Registration Dossier

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19.7.2010-3.8.2010
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2010
Report date:
2010

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
not specified
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Dust, steelmaking
EC Number:
266-005-7
EC Name:
Dust, steelmaking
Cas Number:
65996-72-7
IUPAC Name:
Dust steelmaking
Details on test material:
- Physical state: solid
- Composition of test material, percentage of components: Fe total 57.64% (mainly as oxides), CaO 8.89%, Zn 4.16%, MgO 3.64%, C 0.69%, SiO2 1.56%, Mn 0.57 %, K2O 0.281%, Na2O 0.251%, Al2O3 0.18%
- Lot/batch No.: 21.10.2009
- Expiration date of the lot/batch: unlimited
- Storage condition of test material: stored in PE container at room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories UK Ltd., Oxon, UK
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 200-350 g
- Housing: solid-floor polypropylene cages with stainless steel lids
- Diet (e.g. ad libitum): Harlan 2014 Rodent Diet ad libitum with the exception of the exposure period (source: Harlan Laboratories UK Ltd., Oxon, UK)
- Water (e.g. ad libitum): drinking water ad libitum with the exception of the exposure period
- Acclimation period: min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-25°C
- Humidity (%): 30-70 %
- Air changes (per hr): min 15× per hour
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

Administration / exposure

Route of administration:
inhalation: dust
Type of inhalation exposure:
nose only
Vehicle:
clean air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: SAG 410 (TOPAS GmbH, Dresden, Germany)
- Exposure chamber volume: cca 30 l
- Source and rate of air: oil-free compressor
- Method of conditioning air: compressed air was passed through a water trap and respiratory quality filters before it was introduced into the SAG 410
- System of generating particulates/aerosols: SAG 410
- Method of particle size determination: Marple Personal Cascade Impactor (westech IS Ltd., Beds., UK) with 8.3, 6.0, 3.2, 1.5, 0.82 and 0.34 µm cut points
- Treatment of exhaust air: exhaust air was conducted through scrubber and high efficiency filter
- Temperature, humidity, pressure in air chamber: temperature 21-22°C, humidity 65-73 %

TEST ATMOSPHERE
- Brief description of analytical method used: gravimetric method (increase of weight of the glass filter per defined time)
- Samples taken from breathing zone: no

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution:
cut point (µm) / mean weight (mg)
8.3 / 0.16
6.0 / 0.30
3.2 / 0.48
1.5 / 0.85
0.82 / 0.35
0.34 / 0.24
<0.34 / 0.11
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.23 µm / 2.70

CLASS METHOD (if applicable)
- Rationale for the selection of the starting concentration: GHS Classification System (5 mg/L)
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
4 h
Concentrations:
mean concentration: 5.15 mg/l
No. of animals per sex per dose:
3 animals per sex per dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
+ Clinical signs: hourly during exposure, immediately on removal from the restraining tubes at the end of exposure, one hour after termination of exposure and subsequently once daily for fourteen days
+ Body weight: prior to treatment and on days 1, 3, 7 and 14
- Necropsy of survivors performed: yes

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.15 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No dead animals.
Clinical signs:
other: Any evidence of overt toxicity were recorded at each observation.
Body weight:
Variations in bodyweight gain are frequently seen for female animals of this strain and age during this type of study and, in isolation, are considered not to be significant.
Gross pathology:
With the exception of one male, all animals exhibited dark patches on the lungs at necropsy.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
No deaths occurred in a group of six rats exposed to a mean achieved atmosphere concentration of 5.15 mg/l for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of Dust, steelmaking, in the Wistar strain rat, was greater than 5.15 mg/l.
Executive summary:

Introduction

A study was performed to assess the acute inhalation toxicity of the test item. The method used followed that described in the OECD Guidelines for Testing of Chemicals (2009) No. 403 “Acute Inhalation Toxicity” and was designed to comply with Method B2 (Inhalation) of Commission Regulation (EC) No. 440/2008, with the exception that only six animals (three males and three females) were utilized during the “limit test”.

Methods

A group of six Wistar strain rats (three males and three females) was exposed to a dust atmosphere. The animals were exposed for four hours using a nose only exposure system, followed by a fourteen day observation period.

Results

The mean achieved atmosphere concentration was 5.15 mg/l

The characteristics of the achieved atmosphere were as follows:

Mean Mass Median Aerodynamic Diameter: 2.23 (μm)

Inhalable Fraction (<4 μm): 72.2 %

Geometric Standard Deviation: 2.70

The mortality data were summarised as follows:

Male: 0/3

Female: 0/3

Total: 0/6

Clinical Observations: Common abnormalities noted during the study included increased respiratory rate, generalised brown fur staining by the test item, hunched posture, piloerection and wet fur. Animals recovered to appear normal on Day 7 post exposure.

Body weight: With the exception of one female, all animals exhibited a slight bodyweight loss on the first day post-exposure. Normal bodyweight development was noted for all animals during the remainder of the recovery period.

Necropsy: With the exception of one male, all animals exhibited dark patches on the lungs at necropsy.

Conclusion

No deaths occurred in a group of six rats exposed to a mean achieved atmosphere concentration of 5.15 mg/L for four hours. It was therefore considered that the acute inhalation median lethal concentration (4 hr LC50) of Dust, steelmaking, in the Wistar strain rat, was greater than 5.15 mg/l.