Reaction mass of Fatty acids, montan-wax and Fatty acids, montan-wax, calcium salts and Montan wax

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

50 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):

20

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

no data for dermal pathway available, same absorption rate assumed

AF for dose response relationship:

1

Justification:

ECHA Guidance

AF for differences in duration of exposure:

1

Justification:

subchronic and chronic studies available, no difference observed

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA Guidance

AF for other interspecies differences:

1

Justification:

no LOAEL identified, "real" NOAEL expected to be much higher, NOAEL very conservative

AF for intraspecies differences:

5

Justification:

ECHA Guidiance

AF for the quality of the whole database:

1

Justification:

ECHA Guidiance

AF for remaining uncertainties:

1

Justification:

ECHA Guidiance

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - workers

Workers

Acute Exposure

DNELs for acute exposure - systemic effects are not derived, because no relevant acute toxicity was observed (LD50 oral >2000 mg/kg bw; LD50 dermal >2000 mg/kg bw) and no hazards leading to classification and labeling were identified.

DNELs for acute exposure - local effects are not derived, because the members of this category have not to be classified as irritating to skin or eyes and are considered unlikely to become bioavailable in the skin. Furthermore, exposure of humans via inhalation is considered unlikely taking into account the vapour pressure of the substance and the physical form of the substances.

Finally, there is no established accepted methodology for the derivation of acute toxicity DNELs existing.

Long-term exposure

DNEL long-term dermal exposure - systemic effects:

Several repeated-dose studies with oral exposure exist, which show no toxicity of the test materials. The key study for Montan wax, type S (OECD 422 with extended treatment, Sisti and Oberto, 2010) reveals a NOAEL of 1000 mg/kg bw/day after subchronic exposure duration. This NOAEL is supported by several other, less reliable studies on other members of the Montan waxes group.

Repeated dose studies with Montan waxes:

-       Type S: NOAEL 1000 mg/kg bw/day, rat, subchronic (Sisti and Oberto, 2010)

-       Type WE4: NOAEL 3916-4090 mg/kg bw/day, rat, subchronic (Jung and Hoffmann, 1980)

-       Type KPS: NOAEL 2000-2500 mg/kg bw/day, rat, chronic (Scholz et al., 1969)

-       Type KPS: NOAEL 1250 mg/kg bw/day, dog, subchronic (Scholz and Brunk, 1967)

and reliable supporting studies with structurally related substances:

-       D-003: NOAEL 1500 mg/kg bw/day, rat, 2 years (Gamez et al., 2007)

-       Policosanol: NOAEL 500 mg/kg bw/day, rat, 2 years (Aleman et al., 1994)

The NOAEL for oral exposure of 1000 mg/kg bw/day is regarded as starting point for the derivation of DNELs.

The substances are not likely to be systemically available after dermal exposure. As worst case consideration a DNEL "long-term dermal exposure - systemic effects" can be derived by route-to-route extrapolation of the data after long-term oral exposure. The key study for Montan wax, type S (OECD 422 with extended treatment, Sisti and Oberto, 2010) reveals a NOAEL of 1000 mg/kg bw/day (highest dose tested, no toxicity observed). This NOAEL is supported by several other, less reliable studies on other members of the Montan waxes group and reliable supporting studies with structurally related substances (see below). Assuming, that dermal absorption is not higher than oral absorption the NOAEL for oral exposure of 1000 mg/kg bw/day is regarded as starting point for the derivation of the DNEL "long-term dermal exposure - systemic effects".An allometric scaling factor of 4 is applied to account for constitutionally species differences and a factor 1 for remaining interspecies differences, because no effects were observed at the highest concentration tested in any of the studies, i. e. only NOAELs were derived and the LOAELs after repeated exposure remains unidentified. Due to the very low acute toxicity it is expected that the true NOAEL is much higher than the NOAEL identified in the studies with repeated exposure. Application of the default factor of 2.5 for remaining uncertainties beyond allometric scaling would probably result in an overly conservative DNEL value. The comparison of subchronic with chronic studies does not indicate an increase of toxicity with increasing exposure duration, so a factor 1 is used for time extrapolation. In the absence of any substance specific data a default factor of 5 is used for intraspecies extrapolation. This results in an overall assessment factor of 20 (4 x 5). Based on these data a DNEL long-term dermal exposure - systemic effects of 50 mg/kg bw/day is derived for the members of this category. This procedure is very conservative because no systemic uptake from dermal exposure is expected.

DNEL long-term inhalation exposure - systemic effects:

There are no studies with long term inhalation exposure to the members of the Montan waxes category available.

Exposure of humans via inhalation is considered unlikely taking into account the vapour pressure of the substance

and the physical form of the substances. Therefore, no DNEL "long-term inhalation exposure - systemic effects" is derived.

DNELs for long-term exposure - local effects are not derived, because the members of this category have not to be classified as irritating to skin or eyes. Furthermore, exposure of humans via inhalation is considered unlikely taking into account the vapour pressure and the physical form of the substances.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

25 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):

40

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

no data for dermal pathway available, same absorption rate assumed

AF for dose response relationship:

1

Justification:

ECHA Guidance

AF for differences in duration of exposure:

1

Justification:

subchronic and chronic studies available, no difference observed

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA Guidance

AF for other interspecies differences:

1

Justification:

no LOAEL identified, "real" NOAEL expected to be much higher, NOAEL very conservative

AF for intraspecies differences:

10

Justification:

ECHA Guidance

AF for the quality of the whole database:

1

Justification:

ECHA Guidance

AF for remaining uncertainties:

1

Justification:

ECHA Guidance

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

no hazard identified

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

25 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):

40

Modified dose descriptor starting point:

NOAEL

Value:

