Tall oil, reaction products with diethylenetriamine

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.35 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):

25

Modified dose descriptor starting point:

NOAEC

Value:

8.84 mg/m³

Explanation for the modification of the dose descriptor starting point:

An OECD 408 compliant 90-day study in rat via oral route with AAI-DETA (the major component of DTO_DETA) resulted in an overall NOAEL of 10 mg/kg/day. The oral NOAEL is modified to obtain an inhalation NOAEC as the starting point for DNEL derivation. Following the ECHA REACH Guidance, it is assumed that inhalation absorption is equal to 2 x oral absorption: 10 mg/kg bw/d / 2 = 5 mg/kg bw/d. A correction is made for the standard respiratory volume in the rat: 5 mg/kg bw/d / 0.38 m³/kg/d = 13.2 mg/m³. Finally, a correction is made for the respiratory volume of a worker to give the corrected NOAEC: 13.2 mg/m³ x (6.7 m³/10 m³) = 8.84 mg/m³.

AF for dose response relationship:

1

Justification:

No specific concerns; starting point is a NOAEL and effects at LOAEL are local in nature

AF for differences in duration of exposure:

2

Justification:

ECHA default AF for sub-chronic to chronic duration of exposure

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling has already been considered in calculation of the modified starting point (NOAEC)

AF for other interspecies differences:

2.5

Justification:

ECHA default AF

AF for intraspecies differences:

5

Justification:

ECHA default AF for workers

AF for the quality of the whole database:

1

Justification:

ECHA default AF

AF for remaining uncertainties:

1

Justification:

No further correction required; the starting point (NOAEL) is considered to be conservative as it is based on local effects at the site of contact rather than true systemic toxicity

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

irritation (respiratory tract)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.1 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):

100

Dose descriptor starting point:

NOAEL

Value:

10 mg/kg bw/day

AF for dose response relationship:

1

Justification:

No specific concerns; starting point is a NOAEL and effects at LOAEL are local in nature

AF for differences in duration of exposure:

2

Justification:

ECHA default AF for sub-chronic to chronic duration of exposure

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA default AF for allometric scaling from rat to human

AF for other interspecies differences:

2.5

Justification:

ECHA default AF

AF for intraspecies differences:

5

Justification:

ECHA default AF for workers

AF for the quality of the whole database:

1

Justification:

ECHA default AF

AF for remaining uncertainties:

1

Justification:

No further correction required; the starting point (NOAEL) is considered to be conservative as it is based on local effects at the site of contact rather than true systemic toxicity

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)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - workers

DNEL derivation: workers

Systemic inhalation DNEL values

The NOAEL from the 90 -day oral study is corrected for route of exposure (/2), respiratory volume of the rat (/0.38) and respiratory volume of the worker (*6.7/10). Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 50. Applying the AF to the modified starting point gives an inhalation DNEL (long-term) for workers of 0.35 mg/m³.

In the absence of any identified hazard, a short-term systemic inhalation DNEL is not derived.

Local inhalation DNEL values

DNEL values for local inhalation effects are not derived. No data are available regarding local respiratory effects. Since the substance is irritating to the skin and the eyes, local inhalation effects following acute or repeated exposures would be manifested by respiratory irritation. The substance is classified for skin corrosion in Category 1C, H314 (Causes severe skin burns and eye damage) according to the CLP Regulation and is assigned to the medium hazard category according to ECHA CSA Guidance E, Table E.3-1. A qualitative risk characterisation is required in respect of this endpoint.

Due to the very low vapour pressure of the substance, inhalation exposures would only be possible in the form of aerosol, consisting of larger droplets depositing in the upper airways which could result in local irritation. However, as no dose-response data regarding local respiratory effects are available, a quantitative dose descriptor (e.g. a DNEL) cannot be calculated based on available information. The absence of route specific information is justified based on conditions of use and qualitative risk characterisation. The inhalation DNEL for systemic effects is considered sufficiently protective in respect of potential local effects.

Systemic dermal DNEL values

In the absence of dermal absorption data, the default ECHA assumption is that dermal absorption is equal to oral absorption therefore no correction for absorption is applied to the starting point. Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for interspecies allometric scaling) 2.5 (for other interspecies differences), 5 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 100. Applying the AF to the starting point gives a dermal DNEL (long-term) for workers of 0.1 mg/kg bw/d.

In the absence of any identified hazard, a short-term systemic dermal DNEL is not derived.

Local dermal DNEL values

The substance is classified as a Category 1A Skin Sensitiser H317: May cause an allergic skin reaction; therefore high hazard is assigned for short- and long-term local effects in accordance with the hazard bands defined in Table E.3 -1, ECHA Guidance Part E.

Hazards for the eyes

The substance is classified as Skin Corrosion Category 1C H314: Causes severe skin burns and eye damage; therefore medium hazard is assigned for local eye effects in accordance with the hazard bands defined in Table E.3 -1, ECHA Guidance Part E.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.088 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):

50

Modified dose descriptor starting point:

NOAEC

Value:

4.35 mg/m³

Explanation for the modification of the dose descriptor starting point:

An OECD 408 compliant 90-day study in rat via oral route with AAI-DETA (the major component of DTO_DETA) resulted in an overall NOAEL of 10 mg/kg/day. The oral NOAEL is modified to obtain an inhalation NOAEC as the starting point for DNEL derivation. Following the ECHA REACH Guidance, it is assumed that inhalation absorption is equal to 2 x oral absorption: 10 mg/kg bw/d / 2 = 5 mg/kg bw/d. A correction is made for the standard respiratory volume in the rat to give the corrected NOAEC: 5 mg/kg bw/d / 1.15 m³/kg/d = 4.35 mg/m³.

