Registration Dossier
Registration Dossier
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EC number: 208-167-3 | CAS number: 513-77-9
Toxicological Summary
Administrative data
Workers - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 6.9 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 15
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:
- 0.72 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:
- 41 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 15
- Modified dose descriptor starting point:
- NOAEL
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:
- no hazard identified
Additional information - workers
Long-term DNEL for workers – inhalation, systemic effects for BaCO3
Selection of the relevant dose-descriptor
The available data in laboratory animals suggest that the toxicity of ingested barium is similar across species. The lowest NOAEL for nephrotoxic effects in rats or mice was identified from the 13-week drinking water study with barium chloride dihydrate (Dietz et al., 1992) as the NOAEL of 61 mg Ba/kg bw/d in male rats. Therefore, the oral NOAEL of 61 mg Ba/kg bw/d for subchronic toxicity in male rats is used as a dose descriptor for calculation of DNEL values. None of the inhalation studies established concentration-response relationships of adverse effects, thus the determination of a concentration without effect (no-observed-adverse-effect concentration, NOAEC) in order to provide a basis for quantitative risk assessment purposes, is not possible.
Modification of the dose descriptor to the correct starting point for BaCO3
Based on ASTDR (August 2007), absorption following exposure via the oral route in animals varies considerably depending on the compound and other factors (age, fasted versus non-fasted, strain, etc.), and is very low for barium sulphate but highly variable for acid-soluble barium compounds (1-60%). However, a factor of 7% for oral absorption for non-fasted rats is regarded appropriate based on the studies of Cuddihy and Griffith (1972) and Taylor et al. (1962) and is used as default for calculation purposes. However, concerning barium sulphate, this value can be considered as over-conservative given the use as X-ray contact medium, based upon which an extremely low oral bioavailability may be assumed. Consequently, any risk assessment based on this value is of course inherently conservative.
Furthermore, the International Commission for Radiation Protection (ICRP) estimates that the gastrointestinal absorption of barium is 20% in adults, 30% for children aged 1–15 years, and 60% in infants (ICRP 1993). Thus, based on this weight-of-evidence approach by ICRP (1993), a human oral absorption factor of 20% for adults was selected as the most relevant descriptors for HH risk characterisation.
The systemic availability of different barium substances via the inhalation route can be expected as a function of regional deposition in the respiratory tract, which in turn depends foremost on the particle size distribution of the inhaled dust. From the mass fractions deposited on the impactor stages, the mass median aerodynamic diameter (MMAD) of the airborne material has been determined together with the geometric standard deviation (GSD) of the MMAD (EBRC Report: EBR-20100205/01). In the absence of actual measurements of the distribution of dust particles in the environment, the determined MMAD and GSD can therefore be used as surrogate parameters of the associated particle size distribution.
The fate and uptake of deposited particles depends on the clearance mechanisms present in the different parts of the airway. In the head region, most material will be cleared rapidly, either by expulsion or by translocation to the gastrointestinal tract. A small fraction will be subjected to more prolonged retention, which can result in direct local absorption. More or less the same is true for the trachea-bronchial region, where the largest part of the deposited material will be cleared to the pharynx (mainly by mucociliary clearance) followed by clearance to the gastrointestinal tract, and only a small fraction will be retained (ICRP, 1994).
In consequence, the material deposited in the head and trachea-bronchial regions would be translocated to the gastrointestinal tract without any relevant dissolution in view of the low water solubility of barium compounds, where it would be subject to gastrointestinal uptake at a ratio of 20%. The material that is deposited in the pulmonary region may be assumed by default to be absorbed to 100%. This absorption value is chosen in the absence of relevant scientific data regarding alveolar absorption although knowing that this is a conservative choice. Thus, the following predicted inhalation absorption factors can be derived for each respective barium substance:
Test item | Absorption factors* via inhalation [%] |
|
Barium carbonate (most representative form) | 10.4 |
|
Barium carbonate (fine powder) | 7.6 |
|
*: rounded values
In a first step (I), the oral NOAEL of 61 mg Ba/kg bw/d is converted into the respective doses for the different barium compounds on the basis of the molecular weights.
