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Toxicological Summary

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Workers - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

Workers - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

Workers - Hazard for the eyes

Additional information - workers

The hazard assessment of inorganic UVCBs for the purpose of classification and derivation of safe effect thresholds (i.e. DN(M)EL) is a cumbersome and complex process. Due to the intrinsic variability of the composition of an UVCB, it is difficult to select a sample that would unambiguously be representative for the (eco)toxicological hazard profile of the UVCB and could subsequently be used for testing. Instead of direct testing, a precautionary approach is taken where the UVCB is treated as a complex metal containing substance containing a number of discrete constituents (metals, metal compounds, non-metal inorganic compounds etc.). For each of these constituents, the hazard profile is used for deriving the proper classification of the UVCB (using the mixture rules) and/or for the derivation of the DN(M)ELs of the constituent (forwarded to the risk assessment). Using the DN(M)EL of all individual constituents circumvents indirectly the issue of varying composition of an UVCB as it implicitly assumes that each time the UVCB substance consists of the pure substance, i.e. that each constituent would be present and bioavailable at a 100% concentration in the UVCB substance. This can be considered a conservative approach. A main outcome of the constituents’ based assessment is the selection of all the constituents for which any human health hazard is identified. This selection defines the scope of the further exposure and risk assessment (CSR, Ch. 9&10).

 

The actual hazard profile of the inorganic UVCB substance and the individual constituents is dependent on the speciation of each and every constituent andhence this information needs to be collected in order to obtain a robust classification or DNEL value used for risk assessment purposes. Different scenarios can be encountered.

·      When the speciation of a constituent is known, this is used as such for the human health hazard assessment.

·      When the speciation is unknown or few metal species co-exist, the worst-case speciation for the purpose of human health hazard assessment is selected, i.e. the speciation that would lead to the most severe effects and thus the lowest DN(M)EL

 

Please note that dependent on the exercise (i.e, classification versus risk assessment) different speciation forms could be utilized (see below).

 

Selection of the toxicological information for the purpose of classification

 

The UVCB classification is calculated by applying the CLP mixture rules based on the classification of the known or worst-case speciation for each constituent and worst-case constituent concentration in the UVCB (i.e. maximum of the legal entity typical value), using the MeClas tool. Depending on the availability of information, the UVCB classification can be refined following MeClas Tiered approach.

 

Selection of the toxicological information for the purpose of risk assessment

 

For the purpose of the human health risk assessment for the UVCB, the hazards of each constituent will be assessed and DNEL/DMEL values for all the constituents for which a hazard has been identified are compiled. As indicated above, workers can be exposed on the work floor to different speciation forms than those present in the mineralogical composition of the UVCB. Hence the information onthe intrinsic properties of the UVCB constituents relevant for the hazard assessment (classification) can be refined if it is known which chemical speciation is present in the work place.

 

For the sake of readability of the CSR and the IUCLID, the below sections therefore outlinetoxicity effects derived for the UVCB itself. Information on hazards linked to speciation occurring in case individual constituing species of the UVCB (see CSR 3.0 Introduction to Classification) are released during production/use of the UVCB are reported in a separate annex of this CSR, if deemed relevant for the risk assessment.

Hazard conclusions for the purpose of classification

 

The UVCB is treated as a complex metal containing substance with a number of discrete constituting compounds (metals, metal compounds, non-metal inorganic compounds). The hazard classifications of each compound are then factored into a combined classification of the UVCB as a whole. For health endpoints, UVCB classifications are based on the combined hazards of the compounds whereby additivity or key cut off levels, specified in look-up tables are used, depending on the endpoint and amount of information available for the constituting compounds. The classification was derived using Meclas (MEtals CLASsification tool - see www.meclas.eu), a calculation tool that follows classification guidance and implementation in accordance to legal rules and technical guidance from ECHA and CLP see IUCLID section 13 attachment for MeClas Classification conclusions.

