Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
51.54 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
6
Dose descriptor starting point:
NOAEC
Value:
615.4 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
309.24 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEC = 149 ppm corresponding to 615.4 mg/m³ (at 25°C and 1013 mbar). Two starting point modifications were accounted for: 1) duration of exposure for workers is 8 h, whereas the test animals were exposed for 6h --> dose descriptor * 0.75. 2) Difference in inhalation volume of workers --> dose descriptor * 0.67. Corrected NOAEC: 309.24 mg/m³.

AF for dose response relationship:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as a NOAEC was established in the study.
AF for differences in duration of exposure:
2
Justification:
As per REACH guidance 8.4.3.1, a factor of 2 may be used for duration extrapolation (i.e., sub-chronic to chronic).
AF for interspecies differences (allometric scaling):
1
Justification:
As per REACH guidance 8.4.3.1
AF for other interspecies differences:
1
Justification:
In contrast to the recommendations of the ECHA Guidance, no additional factor of 2.5 for other interspecies differences was applied, as there is no evidence for interspecies differences in the general mode of action or kinetics (recommendation of the VCI Working group "Toxicology", 2008).
AF for intraspecies differences:
3
Justification:
As per REACH guidance 8.4.3.1, a factor of 3 may be supported taking also into account the toxicokinetic evaluation of other structurally similar oximes.
AF for the quality of the whole database:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as the study is robust.
AF for remaining uncertainties:
1
Justification:
No AF for remaining uncertainties deemed necessary.
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.097 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):
216
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
21 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

LOAELcorr = LOAELoral * (ABSoral-rat / ABSdermal-human) * (7 day exposure rat / 5 days exposure worker) = 15 mg/kg bw/day * (100%/100%) * 1.4 = 21 mg/kg bw/day.

ABSoral-rat = oral absorption rate in rats, ABSdermal-human = dermal absorption rate in humans.

AF for dose response relationship:
3
Justification:
As per REACH guidance 8.4.3.1, a factor of 3-10 may be supported as a LOAEL was established in the study. A factor of 3 is taken for assessment due to the fact that a clear concentration-dependent increase in severity and expansion in different organs was seen.
AF for differences in duration of exposure:
6
Justification:
As per REACH guidance 8.4.3.1, a factor of 6 may be used for duration extrapolation (i.e., subacute to chronic).
AF for interspecies differences (allometric scaling):
4
Justification:
According to REACH guidance 8.4.3.1, a factor of 4 is appropriate for allometric scaling between rats and humans.
AF for other interspecies differences:
1
Justification:
In contrast to the recommendations of the ECHA Guidance, no additional factor of 2.5 for other interspecies differences was applied, as there is no evidence for interspecies differences in the general mode of action or kinetics (recommendation of the VCI Working group "Toxicology", 2008).
AF for intraspecies differences:
3
Justification:
As per REACH guidance 8.4.3.1, a factor of 3 may be supported taking also into account the toxicokinetic evaluation of other structurally similar oximes.
AF for the quality of the whole database:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as the study used as starting point is a reliable one, suitable for route-to route extrapolation.
AF for remaining uncertainties:
1
Justification:
No AF for remaining uncertainties deemed necessary.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
low hazard (no threshold derived)

Additional information - workers

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.99 mg/m³
Most sensitive endpoint:
repeated dose toxicity
Route of original study:
By inhalation
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
10
Dose descriptor starting point:
NOAEC
Value:
615.4 mg/m³
Modified dose descriptor starting point:
NOAEC
Value:
109.9 mg/m³
Explanation for the modification of the dose descriptor starting point:

NOAEC = 149 ppm corresponding to 615.4 mg/m³ (at 25 °C and 1013 mbar). Two starting point modifications were accounted for: 1) duration of exposure for consumers is 24 h, whereas the test animals were exposed for 6 h --> dose descriptor * 0.25. 2.) consumers are exposed 7 days/week, whereas the test animals were exposed 5 days/week --> dose descriptor * 0.71

