Slags, ferronickel-manufg.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28.9.2010 - 21.10.2010

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 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: OPPTS 870.1000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

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.

Test animals

Species:

rat

Strain:

other: WISTAR Crl: WI(Han)

Sex:

female

Details on test animals or test system and environmental conditions:

Age at the beginning of the study: 9 - 11 weeks old
Body weight on the day of administration: Step 1 / animals no. 1 - 3: 152 – 162 g; Step 2 / animals no. 4 - 6: 152 – 167 g;
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 the animals were 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: 10 x / hour
-Free access to Altromin 1324 maintenance diet for rats and mice (lot no. 1020)
-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 in IVC cages, type III H, polysulphone cages on Altromin saw fibre bedding (lot no. 150610)
-Certificates of food, water and bedding are filed at BSL BIOSERVICE
-Adequate acclimatisation period (at least five days, for details see Schedule)

The animals were marked for individual identification by tail painting.
Prior to the administration a detailed clinical observation was made of all animals.
Prior to the administration food was withheld from the test animals for 16 to 19 hours (access to water was permitted). Following the period of fasting the animals were weighed and the test item was administered. Food was provided again approximately 4 hours post dosing.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

cotton seed oil

Remarks:

Sigma, lot no. MKBB7604, expiry date: 05/11/2010

Details on oral exposure:

The test item was administered at a single dose by gavage using a feeding tube.
The test item was administered at a dose volume of 10 mL/kg body weight.
2 steps were performed on 3 animals each.

Doses:

2000mg/kg body weight
2 steps were performed

No. of animals per sex per dose:

3 animals per dose. All female

Control animals:

no

Details on study design:

Preparation of the Test Item
In order to get the test item in a solution or suspension, which is applicable to the animals, several vehicles were evaluated and preparation and solubility tests were performed. The test item was weighed out into a tared plastic vial on a precision balance. For all animals of the first and second step, 2 g of the test item were suspended in the vehicle to gain a final volume of 10 mL and to achieve a dose of 2000 mg/kg body weight at a dose volume of 10 mL/kg body weight. The dose formulations were made shortly before each dosing occasion.

All animals were observed for 14 days after dosing for general clinical signs, morbidity and mortality.
The animals were weighed on day 1 (prior to the administration) and on days 8 and 15.
A careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). As soon as symptoms were noticed they were recorded. Thereafter, the animals were observed for clinical signs once daily until the end of the observation period. All abnormalities were recorded.
At the end of the observation period the animals were sacrificed with an overdosage of pentobarbital injected intraperitoneally (Narcoren®, Merial; lot no.: 202070; expiry date: 07/2013) at a dosage of approx. 8 mL/kg bw.All animals were subjected to gross necropsy. All gross pathological changes were recorded and in case of findings the tissues were preserved for possible histopathological evaluation.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

other: LD50 cut-off (rat)

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: LD50 cut-off: unclassified

Mortality:

No deaths.
The test item showed no acute oral toxicity characteristics after a single dose administration.

Gross pathology:

At necropsy animal no. 1 showed red spots on the lung. With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any other animal.

Any other information on results incl. tables

Table 1. Absolute body weights in g and body weight gain in %

Animal No/sex	weight Day 1 (g)	weight Day 8 (g)	weight Day 15 (g)	Day 1 -15 (%)
Step 1 (2000mg/kg body weight)
1/female	152	170	175	15
2/female	152	169	186	22
3/female	162	177	190	17
Step 2 (2000mg/kg body weight)
4/female	152	175	182	20
5/female	160	180	190	19
6/female	167	193	205	23

Table 2. Findings of the necropsy - individual data

Animal No/Sex	Organ	Macroscopic findings
1/female	lung	red spots
2/female	/	no specific findings
3/female	/	no specific findings
Step 2 (2000 mg/kg body weight)
4/female	/	no specific findings
5/female	/	no specific findings
6/female	/	no specific findings

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present study, a single oral application of the test item Slags, ferronickel-manufg. / Electric Furnace Slag / Converter Slag to rats at a dose of 2000 mg/kg body weight was associated with no signs of toxicity or mortality.
The median lethal dose of Slags, ferronickel-manufg. / Electric Furnace Slag / Converter Slag after a single oral administration to female rats, observed over a period of 14 days is:
LD50 cut-off (rat): unclassified
In conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC [7] the test item Slags, ferronickel-manufg. / Electric Furnace Slag / Converter Slag has no obligatory labelling requirement for toxicity.
According to Annex I of Regulation (EC) 1272/2008 [8] the test item Slags, ferronickel-manufg. / Electric Furnace Slag / Converter Slag has no obligatory labelling requirement for toxicity and is unclassified.
According to OECD-GHS (Globally Harmonised Classification System) [9] the test item Slags, ferronickel-manufg. / Electric Furnace Slag / Converter Slag has no obligatory labelling requirement for toxicity.

Executive summary:

Two groups, each of three female WISTAR Crl: WI(Han) rats, were treated with the test item by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was suspended in the cottonseed oil at a concentration of 0.2 g/mL and administered at a dose volume of 10 mL/kg.

All animals used in the study after their entrance at BSL were allowed to acclimatise to the laboratory conditions for at least 5 days. The animals were observed on delivery, on inclusion in the study and before administration for mortality/morbidity and other clinical signs. All animals were examined for clinical signs several times on the day of dosing and once daily until the end of the observation period. Their body weights were recorded on day 1 (prior to the administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.

All animals survived until the end of the study without showing any signs of toxicity.

Throughout the 14-day observation period, the body weight gain of the test animals was within the normal range of variation for this strain.

At necropsy, red spots were found in the lung of animal no. 1, but no other macroscopic findings were observed in any animal of any step.

On the basis of the test results given below and in conformity with the criteria given in Annex VI to Commission Directive 2001/59/EC [7] as well as in Annex I of Regulation (EC) 1272/2008 [8], the substance should be: [not classified]