 

Table: Summary of the information on toxicological information for the purpose of classification:

UVCB constituent

Variability in elemental composition

 

Classification acute toxicity, skin irritation/corrosion, eye damage, skin/respiratory sensitisation, mutagenicity, repeated dose toxicity, carcinogenicity, reproductive effects

 

Chemical Element

Speciation

Cu

CuSO4, see IUCLID/CSR section 1.2 composition

Maximum of typicals

Harmonised and worse selfclassification of the speciation, see MECLAS

Ni

NiSO4, see IUCLID/CSR section 1.2 composition

Maximum of typicals

Harmonised classification of the speciation, see MECLAS

Pb

Pb compounds, see IUCLID/CSR section 1.2 composition

Maximum of typicals

Harmonised and worse selfclassification of the speciation, see MECLAS

As

4.13% As, 10.18% As compounds, 85.69% As2O3, see IUCLID/CSR section 1.2 composition

Maximum of typicals

Harmonised classification of the speciation, see MECLAS

Zn

ZnSO4, see IUCLID/CSR section 1.2 composition

Maximum of typicals

Harmonised classification of the speciation, see MECLAS

Ba

BaSO4, see IUCLID/CSR section 1.2 composition

Maximum of typicals

Selfclassification of the speciation, see MECLAS

Co

CoSO4, see IUCLID/CSR section 1.2 composition

Maximum of typicals

Harmonised classification of the speciation, see MECLAS

Sn

Sn compounds, see IUCLID/CSR section 1.2 composition

Maximum of typicals

Selfclassification of the speciation, see MECLAS

Sb

Sb2O3, see IUCLID/CSR section 1.2 composition

Maximum of typicals

Harmonised classification of the speciation, see MECLAS

Te

TeO2, see IUCLID/CSR section 1.2 composition

Maximum of typicals

Not classified, see MECLAS

Se

Se, see IUCLID/CSR section 1.2 composition

Maximum of typicals

Harmonised classification of the speciation, see MECLAS

Ag

Ag (powder), see IUCLID/CSR section 1.2 composition

Maximum of typicals

Selfclassification of the speciation, see MECLAS

 Bi

Bi sulphate, see IUCLID/CSR 1.2 composition 

Maximum of typicals 

Not classified, see MECLAS 

S

SO42-sulfate, see IUCLID/CSR section 1.2

 

Taken into consideration in corresponding metal sulfates, see MECLAS

 

Selection of the DNEL(s) for the purpose of risk assessment

 

The UVCB is an intermediate, with a very limited life cycle (manufacturing and industrial uses only). Testing the UVCB is difficult because of the large uncertainty involved when selecting representative samples due to the variable elemental concentrations in the composition of the UVCB.Derivation of a DNEL for the UVCB as such is thereforedifficult to interpretand to extrapolate results of testing to the entirety of variations of the UVCBbecause of the uncertainty related to the representativeness of the testing.Exposure to the UVCB cannot be measured or modelled and expressed as portion of the UVCB emitted because of the multi-constituent character of the UVCB. For these reasons, the UVCB toxicological assessment is driven by the assessment of the individual UVCB constituents.

 

The human health assessment is based on all hazardous constituents for human health of all relevant UVCBs in the workplace. The scope of the exposure assessment and type of risk characterization required for workers for each constituent is described in section 9 of this CSR.

 

Table: Summary of the information on toxicological information for the purpose of risk assessment

UVCB constituent

 

Variability in chemical composition

DNELs for systemic and local effects, inhalation and dermal route, short term and long term.

 

Element

Speciation used for occupational exposure assessment

Cu

Cu ion is toxic driver

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

Ni

Ni ion is toxic driver except NiSO4 for systemic acute inhalation and NiS for local acute inhalation

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

Pb

Pb ion is toxic driver

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

As

As ion is toxic driver

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

Zn

Soluble Zn compounds

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

Ba

Speciation (BaSO4, BaCl, BaOH) with worst-case DNEL

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

Co

Speciation (CoCl2, CoCO3, Co) with worst-case DNEL

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

Sn

Sn ion is toxic driver

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

Sb

Sb ion is toxic driver

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

Te

Te compounds

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

Se

Se compounds

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

Ag

Ag compounds

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

S

H2SO4

Hazard assumed as if UVCB consists of 100% worst-case speciation

See respective DNEL summary in IUCLID and table below

 

Different speciation is relevant to consider. In some cases, human health toxicity is driven by free metal ion. In other cases, human health toxicity is different per species and since the speciation of the exposure is not always known, the species with the worst-case DNEL was further considered for the assessment. Toxicological information on the individual UVCB constituents is reported in each constituent summary for which a quantitative exposure and risk assessment was conducted (the information is taken from the respective constituent IUCLID dossiers).