For the resulting oral NOAELs, a conversion of the dose descriptor for threshold effects into a correct starting point is necessary, because there are differences in human (inhalation) and experimental animal (oral) exposure conditions. For this purpose, the default respiratory volume for rats corresponding to a daily dose of human exposure is used (step IIa). Additionally, a correction for the difference in respiratory volume under standard conditions under conditions of light activity of workers is considered (step IIb).
Finally, a factor is applied (step III) which accounts for the difference of oral absorption in rats (7 %) and absorption following exposure via the inhalation route in humans (see table above).
1 6.7 m3 absoral_rat
NAECcorr_inh (mg/m3) = oral NOAEL × ------------------- × ------------- × -------------- mg/m3
0.38 m3/kg/d 10 m3 absinh_hum
Thus, the following corrected NAECs (no adverse effect concentrations) are calculated for the different barium substances based on the above formula.
Barium substances | Molecular weight [g/mol] | Step I oral NOAEL [mg/kg bw/d] | Step II (a+b) NAECcorr_inh [mg/m3] | Step III Absoral rat /Absinh hum | NAECcorr_inh [mg/m3] |
BaCO3 (standard) | 197.3 | 87.8 | 154.8 | 0.673 | 104.2 |
BaCO3 (fine powder) | 197.3 | 87.8 | 154.8 | 0.918 | 142.1 |
Application of assessment factors
The following aspects are taken into account: for inter-species variability (extrapolation from rodent data to humans) only an assessment factor for remaining differences is applied; ECETOC recommendations are used for intra-species variability (variability in chemical sensitivity within humans); differences in duration of exposure are addressed; no further factors for issues related to dose-response, and quality of the whole database are introduced.
Assessment factor | Accounting for | Default values applied |
Inter-species variability | - correction for differences in metabolic rate (AS)* | 11) |
| - remaining differences (e.g. toxicokinetics/-dynamics) | 2.5 |
Intra-species variability | - workers/general population | 32) |
Exposure duration | - subchronic to chronic | 2 |
Dose response | - adequate data available | 1 |
Quality of whole data base | - no need for a further assessment factor | 1 |
Overall |
| 15 |
1) factor for allometric scaling; any metabolism of inorganic barium substances can be excluded. Therefore, it is considered justified to deviate from default assessment factors accounting for a correction for differences in metabolic rate by assigning a factor of “1” instead of using the default factor of 4.
2) The assessment factor is introduced, since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intra-species variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003) for the general population. A lower factor of 3 (i.e. closer to the 90th percentile of the distribution of the variability for these datasets) is proposed for the more homogeneous worker population. In the worker population, the more susceptible groups are typically excluded and/or may be protected from specific exposures. Thus, and in consideration of normal hygiene practices at the workplace, a lower value for the assessment factor is considered appropriate for workers.
Calculation of DNEL workers – inhalation, systemic effects for BaCO3
The DNELs are derived by applying the overall assessment factor to the corrected NAECs as dose descriptor in the following way:
NAECcorr
DNEL (mg/m3) = -------------------- mg/m3
Overall AF (15)
Accordingly, the following long-term DNELs for systemic effects in workers exposed by inhalation are calculated for the different barium substances.
Barium substances | NAECcorr_inh | Overall AF | DNELinhalation_worker |
BaCO3 (standard) | 104.2 | 15 | 6.9 |
BaCO3 (fine powder) | 142.1 | 15 | 9.5 |
Long-term DNEL for workers – dermal, systemic effects for BaCO3
Selection of the relevant dose-descriptor
The available data in laboratory animals suggest that the toxicity of ingested barium is similar across species. The lowest NOAEL for nephrotoxic effects in rats or mice was identified from the 13-week drinking water study by Dietz et al. (1992) as the NOAEL of 61 mg Ba/kg bw/d in male rats. Therefore, the oral NOAEL of 61 mg Ba/kg bw/d for subchronic toxicity in male rats is used as a dose descriptor for calculation of DNEL values.
