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 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.

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)

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

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 No classification

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 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 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 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) nickel slag.

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% 

Nickel slag granules do contain small inhalable fraction (particles less than 100 μm) about 0.22% but do not contain particles smaller than 20 μm.

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

A conservative assumption is made that all nickel and lead containing particles in the slag will deposit in the upper airways, such particles will than enter the gastrointestinal 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 reduced relative bio- accessibility of metals (Cu 0.04, Ni 0.05, Co 0.06).Dissolved concentrations of Pb and As were below detection limit.

The measurements allowed to demonstrate that the maximum level of bio-accessible Ni fraction in nickel slag is 0.02 % (based on worst case composition)

Based on the above it is concluded that slag, nickel 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