Registration Dossier

Diss Factsheets

Toxicological information

Toxicological Summary

Currently viewing:

Administrative data

Workers - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
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

Workers - Hazard via dermal route

Systemic effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
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

5.0. Introduction

 

The hazard assessment of inorganic UVCBs for the purpose of classification and derivation of threshold values (i.e. DNELs) is a complex process. Due to the variability of the composition of an UVCB, it is not possible to select a sample that would be representative for the hazard profile of the UVCB and could subsequently be used for toxicity testing. Instead of testing, a precautionary approach is followed in which the UVCB nature of a complex metal containing substance having a number of constituents (metals and their compounds or other inorganic compounds) is acknowledged. The hazard profile of each individual constituent is used for deriving the classification of the UVCB (using the mixture rules) and for the derivation of the DNELs of the constituent. Using the unmodified DNEL values of all individual constituents addresses the varying composition of an UVCB on a pre-cautionary basis as it implicitly assumes that the UVCB entirely consists of the specific constituent, i.e. that each constituent would be present to 100% in the UVCB. Thus, this hazard assessment can be considered a conservative approach. The identificationof constituents which are hazardousfor human health also defines the scope of the exposure assessment and risk characterisation (Chapters 9&10).

 

The hazard profile of the inorganic UVCB and the individual constituents is dependent on their chemical speciation.Depending on the level of knowledge, the following situations can be distinguished:

 

·      If chemical speciation of the constituent in the UVCB is known, this is used for classification.

·      If chemical speciation of the constituent as present in the workplace is known, this is used for risk characterisation.

·      When information on chemical speciation is not complete, the worst-case speciation for the purpose of risk characterisation and classificationis assumed, i.e. the speciation that would lead to the most severe classification or to the lowest DNEL.It is noted that different chemical species could be relevant (see below).

 

Selection of toxicological information for classification

 

The UVCB classification is calculated by applying the CLP mixture rules based on the classification of the known or worst-case speciation of each constituent and worst-case constituent concentration in the UVCB (i.e. the maximum value of the typical concentration reported by the individual legal entities), using the MeClas tool.

 

Selection of toxicological information for risk assessment

 

For the purpose of the human health risk assessment for the UVCB,the hazards of each constituent will be assessed and DNEL values for constituentsfor which a hazard has been identifiedare compiled. As indicated above, workers may be exposed to different chemical species compared to those present in the UVCB. Hence, the information onthe intrinsic properties of the UVCB constituents relevant for classification can be refined if it is known which chemical species is present in the workplace. If speciation is unknown, the chemical species of an individual constituent is considered having the lowest DNEL which could be different when compared to the species used for classification.

 

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 and 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 (mainly metals). 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.

 

Table34:Summary of the information on toxicological information for the purpose of classification

UVCB constituent

Variabiliy of elemental composition

Classification according each relevant endpoint

Element

Speciation* taken forward for Tier 1 human health classification

 

 

Sn

Sn metallic

Maximum

Self classification of the speciation, see MECLAS report in CSR Annex I

Ag

Ag massive

Maximum

Not classified, see MECLAS report in CSR Annex I

C

inorganic C and C compounds

Maximum

Not classified, see MECLAS report in CSR Annex I

Cd

Cd metallic

Maximum

Harmonised classification of the speciation, see MECLAS report in CSR Annex I

Cu

Cu massive

Maximum

Not classified, see MECLAS report in CSR Annex I

Fe

Fe/Fe compounds

Maximum

Not classified, see MECLAS report in CSR Annex I

Pb

Pb massive

Maximum

Self- classification of the speciation, see MECLAS report in CSR Annex I

Sb

Sb

Maximum

Not classified, see MECLAS report in CSR Annex I

Zn

Zn massive

Maximum

Not classified, see MECLAS report in CSR Annex I

Minors: As, Ni

Metallic (massive)

Maximum

Below 0.1% and/or the speciation not impacting classification, see MECLAS report in CSR Annex I

* see IUCLID/CSR section 1.2 composition and IUCLID 4.23 additional Physico-chemical Information

 

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 therefore difficult to interpret and to extrapolateresults of testing to the entirety of variations of the UVCB because of the uncertainty related to the representativeness of the testing. Also, exposure to the UVCB cannot be measured or modelled 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 the UVCB. 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, 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 and lead oxide. 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 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 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 sulfide has a DNEL of 0.47 mg/m3for the local acute inhalation effects (range 0.47-4 mg Ni/m3). The local long-term dermal DNEL of 0.00044 mg Ni/cm2/day (range 0.00044 -0.07 mg Ni/cm2/day) is taken forward to risk characterisation.

