Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
66.1 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 adaptations
Overall assessment factor (AF):
20
Modified dose descriptor starting point:
NOAEC
Value:
1 322 mg/m³
Explanation for the modification of the dose descriptor starting point:
No data for registration substance on repeated doese toxicity following repeated inhalation exposure available
AF for dose response relationship:
1
Justification:
ECHA Guidance (reliable dose-response, POD is NOAEL)
AF for differences in duration of exposure:
2
Justification:
ECHA Guidance (subchronic to chronic)
AF for interspecies differences (allometric scaling):
1
Justification:
ECHA Guidance (inhalation route)
AF for other interspecies differences:
1
Justification:
No systemic toxicity profile pointing to interspecies differences identified.
AF for intraspecies differences:
5
Justification:
combined AF for intraspecies and remaining uncertainty (toxicokinetic plus toxicodynamic aspect) based on German Committe on Hazardous Substances (AGS; BekGS 901 dated April 2010) and ECETOC Technical Report 110 (2010).
AF for the quality of the whole database:
1
Justification:
Available data set comprehensive and plausible
AF for remaining uncertainties:
2
Justification:
ECHA Guidance, route-to-route extrapolation (oral to inhalation)
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:
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:
18.75 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 adaptations
Overall assessment factor (AF):
40
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
No data for registration substance on repeated doese toxicity following repeated dermal exposure available
AF for dose response relationship:
1
Justification:
ECHA Guidance (reliable dose-response, PoD is NOAEL)
AF for differences in duration of exposure:
2
Justification:
ECHA Guidance (subchronic to chronic)
AF for interspecies differences (allometric scaling):
4
Justification:
ECHA Guidance
AF for other interspecies differences:
1
Justification:
Modified according to German Committee of Hazardous Substances (AGS) and ECETOC (Technical Report 110, 2010), no differences in toxicokinetics between species expected
AF for intraspecies differences:
5
Justification:
Modified according to German Committee of Hazardous Substances (AGS) and ECETOC (Technical Report 110, 2010), no differences in toxicokinetics between species expected
AF for the quality of the whole database:
1
Justification:
Available data set comprehensive and plausible
AF for remaining uncertainties:
1
Justification:
ECHA Guidance (no species specific differences expected justifying additional uncertainty factor)
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)

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

Wokers - Hazard via inhalation route

No route-specific acute and/or repeated inhalation toxicity data is available for the registration substance. With regard to potential long-term exposure, as default, route-to-route extrapolation is performed using the NOAEL of 750 mg/kg body weight per day from a 90 -day oral toxicity study, which was identified as key study for repeated dose toxicity. This NOAEL is used as starting point for the derivation of the worker DNEL "long-term inhalation exposure - systemic effects". Although no significant systemic toxic effects and/or with relevance for human health have been derived in this subchronic toxicity study or various other studies with repeated oral administration (see section "repeated dose toxicity") and no species differences due to comparable toxicokinetics are expected, a conservative approach is taken and the default factor of 2 for remaining uncertainties using route-to-route extrapolation is applied. The corrected inhalatory NOAEC is obtained according REACH Guidance R.8 as 1322 mg/m3. 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 toxicokinetics differed not between species. However, 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 2010 [Technische Regeln für Gefahrstoffe. Begründungen und Erläuterungen zu Grenzwerten in der Luft am Arbeitsplatz. Ausschuss für Gefahrstoffe.BekGS 901, April 2010]) . Since the assessment is based on the outcome of a 90 -day repeated dose toxicity study, time extrapolation to chronic exposure conditions generally have to be considered and the default factor of 2 is used. Since the available data set is considered comprehensive and plausible as well as 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 20 (2 x 5 x 2) resulting in a DNEL "long-term inhalation exposure - systemic effects" of 66.1 mg/m3.

Wokers - Hazard via dermal route

No route-specific acute and/or repeated inhalation toxicity data is available for the registration substance. With regard to potential long-term exposure, as default, route-to-route extrapolation is performed using the NOAEL of 750 mg/kg body weight per day from a 90 -day oral toxicity study, which was identified as key study for repeated dose toxicity. This NOAEL is used as starting point for the derivation of the worker DNEL "long-term dermal exposure - systemic effects". The DNEL derivation as well as the selection of assessment factors for the extrapolations followed the same rational like for the inhalation route. Assessment factors of 1 for dose-response and quality of data base are appropriate. Since the PoD is a NOAEL coming from a subchronic (90-day) study, an assessment factor of 2 for time extrapolation is used according to ECHA guidance. Likewise, allometric scaling is performed using an AF of 4 (rat to human). As explained in more detail above, a combined AF of 5 is used to account for potential inter- / intraspecies differences, although differences in toxicokinetics due to a significant distinct metabolism between species is not to be expected. The resulting overall assessment factor is 40 (2 x 4 x 5) resulting in a DNEL "long-term dermal exposure - systemic effects" of 18.75 mg/kg body weight per day.

Additional information

No DNELs are derived for acute systemic toxicity and for local effects following acute exposure. It is concluded that short-term exposures are well-controlled by conditions for long-term exposure. Additionally, proper technical and personal risk management measures are in place to protect against local effects and ensure safe use conditions.

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:
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

General Population - Hazard via oral 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

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - General Population

The registration substance is used only in industrial settings. Consumer uses have not been identified and are not supported and thus no exposure.