Modification of the dose descriptor to the correct starting point for BaCO3
A conversion of the dose descriptor for threshold effects into a correct starting point is necessary, because there are differences in human (dermal) and experimental animal (oral) exposure conditions. For this purpose, the different default dermal absorption factors for rats and humans are taken into consideration.
Based on ASTDR (August 2007), absorption for the oral route in animals varies very much depending on the substances and other factors (age, fasted versus non-fasted, strain, etc.), and is very little for barium sulphate, but highly variable for acid-soluble barium compounds (1-60%). However, a factor of 7% oral absorption for non-fasted rats is regarded as most appropriate based on the studies of Cuddihy and Griffith (1972) and Taylor et al. (1962) and is used as default for calculation purposes.
In the absence of measured data on dermal absorption, current guidance suggests the assignment of either 10% or 100% default dermal absorption rates. In contrast, the currently available scientific evidence on dermal absorption of metals (predominantly based on the experience from previous EU risk assessments) yields substantially lower figures. Therefore, the following default dermal absorption factor for metal cations is taken into consideration (reflective of full-shift exposure, i.e. 8 hours):
From exposure to liquid/wet media: 1.0 %
This approach is consistent with the methodology proposed in HERAG guidance for metals (HERAG fact sheet - assessment of occupational dermal exposure and dermal absorption for metals and inorganic metal substances; EBRC Consulting GmbH / Hannover /Germany; August 2007).
In the first step (I), the oral NOAEL of 61 mg Ba/kg bw/d is converted into the respective doses for the different barium compounds on the basis of the molecular weights.
For the resulting oral NOAELs, a conversion of the dose descriptor for threshold effects into a correct starting point is necessary, because there are differences between human (dermal 1 %) and experimental animal (oral 7 %) absorption rates.
absoral_rat
NAELcorr_dermal (mg/kg bw/d) = oral NOAEL × ------------------- mg/kg bw/d
absdermal_hum
The following corrected starting points (NAEL) are calculated for the different barium substances based on the above formula using NOAEL of 61 mg Ba/kg bw./d for the dermal route of exposure.
Barium substances | Molecular weight [g/mol] | Step I | Step II /Absdermal hum | NAELcorr_dermal [mg/kg bw/d] |
BaCO3 (standard) | 197.3 | 87.8 | 7 | 614.6 |
BaCO3 (fine powder) | 197.3 | 87.8 | 7 | 614.6 |
Application of assessment factors
The following aspects are taken into account: for inter-species variability (extrapolation from rodent data to humans) only a factor for remaining differences is considered; ECETOC recommendations for intra-species variability (variability in chemical sensitivity within humans) are introduced; differences in duration of exposure are considered; no further factors are applied for issues related to dose-response, and quality of the whole database.
Assessment factor | Accounting for | Default values applied |
Inter-species variability | - correction for differences in metabolic rate (AS)* | 11) |
| - remaining differences (e.g. toxicokinetics/-dynamics) | 2.5 |
Intra-species variability | - workers | 32) |
Exposure duration | - subchronic to chronic | 2 |
Dose response | - adequate data available | 1 |
Quality of whole data base | - no need for a further assessment factor | 1 |
Overall |
| 15 |
1) factor for allometric scaling; any metabolism of inorganic barium substances can be excluded. Therefore, it is considered justified to deviate from default assessment factors accounting for a correction for differences in metabolic rate by assigning a factor of “1” instead of using the default factor of 4.
2) This assessment factor is introduced since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intraspecies variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003). A lower factor of 3 (i.e. closer to the 90th percentile of the distribution of the variability for these datasets) is proposed for the more homogeneous worker population. In the worker population, the more susceptible groups are typically excluded and/or may be protected from specific exposures. Thus, and in consideration of normal hygiene practices at the workplace, a lower value for the assessment factor is considered appropriate for workers.
Calculation of DNEL workers – dermal, systemic effects for BaCO3
The DNEL is derived by applying the overall assessment factor to the corrected NAEL as dose descriptor in the following way:
NAEL
DNEL (mg/kg bw/d) = ------------------------ mg/kg bw/d
Overall AF (15)
Accordingly, the following long-term DNELs for systemic effects in workers exposed by dermal route are calculated for the different barium substances.