 

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

 

Carbon is speciated as charcoal. There are no other relevant speciations to consider.

 

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.

 

Table35: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

Sn

Sn metal considered

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

See respective DNEL summary in IUCLID or table below

Cu

Cu ion is toxic driver

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

See respective DNEL summary in IUCLID or table below

Fe

Fe ion is toxic driver

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

See respective DNEL summary in IUCLID or 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 or table below

Ag

Ag compounds

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

See respective DNEL summary in IUCLID or table below

Cd

Cd ion is toxic driver

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

See respective DNEL summary in IUCLID or table below

As

Arsenic ion is the driver for toxicity

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

See respective DNEL summary in IUCLID or table below

Ni

Difference between Ni metal,

Ni sulphide, Ni oxide

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

See respective DNEL summary in IUCLID or table below

Zn

2 solubility groups:

1) "soluble" substances

2) "slightly soluble" and 'insoluble" substances

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

See respective DNEL summary in IUCLID or table below

 


Table36: Human health hazard conclusions taken forward to CSA

 

Route

Type of effect

Cu

Pb

As

Ni

Cd

Zn

Ni metal

 

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,

Ni sulphide, Ni oxide

Cd and Cd compounds effect assessment based on Cd

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)

0.004 mg/m3(respirable fraction)

1.25 mg/m3(soluble)

5 mg/m3(insoluble)

Systemic Acute

20.0 mg/m3

DNEL not relevant (Pb is not acutely toxic)

DNEL not relevant

680 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 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

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

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

 

0.47 mg/m3

3.9 mg/m3

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

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)

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

Exposure based waiving

83.3 mg/kg bw/day

Systemic Acute

273 mg/kg bw/day

DNEL not relevant (Pb is not acutely toxic)

DNEL not relevant

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

Local Long Term

Exposure based waiving

DNEL not relevant

DNEL not relevant

0.07 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

Local Acute

Exposure based waiving

DNEL not relevant (Pb is not acutely toxic)

DNEL not relevant

Not applicable

 

Not applicable

Not applicable

Exposure based waiving

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/dLblood

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

Sb

C

Fe

Al

Assessment rationale for different speciation

Not in multimetallic database

Read across from antimony trioxide

(Data are for Sb)

Not in multimetallic database,Charcoal speciation

 most relevant

Metallic speciation

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

Inhalation

Systemic Long Term

11.75 mg/m3

/

10 mg/m3

No DNEL needs to be derived

No-threshold effect available

Systemic Acute

11.75 mg/m3

No acute effects

No-threshold effect available

No DNEL needs to be derived

No-threshold effect available

Local Long Term

No hazard identified

0.5 mg/m3

10 mg/m3

No DNEL needs to be derived

3.72 mg/m3

Local Acute

No hazard identified

No acute local effects

No-threshold effect available

No DNEL needs to be derived

No-threshold effect available

OEL (Long Term)

 

0.5mg/m3

14.3 mg/kg bw/d

 

 

Dermal

Systemic Long Term

133.3 mg/kg bw/day

 

234.7 mg/kg bw/day

281 for Sb2O3

No-threshold effect available

No DNEL needs to be derived

 

No-threshold effect available

Systemic Acute

133.33 mg/kg bw/day

No acute effects

No-threshold effect available

No DNEL needs to be derived

No-threshold effect available

Local Long Term

No hazard identified

No local long term effects expected

No-threshold effect available

No DNEL needs to be derived

No-threshold effect available

Local Acute

No hazard identified

No acute local effects

 

 

 

 

Eye

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

 

General Population - Hazard via inhalation route

Systemic effects

Long term exposure
Hazard assessment conclusion:
high hazard (no threshold derived)
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:
high hazard (no threshold derived)
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:
high hazard (no threshold derived)
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

DNELs for the general population are currently not included because an assessment of exposure of man via the environment is not reported but instead considered to be already included in the dossiers of the constituents. However, DNELs for the general population and the assessment of exposure of man via the environment might be amended by further analysis (please refer to Chapter 9.0.2.3. for further details).

Categories Display