Registration Dossier

Administrative data

Endpoint:
repeated dose toxicity: oral
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.
GLP compliance:
no
Remarks:
other quality assurance

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)

Results and discussion

Effect levels

Dose descriptor:
conc. level:
Effect level:
> 100 mg/kg bw/day (nominal)
Based on:
test mat.
Basis for effect level:
other: not specified
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 oral route (see EU CLP Guidance Annex IAnnex 3.9.2.9.7,Table 3.9.3) : Oral(rat), dose concentration >100 mg/kg body weight /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 oral 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.

It is concluded that slag, copper smelting is not to be classified for STOT RE. Therefore estimated dose/concentration value at or below which no significant toxic effects would be observed in a 90-day repeated-dose studyis : >100 mg/kg body weight /day

The result is applicable to all copper slags that fall under the defined concentration ranges (IUCLID section 1.2) up to Pb 0.7% for granules, primary and slag powders and 0.4 % for granules secondary and slow cooled slags

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% 

In vitro measurements of bio-accessibility in solvent that resembles gastric fluid performed according to ASTM D5517.07.(pH 1.5) The fraction of metals that solubilize under these conditions can be considered as worst case determinant of bio-assesability of metals contained in the slag. 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)

Furthermore, conclusions on bioavailability are supported the physical properties of the substance.

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)

Therefore consideration of reduced bio-accessibility of Pb will lead to No classification of copper slags for STOT repeated exposure by oral route.