Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
3.9 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):
225
Modified dose descriptor starting point:
NOAEC
Value:
881.6 mg/m³
Explanation for the modification of the dose descriptor starting point:
A long-term systemic inhalation DNEL is derived from the oral NOAEL of 1000 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that the oral absorption rate is 50% that of the inhalation rate (i.e. oral and inhalation absorption values of 50% and 100% respectively are assumed). The corrected inhalation NOAEC for workers is derived as: oral NOAEL x (1/0.38 m3/kg/day) x (6.7 m3/10m3 (8 h)) x (% oral absorption/ % inhalation absorption) = 1000 mg/kg bw/day x (1/0.38) x 0.67 x (50/100) = 881.6 mg/m3.
AF for dose response relationship:
1
Justification:
A default factor: based on the available data, the substance is of low toxicity
AF for differences in duration of exposure:
6
Justification:
A default factor for extrapolation from a sub-acute study to chronic exposure.
AF for other interspecies differences:
2.5
Justification:
A default factor (remaining difference)
AF for intraspecies differences:
5
Justification:
A default factor for workers
AF for the quality of the whole database:
1
Justification:
Default factor
AF for remaining uncertainties:
3
Justification:
No analytical concentration verification was obtained in the study; a factor of 3 is proposed to account for any associated uncertainties.
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:
1.1 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):
900
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A long-term systemic dermal DNEL is derived from the oral NOAEL of 1000 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that dermal absorption will not exceed oral absorption (i.e. oral and dermal absorption values of 50% respectively are assumed). The equivalent dermal NOAEL is derived as: oral NOAEL x (% oral absorption/ % dermal absorption) = 1000 mg/kg bw/day x (50/50) = 1000 mg/kg bw/day.
AF for dose response relationship:
1
Justification:
A default factor: based on the available data, the substance is of low toxicity
AF for differences in duration of exposure:
6
Justification:
A default factor for extrapolation from a sub-acute study to chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor: (allometric scaling: rat)
AF for other interspecies differences:
2.5
Justification:
Default factor (remaining differences)
AF for intraspecies differences:
5
Justification:
A default factor for workers
AF for the quality of the whole database:
1
Justification:
A default factor
AF for remaining uncertainties:
3
Justification:
No analytical concentration verification was obtained in the study; a factor of 3 is proposed to account for any associated uncertainties.
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

Identity of the substance and approach to meeting the data requirements

Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine

 

Toxicokinetics

Based on physicochemical data, toxicity data and theoretical assessment, the basic toxicokinetics of Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine can be adequately characterised. According to Lipinski’s Rule of Five (OECD QSAR Toolbox prediction using a representative structure), the substance will not be bioavailable, therefore oral absorption is not predicted. Dermal absorption is also considered to be unlikely. No reliable quantitative prediction of the extent of inhalation absorption can be made; however inhalation absorption is also likely to be low.

 

Acute toxicity

 

Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine is of low acute oral and dermal toxicity: the LD50 via both routes respectively is > 2000 mg/kg bw. A waiver is proposed in accordance with Column 2 of Annex VIII of the REACH Regulation for acute inhalation toxicity on the basis that acute toxicity data are available for the oral and dermal routes.  Inhalation is not predicted to be a significant route of exposure based on the physicochemical properties of the substance.

 

Irritation/corrosion

Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine was found to be irritating to skin, but not corrosive, in in vitro studies using the EpiDerm™ skin model (Dreher, 2012a and b), according to OECD Test Guidelines. The substance meets the criteria for classification as Category 2, H315 “Causes skin irritation” according to Regulation (EC) No 1272/2008, and as Xi, R38 “Irritating to skin” according to Directive 67/548/EEC.

In eye irritation studies, while the substance was not irritating in an in vitro BCOP assay, it was severely irritating to the eyes in a study in vivo. The substance meets the criteria for classification as Category 1, H318 “Causes serious eye damage” according to Regulation (EC) No 1272/2008 and Xi, R41 “Risk of serious damage to eyes” according to Directive 67/548/EEC.

