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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
experimental study
Adequacy of study:
key study
Study period:
October 17 - 22, 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

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 405 (Acute Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.2400 (Acute Eye Irritation)
Deviations:
no
GLP compliance:
yes (incl. QA statement)

Test material

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 / tissue source

Species:
rabbit
Strain:
New Zealand White
Details on test animals or tissues and environmental conditions:
Species/strain: healthy New Zealand White Rabbits, Crl: KBL (NZW)
Source: Charles River Deutschland, 97633 Sulzfeld, Germany
Sex: female
Body weight at the beginning of the study: > 2kg
Age at the beginning of the study: approximately 13 weeks old
Number of animals: 3
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 [8] the animals were bred for experimental purposes.

Housing and Feeding Conditions
- Semi barrier in an air-conditioned room
- Temperature: 18 3 °C (recommendations of TVT [9], GV-SOLAS [10])
- Relative humidity: 55 10%
- Artificial light, sequence being 12 hours light, 12 hours dark
- Air change: at least 10 x / hour
- Free access to autoclaved hay and to Altromin 2123 maintenance diet for rabbits (lot no. 1325), rich in crude fibre
- Free access to tap water (drinking water, municipal residue control, microbiological controls at regular intervals)
- Certificates of food, water and bedding are filed at BSL BIOSERVICE
- Housed in ABS - plastic rabbit cages, floor 4200 cm2
- Adequate acclimatisation period (at least 5 days)

Test system

Vehicle:
unchanged (no vehicle)
Controls:
other: the untreated eye served as control
Amount / concentration applied:
0.1g
It was applied at a single dose in the conjunctival sac of one eye of each test animal after pulling the lower lid away from the eyeball. The lids were then gently held together for 1 second in order to prevent loss of material. The untreated eye served as control. The treated eyes were not rinsed within 24 hours after application.
Duration of treatment / exposure:
The lids were then gently held together for 1 second in order to prevent loss of material. The untreated eye served as control. The treated eyes were not rinsed within 24 hours after application.
Observation period (in vivo):
72h after application
Number of animals or in vitro replicates:
3
Details on study design:
The test item was used as provided by the sponsor and ground to a fine dust using a mortar and pestle.
In order to avoid the unnecessary use of animals and to minimise any testing that is likely to produce severe responses in animals, a weight-of-evidence analysis was performed with the available data (data from the test substance data sheet). The paperwork is archived in the project file. Additionally the confirmation in writing that the studies are required for submission to regulatory authorities or to fulfill obligations postulated by law was taken into account.
Approximately 24 hours before the test and immediately prior to the application both eyes of each animal were examined. A health inspection was performed to ensure the good state of health of the animals.
Approximately 24 hours before the application the eyes were also examined with the aid of a fluorescein solution (Fluoreszein SE Thilo, lot no. H 001, expiry date: 02/2012). The eyes were rinsed with physiological saline 0.9% NaCl (B. Braun Melsungen, lot. no. 9474A121, expiry date: 10/2012) after the examination.
None of the animals showed eye irritation, ocular defects, or pre-existing corneal injury.
The in vivo test was performed initially using one animal.
The results of the initial test did not indicate the test item to be corrosive or a severe irritant to the eye using the procedure described. In order to confirm the response, two additional animals were treated in the same manner.
The eyes were examined for signs of irritation throughout the observation period. The eye irritation was scored and recorded according to the grades in the table below.
For the calculation only the 24, 48 and 72-hour readings were used.
At the end of the observation period the treated eyes were examined with the aid of a fluorescein solution (Fluoreszein SE Thilo, lot no. H 001, expiry date: 02/2012). The eyes were rinsed with physiological saline 0.9% NaCl (B. Braun Melsungen, lot. no. 9474A121, expiry date: 10/2012) after the examination.

Results and discussion

In vivo

Resultsopen allclose all
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
(mean score)
Time point:
other: "24h, 48h, 72h"
Score:
0.67
Max. score:
1
Reversibility:
fully reversible within: 72h after application
Irritation parameter:
conjunctivae score
Basis:
animal #2
Remarks:
(mean score)
Time point:
other: "24h, 48h, 72h"
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48h after application
Irritation parameter:
conjunctivae score
Basis:
animal #1
Remarks:
(mean score)
Time point:
other: "24h, 48h, 72h"
Score:
0.33
Max. score:
1
Reversibility:
fully reversible within: 48h after application
Irritation parameter:
chemosis score
Basis:
mean
Remarks:
of all 3 animals
Time point:
other: "24h, 48h, 72h"
Score:
0
Max. score:
0
Reversibility:
other: no chemosis observed
Remarks on result:
other: animals 1 and 3 showed a score 1 chemosis after 1h that was fully gone after 24h
Irritation parameter:
iris score
Basis:
mean
Remarks:
of all three animals
Time point:
other: "24h, 48h, 72h"
Score:
0
Max. score:
0
Reversibility:
other: no effects observed
Irritation parameter:
cornea opacity score
Basis:
mean
Remarks:
of all three animals
Time point:
other: "24h, 48h, 72h"
Score:
0
Max. score:
0
Reversibility:
other: no effects observed
Irritant / corrosive response data:
The test item produced slightly irritant but no corrosive ocular effects after the application into the eyes of three female NZW rabbits. Upon fluorescein examinations at the end of the observation period of 72 hours no corneal lesions were found in any animal. Conjunctival redness, chemosis and discharge were observed in all animals.
Other effects:
Neither mortalities nor significant clinical signs of toxicity were observed

Applicant's summary and conclusion

Interpretation of results:
not irritating
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the conditions of the present study, a single ocular application of the test item Slags, ferronickel-manufg. / Electric Furnace Slag / Converter Slag to rabbits at a dose of 0.1 g produced slightly irritant effects, which were fully reversible within 48 and 72 hours after the application. Neither mortalities nor significant clinical signs of toxicity were observed.
In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of Commission Directive 2001/59/EC [6] and Annex I of Regulation (EC) 1272/2008 [4], the test item Slags, ferronickel-manufg. / Electric Furnace Slag / Converter Slag does not have to be classified and has no obligatory labelling requirement for eye irritation (for details of the classification criteria see Evaluation of Results).
Executive summary:

An acute in vivo eye irritation/corrosion study was performed on the substance to determine irritant or corrosive properties of the substance on the eyes. The in vivo test was chosen because no validated in vitro method is available for assessing acute eye irritation/corrosion. The study was performed according to the OECD 405 “Acute Eye Irritation/Corrosion” guideline.

Under the conditions of the study, a single ocular application of the test item Slags, ferronickel-manufg. / Electric Furnace Slag / Converter Slag to rabbits at a dose of 0.1 g produced slightly irritant effects, which were fully reversible within 48 and 72 hours after the application. The highest score that was observed on any of the animals during the observation period was 1 and all effects were fully reversible after 48h or 72h after application. Neither mortalities nor significant clinical signs of toxicity were observed.

In conformity with the EC criteria for classification and labelling requirements for dangerous substances and preparations according to Annex VI of Commission Directive 2001/59/EC [6] and Annex I of Regulation (EC) 1272/2008 [4], the test item Slags, ferronickel-manufg. / Electric Furnace Slag / Converter Slag does not have to be classified and has no obligatory labelling requirement for eye irritation (for details of the classification criteria see Evaluation of Results).