AF for dose response relationship:

1

Justification:

No specific concerns; starting point is a NOAEL and effects at LOAEL are local in nature

AF for differences in duration of exposure:

2

Justification:

ECHA default AF for sub-chronic to chronic duration of exposure

AF for interspecies differences (allometric scaling):

1

Justification:

Allometric scaling has already been considered in calculation of the modified starting point (NOAEC)

AF for other interspecies differences:

2.5

Justification:

ECHA default AF

AF for intraspecies differences:

10

Justification:

ECHA default AF for general population

AF for the quality of the whole database:

1

Justification:

ECHA default AF

AF for remaining uncertainties:

1

Justification:

No further correction required; the starting point (NOAEL) is considered to be conservative as it is based on local effects at the site of contact rather than true systemic toxicity

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

irritation (respiratory tract)

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

irritation (respiratory tract)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.05 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):

200

Dose descriptor starting point:

NOAEL

Value:

10 mg/kg bw/day

AF for dose response relationship:

1

Justification:

No specific concerns; starting point is a NOAEL and effects at LOAEL are local in nature

AF for differences in duration of exposure:

2

Justification:

ECHA default AF for sub-chronic to chronic duration of exposure

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA default AF for allometric scaling from rat to human

AF for other interspecies differences:

2.5

Justification:

ECHA default AF

AF for intraspecies differences:

10

Justification:

ECHA default AF for general population

AF for the quality of the whole database:

1

Justification:

ECHA default AF

AF for remaining uncertainties:

1

Justification:

No further correction required; the starting point (NOAEL) is considered to be conservative as it is based on local effects at the site of contact rather than true systemic toxicity

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)

Most sensitive endpoint:

sensitisation (skin)

Acute/short term exposure

Hazard assessment conclusion:

high hazard (no threshold derived)

Most sensitive endpoint:

sensitisation (skin)

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.05 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):

200

Dose descriptor starting point:

NOAEL

Value:

10 mg/kg bw/day

AF for dose response relationship:

1

Justification:

No specific concerns; starting point is a NOAEL and effects at LOAEL are local in nature

AF for differences in duration of exposure:

2

Justification:

ECHA default AF for sub-chronic to chronic duration of exposure

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA default AF for allometric scaling from rat to human

AF for other interspecies differences:

2.5

Justification:

ECHA default AF

AF for intraspecies differences:

10

Justification:

ECHA default AF for general population

AF for the quality of the whole database:

1

Justification:

ECHA default AF

AF for remaining uncertainties:

1

Justification:

No further correction required; the starting point (NOAEL) is considered to be conservative as it is based on local effects at the site of contact rather than true systemic toxicity

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

medium hazard (no threshold derived)

Additional information - General Population

DNEL derivation: general population

Systemic inhalation DNEL values

The NOAEL from the 90 -day oral study is corrected for route of exposure (/2) and respiratory volume of the rat (/1.15). Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 50. Applying the AF to the modified starting point gives an inhalation DNEL for the general population of 0.088 mg/m³.

In the absence of any identified hazard, a short-term systemic inhalation DNEL is not derived.

Local inhalation DNEL values

DNEL values for local inhalation effects are not derived. No data are available regarding local respiratory effects. Since the substance is irritating to the skin and the eyes, local inhalation effects following acute or repeated exposures would be manifested by respiratory irritation. The substance is classified for skin corrosion in Category 1C, H314 (Causes severe skin burns and eye damage) according to the CLP Regulation and is assigned to the medium hazard category according to ECHA CSA Guidance E, Table E.3-1.

It should be noted, however, that there are no consumer uses associated with this substance and therefore the general public will not be exposed.

Systemic dermal DNEL values

In the absence of dermal absorption data, the default ECHA assumption is that dermal absorption is equal to oral absorption therefore no correction for absorption is applied to the starting point. Individual assessment factors of 1 (for dose-response relationship), 2 (for duration of exposure), 4 (for interspecies allometric scaling) 2.5 (for other interspecies differences), 10 (for intraspecies differences), 1 (for database quality) and 1 (for remaining uncertainties) give an overall assessment factor of 200. Applying the AF to the starting point gives a dermal DNEL for the general population of 0.05 mg/kg bw/d.

In the absence of any identified hazard, a short-term systemic dermal DNEL is not derived.

Local dermal DNEL values

The substance is classified as a Category 1A Skin Sensitiser H317: May cause an allergic skin reaction; therefore high hazard is assigned for short- and long-term local effects in accordance with the hazard bands defined in Table E.3 -1, ECHA Guidance Part E. However, it should be noted that there are no consumer uses associated with this substance and therefore the general public will not be exposed.

Hazards for the eyes

The substance is classified as Skin Corrosion Category 1C H314: Causes severe skin burns and eye damage; therefore medium hazard is assigned for local eye effects in accordance with the hazard bands defined in Table E.3 -1, ECHA Guidance Part E. However, it should be noted that there are no consumer uses associated with this substance and therefore the general public will not be exposed.