Skin sensitisation

Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine was considered to be a skin sensitiser in the Local Lymph Node Assay (LLNA). The substance meets the criteria for classification for skin sensitisation as: Category 1A, H317 “May cause an allergic skin reaction” according to Regulation (EC) No 1272/2008 and as Xi, R43 “May cause sensitisation by skin contact” according to Directive 67/548/EEC.

Repeated dose toxicity

 

The sub-acute repeated dose oral toxicity of Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine was investigated in rats in a combined repeated dose toxicity study with the reproduction/developmental toxicity screening test conducted according to OECD Test Guideline 422 (Perks, 2013). In the study, no treatment related effects were observed following the administration of the substance by oral gavage at doses up to 1000 mg/kg bw/day. Based on this study, The No-Observed-Adverse-Effect-Level (NOAEL) for the sub-acute repeated dose oral toxicity of the substance in male and female rats was considered to be 1000 mg/kg bw/day (i.e. the highest dose tested).

The 90-day oral repeated dose toxicity study in the rat (OECD Test Guideline 408) is proposed to further characterise the repeated dose toxicity of Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine.

Waivers are proposed for repeated dose toxicity tests via the inhalation and dermal routes in accordance with Column 2 of Annex VIII of the REACH Regulation. The repeated dose toxicity of the substance will be adequately elucidated by the oral route, with additional testing proposed. Further testing via the dermal and inhalation routes is not required.

 

Genetic toxicity

No evidence of mutagenicity was seen for Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine in a bacterial reverse mutation assay (Ames test). Negative results were obtained in in vitro mammalian cytogenicity and gene mutation studies. The substance is not genotoxic in vitro in bacterial or in mammalian cell systems. 

Toxicity to reproduction

 

The effects of Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine on fertility and on developmental parameters have been investigated in a combined repeated dose/reproductive screening toxicity study conducted according to OECD Test Guideline 422 (Perks, 2013). No developmental effects, effects on reproductive parameters or treatment-related signs of systemic toxicity were observed in the study. Based on this study, The No-Observed-Adverse-Effect-Level (NOAEL) for the effects of the substance on fertility in male and in female rats and for developmental toxicity was considered to be 1000 mg/kg bw/day (i.e. the highest dose tested).

A pre-natal developmental toxicity study using Fatty acids, C18-unsatd., dimers, oligomeric reaction products with tall-oil fatty acids and triethylenetetramine in the rat (OECD Test Guideline 414) is proposed in order to further evaluate the developmental (and reproductive) hazard potential of the substance.

In accordance with Column 2 of Annex X of the REACH regulation, a waiver is proposed for the two-generation reproductive toxicity study. No adverse effects or indication of systemic exposure were observed in the combined repeated dose toxicity with reproduction/developmental toxicity screening test (OECD 422) at dose levels up to and including the limit dose. Also, according to Lipinski’s Rule of Five, the substance is not predicted to be bioavailable (OECD QSAR Toolbox). No additional testing is therefore considered necessary on scientific grounds and in the interests of avoiding unnecessary animal testing in accordance with EU Directive 86/609/EEC.

 

DNEL derivation [Workers]

 

Based on the data available, the substance is of low acute toxicity, is not mutagenic, does not cause target organ or systemic toxicity and is not a developmental or reproductive toxin. The substance is irritating to the skin and the eyes and is a skin sensitiser. Classification in respect of these effects is proposed.

 

The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 1000 mg/kg bw/day from a combined repeated oral dose and reproductive/developmental screening study conducted in rats according to OECD Test Guideline 422.

 

Local effects

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. 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.

