Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
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
DNEL related information
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

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 E: NOAEL 2500 mg/kg bw/day, rat, up to 2 years (Scholz and Weigand, 1963)

-        Type E: NOAEL 1609 mg/kg bw/day, dogs, 140 days (Doerr et al., 1967)

-        Type OP: NOAEL 2500 mg/kg bw/day, rat, up to 2 years (Scholz and Weigand, 1963)

-        Type OP: NOAEL 1657 mg/kg bw/day, dogs, 140 days (Doerr et al., 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

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
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
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

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
DNEL related information
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

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, 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.

Repeated dose studies with Montan waxes:

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

-        Type E: NOAEL 2500 mg/kg bw/day, rat, up to 2 years (Scholz and Weigand, 1963)

-        Type E: NOAEL 1609 mg/kg bw/day, dogs, 140 days (Doerr et al., 1967)

-        Type OP: NOAEL 2500 mg/kg bw/day, rat, up to 2 years (Scholz and Weigand, 1963)

-        Type OP: NOAEL 1657 mg/kg bw/day, dogs, 140 days (Doerr et al., 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.