C12-18-(even numbered, C18 unsaturated)-alkylamines acetates

Toxicological Summary

Workers - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.38 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance with substance specific modifications

Overall assessment factor (AF):

15

Modified dose descriptor starting point:

NOAEC

Value:

5.73 mg/m³

Explanation for the modification of the dose descriptor starting point:

No data for the registration substance after long-term inhalation exposure available

AF for dose response relationship:

1

Justification:

ECHA Guidance

AF for differences in duration of exposure:

3

Justification:

ECHA Guidance (reduced factor based on nature of effects (irritative) and available limited chronic data)

AF for interspecies differences (allometric scaling):

1

Justification:

ECHA Guidance (inhalation route)

AF for other interspecies differences:

1

Justification:

Substance excert effects most probably directly (local point of entry effects due to irritative nature), no species differences expected

AF for intraspecies differences:

5

Justification:

Overall AF for combined intraspecies and remaining uncertainty (modified from ECETOC and German AGS )

AF for the quality of the whole database:

1

Justification:

ECHA Guidance

AF for remaining uncertainties:

1

Justification:

No remaining uncertainties identified (unspecific mechanism due to point of entry irritative effects)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.054 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance with substance specific modifications

Overall assessment factor (AF):

60

Modified dose descriptor starting point:

NOAEL

Value:

3.75 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No data for the submission substance after long-term dermal exposure available (oral absorption equal dermal absorption 100% by default).

AF for dose response relationship:

1

Justification:

ECHA Guidance

AF for differences in duration of exposure:

3

Justification:

Reduced default due to concentration dependent local irritation of registration substance (leading effect less duration dependent)

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA Guidance

AF for other interspecies differences:

5

Justification:

Modified according to ECETOC and German AGS (combined inter-/intraspecies AF)

AF for intraspecies differences:

1

Justification:

Modified according to ECETOC and German AGS (combined inter-/intraspecies AF)

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:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - workers

Workers - Hazard via inhalation route

No route-specific acute and/or repeated inhalation toxicity data is available for the registration substance. As default, route-to-route extrapolation is performed using the NOAEL of 3.25 mg/kg body weight per day from the 28 -day oral toxicity study with a surrogate substance, which was identified as key study for repeated dose toxicity based on read-across principles. This NOAEL is used as starting point for the derivation of the worker DNEL "long-term inhalation exposure - systemic effects". The leading adverse findings are considered to be induced by local effects in the gastrointestinal tract due to the irritative properties and thus no species differences and/or additional uncertainties are to be expected. The corrected inhalatory NOAEC is obtained according REACH Guidance R.8 as 5.73 mg/m³. Based on the overall toxicity profile, a treshold mechanism in form of local effects with implications for secondary systemic inflammatory toxicity is most likely. With regard to interspecies differences, allometric scaling concerning oral-to-inhalation extrapolation is not appropriate and no assessment factor is applied (ECHA Guidance). The adjustment for remaining differences is not considered scientifically justified (ECETOC 2010). Analysis of various data sets have revealed that a separate factor for remaining interspecies differences need not always be established because these are being accounted for by the assessment of intraspecies variability. Based on scientific evidence, ECETOC is proposing overall assessment factors of 3 for workers, which includes the remaining interspecies differences. A factor of 1 for remaining interspecies differences is also supported, because it is unlikely that effects driven by irritation differ between species. However, taking into account the overall toxicity profile of the submission substance, a somewhat more conservative approach is taken and a combined inter-/intraspecies assessment factor of 5 is considered. This is in line with a similar concept developed by the German Committee for Hazardous Substances (AGS 2006 [Technische Regeln für Gefahrstoffe. Begründungen und Erläuterungen zu Grenzwerten in der Luft am Arbeitsplatz. Ausschuss für Gefahrstoffe. TRGS 901, BArbBl. Heft 1/2006.www.baua.de]) . Since the assessment is based on the outcome of a 28 -day repeated dose toxicity study, time extrapolation to chronic exposure conditions generally have to be considered. However, because a point of entry "local cytotoxicity" as concentration dependent effect seems to be dominating in the overall toxicity profile of the submission substance, the full set of default assessment factors for duration extrapolation is not appropriate. Based hereupon, duration adjustment using an assessment factor of 3 seems to be justified and is used. This approach is further supported by available limted data with chronic oral exposure of analogues substances, which revealed NOAELs in the range of the one used as starting point for the present assessment. Since the available data are considered adequate for labelling and classification purposes of the registration substance, the quality of the data base is judged sufficient for evaluation and thus, an assessment factor of 1 is applied. The resulting overall assessment factor is 15 (3 x 5) resulting in a DNEL "long-term inhalation exposure - systemic effects" of 0.382 mg/m³.

