Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
10.6 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
25
Modified dose descriptor starting point:
NOAEC
Value:
265 mg/m³
Explanation for the modification of the dose descriptor starting point:
Based on Guidance Document, Chapter R.8, Appendix R.8-2. A 50% absorption via oral vs. inhalation was assumed
AF for dose response relationship:
1
Justification:
Clear NOAEC value was assigned
AF for differences in duration of exposure:
1
Justification:
Based on a develpmental effect, no exposure duration adjustment applied
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable, correction of oral to inhalation (rat to human) already performed
AF for other interspecies differences:
1
Justification:
Not applicable
AF for intraspecies differences:
5
Justification:
Default value
AF for the quality of the whole database:
1
Justification:
The quality of the whole database was judged adequate
AF for remaining uncertainties:
5
Justification:
Remaining uncertainty for result based on a positive finding in an OECD 422 study (Guidance Document, Chapter R.8, Appendix R.8-12)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
1.2 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
250
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assumed equivalent bioavailability between oral and dermal routes of exposure.
AF for dose response relationship:
1
Justification:
Clear NOAEL value was assigned
AF for differences in duration of exposure:
1
Justification:
Based on a develpmental effect, no exposure duration adjustment applied
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
Default value
AF for intraspecies differences:
5
Justification:
Default value
AF for the quality of the whole database:
1
Justification:
The quality of the whole database was judged adequate
AF for remaining uncertainties:
5
Justification:
Remaining uncertainty for result based on a positive finding in an OECD 422 study (Guidance Document, Chapter R.8, Appendix R.8-12)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - workers

Default procedures for the calculation of DNEL values were employed as described in the REACH technical guidance documents (Chapter R.8). The most relevant dose descriptor chosen for generation of worker DNEL values was a 300 mg/kg bw/d NOAEL from an oral rat study conducted according to OECD Guideline 422. The highest dose level tested of 1000 mg/kg bw/day showed only minimal systemic toxicological effects and was assigned as the NOAEL. A NOAEL for local effects of 300 mg/kg bw/d was also assigned in this study based on minimal irritation of the forestomach in the rat. However, developmental toxicity was observed at the highest dose level tested consisting of a significantly altered sex ratio of offspring. Since a possible relationship to treatment could not be excluded, this effect gave a NOAEL for developmental effects of 300 mg/kg bw/day. This latter value was chosen for purposes of risk assessment and calculation of DNEL values.

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.6 mg/m³
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
50
Modified dose descriptor starting point:
NOAEC
Value:
130 mg/m³
Explanation for the modification of the dose descriptor starting point:
Based on Guidance Document, Chapter R.8, Appendix R.8-2. A 50% absorption via oral vs. inhalation was assumed
AF for dose response relationship:
1
Justification:
A clear NOAEC value was derived
AF for differences in duration of exposure:
1
Justification:
Based on a develpmental effect, no exposure duration adjustment applied
AF for interspecies differences (allometric scaling):
1
Justification:
Not applicable, correction of oral to inhalation (rat to human) already performed
AF for other interspecies differences:
1
Justification:
Not applicable
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
The quality of the whole database was judged adequate
AF for remaining uncertainties:
5
Justification:
Remaining uncertainty for result based on a positive finding in an OECD 422 study (Guidance Document, Chapter R.8, Appendix R.8-12)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
Acute/short term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
0.6 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
500
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
Assumed equivalent bioavailability between oral and dermal routes of exposure.
AF for dose response relationship:
1
Justification:
A clear NOAEL was defined
AF for differences in duration of exposure:
1
Justification:
Based on a develpmental effect, no exposure duration adjustment applied
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
The quality of the whole database was judged adequate
AF for remaining uncertainties:
5
Justification:
Remaining uncertainty for result based on a positive finding in an OECD 422 study (Guidance Document, Chapter R.8, Appendix R.8-12)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
hazard unknown (no further information necessary)
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:
0.6 mg/kg bw/day
Most sensitive endpoint:
developmental toxicity / teratogenicity
Route of original study:
Oral
DNEL related information
DNEL derivation method:
ECHA REACH Guidance
Overall assessment factor (AF):
500
Modified dose descriptor starting point:
NOAEL
Value:
300 mg/kg bw/day
AF for dose response relationship:
1
Justification:
A clear NOAEL was defined
AF for differences in duration of exposure:
1
Justification:
Based on a develpmental effect, no exposure duration adjustment applied
AF for interspecies differences (allometric scaling):
4
Justification:
Rat to human
AF for other interspecies differences:
2.5
Justification:
Default
AF for intraspecies differences:
10
Justification:
Default
AF for the quality of the whole database:
1
Justification:
The quality of the whole database was judged adequate
AF for remaining uncertainties:
5
Justification:
Remaining uncertainty for result based on a positive finding in an OECD 422 study (Guidance Document, Chapter R.8, Appendix R.8-12)
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

General Population - Hazard for the eyes

Local effects

Hazard assessment conclusion:
medium hazard (no threshold derived)

Additional information - General Population

Default procedures for the calculation of DNEL values were employed as described in the REACH technical guidance documents (Chapter R.8). As discussed for worker DNEL derivations, a NOAEL value of 300 mg/kg bw/day for developmental toxicity from a sub-acute oral gavage study in the rat was selected as the key endpoint.