DNEL values for local dermal effects are not derived. The substance is irritating and sensitising to the skin. The substance is classified for skin irritation as: Category 2, H315 “Causes skin irritation” according to Regulation (EC) No 1272/2008, and as Xi, R38 “Irritating to skin” according to Directive 67/548/EEC. The substance is classified for skin sensitisation as Category 1A, H317 “May cause an allergic skin reaction” according to Regulation (EC) No 1272/2008 and as Xi, R43 “May cause sensitisation by skin contact” according to Directive 67/548/EEC. According to ECHA CSA Guidance Part E Table E3-1, “ low” hazard is assigned in respect of the skin irritation potential of the substance, however, on account of its skin sensitisation potential, “high” hazard is assigned overall in respect of both endpoints.

A qualitative risk characterisation is required in respect of the local inhalation and dermal effects of the substance.

Systemic effects

The substance is of low systemic toxicity. No acute toxicity hazard resulting in classification has been identified, therefore DNELs for acute systemic effects are not proposed.

The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 1000 mg/kg bw/day from a combined repeated oral dose and reproductive/developmental screening study conducted in rats according to OECD Test Guideline 422.

[Dermal – long-term systemic DNEL]

A long-term systemic dermal DNEL is derived from the oral NOAEL of 1000 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that dermal absorption will not exceed oral absorption (i.e. oral and dermal absorption values of 50% respectively are assumed). The equivalent dermal NOAEL is derived as: oral NOAEL x (% oral absorption/ % dermal absorption) = 1000 mg/kg bw/day x (50/50) = 1000 mg/kg bw/day. 

The use of assessment factors according to REACH guidance is considered below:

Interspecies: default values of 4 (allometric scaling: rat) and 2.5 (remaining differences) are proposed.

Intraspecies: a default value of 5 is proposed for workers

Exposure duration: a default value of 6 is proposed for extrapolation from a sub-acute study to chronic exposure. This represents a conservative approach, as the data indicate low toxicity following single and repeated exposures

Dose-response: a default value of 1 is proposed as, based on the available data, the substance is of low toxicity

Quality of the data base: a default factor of 1 is proposed

Remaining uncertainties: no analytical concentration verification was obtained in the study; a factor of 3 is proposed to account for any associated uncertainties. 

An overall assessment factor of 900 for long-term dermal effects is therefore calculated for workers.

Applying the assessment factor of 900 to the dermal equivalent NOAEL of 1000 mg/kg bw/day gives a dermal DNEL value of 1.1 mg/kg bw/day for long-term systemic effects.

[Inhalation – long-term systemic DNEL]

A long-term systemic inhalation DNEL is derived from the oral NOAEL of 1000 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that the oral absorption rate is 50% that of the inhalation absorption rate (i.e. oral and inhalation absorption values of 50% and 100% respectively are assumed). The corrected inhalation NOAEC for workers is derived as: oral NOAEL x (1/0.38 m3/kg/day) x (6.7 m3/10m3(8 h)) x (% oral absorption/ % inhalation absorption) = 1000 mg/kg bw/day x (1/0.38) x 0.67 x (50/100) = 881.6 mg/m3

The use of assessment factors according to REACH guidance is considered below:

Interspecies: a default factor of 2.5 (remaining differences) is proposed (the application of a factor for allometric scaling is not required for the inhalation route).

Intraspecies: a default factor of 5 is proposed for workers.

Exposure duration: a default factor of 6 is proposed for extrapolation from a sub-acute study to chronic exposure. This represents a conservative approach, as the data indicate low toxicity following single and repeated exposures

Dose-response: a default factor of 1 is proposed as, based on the available data, the substance is of low toxicity

Quality of the data base: a default factor of 1 is proposed

Remaining uncertainties: no analytical concentration verification was obtained in the study; a factor of 3 is proposed to account for any associated uncertainties. 

An overall assessment factor of 225 for long-term inhalational effects is therefore calculated for workers.