Barium substances | NAELcorr_dermal [mg/kg bw/d] | Overall AF | DNELdermal_worker |
BaCO3 (standard) | 614.6 | 15 | 41.0 |
BaCO3 (fine powder) | 614.6 | 15 | 41.0 |
Long-term DNEL for workers – inhalation, local effects for BaCO3
No DNEL was derived for local effects in workers exposed by inhalation with BaCO3 at the work place, because no reliable studies are available for the derivation of an NOAEL of long term local effects via inhalation route. However, local effects (e.g. baritosis) cannot be totally excluded. Therefore, and as a worst case consideration the official indicative occupational exposure limit value is used as DNEL for long term inhalation local effects. It is explicitly note here, that the concentration that gives local effects in human lungs would be much higher than the IOEL of 0.5 mg Ba/m3. However, it should also be mentioned that the value was derived for soluble barium substances but barium carbonate is only high soluble in acid media not in media at neutral pH.
IOEL: 0.5 mg Ba/m3, corresponding to 0.72 mg/m3 BaCO3
General Population - Hazard via inhalation route
Systemic effects
Long term exposure
- Hazard assessment conclusion:
- DNEL (Derived No Effect Level)
- Value:
- 2.1 mg/m³
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 25
- Modified dose descriptor starting point:
- NOAEC
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:
- 0.12 mg/m³
DNEL related information
- Overall assessment factor (AF):
- 5
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:
- DNEL (Derived No Effect Level)
- Value:
- 3.5 mg/kg bw/day
- Most sensitive endpoint:
- repeated dose toxicity
DNEL related information
- Overall assessment factor (AF):
- 25
- Modified dose descriptor starting point:
- NOAEL
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
Long-term DNEL for general population – inhalation, systemic effects for BaCO3
Selection of the relevant dose-descriptor
The available data in laboratory animals suggest that the toxicity of ingested barium is similar across species. The lowest NOAEL for nephrotoxic effects in rats or mice was identified from the 13-week drinking water study with barium chloride dihydrate (Dietz et al., 1992) as the NOAEL of 61 mg Ba/kg bw/d in male rats. Therefore, the oral NOAEL of 61 mg Ba/kg bw/d for subchronic toxicity in male rats is used as a dose descriptor for calculation of DNEL values.
Modification of the dose descriptor to the correct starting point for BaCO3
Based on ASTDR (August 2007), absorption following exposure to the oral route in animals varies very much depending on the compound and other factors (age, fasted versus non-fasted, strain, etc.), and is very little for barium sulphate, but highly variable for acid-soluble barium compounds (1-60%). However, a factor of 7% for oral absorption for non-fasted rats is regarded as most appropriate based on the studies of Cuddihy and Griffith (1972) and Taylor et al. (1962) and is used as default for calculation purposes.
Furthermore, the International Commission for Radiation Protection (ICRP) estimates that the gastrointestinal absorption of barium is 20% in adults, 30% for children aged 1–15 years, and 60% in infants (ICRP 1993). Thus, based on this weight-of-evidence approach by ICRP (1993), a human oral absorption factor of 20% for adults was selected as the most relevant descriptors for HH risk characterisation.
The systemic availability of different barium substances via the inhalation route can be expected as a function of regional deposition in the respiratory tract, which in turn depends foremost on the particle size distribution of the inhaled dust. From the mass fractions deposited on the impactor stages, the mass median aerodynamic diameter (MMAD) of the airborne material has been determined together with the geometric standard deviation (GSD) of the MMAD (EBRC Report: EBR-20100205/01). In the absence of actual measurements of the distribution of dust particles in the environment, the above determined MMAD and GSD can therefore be used as surrogate parameters of the associated particle size distribution.
The fate and uptake of deposited particles depends on the clearance mechanisms present in the different parts of the airway. In the head region, most material will be cleared rapidly, either by expulsion or by translocation to the gastrointestinal tract. A small fraction will be subjected to more prolonged retention, which can result in direct local absorption. More or less the same is true for the trachea-bronchial region, where the largest part of the deposited material will be cleared to the pharynx (mainly by mucociliary clearance) followed by clearance to the gastrointestinal tract, and only a small fraction will be retained (ICRP, 1994).