Wokers - Hazard via dermal route

No route-specific acute and/or repeated dermal toxicity data is available for the submission substance. As default, route-to-route extrapolation is performed using the NOAEL of 3.25 mg/kg body weight per day from the 28 -day oral toxicity study with a surrogate substance, which was identified as key study for repeated dose toxicity based on read-across principles. In the absence of dermal penetration data, 100 % absorption via the skin is assumed as default for the route-to-route extrapolation. Hence, 3.25 mg/kg body weight per day is used as point of departure for the derivation of the worker DNEL "long-term dermal exposure - systemic effects". An allometric scaling factor of 4 as default for interspecies extrapolation (rat to human) is used (ECHA Guidance). Duration adjustment is performed using an reduced assessment factor of 3 which is lower because local irritation as concentration dependent effect is less dependent on duration of exposure. To account for intraspecies variability and remaining uncertainties a combined inter-/intraspecies assessment factor of 5 is included (based on the approaches from ECETOC and AGS from Germany). Based hereupon, an overall assessment factor of 60 is calculated and a worker DNEL "long-term dermal exposure - systemic effects" of 0.054 mg/kg body weight per day is derived.

No DNEL is derived for acute systemic toxicity and for local effects following acute and/or prolonged dermal exposure. The submission substance is irritative to skin and thus, proper technical and personal risk reduction measures are in place to ensure safe use conditions. According to ECHA Guidance R.14, the emphasis for properly labelled corrosives should be on the presentation of adequate risk management measures rather than on the assessment of the risks from dermal exposure,

General Population - Hazard via inhalation route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.155 mg/m³

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance with substance specific modifications

Overall assessment factor (AF):

21

Modified dose descriptor starting point:

NOAEC

Value:

3.26

Explanation for the modification of the dose descriptor starting point:

See discussion section for adjustment of NOAEL and for justification of assessment factors used

AF for dose response relationship:

1

Justification:

ECHA Guidance

AF for differences in duration of exposure:

3

Justification:

Reduced factor based on nature of effects (irritative) and available limzed chronic data

AF for interspecies differences (allometric scaling):

1

Justification:

ECHA Guidance (inhalation route)

AF for other interspecies differences:

1

Justification:

Substance exert effects most probably directly (local point of entry effects due to irritative nature), no species differences to be expected

AF for intraspecies differences:

7

Justification:

Overall AF for combined intraspecies and remaining uncertainty (modified from ECETOC and German AGS)

AF for the quality of the whole database:

1

Justification:

ECHA Guidance

AF for remaining uncertainties:

1

Justification:

No remaining uncertainty identified (unspecific mechanism due to point of entry irritative effects)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

Acute/short term exposure

Hazard assessment conclusion:

low hazard (no threshold derived)

DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.045 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance with substance specific modifications

Overall assessment factor (AF):

84

Modified dose descriptor starting point:

NOAEL

Value:

3.75 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No data for the submission substance after long-term dermal exposure available (oral absorption equal dermal absorption; 100% by default used is a conservative assumption)

AF for dose response relationship:

1

Justification:

ECHA Guidance

AF for differences in duration of exposure:

3

Justification:

Reduced default due to concentration dependent local irritation of registration substance (leading effect less duration dependent)

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA Guidance

AF for other interspecies differences:

7

Justification:

Modified according to ECETOC and German AGS (combined inter-/intraspecies AF)

AF for intraspecies differences:

1

Justification:

Modified according to ECETOC and German AGS (combined inter-/intraspecies AF)

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:

low hazard (no threshold derived)

DNEL related information

Local effects

Long term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

Acute/short term exposure

Hazard assessment conclusion:

medium hazard (no threshold derived)

Most sensitive endpoint:

skin irritation/corrosion

General Population - Hazard via oral route

Systemic effects

Long term exposure

Hazard assessment conclusion:

DNEL (Derived No Effect Level)

Value:

0.045 mg/kg bw/day

Most sensitive endpoint:

repeated dose toxicity

Route of original study:

Oral

DNEL related information

DNEL derivation method:

other: ECHA REACH Guidance with substance specific modifications

Overall assessment factor (AF):

84

Modified dose descriptor starting point:

NOAEL

Value:

3.75 mg/kg bw/day

Explanation for the modification of the dose descriptor starting point:

No data for the submission substance after long-term oral exposure availabe

AF for dose response relationship:

1

Justification:

ECHA Guidance

AF for differences in duration of exposure:

3

Justification:

Reduced default due to concentration dependent local irritation of registration substance (leading effect less duration dependent).

AF for interspecies differences (allometric scaling):

4

Justification:

ECHA Guidance

AF for other interspecies differences:

7

Justification:

Modified according to ECETOC and German AGS (combined inter-/intraspecies AF)

AF for intraspecies differences:

1

Justification:

Modified according to ECETOC and German AGS (combined inter-/intraspecies AF)

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:

low hazard (no threshold derived)

DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:

high hazard (no threshold derived)

