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Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
118 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):
3
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
353 mg/m³
Explanation for the modification of the dose descriptor starting point:

Correction of the starting point based on ECHA Guidance Chapter R.8 (Nov. 2012), Figure R.8-3:

(Absorption oral compared to inhalative 1; no additional default factor is warranted, since only unspecific effects are seen at high doses. Systemic toxicity is not the primary hazard of this compound.)

Corrected inhalatory NOAEL = oral NOAEL * 1/0.38 m³/kg * 6.7 m³/10m³

AF for dose response relationship:
1
Justification:
When the starting point is a NOAEL, the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
1
Justification:
Since the NOAEL is based on a chronic study no assessment factor for duration extrapolation is needed.
AF for interspecies differences (allometric scaling):
1
Justification:
Already covered by correction of starting point.
AF for other interspecies differences:
1
Justification:
ECHA suggests a default factor of 2.5 for remaining interspecies differences, but justified deviations are possible. For the substance there are substance-specific reasons to ommit the proposed factor: The spacing of doses was large in the chronic study (40, 200, and 1000 mg/kg) and the effects at the LOAEL (1000 mg/kg) were non-specific and without any functional or structural changes (i.e. impaired grooming activity and retarded body weight gain). Systemic availability could not be demonstrated in that study, but interspecies differences do in principle rely on systemic availability. For these reasons no further factor for remaining interspecies differences was used; possible interspecies differences are already covered by the correction of the starting point from oral-rat to inhalation-human. In addition, ECETOC (TR 86, 2003 and TR 110, 2010) considered that routine application of the factor of 2.5 as a default factor is scientifically unjustified. This view was supported by data generated by the ERASM project (Batke et al, 2010).
AF for intraspecies differences:
3
Justification:
Based on a scientific evaluation ECETOC concluded that a factor of 3 is sufficient for intraspecies differences in workers (ECETOC TR 86, 2003; ECETOC TR 110, 2010; further information: Schenk & Johanson, Crit. Rev. in Toxicol. 40(9): 791-798, 2010, Escher et al., Toxicol. Letters 218:159-165, 2013).
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: Messinger, Reg. Toxicol. Pharm 68: 317 -324, 2014
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: Messinger, Reg. Toxicol. Pharm 68: 317 -324, 2014

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
17 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):
12
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the substance it is not expected that dermal absorption will be higher than oral absorption, therefore no default factor (i.e. factor 1) is used for oral-to-dermal extrapolation.

AF for dose response relationship:
1
Justification:
When the starting point is a NOAEL, the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
1
Justification:
Since the NOAEL is based on a chronic study no assessment factor for duration extrapolation is needed.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for rat to human.
AF for other interspecies differences:
1
Justification:
ECHA suggests a default factor of 2.5 for remaining interspecies differences, but justified deviations are possible. For the substance there are substance-specific reasons to ommit the proposed factor: The spacing of doses was large in the chronic study (40, 200, and 1000 mg/kg) and the effects at the LOAEL (1000 mg/kg) were non-specific and without any functional or structural changes (i.e. impaired grooming activity and retarded body weight gain). Systemic availability could not be demonstrated in that study, but interspecies differences do in principle rely on systemic availability. For these reasons no further factor for remaining interspecies differences was used; possible interspecies differences are already covered by allometric scaling. In addition, ECETOC (TR 86, 2003 and TR 110, 2010) considered that routine application of the factor of 2.5 as a default factor is scientifically unjustified. This view was supported by data generated by the ERASM project (Batke et al, 2010).
AF for intraspecies differences:
3
Justification:
Based on a scientifical evaluation ECETOC concluded that a factor of 3 is sufficient for intraspecies differences in workers (ECETOC TR 86, 2003; ECETOC TR 110, 2010; further information: Schenk & Johanson, Crit. Rev. in Toxicol. 40(9): 791-798, 2010, Escher et al., Toxicol. Letters 218:159-165, 2013).
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Acute/short term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
136 mg/kg bw/day
DNEL related information
DNEL extrapolated from long term DNEL

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

Acute toxicity:

Systemic toxicity:

Acute oral: LD50 1271 mg/kg; non-specific signs of toxicity were observed, including depression, ruffles fur and dyspnoea. The signs tended to persist longer in the higher dosages where animals survived the investigation period. No particular specific effect was noted in the body weight data. Gross necropsy observations were also non-specific in animals at termination. Rats which died during the first few days after dosing showed gastrointestinal lesions and some other congested organs. The cause of death of these animals may have been related to the intestinal lesions. Histopathology was not performed.