Applying the assessment factor of 225 to the corrected inhalation NOAEC of 881.6 mg/m3 gives an inhalation DNEL value of 3.9 mg/m3 for long-term systemic effects.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.97 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):
450
Modified dose descriptor starting point:
NOAEC
Value:
434.8 mg/m³
Explanation for the modification of the dose descriptor starting point:
A long-term systemic inhalation DNEL is derived from the oral NOAEL of 1000 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that the oral absorption rate is 50% that of the inhalation absorption rate (i.e. oral and inhalation absorption values of 50% and 100% respectively are assumed). The corrected inhalation NOAEC for the general population is derived as: oral NOAEL x (1/1.15 m3/kg/day) x (% oral absorption/ % inhalation absorption) = 1000 mg/kg bw/day x (1/1.15) x (50/100) = 434.8 mg/m3.
AF for dose response relationship:
1
Justification:
Default factor : based on the available data, the substance is of low toxicity
AF for differences in duration of exposure:
6
Justification:
Default factor for extrapolation from a sub-acute study to chronic exposure.
AF for other interspecies differences:
2.5
Justification:
Default factor (remaining difference)
AF for intraspecies differences:
10
Justification:
Default factor for the general population
AF for the quality of the whole database:
1
Justification:
Default factor
AF for remaining uncertainties:
3
Justification:
No analytical concentration verification was obtained in the study; a factor of 3 is proposed to account for any associated uncertainties.
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:
0.56 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):
1 800
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
A long-term systemic dermal DNEL is derived from the oral NOAEL of 1000 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that dermal absorption will not exceed oral absorption (i.e. oral and dermal absorption values of 50% respectively are assumed). The equivalent dermal NOAEL is derived as: oral NOAEL x (% oral absorption/ % dermal absorption) = 1000 mg/kg bw/day x (50/50) = 1000 mg/kg bw/day.
AF for dose response relationship:
1
Justification:
Default factor: based on the available data, the substance is of low toxicity
AF for differences in duration of exposure:
6
Justification:
Default factor for extrapolation from a sub-acute study to chronic exposure.
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (allometric scaling: rat)
AF for other interspecies differences:
2.5
Justification:
Default factor (remaining differences)
AF for intraspecies differences:
10
Justification:
Default factor for the general population
AF for the quality of the whole database:
1
Justification:
Default factor
AF for remaining uncertainties:
3
Justification:
No analytical concentration verification was obtained in the study; a factor of 3 is proposed to account for any associated uncertainties.
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:
0.56 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):
1 800
Modified dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
AF for dose response relationship:
1
Justification:
Default factor: based on the available data, the substance is of low toxicity
AF for differences in duration of exposure:
6
Justification:
Default factor for extrapolation from a sub-acute study to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
Default factor (allometric scaling;rat)
AF for other interspecies differences:
2.5
Justification:
Default factor (remaining differences)
AF for intraspecies differences:
10
Justification:
Default factor for the general population
AF for the quality of the whole database:
1
Justification:
Default factor
AF for remaining uncertainties:
3
Justification:
No analytical concentration verification was obtained in the study; a factor of 3 is proposed to account for any associated uncertainties
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]

Based on the data available, the substance is of low acute toxicity, is not mutagenic, does not cause target organ or systemic toxicity and is not a developmental or reproductive toxin. The substance is irritating to the skin and the eyes and is a skin sensitiser. Classification in respect of these effects is proposed.

 

The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 1000 mg/kg bw/day from a combined repeated oral dose and reproductive/developmental screening study conducted in rats according to OECD Test Guideline 422.

 

Local effects

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. 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.

DNEL values for local dermal effects are not derived. The substance is irritating and sensitising to the skin. The substance is classified for skin irritation as: Category 2, H315 “Causes skin irritation” according to Regulation (EC) No 1272/2008, and as Xi, R38 “Irritating to skin” according to Directive 67/548/EEC. The substance is classified for skin sensitisation as Category 1A, H317 “May cause an allergic skin reaction” according to Regulation (EC) No 1272/2008 and as Xi, R43 “May cause sensitisation by skin contact” according to Directive 67/548/EEC. According to ECHA CSA Guidance Part E Table E3-1, “ low” hazard is assigned in respect of the skin irritation potential of the substance, however, on account of its skin sensitisation potential, “high” hazard is assigned overall in respect of both endpoints.