In consequence, the material deposited in the head and tracheo-bronchial regions would be translocated to the gastrointestinal tract without any relevant dissolution in view of the low water solubility of barium compounds, where it would be subject to gastrointestinal uptake at a ratio of 20%. The material that is deposited in the pulmonary region may be assumed by default to be absorbed to 100%. This absorption value is chosen in the absence of relevant scientific data regarding alveolar absorption although knowing that this is a conservative choice. Thus, the following predicted inhalation absorption factors can be derived for each respective barium substance:
Test item | Absorption factors* via inhalation [%] |
|
Barium carbonate (most representative form) | 10.4 |
|
Barium carbonate (fine powder) | 7.6 |
|
*: rounded values
In the first step (I), the oral NOAEL of 61 mg Ba/kg bw/d is converted into the respective doses for the different barium compounds on the basis of the molecular weights.
For the resulting oral NOAELs, a conversion of the dose descriptor for threshold effects into a correct starting point is necessary (step II), because there are differences in human (inhalation) and experimental animal (oral) exposure conditions. For this purpose, the default respiratory volume for rats corresponding to a daily dose of human exposure is used.
Finally, a factor is applied (Step III) which accounts for the difference of oral absorption in rats (7 %) and absorption following exposure via the inhalative route in humans (see above).
1 absoral_rat
NAECcorr_inh (mg/m3) = oral NOAEL × -----------------× ---------------- mg/m3
1.15 m3/kg/d absinh_hum
Thus, the following corrected NAECs (no adverse effect concentrations) are calculated for the different barium substances based on the above formula.
Barium substances | Molecular weight [g/mol] | Step I oral NOAEL [mg/kg bw./d] | Step II NAECcorr_inh [mg/m3] | Step III Absoral rat /Absinh hum | NAECcorr_inh [mg/m3] |
BaCO3 (standard) | 197.3 | 87.8 | 76.3 | 0.673 | 51.4 |
BaCO3 (fine powder) | 197.3 | 87.8 | 76.3 | 0.918 | 70.1 |
Application of assessment factors
The following aspects are taken into account: for inter-species variability (extrapolation from rodent data to humans) only an assessment factor for remaining differences is applied; ECETOC recommendations are used for intra-species variability (variability in chemical sensitivity within humans); differences in duration of exposure are addressed; no further factors for issues related to dose-response, and quality of the whole database are introduced.
Assessment factor | Accounting for | Default values applied |
Inter-species variability | - correction for differences in metabolic rate (AS)* | 11) |
| - remaining differences (e.g. toxicokinetics/-dynamics) | 2.5 |
Intra-species variability | - general population | 52) |
Exposure duration | - subchronic to chronic | 2 |
Dose response | - adequate data available | 1 |
Quality of whole data base | - no need for a further assessment factor | 1 |
Overall |
| 25 |
1) factor for allometric scaling; any metabolism of inorganic barium substances can be excluded. Therefore, it is considered justified to deviate from default assessment factors accounting for a correction for differences in metabolic rate by assigning a factor of “1” instead of using the default factor of 4.
2) This assessment factor is introduced since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intraspecies variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003).
Calculation of DNEL general population – inhalation, systemic effects for BaCO3
The DNEL is derived by applying the overall assessment factor to the corrected NAEC as dose descriptor in the following way:
NAECcorr
DNEL (mg/m3) = ------------------------ mg/m3
Overall AF (25)
Accordingly, the following long-term DNELs for systemic effects in the general population exposed by inhalation are calculated for the different barium substances.
Barium substances | NAECcorr_inh | Overall AF | DNELinhalation_gen. pop. |
BaCO3 (standard) | 51.4 | 25 | 2.1 |
BaCO3 (fine powder) | 70.1 | 25 | 2.8 |
Long-term DNEL for general population – oral, systemic effects for BaCO3
Selection of the relevant dose-descriptor
The available data in laboratory animals suggest that the toxicity of ingested barium is similar across species. The lowest NOAEL for nephrotoxic effects in rats or mice was identified from the 13-week drinking water study by Dietz et al. (1992) as the NOAEL of 61 mg Ba/kg bw/d in male rats. Therefore, the oral NOAEL of 61 mg Ba/kg bw/d for subchronic toxicity in male rats is used as a dose descriptor for calculation of DNEL values.
