Slags, ferronickel-manufg.

Skin sensitisation

Administrative data

Endpoint:

skin sensitisation: in vivo (LLNA)

Type of information:

experimental study

Adequacy of study:

key study

Study period:

October 10-29, 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study generated according to internationally accepted testing guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2010

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 429 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.42 (Skin Sensitisation: Local Lymph Node Assay)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2600 (Skin Sensitisation)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Type of study:

mouse local lymph node assay (LLNA)

Test material

Test material information

Constituent 1

Reference substance name:

Slags, ferronickel-manufg.

EC Number:

273-729-7

EC Name:

Slags, ferronickel-manufg.

Cas Number:

69012-29-9

Molecular formula:

This is a UVCB substance, consisting of oxides of aluminum, iron, magnesium and silicon. Due to the nature of the substance, specific molecular formula is not relevant.

Details on test material:

Slag from Ferronickel Converter containing Iron in the form of the element and its oxides, metalic oxides and Nickel.
Solid / dark brown to grey.
Chemical name: Slags, Ferronickel-manufg.

In vivo test system

Test animals

Species:

mouse

Strain:

other: CBA/CaOlaHsd

Sex:

female

Details on test animals and environmental conditions:

Species/strain: healthy CBA/CaOlaHsD mice
Source: Harlan Winkelmann, 33178 Borchen, Germany
Sex: female (nulliparous and non-pregnant)
Age at the
beginning of the study: 8 – 9 weeks
Number of animals: 5 mice / test group
3 mice / preliminary test
The animals were derived from a controlled full-barrier maintained breeding system (SPF). According to Art. 9.2, No. 7 of the German Act on Animal Welfare German Animal Welfare Act, Art. 9.2, No. 7 (Deutsches Tierschutzgesetz, 24. Juli 1972 (BGBl. I S. 1277), Inkrafttreten der letzten Änderung: 22. Juli 2009, (Art. 2 ÄndG vom 15. Juli 2009) the animals are bred for experimental purposes.

Housing and Feeding Conditions
Full barrier in an air-conditioned room
Temperature: 22 ± 3 °C
Relative humidity: 55 ± 10%
Artificial light, sequence being 12 hours light, 12 hours dark
Air change: at least 10 x / hour
Free access to Altromin 1324 maintenance diet for rats and mice (preliminary test: lot no. 1305, main study: lot no. 1315)
Free access to tap water, sulphur acidified to a pH value of approx. 2.8 (drinking water, municipal residue control, microbiological controls at regular intervals)
The animals were kept in groups of 5 animals in IVC cages, type II L, polysulphone cages on Altromin saw fibre bedding (preliminary test: lot no. 15062010, main study: lot no. 150610)
Certificates of food, water and bedding are filed at BSL BIOSERVICE
Adequate acclimatisation period (at least five days)

Study design: in vivo (LLNA)

Vehicle:

other: acetone/olive oil (3:1 v/v)

Concentration:

a ratio of 4 g of sample to 20 mL of extraction medium was used.
the following test item concentrations were selected for the main study:
25%, 50% and 100% (diluted with AOO)

No. of animals per dose:

5 mice / test group
3 mice / preliminary test

Positive control substance(s):

other: p-phenylenediamine

Results and discussion

Positive control results:

DPM/Node (negative control): 593.7+/-148.0
DPM/Node (P-phenylenediamine): 5121.4+/-1050.8
Stimulation Index: 8.1

In vivo (LLNA)

Results

Results 1

Parameter:

SI

Remarks on result:

other: The stimulation index at an extract concentration of 25% was 1.1 The stimulation index at an extract concentration of 50% was 1.2 The stimulation index at an extract concentration of 100% was 1.1

Results 2

Parameter:

other: disintegrations per minute (DPM)

Remarks on result:

other: see Remark

Remarks:

DPM/Node (negative control): 776.9+/-124.6 DPM/Node (25%): 829.5+/-36.5 DPM/Node (50%): 951.5+/-316.4 DPM/Node (100%): 821.1+/-163.3 All results are pooled. No specific trend appears based on the different concentrations of the extract. Higher DPM is observed for middle concentrations (50%), while it is at about the same levels in the other two concentrations (25% and 100%). More can be seen in the attached study report.

Any other information on results incl. tables

All animals survived throughout the test period without showing any clinical signs.

All animals showed the expected weight development, which includes a weight loss of up to 2 g throughout the study.

Applicant's summary and conclusion

Interpretation of results:

not sensitising

Remarks:

Migrated information

Conclusions:

The EC3 value (derived by linear interpolation) could not be calculated as the stimulation indices of all concentrations were below 3. Consequently, according to OECD 429 ISO 10993-12: 2007 “Sample preparation and reference materials” and the criteria given in Annex I of Regulation (EC) 1272/2008 Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. Official Journal of the European Communities, L 353, 31.12.2008, the test item Slags, ferronickel-manufg./Electric Furnace Slag/ Converter Slag, as described in this report is expected to have no sensitising properties and therefore, should not be regarded as a dermal sensitiser.

Executive summary:

Slags, ferronickel-manufg./Electric Furnace Slag/ Converter Slag was tested for dermal sensitising properties according to the

OECD Guidelines for Testing of Chemicals, number 429, “Skin Sensitisation: Local Lymph Node Assay” (adopted: July 22, 2010).

Based on the results of the preliminary test the test item was extracted according to ISO 10993-12 and assessed for sensitising properties at extract concentrations of 25 %, 50 % and 100 % (v/v).

None of the three tested concentrations of the test item extract reached the stimulation index of3.

The extract of the test item was assessed at three concentrations: 25%, 50% (each diluted with AOO 3+1, v/v) and 100% (undiluted test item extract).

The 100% extract concentration corresponded to an extraction ratio of 4 g / 20 mL.Extraction vehicle / negative control:AOO (3+1 (v/v) acetone/ olive oil).

The stimulation index at an extract concentration of 25% was 1.1

The stimulation index at an extract concentration of 50% was 1.2

The stimulation index at an extract concentration of 100% was 1.1

At the daily clinical observation the animals did not show any visible clinical symptoms and no case of mortality were observed.

Species/strain:Mice, CBA/CaOlaHsd

Number of animals:20/main test

Vehicle:AOO (3+1(v/v) acetone/olive oil)

The EC3 value (derived by linear interpolation) could not be calculated as the stimulation indices of all concentrations were below 3. Consequently, according to OECD 429 ISO 10993-12: 2007 “Sample preparation and reference materials” and the criteria given in Annex I of Regulation (EC) 1272/2008 Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008 on classification, labelling and packaging of substances and mixtures, amending and repealing Directives 67/548/EEC and 1999/45/EC, and amending Regulation (EC) No 1907/2006. Official Journal of the European Communities, L 353, 31.12.2008, the test item Slags, ferronickel-manufg./Electric Furnace Slag/ Converter Slag, as described in this report is expected to have no sensitising properties and therefore, should not be regarded as a dermal sensitiser.