Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
35.3 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
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
Value:
35.3 mg/m³
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects in workers after long-term inhalation exposure to the test item was derived via route-to-route extrapolation from the lowest NOAEL obtained in the repeated dose reproductive toxicity screening study (OECD422),1000 mg/kg bw/day, with the read-across substance antimony nickel titanium oxide yellow. To convert the oral NOAEL in rats to an inhalation NOAEC in humans, a rat default respiratory volume was used corresponding to the daily duration of human exposure (sRVrat: 0.38m3/kg bw/8h). For workers a correction was added for the difference between respiratory rates under standard conditions (sRVhuman: 6.7 m3for an 8-hour exposure period) and under conditions of light activity (wRV: 10 m3for an 8-hour exposure period); extrapolation from 50% bioavailability oral to 100% bioavailability inhalation. Therefore, inhalatory NOAEC = oral NOAEL*(1/sRVrat 8h)*(ABSoral/ABSinh)*(sRVhuman/wRV) OR 1000*(1/0.38)*(50/100)*(6.7/10) = 881.6 mg/m3. Therefore, DNEL = Corrected inhalation NOAEC (881.6 mg/m3)*(1/25{Overall AF}) = 35.3 mg/m3.

AF for dose response relationship:
1
Justification:
Not required as starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
Not required when route to route extrapolation conducted
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Not required (source study K2)
AF for remaining uncertainties:
1
Justification:
Not required
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:
4 mg/m³
Most sensitive endpoint:
irritation (respiratory tract)
DNEL related information
DNEL derivation method:
other: German occupational value of the respirable fraction for inert dusts (Staubgrenzwert)
Overall assessment factor (AF):
1
Dose descriptor:
other: German occupational value of the respirable fraction for inert dusts (Staubgrenzwert)
Value:
4 mg/m³
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:
10 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):
100
Dose descriptor starting point:
NOAEL
Value:
1 000 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
Value:
10 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The DNEL for systemic effects in workers after long-term dermal exposure to the test item was derived via route-to-route extrapolation from the lowest NOAEL of 1000 mg/kg bw/day obtained in the repeated dose reproductive toxicity screening study (OECD422), 1000 mg/kg bw/day, with the read-across substance antimony nickel titanium oxide yellow. Therefore, DNEL = 1000 mg/kg bw/day*(1/2{exposure duration sub-chronic to chronic}*4{allometric scaling rat-human}*2.5{interspecies differences}*5{intraspecies differences-worker population}) = 10.0 mg/kg bw/day. This is considered to be the worst-case scenario assuming similar potential for dermal absorption compared to oral at this level.

AF for dose response relationship:
1
Justification:
Not required as starting point is NOAEL
AF for differences in duration of exposure:
2
Justification:
Sub-chronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
Allometric scaling rat to human
AF for other interspecies differences:
2.5
Justification:
Default factor for remaining differences
AF for intraspecies differences:
5
Justification:
Default factor for workers
AF for the quality of the whole database:
1
Justification:
Not required (source study K2)
AF for remaining uncertainties:
1
Justification:
Not required
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
DNEL related information

Local effects

Long term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion
Acute/short term exposure
Hazard assessment conclusion:
no hazard identified
Most sensitive endpoint:
skin irritation/corrosion

Workers - Hazard for the eyes

Local effects

Hazard assessment conclusion:
no hazard identified

Additional information - workers

The basis for the inhalation and dermal systemic DNELs for worker exposure to the test item is the findings in the repeated dose reproductive toxicity screening study (OECD422) with the read-across substance antimony nickel titanium oxide yellow, from which the lowest NOAEL was determined to be 1000 mg/kg bw/day. This dose level was the highest dose level tested and there were no changes considered to be related to treatment with the read-across test item. The lowest NOAEL (No Observed Adverse Effect Level) of 1000 mg/kg bw/day was used as the basis of the DNEL calculations using appropriate assessment factors for relevant indicators including route to route extrapolation, allometric scaling, exposure duration and study length.

For local effects via the inhalation route of exposure the German AGW (maximum occupational limit; formerly MAK) for inert dusts was taken into account. The target substance, predicted form the read-across substance, is considered to be insoluble and relatively inert. In addition, bioelution tests on the source substance revealed limited bioavailability of the metal ions for inhalation and oral routes of exposure. In 1997, the German MAK commission stated the AGW of the respirable fraction of inert dusts to be 4 mg/m3in order to prevent unspecified local effects in the respiratory tract. This value is used for the derivation of the No Effect Level for long-term exposure of local effects. For local effects from the short-term inhalation exposure it is considered that the systemic DNEL for inhalation exposure would be protective for this exposure in the absence of specific data. For dermal exposure the combination of physchem data and in vitro skin irritation studies with the target material, Uverithe, would indicate no hazard.

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