as the starting point for systemic DNEL derivation is calculated proportionally, to give an estimated DNEL.

The NOAEL value is derived from a combined dermal repeat dose/reproductive toxicity screening study in rats (Thorsrud, 2011) and an oral reproductive toxicity screening study in rats (Inveresk Research, 2003).

Based on the above calculation, a NOAEL of 849 mg/kg bw/d was derived ((70% x 1089.75 mg/kg bw/d) + (30% x 288 mg/kg bw/d)).

Dermal DNEL (systemic)

Dose descriptor

The calculated NOAEL of 849 /kg bw/d will be used as the starting point.

Modification of dose descriptor

100% absorption after ingestion and 100% after skin contact are assumed.

Assessment factors (ECHA Guidance Chapter R8, Table R8-6, November 2012

Long-term DNEL Assessment Factors (Dermal)
Assessment Factor	General Population
Interspecies	2.5 (for systemic effects)   4 (Allometric scaling for rats)
Intraspecies	10 (for general population)
Exposure duration	6 (subacute to chronic)
Issues related to dose-response	1
Issues related to dose-response	1
Overall AF	600

DNEL General Population long-term dermal-systemic = 849 / 600 = 1.415 mg/kg bw/day

Oral DNEL (systemic)

Dose descriptor

The calculated NOAEL of 849 /kg bw/d will be used as the starting point.

Modification of dose descriptor

100% absorption after ingestion and 100% after skin contact are assumed.

Assessment factors (ECHA Guidance Chapter R8, Table R8-6, November 2012

Long-term DNEL Assessment Factors (Oral)
Assessment Factor	General Population
Interspecies	2.5 (for systemic effects)   4 (Allometric scaling for rats)
Intraspecies	10 (for general population)
Exposure duration	6 (subacute to chronic)
Issues related to dose-response	1
Issues related to dose-response	1
Overall AF	600

DNEL General Population long-term oral-systemic = 849 / 600 = 1.415 mg/kg bw/day

Read across justification for Distilled Tall Oil, Magnesium Salts

Distilled tall oil, magnesium salts is produced by reacting magnesium hydroxide and distilled tall oil. The resulting substance is a UVCB, with the following generic structure:

RCOO—Mg—OOCR

The R groups are derived from the distilled tall oil starting material, which is a UVCB substance derived from natural sources, with varying composition. Therefore there are a number of different possible combinations for the resulting carboxylic acid groups present in the complex mixture of divalent magnesium salts.

Based on supplier analysis, the distilled tall oil comprises a mixture of unsaturated fatty acids – primarily C18 (~70%) and mixed rosin acids (~30%); typical analysis of a sample of distilled tall oil is presented in Table 1. The variable composition of distilled tall oil means that Distilled tall oil, magnesium salts will comprise a complex mixture of the divalent magnesium salts of both fatty acid and rosin components, in proportion to the ratio of fatty acids:rosin acids found in the starting distilled tall oil. In the absence of data on Distilled tall oil, magnesium salts, the environmental fate, ecotoxicity and toxicology properties are predicted based on read across to related fatty acid and rosin acid salts. Analytical data (Mass Spec., FTIR and NMR) confirm the presence of divalent magnesium carboxylic acid salts and NMR shows the presence of a proportion of cyclic carboxylic acid structures.

No data were identified for magnesium salts of C18 unsaturated fatty acids, which comprises approximately 70% of the registered substance. Data were available however for a similar lithium salt – fatty acids, C18-(unsaturated) lithium salts. Read across to this compound is justified based on the fact that it is also a divalent salt of fatty acids derived from distilled tall oil, which has similar physic-chemical properties. The lithium and magnesium ions present in these salts are not likely to contribute to the toxicity and therefore any effects observed are likely to be due to the fatty acid component.

For the rosin acid salt component (~30%) of Distilled tall oil, magnesium salts, data are read across from a category of substances with similar composition, containing rosin, hydrogenated rosin and rosin acid salts. This category of rosin substances have been registered under REACH using a category approach, and members of this category are considered to be representative of the rosin acid salts found in Distilled tall oil, magnesium salts. The category of rosin substances includes both monovalent and divalent salts of rosin acids, including a magnesium salt. Therefore the rosin acid component of Distilled tall oil, magnesium salts would fit within this category and read across is considered to be appropriate.

Further details are given in the attachment in Section 13.