Additional information - General Population

Consumer - Hazard via inhalation route

No route-specific acute and/or repeated inhalation toxicity data is available for the registration substance. As default, route-to-route extrapolation is performed using the NOAEL of 3.25 mg/kg body weight per day from the 28 -day oral toxicity study with a surrogate substance, which was identified as key study for repeated dose toxicity based on read-across principles. This NOAEL is used as starting point for the derivation of the consumer DNEL "long-term inhalation exposure - systemic effects". The leading adverse findings are considered to be induced by local effects in the gastrointestinal tract (point of entry) due to the irritative properties and thus no species differences and/or additional uncertainties are to be expected. The corrected inhalatory NOAEC is obtained according REACH Guidance R.8 as 3.26 mg/m³. Based on the overall toxicity profile, a treshold mechanism in form of local effects with implications for secondary systemic inflammatory toxicity is most likely. With regard to interspecies differences, allometric scaling concerning oral-to-inhalation extrapolation is not appropriate and no assessment factor is applied (ECHA Guidance). The adjustment for remaining differences is not considered scientifically justified (ECETOC 2010). Analysis of various data sets have revealed that a separate factor for remaining interspecies differences need not always be established because these are being accounted for by the assessment of intraspecies variability. Based on scientific evidence, ECETOC is proposing overall assessment factors of 5 for consumers, which includes the remaining interspecies differences. A factor of 1 for remaining interspecies differences is also supported, because it is unlikely that effects driven by irritation differ between species. However, taking into account the overall toxicity profile of the submission substance, a somewhat more conservative approach is taken and a combined inter-/intraspecies assessment factor of 7 is considered for consumers. This is in line with a similar concept developed by the German Committee for Hazardous Substances (AGS 2006 [Technische Regeln für Gefahrstoffe. Begründungen und Erläutetungen zu Grenzwerten in der Luft amArbeitsplatz. Ausschuss für Gefahrstoffe. TRGS 901, BArbBl. Heft 1/2006.www.baua.de]) . Since the assessment is based on the outcome of a 28 -day repeated dose toxicity study, time extrapolation to chronic exposure conditions generally have to be considered. However, because a point of entry "local cytotoxicity" as concentration dependent effect seems to be dominating in the overall toxicity profile of the submission substance, the full set of default assessment factors for duration extrapolation is not appropriate. Based hereupon, duration adjustment using an assessment factor of 3 seems to be justified and is used. This approach is further supported by available limited data with chronic oral exposure of analogues substances, which revealed NOAELs in the range of the one used as starting point for the present assessment. Since the available data are considered adequate for labelling and classification purposes of the registration substance, the quality of the data base is judged sufficient for evaluation and thus, an assessment factor of 1 is applied. The resulting overall assessment factor is 21 (3 x 7) resulting in a DNEL "long-term inhalation exposure - systemic effects" of 0.155 mg/m³.

Consumer - Hazard via dermal route

No route-specific acute and/or repeated dermal toxicity data is available for the submission substance. As default, route-to-route extrapolation is performed using the NOAEL of 3.25 mg/kg body weight per day from the 28 -day oral toxicity study with a surrogate substance, which was identified as key study for repeated dose toxicity based on read-across principles. In the absence of dermal penetration data, 100 % absorption via the skin is assumed as default for the route-to-route extrapolation( this is a conservative assumption as the expected dermal absorption is considered to be around 60%). Hence, 3.25 mg/kg body weight per day is used as point of departure for the derivation of the consumer DNEL "long-term dermal exposure - systemic effects". An allometric scaling factor of 4 as default for interspecies extrapolation (rat to human) is used (ECHA Guidance). Duration adjustment is performed using an reduced assessment factor of 3 which is lower because local irritation as concentration dependent effect is less dependent on duration of exposure. To account for intraspecies variability and remaining uncertainties a combined inter-/intraspecies assessment factor of 7 is included (based on the approaches from ECETOC and AGS from Germany). Based hereupon, an overall assessment factor of 84 is calculated and a consumer DNEL "long-term dermal exposure - systemic effects" of 0.045 mg/kg body weight per day is derived.

Consumer - Hazard via oral route

No route-specific acute and/or repeated oral toxicity data is available for the submission substance. The NOAEL of 3.25 mg/kg body weight per day from the 28 -day oral toxicity study with a surrogate substance, which was identified as key study for repeated dose toxicity based on read-across principles is used for the DNEL derivation. Considering 100 % absorption, 3.25 mg/kg body weight per day is used as point of departure for the derivation of the consumer DNEL "long-term oral exposure - systemic effects". An allometric scaling factor of 4 as default for interspecies extrapolation (rat to human) is used (ECHA Guidance). Duration adjustment is performed using an reduced assessment factor of 3 which is lower because local irritation as concentration dependent effect is less dependent on duration of exposure. To account for intraspecies variability and remaining uncertainties a combined inter-/intraspecies assessment factor of 7 is included (based on the approaches from ECETOC and AGS from Germany). Based hereupon, an overall assessment factor of 84 is calculated and a consumer DNEL "long-term oral exposure - systemic effects" of 0.045 mg/kg body weight per day is derived.

No DNEL is derived for acute systemic toxicity after oral or inhalation as well as for local effects following acute and/or prolonged dermal exposure. The submission substance is irritative to skin and thus a self warning effect has to be consiered. In addition, the registration substance is of low acute toxicity and the concentration used in consumer applications is regarded to be generally low. Any related hazards / risks are thus not identifiable.