Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
19.591 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):
18
Dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
352.632 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for inhalation exposure for workers is given by the formula: corrected inhalation NOAEC= NOAEL(oral-rat)* 1/sRVrat * (Absorption (oral-rat)/Absorption(inhal-human))* (sRVhuman/wRV) Where SRV is the standard Respiratory Volume and wRV is the worker Respiratory Volume.  The default values assumed for these factors are as follows: Absorption(oral-rat)=50%; Absorption(inhal-human) =100%; sRVrat=0.38 m3/kg/d; sRVhuman= 6.7m3 (8hr); wRV=10m3(8hr). NOAEC(corrected)= 400 mg/kg bw/day* (1/0.38 m3/kg/d)*(50%/100%)* 6.7m3 (8hr)/ 10m3(8hr) NOAEC(corrected)= 352.632 mg/m3

AF for dose response relationship:
1
Justification:
A NOAEL of 400mg/kg derived from the 28 day repeat dose study is being selected as the point of departure so factor of 1 used
AF for differences in duration of exposure:
6
Justification:
ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 28-day study are derived using an assessment factor of 6 for extrapolation of the study duration to chronic exposure.)
AF for interspecies differences (allometric scaling):
1
Justification:
In the absence of dermal absorption data, equivalence is assumed. A default allometric scaling factor of 4 between rats and humans is applied based on ECHA guidance for allometric scaling of data from rats to humans. This is already accounted for in the modification of the dose descriptor starting point.)
AF for other interspecies differences:
1
Justification:
(ECETOC reported in 2010 after an extensive review (see discussion) that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied)
AF for intraspecies differences:
3
Justification:
(ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for workers is 3 and not 5 as ECHA proposed. See discussion for detailed justification.)
AF for the quality of the whole database:
1
Justification:
A full Annex VIII dataset is available for this substance, including a combined 28 day/reproductive screening study.
AF for remaining uncertainties:
1
Justification:
uncertainties are already included so a factor of 1 is applied
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:
5.556 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):
72
Dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
400 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The value selected is the lowest NOAEL, derived from the OECD 422 Combined Repeat Dose and Reproduction/Development toxicity screening study.

Its relatively low water solubility and molecular weight of 577 indicates that the substance may be not be absorbed readily. The substance is non-irritating to the skin and non-corrosive in animal studies therefore if inhaled effects would be expected to be minimum and limited to local irritation effects, systemic effects are not expected. Based on the conditions of use and qualitative risk assessment it is considered not necessary to establish a DNEL for acute effects from inhalation exposure. As a conservative value 100% absorption is assumed.

AF for dose response relationship:
1
Justification:
NOAEL being used as the point of departure so factor of 1 used
AF for differences in duration of exposure:
6
Justification:
ECHA guidance document Chapter R8, in Appendix R.8-12, indicates that DNELS derived using a NOAEL from a 28-day study are derived using an assessment factor of 6 for extrapolation of the study duration to chronic exposure
AF for interspecies differences (allometric scaling):
4
Justification:
In the absence of dermal absorption data, equivalence is assumed. A default allometric scaling factor of 4 between rats and humans is applied
AF for other interspecies differences:
1
Justification:
ECETOC reported in 2010 after an extensive review (see discussion) that there is no justification for the suggested additional factor of 2.5 for this, therefore a factor of 1 has been applied
AF for intraspecies differences:
3
Justification:
ECETOC reported in 2010 after an extensive scientific review that the appropriate fact for intraspecies differences for workers is 3 and not 5 as ECHA proposed. See discussion for detailed justification.
AF for the quality of the whole database:
1
Justification:
A full Annex VIII dataset is available for this substance, including a combined 28 day/reproductive screening study
AF for remaining uncertainties:
1
Justification:
uncertainties are already included so a factor of 1 is applied
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:
low hazard (no threshold derived)

Additional information - workers

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