 

The relevant copper speciations for occupational exposure are Cu2+ion, CuSO4, Cu2O and CuO. There is no difference between the DNEL values of these speciations (apart from the molecular weight conversion). The DNEL values are therefore based on the soluble form. There is no separate DNEL derived for powder form. The common DNEL values are taken forward to risk characterisation.

 

The relevant lead speciations for occupational exposure are lead metal, lead oxide and lead sulfate. All DNELs are based upon systemic biomarkers of exposure and not on external exposure. The DNEL values used for occupational exposure assessment are therefore based on internal concentration of soluble lead concentrations.

 

Workers can be exposed to arsenic under different speciations i.e. arsenic metal, arsenic sulfide, arsenic sulphate and diarsenic trioxide. Only DNEL values are available for diarsenic trioxide. It is assumed that the arsenic ion is the driver for toxicity. The DNEL for arsenic can therefore be calculated based on the DNEL of arsenic oxide using the molecular weight conversion. These recalculated DNEL values are used for the risk assessment of arsenic. The same rationale holds for antimony.

 

The relevant nickel speciations are Ni metal, Ni sulphates, Ni sulfide and Ni oxide. There are differences in DNEL values between these speciations for a few type of effects. The DNEL values of the worst-case speciation form are therefore taken forward to risk characterisation. Ni sulphate has the lowest systemic acute inhalation DNEL of 16 mg/m3(16-680 mg/m3). Ni sulfide has a DNEL of 0.47 mg/m3for the local acute inhalation effects (range 0.47-4 mg/m3). The local long-term dermal DNEL of 0.00044 mg/cm2/day (range 0.00044 -0.07 mg/cm2/day) is taken forward to risk characterisation.

 

The effect assessment of Cd and Cd compounds is based on Cadmium. The cadmium DNEL values are therefore used for the occupational effect assessment and risk characterisation.

 

Zn substances are divided in 2 solubility groups: “soluble” substances or “slightly soluble” and “insoluble” substances. The “soluble” DNEL values are selected since these have the lowest (worst-case) DNEL values.

 

SnSO4has the lowest DNEL values compared to SnS and Sn metal and are taken forward to risk characterisation. For Co and Ba, the same approach has been taken for the relevant metallic, sulfide, sulfate, and oxide speciations.


Table: Human health hazard conclusions taken forward to CSA

 

Route

Type of effect

Cu

Pb

As

Ni

Cd

H2SO4

Se

Zn

Ni metal

NiSO4

NiS

NiO

Assessment rationale for different speciation

Conservative read-across from Cu2+

Lead cation is the primary mediator of lead toxicity

Arsenic ion is the driver for toxicity

Difference between Ni metal and Ni sulphate,

Ni sulphide, Ni oxide

Cd and Cd compounds effect assessment based on Cd

Not relevant

/

2 solubility groups:

1) "soluble" substances

2) "slightly soluble" and 'insoluble" substances

Inhalation

Systemic Long Term

See internal DNEL

See internal DNEL

1.9mg As/m3(read across from As2O3: 5mg/m3)

0.05 mg/m3

(inhalable)

0.05 mg/m3

(inhalable)

0.05 mg/m3

(inhalable)

0.05 mg/m3

(inhalable)

0.004 mg/m3(respirable fraction)

No threshold effect and/or no dose-response available

0.05 mg/m3

 

1.25 mg/m3(soluble)

5 mg/m3(insoluble)

Systemic Acute

20.0 mg/m3

DNEL not relevant (Pb is not acutely toxic)

No hazard

680 mg/m3

16 mg/m3

16.8 mg/m3

520 mg/m3

No threshold effect and/or no dose-response information available

No threshold effect and/or no dose-response available

/

No threshold effect and/or no dose-response information available

Local Long Term

OEL

1 mg/m3

DNEL not relevant

DNEL not relevant

0.05 mg/m3

0.05 mg/m3

0.05 mg/m3

0.05 mg/m3

No threshold effect and/or no dose-response information available

0.05 mg/m3

/

No threshold effect and/or no dose-response information available

Local Acute

OEL

1 mg/m3

DNEL not relevant (Pb is not acutely toxic)

