Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
66.12 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):
20
Dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
1 322.4 mg/m³
Explanation for the modification of the dose descriptor starting point:
Route-to-route extrapolation conducted as no data for registration substance on repeated dose toxicity following inhalation exposure available.
AF for dose response relationship:
1
Justification:
ECHA Guidance (reliable dose-response, POD is NOAEL [no systemic effects])
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 effects of relevance noted, ADME suggests no significant interspecies differences
AF for intraspecies differences:
5
Justification:
Combine AF for intraspecies and remaining uncertainty (toxicokinetic plus toxicodynamic aspect) based on German Committee on Hazardous Substances (AGS; BekGS901 dated April 2010) and ECETOC
AF for the quality of the whole database:
1
Justification:
Available data package 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:
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:
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 Guidance with substance specific modifications
Overall assessment factor (AF):
40
Dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
750 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Route-to-route extrapolation a no data for registration substance on repeated dose toxicity following dermal exposure available.
AF for dose response relationship:
1
Justification:
ECHA Guidance (reliable dose-response, POD is NOAEL [no systemic effects])
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, no differences in toxicokinetics between species expected
AF for intraspecies differences:
5
Justification:
Modified according to German Committee of Hazardous Substances (AGS) and ECETOC, combined inter-/intraspecies AF (toxicokinetic and toxicodynamic aspect)
AF for the quality of the whole database:
1
Justification:
Available data package comprehensive and plausible, read-across robust and scientifically valid
AF for remaining uncertainties:
1
Justification:
No relevant effects observed
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Acute/short term exposure
Hazard assessment conclusion:
no DNEL required: short term exposure controlled by conditions for long-term

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low 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 submission substance. 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 systemic relevant toxicity was observed in this study (NOAEL = 750 mg/kg body weight per day) and no species differences due to differences in 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 1322.4 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, although the available data from studies with repeated exposure have not revealed significant systemic toxicity 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 (subchronic to chronic) is used. Since the available data are considered adequate for labelling and classification purposes of the submission 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 66.12 mg/m3.

Workers - Hazard via dermal route

Based on the LD50 of greater 2000 mg/kg body weight revealed in an acute dermal toxicity study, no concern with respect to acute dermal exposure is deducible for the registration substance. However, no route-specific repeated dermal toxicity data is available for the submission substance. 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". With respect to dermal DNEL derivation, the same rational apply like for the inhalation route. As no systemic toxic relevant effetcs were noted and thus the POD used can be considered to be conservative, assessment factors of 1 for dose-response and quality of data base seem to be appropriate. Additionally, a reduced assessment factor of 2 for time extrapolation is used as neither relevant systemic toxicity nor specific target organs have been identified in the available studies with repeated exposure. This is also justified because the dermal penetration potential is considered low but risk characterization is conservatively performed using 100% absorption. Although it is concluded from the anticipated metabolism that no toxic metabolites are to be expected during catabolic degradation of the registration substance, 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. The resulting overall assessment factor is 40 (2 x 4 x 5) leading to 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. Based on the result from an available acute dermal toxicity study resulting in a LD50 value greater 2000 mg/kg body weight, it is concluded that no risk is deducible for this exposure condition. It is further 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

No consumer use identified and/or supported.