1 000 mg/kg bw/day

AF for dose response relationship:

1

Justification:

ECHA Guidance

AF for differences in duration of exposure:

1

Justification:

subchronic and chronic studies available, no difference observed

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA Guidance

AF for other interspecies differences:

1

Justification:

no LOAEL identified, "real" NOAEL expected to be much higher, NOAEL very conservative

AF for intraspecies differences:

10

Justification:

ECHA Guidance

AF for the quality of the whole database:

1

Justification:

ECHA Guidance

AF for remaining uncertainties:

1

Justification:

ECHA Guidance

Acute/short term exposure

Hazard assessment conclusion:

no hazard identified

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

no hazard identified

Additional information - General Population

General population

Acute exposure

DNELs for acute exposure - systemic effects are not derived, because no relevant acute toxicity was observed (LD50 oral >2000 mg/kg bw; LD50 dermal >2000 mg/kg bw) and no hazards leading to classification and labeling were identified.

DNELs for acute exposure - local effects are not derived, because the members of this category have not to be classified as irritating to skin or eyes and are considered unlikely to become bioavailable in the skin. Furthermore,exposure of humans via inhalation is considered unlikely taking into account the vapour pressure of the substance and the physical form of the substances.

Finally, there is no established accepted methodology for the derivation of acute toxicity DNELs existing.

Long-term exposure

DNEL long-term inhalation exposure - systemic effects:

There are no studies with long term inhalation exposure to the members of the Montan waxes category available.

Exposure of humans via inhalation is considered unlikely taking into account the vapour pressure and the physical form of the substances.

It is considered unlikely that the substances will become systemically available after inhalation exposure. Therefore, no DNEL "long-term inhalation exposure - systemic effects" is derived.

DNEL long-term oral exposure - systemic effects:

Several repeated-dose studies with oral exposure exist, which show no toxicity of the test materials. The key study for Montan wax, type S (OECD 422 with extended treatment, Sisti and Oberto, 2010) reveals a NOAEL of 1000 mg/kg bw/day after subchronic exposure duration. This NOAEL is supported by several other, less reliable studies on other members of the Montan waxes group.

Repeated dose studies with Montan waxes:

-      Type S: NOAEL 1000 mg/kg bw/day, rat, subchronic (Sisti and Oberto, 2010)

-      Type WE4: NOAEL 3916-4090 mg/kg bw/day, rat, subchronic (Jung and Hoffmann, 1980)

-      Type KPS: NOAEL 2000-2500 mg/kg bw/day, rat, chronic (Scholz et al., 1969)

-      Type KPS: NOAEL 1250 mg/kg bw/day, dog, subchronic (Scholz and Brunk, 1967)

and reliable supporting studies with structurally related substances:

-      D-003: NOAEL 1500 mg/kg bw/day, rat, 2 years (Gamez et al., 2007)

-      Policosanol: NOAEL 500 mg/kg bw/day, rat, 2 years (Aleman et al., 1994)

 

The NOAEL for oral exposure of 1000 mg/kg bw/day is regarded as starting point for the derivation of the DNEL. An allometric scaling factor of 4 is applied to account for constitutionally species differences and a factor 1 for remaining interspecies differences, because no effects were observed at the highest concentration tested in any of the studies, i. e. only NOAELs were derived and the LOAELs after repeated exposure remains unidentified. Due to the very low acute toxicity it is expected that the true NOAEL is much higher than the NOAEL identified in the studies with repeated exposure. Application of the default factor of 2.5 for remaining uncertainties beyond allometric scaling would probably result in an overly conservative DNEL value. The comparison of subchronic chronic studies does not indicate an increase of toxicity with increasing exposure duration, so a factor 1 is used for time extrapolation. In the absence of any substance specific data a default factor of 10 is used for intraspecies extrapolation. This results in an overall assessment factor of 40 (4 x 10). Based on these data a DNEL long-term oral exposure ¿ systemic effects of 25 mg/kg bw/day is derived for the members of this category. This procedure is very conservative because no LOAEL could be identified.

DNEL long-term dermal exposure - systemic effects:

No data on toxicity of the members of this category after long-term dermal exposure are available. The substances are not likely to be systemically available after dermal exposure. As worst case consideration a DNEL "long-term dermal exposure - systemic effects" can be derived by route-to-route extrapolation of the data after long-term oral exposure. The key study for Montan wax, typeS (OECD 422 with extended treatment, Sisti and Oberto, 2010)reveals a NOAEL of 1000 mg/kg bw/day after subchronic exposure duration. This NOAEL is supported by several other, less reliable studies on other members of the Montan waxes group and reliable supporting studies with structurally related substances (see below). Assuming, that dermal absorption is not higher than oral absorption the NOAEL for oral exposure of 1000 mg/kg bw/day is regarded as starting point for the derivation of the DNEL "long-term dermal exposure - systemic effects". In analogy to oral exposure, an overall assessment factor of 40 (4 x 10) is used. Based on these data a DNEL long-term dermal exposure ¿ systemic effects of 25 mg/kg bw/day is derived for the members of this category. This procedure is very conservative because no systemic uptake from dermal exposure is expected.

DNELs for long-term exposure - local effects are not derived, because the members of this category do not show irritating effects and have not to be classified as irritating to skin or eyes. Furthermore,

exposure of humans via inhalation is considered unlikely taking into account the vapour pressure and the physical form of the substances.

DNELs for long-term exposure - local effects:

DNELs for long-term exposure - local effects (dermal and inhalative) are not derived, because the members of this category have not to be classified as irritating to skin or eyes and are considered unlikely to become bioavailable in the skin. Furthermore, exposure of humans via inhalation is considered unlikely taking into account the vapour pressureand the physical form of the substances.