DNEL not relevant

4 mg/m3

0.7 mg/m3

0.47 mg/m3

3.9 mg/m3

No threshold effect and/or no dose-response information available

0.1 mg/m3

/

No threshold effect and/or no dose-response information available

OEL (Long Term)

1 mg/m3

(Inhalable)

0.1-0.2 mg/m3(respirable)

0.05-0.15 mg/m3(Inhalable)

0.01 -0.05 mg/m3(Inhalable)

0.05-1mg/m3

(Inhalable)

0.01 – 0.15 mg/m3(inhalable)

0.002-0.01 mg/m3(respirable)

0.1-1mg/m3

0.05-0.2mg/m3

ZnO fume: 4-5 mg/m3

ZnO dust: 3-15 mg/m3

ZnCl: 0.5-5 mg/m3

Dermal

Systemic Long Term

137 mg/kg bw/day

See internal DNEL

As2O3: 112μg/kg bw/day

As acid: 85 μg/kg bw/d

Negligible absorption

Negligible absorption

Negligible absorption

Negligible absorption

Exposure based waiving

No threshold effect and/or no dose-response information available

7 mg/kg bw/day

83.3 mg/kg bw/day

Systemic Acute

273 mg/kg bw/day

DNEL not relevant (Pb is not acutely toxic)

no hazard

Not relevant (negligible absorption)

Not relevant (negligible absorption)

Not relevant (negligible absorption)

Not relevant (negligible absorption)

Exposure based waiving

No threshold effect and/or no dose-response information available

/

No threshold effect and/or no dose-response information available

Local Long Term

Exposure based waiving

DNEL not relevant

DNEL not relevant

0.07 mg/cm2/day

0.00044 mg/cm2/day

0.0048 mg/cm2

0.024 mg/cm2/day

Exposure based waiving

No threshold effect and/or no dose-response information available

/

No threshold effect and/or no dose-response information available

Local Acute

Exposure based waiving

DNEL not relevant (Pb is not acutely toxic)

DNEL not relevant

Not applicable

Not applicable

Not applicable

Not applicable

Exposure based waiving

No threshold effect and/or no dose-response available

/

No threshold effect and/or no dose-response information available

Internal

Systemic Long Term

Internal DNEL (using MPPD model) 0.04075 mg/kg/day

DNEL:

Male: 40 μg/dL blood

Female: 30 μg/dL blood 

Female of reproductive capacity: 10 μg/dL blood 

BLV 0.9739 μg/dL blood, 30 μg/g creatinine in urine

Notassessed (indicative 1μg/dL blood)

European Commission

BLV: 2 μg/g creatinine in urine, 0.5 μg/dL blood

/

/

/

 

Eye

Not to be assessed since safety goggle are used where needed.

*PTWI: Provisional Tolerable Weekly Intake (FAO/WHO)

**Arsenic drinking water:http://www.who.int/water_sanitation_health/dwq/chemicals/nitratenitritesum.pdf


Route

Type of effect

Sn

Mn

Co

Sb

Ba

Hg

Te

Assessment rationale for different speciation

Not in multimetallic database

Not in multimetallic database

Not in multimetallic database

Read across from antimony trioxide

(Data are for Sb)

Not in multimetallic database

Not in multimetallic database

Not in multimetallic database

Inhalation

Systemic Long Term

8 mg/m3(SnSO4)

0.2 mg/m3

Not derived, since the available data are considered insufficient for a quantitative hazard assessment. Testing proposal is issued.

/

8.8 mg/m3BaCl

10 mg/m3BaSO4

0.02 mg/m3

Insufficient info, testing proposal

Systemic Acute

8 mg/m3(SnSO4)

No threshold effect and/or no dose-response information available

Not derived. No reason of concern for systemic toxicity because high exposure levels not covered by the long-term DNEL are not expected.

No acute effects

No information available

No information available

Low hazard (no threshold level)

Local Long Term

8 mg/m3(SnSO4)

/

88.2 ug/m3CoCl2

80.7 ug/m3CoCO3

40 ug/m3Co

0.5 mg/m3

0.62 mg/m3BaOH

10 mg/m3BaSO4

No information available

Hazard unknown (no further info necessary)

Local Acute

8 mg/m3(SnSO4)

No threshold effect and/or no dose-response information available

No DNEL derived, since there is no reason of concern for systemic toxicity, because high exposure levels not covered by the long-term DNEL are not expected.

