Registration Dossier

Administrative data

Endpoint:
repeated dose toxicity: inhalation
Remarks:
other: calculation based on classification
Type of information:
calculation (if not (Q)SAR)
Remarks:
Migrated phrase: estimated by calculation
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Automatic calculation with MeClas tool
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
other: software
Title:
Unnamed
Year:
2019

Materials and methods

Principles of method if other than guideline:
The potential of the UVCB substance to cause specific target organ toxicity following repeated exposure by oral route was established by classifying the complex metal substance according to rules for classification of mixtures for STOT RE (EU CLP guidance section 3.9.3 pg 382ff). The classification criteria (as set out in EU CLP Annex I: 3.9.3.4.1.) can be used to estimate effects derived from that classification/hazard.

Test material

Constituent 1
Reference substance name:
slag, copper smelting
EC Number:
266-968-3
Cas Number:
67711-92-6
IUPAC Name:
slag, copper smelting
Details on test material:
Typical across industry as defined in IUCLID 1.2;
See IUCLID Section 1.4, for company specific elemental composition; and representative sample for mineralogical information (IUCLID Section 4.23 -Outotec report)

Administration / exposure

Route of administration:
inhalation: dust
Duration of treatment / exposure:
90 days

Results and discussion

Effect levels

Dose descriptor:
conc. level:
Effect level:
> 2 mg/L air (nominal)
Based on:
dissolved
Remarks on result:
not measured/tested
Remarks:
calculated

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

The calculated classification via rules for mixtures (Lower Tier) resulted in “STOT repeated : Category 2 ”triggered by Pb compounds at actual levels above 0,5%.

Consideration of reduced bio-accessibility of Pb (Higher Tier) resulted in” STOT repeated :: Not classified” 

Based on this result, the related criteria provided theestimated dose/concentration value at or below which nosignificant toxic effects would be observed in a 90-day repeated-dose studyby inhalation route (see EU CLP Guidance Annex IAnnex 3.9.2.9.7,Table 3.9.3) : Inhalation rat dust/mist/fume , dose /concentration >2 mg/litre/6h/day

 

For more details, see "Human Health classification of C1 copper slag", attachment in Section7 "Summary record Toxicological information”

Applicant's summary and conclusion

Conclusions:
Study can be used to predict the single organ toxicity effect by inhalation route and to determine hazard/classification of the UVCB substance
Executive summary:

The study provided a conservative estimate of the Single organ toxicity effect, derived on basis of the Classification outcome by applying the rules for mixtures of a Typical (across industry) copper slag.

Chemistry of the substance (see IUCLID section 4.23 chemical and mineralogical characterization) shows that copper slag does contain only minor constituents classified as a STOT RE Cat 1 (Ni compounds) at actual levels max 0.21 % (in representative samples and maximum levels across industry. It can be also demonstrated that copper slag contains minor constituents classified as STOT RE Cat 2 ( ex.Pb compounds) above 0.5% which trigger classification.

Copper slag stones do not contain inhalable fraction (particles less than 100 μm) .Copper slag granules do contain small inhalable fraction between 1.4 and 15% but do not contain particles smaller than 20 μm.Copper slag powders contain 100% inhalable fraction (particles less than 100 μm), which is capable of entering the respiratory tract under realistic breathing conditions. Further particles smaller than 20 μm present (16 to 40%), which constitute the “thoracic” fraction and are capable of penetrating to the trachea bronchial regions of the lung or deeper. 

Therefore inhalation route is relevant for copper slag due to possibility of exposure to particles of an inhalable size.

Lead particles have systemic mode of action so resorption of dissolved lead particles can take place from deposition locations in the entire respiratory tract and contribute to systemic toxicity.

An acute inhalation toxicity study conducted with lead oxide powder (MMAD= 5.8µm)showed that deep lung penetration would be minimal and upper respiratory tract deposition would predominate ( Ref, Lead voluntary risk assessment)/ Upper respiratory tract deposition would in turn be followed by clearance to the gastrointestinal tract. Pulmonary deposition modelling further showed that deposition patterns for all thirteen lead compounds modeled will be rather similar. No signs of any respiratory irritation or any other clinical observations.

Thus, systemic lead uptake from slag is predicted to be similar to that for lead oxide.

Finally, a conservative assumption is made that all lead containing particles in the slag will deposit in the upper airways, such particles will than enter thegastrointestinal tract,where further uptake of all dissolved particles will take place.

In vitro measurements of bio-accessibility in solvent that resembles gastric fluid performed according to ASTM D5517.07.(pH 1.5) Results demonstrate low relative bio-accesabilty of metals(Cu 0.06 – 0.2, Ni 0.09 – 0.33) and medium bioaccesability of Pb (0.13 – 0.74)

The measurements allowed to demonstrate that the maximum level of bio-accessible Pb in copper slag is below 0.5% (based on worst case release rate per different sample type)

Based on the above it is concluded that slag, copper smelting does not need classification for STOT repeated exposure by inhalation route. Therefore estimated dose/concentration value at or below which no significant toxic effects would be observed in a 90-day repeated-dose studyis : Inhalation rat dust/mist/fume dose/concentration >2 mg/litre/6h/day