Local effects:

Acute dermal: Solely irritant potency on skin detected. The same applies for skin and eye irritation studies. The substance is classified with Skin Irrit Cat. 2 (Regulation (EU) 1272/2008); according to ECHA Guidance ECHA Guidance Part E: Risk Characterisation (May 2016) this translates into “low hazard”.

Repeated dose toxicity:

Systemic toxicity:

A chronic oral study is available in rats: NOAEL approx. 200 mg/kg bw. The substance is not carcinogenic and has no primary effect on fertility or development, consequently the effects on body weight observed in the chronic study will be used as a starting point for the long-term DNEL calculation.

Local toxicity:

The substance is classified with Skin Irrit Cat. 2 (Regulation (EU) 1272/2008); according to ECHA Guidance ECHA Guidance Part E: Risk Characterisation (May 2016) this translates into “low hazard”.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
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:
10 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):
20
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

For the substance it is not expected that dermal absorption will be higher than oral absorption, therefore no default factor (i.e. factor 1) is used for oral-to-dermal extrapolation.

AF for dose response relationship:
1
Justification:
When the starting point is a NOAEL, the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
1
Justification:
Since the NOAEL is based on a chronic study no assessment factor for duration extrapolation is needed.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for rat to human.
AF for other interspecies differences:
1
Justification:
ECHA suggests a default factor of 2.5 for remaining interspecies differences, but justified deviations are possible. For the substance there are substance-specific reasons to ommit the proposed factor: The spacing of doses was large in the chronic study (40, 200, and 1000 mg/kg) and the effects at the LOAEL (1000 mg/kg) were non-specific and without any functional or structural changes (i.e. impaired grooming activity and retarded body weight gain). Systemic availability could not be demonstrated in that study, but interspecies differences do in principle rely on systemic availability. For these reasons no further factor for remaining interspecies differences was used; possible interspecies differences are already covered by allometric scaling. In addition, ECETOC (TR 86, 2003 and TR 110, 2010) considered that routine application of the factor of 2.5 as a default factor is scientifically unjustified. This view was supported by data generated by the ERASM project (Batke et al, 2010).
AF for intraspecies differences:
5
Justification:
Based on a scientifical evaluation ECETOC concluded that a factor of 5 is sufficient for intraspecies differences in the general population (ECETOC TR 86, 2003; ECETOC TR 110, 2010).
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
low 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:
10 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):
20
Dose descriptor starting point:
NOAEL
DNEL value:
200 mg/kg bw/day
AF for dose response relationship:
1
Justification:
When the starting point is a NOAEL, the default assessment factor, as a standard procedure, is 1.
AF for differences in duration of exposure:
1
Justification:
Since the NOAEL is based on a chronic study no assessment factor for duration extrapolation is needed.
AF for interspecies differences (allometric scaling):
4
Justification:
Default allometric scaling factor for rat to human.
AF for other interspecies differences:
1
Justification:
ECHA suggests a default factor of 2.5 for remaining interspecies differences, but justified deviations are possible. For the substance there are substance-specific reasons to ommit the proposed factor: The spacing of doses was large in the chronic study (40, 200, and 1000 mg/kg) and the effects at the LOAEL (1000 mg/kg) were non-specific and without any functional or structural changes (i.e. impaired grooming activity and retarded body weight gain). Systemic availability could not be demonstrated in that study, but interspecies differences do in principle rely on systemic availability. For these reasons no further factor for remaining interspecies differences was used; possible interspecies differences are already covered by allometric scaling. In addition, ECETOC (TR 86, 2003 and TR 110, 2010) considered that routine application of the factor of 2.5 as a default factor is scientifically unjustified. This view was supported by data generated by the ERASM project (Batke et al, 2010).
AF for intraspecies differences:
5
Justification:
Based on a scientifical evaluation ECETOC concluded that a factor of 5 is sufficient for intraspecies differences in the general populatopn (ECETOC TR 86, 2003; ECETOC TR 110, 2010).
AF for the quality of the whole database:
1
Justification:
The default assessment factor to be applied for good/standard quality of the database, taking into account completeness, consistency and the standard information requirements, is 1.
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:
low hazard (no threshold derived)

Additional information - General Population

Local effects:

Acute dermal: Solely irritant potency on skin detected. The same applies for skin and eye irritation studies. The substance is classified with Skin Irrit Cat. 2 (Regulation (EU) 1272/2008); according to ECHA Guidance ECHA Guidance Part E: Risk Characterisation (May 2016) this translates into “low hazard”.

Systemic effects:

See for further details "Additional information for worker"

Due to the very low aerosol / dust generation during realistic use conditions, risks for consumers are regarded to be negligible and no DNEL is calculated.