Modification of the dose descriptor to the correct starting point for BaCl2, BaCO3 and Ba(OH)2
In principle, modification is not necessary because there are no differences in human (oral) and experimental animal (oral) exposure conditions. However, the oral NOAEL of 61 mg Ba/kg bw/d needs to be converted into the respective doses for the different barium compounds on the basis of the molecular weights.
Barium substances | Molecular weight [g/mol] | Oral NOAEL |
BaCO3 (standard) | 197.3 | 87.8 |
BaCO3 (fine powder) | 197.3 | 87.8 |
Application of assessment factors
The following aspects are taken into account: for inter-species variability (extrapolation from rodent data to humans) only a factor for remaining differences is considered; ECETOC recommendations for intra-species variability (variability in chemical sensitivity within humans) are introduced; differences in duration of exposure are considered; no further factors are applied for issues related to dose-response, and quality of the whole database.
Assessment factor | Accounting for | Default values applied |
Inter-species variability | - correction for differences in metabolic rate (AS)* | 11) |
| - remaining differences (e.g. toxicokinetics/-dynamics) | 2.5 |
Intra-species variability | - general population | 52) |
Exposure duration | - subchronic to chronic | 2 |
Dose response | - adequate data available | 1 |
Quality of whole data base | - no need for a further assessment factor | 1 |
Overall |
| 25 |
1) factor for allometric scaling; any metabolism of inorganic barium substances can be excluded. Therefore, it is considered justified to deviate from default assessment factors accounting for a correction for differences in metabolic rate by assigning a factor of “1” instead of using the default factor of 4.
2) This assessment factor is introduced since it is expected that a greater variability in response from the most to least sensitive human would be seen, relative to an experimental animal population. ECETOC (2003) has reviewed scientific literature on the distribution of human data for various toxicokinetic and toxicodynamic parameters to assess intraspecies variability within the human population, specifically by Renwick and Lazarus (1998) and Hattis et al. (1999). Considering that the data analysed by these authors includes both sexes, a variety of disease states and ages, the use of the 95th percentile of the distribution of the variability for these datasets is considered sufficiently conservative to account for intraspecies variability for the general population. Based on this, a default assessment factor of 5 is recommended by ECETOC (2003).
Calculation of DNEL general population – oral, systemic effects for BaCO3
The DNEL is derived by applying the overall assessment factor to the corrected NOAEL as dose descriptor in the following way:
NOAEL
DNEL (mg/kg bw/d) = ------------------------ mg/kg bw/d
Overall AF (25)
The following corrected long-term DNELs for systemic effects in humans exposed orally are calculated for the different barium substances based on the above formula using NOAEL of 61 mg Ba/kg bw/d.
Barium substances | oral NOAEL | Overall AF | DNELcorr_general population |
BaCO3 (standard) | 87.8 | 25 | 3.5 |
BaCO3 (fine powder) | 87.8 | 25 | 3.5 |
Long-term DNEL for general population – inhalation, local effects for BaCO3
No DNEL was derived for local effects in workers exposed by inhalation with BaCO3 at the work place, because no reliable studies are available for the derivation of an NOAEL of long term local effects via inhalation route. However, local effects (e.g. baritosis) cannot be totally excluded. Therefore, and as a worst case consideration the official indicative occupational exposure limit value is used as DNEL for long term inhalation local effects. It is explicitly note here, that the concentration that gives local effects in human lungs would be much higher than the IOEL of 0.5 mg Ba/m3. However, it should also be mentioned that the value was derived for soluble barium substances but barium carbonate is only high soluble in acid media not in media at neutral pH.
To account for a potential exposure of the general population, the application of an additional AF of 5 (according to ECETOC) for intra-species variability of the general population is considered which results in the following DNEL:
DNEL: 0.1 mg Ba/m3, corresponding to 0.14 mg/m3 BaCO3
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