Corrected NOAEC: 109.9 mg/m3

AF for dose response relationship:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as a NOAEC was established in the study.
AF for differences in duration of exposure:
2
Justification:
As per REACH guidance 8.4.3.1, a factor of 2 may be used for duration extrapolation (i.e., sub-chronic to chronic).
AF for interspecies differences (allometric scaling):
1
Justification:
As per REACH guidance 8.4.3.1
AF for other interspecies differences:
1
Justification:
In contrast to the recommendations of the ECHA Guidance, no additional factor of 2.5 for other interspecies differences was applied, as there is no evidence for interspecies differences in the general mode of action or kinetics (recommendation of the VCI Working group "Toxicology", 2008).
AF for intraspecies differences:
5
Justification:
As per REACH guidance 8.4.3.1, a factor of 5 may be supported taking also into account the toxicokinetic evaluation of other structurally similar oximes.
AF for the quality of the whole database:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as the study is robust.
AF for remaining uncertainties:
1
Justification:
No AF for remaining uncertainties deemed necessary.
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:
DNEL (Derived No Effect Level)
Value:
0.042 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):
360
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

In the absence of study data for the dermal route, route-to-route extrapolation needed to be considered in the present case. Dose descriptor starting value for the dermal DNEL is equal to the one determined in the oral study as (in the absence of toxicokinetics information) it can be assumed that dermal absorption will not be higher than oral absorption.

AF for dose response relationship:
3
Justification:
As per REACH guidance 8.4.3.1, a factor of 3-10 may be supported as a LOAEL was established in the study. A factor of 3 is taken for assessment due to the fact that a clear concentration-dependent increase in severity and expansion in different organs was seen.
AF for differences in duration of exposure:
6
Justification:
As per REACH guidance 8.4.3.1, a factor of 6 may be used for duration extrapolation (i.e., subacute to chronic).
AF for interspecies differences (allometric scaling):
4
Justification:
According to REACH guidance 8.4.3.1, a factor of 4 is appropriate for allometric scaling between rats and humans.
AF for other interspecies differences:
1
Justification:
In contrast to the recommendations of the ECHA Guidance, no additional factor of 2.5 for other interspecies differences was applied, as there is no evidence for interspecies differences in the general mode of action or kinetics (recommendation of the VCI Working group "Toxicology", 2008).
AF for intraspecies differences:
5
Justification:
As per REACH guidance 8.4.3.1, a factor of 5 may be supported taking also into account the toxicokinetic evaluation of other structurally similar oximes.
AF for the quality of the whole database:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as the study is used as starting point is a reliable one, suitable for route-to route extrapolation.
AF for remaining uncertainties:
1
Justification:
No AF for remaining uncertainties deemed necessary.
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown but no further hazard information necessary as no exposure expected
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:
DNEL (Derived No Effect Level)
Value:
0.042 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):
360
Dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Modified dose descriptor starting point:
LOAEL
Value:
15 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No starting point modification was necessary.

AF for dose response relationship:
3
Justification:
As per REACH guidance 8.4.3.1, a factor of 3-10 may be supported as a LOAEL was established in the study. A factor of 3 is taken for assessment due to the fact that a clear concentration-dependent increase in severity and expansion in different organs was seen.
AF for differences in duration of exposure:
6
Justification:
As per REACH guidance 8.4.3.1, a factor of 6 may be used for duration extrapolation (i.e., subacute to chronic).
AF for interspecies differences (allometric scaling):
4
Justification:
According to REACH guidance 8.4.3.1, a factor of 4 is appropriate for allometric scaling between rats and humans.
AF for other interspecies differences:
1
Justification:
In contrast to the recommendations of the ECHA Guidance, no additional factor of 2.5 for other interspecies differences was applied, as there is no evidence for interspecies differences in the general mode of action or kinetics (recommendation of the VCI Working group "Toxicology", 2008).
AF for intraspecies differences:
5
Justification:
As per REACH guidance 8.4.3.1, a factor of 5 may be supported taking also into account the toxicokinetic evaluation of other structurally similar oximes.
AF for the quality of the whole database:
1
Justification:
As per REACH guidance 8.4.3.1, a factor of 1 may be supported as the study is robust.
AF for remaining uncertainties:
1
Justification:
No AF for remaining uncertainties deemed necessary.
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