No acute local effects

1.24 mg/m3BaOH

No information available

No hazard identified

OEL (Long Term)

2mg/m3

0.2-5mg/m3

 

0.5mg/m3

No information available

No information available

Insufficient info, testing proposal

Dermal

Systemic Long Term

0.11 mg/kg bw/day

(SnSO4)

0.00414 mg/kg bw/day

Not required: overall, there is no reason of concern for systemic toxicity with respect to long-term dermal exposure, because absorption can be regarded as negligible.

234.7 mg/kg bw/day

281 for Sb2O3

43.2 mg/kg/d

No information available

Hazard unknown (no further information necessary)

Systemic Acute

0.11 mg/kg bw/day

(SnSO4)

No threshold effect and/or no dose-response information available

Not derived, because dermal absorption is negligible and there is no data available which indicate systemic toxicity.

No acute effects

No information available

No information available

No hazard identified

Local Long Term

/

/

No DNEL derived, because with no dose-response relationship available

No local long term effects expected

No information available

No information available

Hazard unknown (no further info necessary)

Local Acute

/

/

Not relevant, because no acute local effects are expected.

No acute local effects

No information available

No information available

No hazard identified

 

Eye

Not to be assessed since safety goggle are used where needed.

 

Route

Type of effect

Bi

 C

Fe

Al

Cr

Si

SO2

Mg, K, Na, Ca

Assessment rationale for different speciation

Not in multimetallic database, Bi is toxic driver

Not in multimetallic database,Charcoal speciation

 most relevant

Metallic speciation

Toxicological effects can be attributed to the aluminium ion, Al3+

Not in multimetallic database, Cr 3+ speciation

Not in multimetallic database, non-crystalline speciation

Not in multimetallic database

Not in multimetallic database,

Inhalation

Systemic Long Term

13.1 mg/m3

10 mg/m3

No DNEL needs to be derived

No-threshold effect available

No-threshold effect available

4 mg/m3

No-threshold effect available

 

 

 

 

cation no hazard, anion covered by metal speciation

Systemic Acute

No-threshold effect available

No-threshold effect available

No DNEL needs to be derived

No-threshold effect available

No-threshold effect available

No-threshold effect available

No-threshold effect available

Local Long Term

No-threshold effect available

10 mg/m3

No DNEL needs to be derived

3.72 mg/m3

0.5 mg/m3

No-threshold effect available

1.3 mg/m3

Local Acute

No-threshold effect available

No-threshold effect available

No DNEL needs to be derived

No-threshold effect available

2 mg/m3

No-threshold effect available

2.7 mg/m3

Dermal

Systemic Long Term

No-threshold effect available

14.3 mg/kg bw/d

No DNEL needs to be derived

No-threshold effect available

No-threshold effect available

No-threshold effect available

No-threshold effect available

Systemic Acute

No-threshold effect available

No-threshold effect available

No DNEL needs to be derived

No-threshold effect available

No-threshold effect available

No-threshold effect available

No-threshold effect available

Local Long Term

No-threshold effect available

No-threshold effect available

No DNEL needs to be derived

No-threshold effect available

No-threshold effect available

No-threshold effect available

No-threshold effect available

Local Acute

No-threshold effect available

No-threshold effect available

No DNEL needs to be derived

No-threshold effect available

No-threshold effect available

No-threshold effect available

No-threshold effect available

 

Eye

Not to be assessed since safety goggle are used where needed.

 

General Population - Hazard via inhalation route

Systemic effects

Acute/short term exposure
DNEL related information

Local effects

Acute/short term exposure
DNEL related information

General Population - Hazard via dermal route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard via oral route

Systemic effects

Acute/short term exposure
DNEL related information

General Population - Hazard for the eyes

Additional information - General Population

The UVCB is an intermediate, with a very limited life cycle (manufacturing and industrial uses only). Exposure of the general population to the UVCB as such is highly unlikely, derivation of DNELs for the UVCB as such is not appropriate due to the high variability in elemental composition.