A qualitative risk characterisation is required in respect of the local inhalation and dermal effects of the substance.

Systemic effects

The substance is of low systemic toxicity. No acute toxicity hazard resulting in classification has been identified, therefore DNELs for acute systemic effects are not proposed.

The relevant (lowest) NOAEL for general/systemic toxicity for DNEL derivation is the NOAEL of 1000 mg/kg bw/day from a combined repeated oral dose and reproductive/developmental screening study conducted in rats according to OECD Test Guideline 422.

[Dermal – long-term systemic DNEL]

A long-term systemic dermal DNEL is derived from the oral NOAEL of 1000 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that dermal absorption will not exceed oral absorption (i.e. oral and dermal absorption values of 50% respectively are assumed). The equivalent dermal NOAEL is derived as: oral NOAEL x (% oral absorption/ % dermal absorption) = 1000 mg/kg bw/day x (50/50) = 1000 mg/kg bw/day. 

The use of assessment factors according to REACH guidance is considered below:

Interspecies: default factors of 4 (allometric scaling: rat) and 2.5 (remaining differences) are proposed.

Intraspecies: a default factor of 10 is proposed (default for the general population)

Exposure duration: a default factor of 6 is proposed for extrapolation from a sub-acute study to chronic exposure. This represents a conservative approach, as the data indicate low toxicity following single and repeated exposures

Dose-response: a default factor of 1 is proposed as, based on the available data, the substance is of low toxicity

Quality of the data base: a default factor of 1 is proposed

Remaining uncertainties: no analytical concentration verification was obtained in the study; a factor of 3 is proposed to account for any associated uncertainties. 

An overall assessment factor of 1800 for long-term dermal effects is therefore calculated for the general population

Applying the assessment factor of 1800 to the dermal equivalent NOAEL of 1000 mg/kg bw/d gives a dermal DNEL value of 0.56 mg/kg bw/d for long-term systemic effects.

[Inhalation – long-term systemic DNEL]

A long-term systemic inhalation DNEL is derived from the oral NOAEL of 1000 mg/kg bw/day using the route-to-route extrapolation approach and default assumptions given in the REACH guidance. It is assumed that the oral absorption rate is 50% that of the inhalation absorption rate (i.e. oral and inhalation absorption values of 50% and 100% respectively are assumed). The corrected inhalation NOAEC for the general population is derived as: oral NOAEL x (1/1.15 m3/kg/day) x (% oral absorption/ % inhalation absorption) = 1000 mg/kg bw/day x (1/1.15) x (50/100) = 434.8 mg/m3

The use of assessment factors according to REACH guidance is considered below:

Interspecies: a default factor of 2.5 (remaining differences) is proposed (the application of a factor for allometric scaling is not required for the inhalation route).

Intraspecies: a default factor of 10 is proposed (default for the general population)

Exposure duration: a default factor of 6 is proposed for extrapolation from a sub-acute study to chronic exposure. This represents a conservative approach, as the data indicate low toxicity following single and repeated exposures

Dose-response: a default factor of 1 is proposed as, based on the available data, the substance is of low toxicity

Quality of the data base: a default factor of 1 is proposed

Remaining uncertainties: no analytical concentration verification was obtained in the study; a factor of 3 is proposed to account for any associated uncertainties. 

An overall assessment factor of 450 for long-term inhalational effects is therefore calculated for the general population.

Applying the assessment factor of 450 to the corrected inhalation NOAEC of 434.8 mg/m3gives an inhalation DNEL value of 0.97 mg/m3for long-term systemic effects.

[Oral – long-term systemic DNEL]

Applying the assessment factor of 1800 to the oral NOAEL of 1000 mg/kg bw/d gives an oral DNEL of 0.56 mg/kg bw/day.