Registration Dossier

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
DNEL (Derived No Effect Level)
Value:
2.73 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):
25
Dose descriptor starting point:
NOAEL
DNEL value:
116.3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
68.35 mg/m³
Explanation for the modification of the dose descriptor starting point:
The NOAEL in the 13 weeks oral repeated dose study of the read-across substance barium chloride dihydrate was used to derive a DNEL long-term, systemic effects via the inhalation route. For the route-to-route extrapolation from oral to inhalation, the dose descriptor starting point = 116.3 mg barium nitrate/kg bw/day x 1/(0.38 m³/kg/day) x 6.7m³/10m³ x (7/21) = 68.35 mg/m³. The oral dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (0.38 m³/kg for 8 hours exposure of workers). For workers the resulting air concentration needs to be additionally corrected for the difference between basal caloric demand and caloric demand under light activity. This correction factor is derived from the inhaled volumes in 8 hours under the respective conditions (6.7 m³ for base level, 10 m³ for light activity). In addition, the NOAEL need to be multiplied by 0.33 as the bioavailability via the inhalation route is considered as 21%, while for oral exposure this is only 7%.
AF for dose response relationship:
1
Justification:
adequate data available
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
covered in route-to-route extrapolation
AF for other interspecies differences:
2.5
Justification:
rat to human
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
Justification:
no need for a further assessment factor
AF for remaining uncertainties:
1
Justification:
no need for a further assessment factor
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
8.141 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):
100
Modified dose descriptor starting point:
NOAEL
DNEL value:
814.1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

No long-term dermal tox studies are available for barium nitrate. However, read-across data from a 13 -week repeated dose study (oral) of barium chloride dihydrate could be used after extrapolation to the dermal route.

Exposures were continuous, via drinking water during 92 days (Dietz et al., 1992). Parental Fischer 344 rats (10 per sex and per dose) were treated, starting at 32 days old and ending when the animals were euthanized, at dose levels of 125, 500, 1000, 2000 and 4000 ppm BaCl2.H2O. A control group of 10 males and 10 females didn’t receive treatment. The No Observed Adverse Effect Level (NOAEL) was considered to be 61.1 mg Ba/kg/day. The NOAEL level recalculated for Ba nitrate (Ba(NO3)2) is 61.1 mg/kg/day x 52.55% (for Ba content) = 116.3 mg barium nitrate/kg/day. For route-to-route extrapolation (oral to dermal), a factor of 1/7 should be applied as part of the overall assessment factor, as it is assumed that dermal absorption (assumed to be 1%) will be lower than oral absorption (assumed to be 7%). The dose descriptor starting point is 116.3 mg/kg bw/day x 7 = 814.1 mg/kg bw/day.

AF for dose response relationship:
1
Justification:
adequate data available
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
rat to human
AF for intraspecies differences:
5
Justification:
worker
AF for the quality of the whole database:
1
Justification:
no need for a further assessment factor
AF for remaining uncertainties:
1
Justification:
no need for a further assessment factor
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

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:
0.67 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):
50
Dose descriptor starting point:
NOAEL
DNEL value:
116.3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEC
DNEL value:
33.71 mg/m³
Explanation for the modification of the dose descriptor starting point:

The NOAEL observed in the 13 -weeks oral repeated dose study with the read-across substance barium chloride dihydrate was used to derive a DNEL long-term, systemic effects via the inhalation route.

For the route-to-route extrapolation from oral to inhalation, the dose descriptor starting point = 116.3 mg barium nitrate/kg bw/day x 1/(1.15 m³/kg/day) x (7/21) = 33.71 mg/m³. The dermal dose for rats was converted to the corresponding air concentration using a standard breathing volume for the rat (1.15 m³/kg for 24 hours exposure). In addition, the NOAEL needed to be multiplied by 0.33 as the bioavailability via the inhalation route is considered as 21%, while for oral exposure this is only 7%. No correction for the exposure duration was added as the animals in the reference study were exposed continuously.

AF for dose response relationship:
1
Justification:
adequate data available
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
1
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
rat to human
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
no need for a further assessment factor
AF for remaining uncertainties:
1
Justification:
no need for a further assessment factor
Acute/short term exposure
Hazard assessment conclusion:
low hazard (no threshold derived)
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:
4.07 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):
200
Dose descriptor starting point:
NOAEL
DNEL value:
116.3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
814.1 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:

The long term systemic DNEL for the dermal route was derived based on the combined repeated dose toxicity study with reproduction/developmental toxicity screening of the read-across

substance barium chloride dihydrate. No correction for the exposure duration was added as the animals in the refernce study were exposed continuously. The dose descriptor starting point = 116.3 mg/kg/day x 7 = 814.1 mg/kg/day. The NOAEL needed to be multiplied by 7 as the bioavailability via the dermal route is considered 1%, while for oral this is 7%.

AF for dose response relationship:
1
Justification:
adequate data available
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
rat to human
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
no need for a further assessment factor
AF for remaining uncertainties:
1
Justification:
no need for a further assessment factor
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:
DNEL (Derived No Effect Level)
Value:
0.58 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):
200
Dose descriptor starting point:
NOAEL
DNEL value:
116.3 mg/kg bw/day
Modified dose descriptor starting point:
NOAEL
DNEL value:
116.3 mg/kg bw/day
Explanation for the modification of the dose descriptor starting point:
no route to route extrapolation
AF for dose response relationship:
1
Justification:
adequate data available
AF for differences in duration of exposure:
2
Justification:
subchronic to chronic
AF for interspecies differences (allometric scaling):
4
Justification:
rat to human
AF for other interspecies differences:
2.5
Justification:
rat to human
AF for intraspecies differences:
10
Justification:
general population
AF for the quality of the whole database:
1
Justification:
no need for a further assessment factor
AF for remaining uncertainties:
1
Justification:
no need for a further assessment factor
Acute/short term exposure
Hazard assessment conclusion:
medium 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