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 tool in development at Eurometaux
Cross-reference
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
other: software
Title:
Unnamed
Year:
2010

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

Reference
Name:
Unnamed
Type:
Constituent
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.

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 : Not classified.

Based on this result, the related criteria provided the estimated dose/concentration value at or below which no significant 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 C2 nickel 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) nickel slag.

It is concluded that slag, nickel 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 nickel slags that fall under the defined concentration ranges (IUCLID section 1.2).

Chemistry of the substance (see IUCLID section 4.23 chemical and mineralogical characterization) shows that nickel slag does contains only minor constituents classified as a STOT RE Cat 1 (Ni compounds) at actual levels 0.15% in typical samples and 0.44%.maximum levels accross industry.

It can be also demonstrated that nickel lag contains minor constituents classified as STOT RE Cat 2 ( ex.Pb compounds) at actual levels <0.02% 

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 0.04, Ni 0.05, Co 0.06).Dissolved concentrations of Pb and As were below detection limit.

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

The measurements allowed to demonstrate that the maximum level of bio-accessible NI in nickel slag is 0.02%.

Therefore consideration of reduced bio-accessibility of Ni will further confirm No classification of nickel slags for STOT repeated exposure by oral route.