Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
8. October 2010 - 20. October 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
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

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

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Sprague-Dawley albino rats, 5 male and 5 female.
Age/Body weight: Young adult (8-9 weeks)/males 268-300 grams and females 192-242 grams at experimental start.

Housing: The animals were singly housed in suspended stainless steel caging with mesh floors, which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 1996). Litter paper was placed beneath the cage and was changed at least three times per week.
Animal Room Temperature and Relative Humidity Ranges: 19-22ºC and 50-72%, respectively. The humidity was above the targeted upper limit fortwo days during the study. A portable dehumidifier was used to lower the humidity levels during this time.
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 10 days
Food: Purina Rodent Chow #5012
Water: Tap water was supplied ad libitum by an automatic water dispensing system except during exposure.
Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study. Analyses of the food and water are conducted regularly and the records are kept on file at Eurofins PSL.

Administration / exposure

Route of administration:
other: inhalation: aerosolised dust
Type of inhalation exposure:
nose only
Vehicle:
other: filtered air
Details on inhalation exposure:
A nose-only inhalation chamber with an internal volume of approximately 6.7 liters (Nose-Only Inhalation Chamber, ADG Developments LTD) was used for exposure. Animals were individually housed in polycarbonate holding tubes, which seal to the chamber with an “O” ring during exposure. The base unit terminates the chamber with a 0.5-inch diameter tube for discharged air.

Approximately 28.4 liters per minute (Lpm) of filtered air was supplied by an air compressor (JUN-AIR, Model #6-15) to the dust generator. An additional 3.3 Lpm of compressed mixing air, supplied using air from a compressed air tank (Airgas), was introduced into the chamber to help uniformly distribute the test atmosphere by creating a vortex at the chamber inlet. Compressed airflow was measured with a Mass Flowmeter (Omega, Model #FMA-5613). Chamber airflow was monitored throughout the exposure period and recorded periodically. Total airflow ranged from 31.5 to 31.9 with a mean of 31.7 Lpm. Based on the volume of the inhalation chamber, this airflow provided approximately 284 air changes per hour during the study.

The exposure tube temperature and relative humidity ranges during exposure were 21-23ºC and 67-75%, respectively. The room temperature and relative humidity ranges during exposure were 21-22ºC and 66-69%, respectively. Temperature and relative humidity values were recorded every 15 minutes for the first hour of exposure and every 30 minutes thereafter.

The ground test substance was aerosolized using a modified Wright Dust Generator driven by a variable speed motor (Dayton, Model #4Z538A) D.C. speed control with 0-100 potentiometer. The test substance was packed into the dust container (Wright, Model DF183) and compressed to 500 lbs/in2 using a lab press (Carver, Model C). The container was then fitted with a stainless steel cutting head (Model DF194SS) and cutting blade (Model DF191SS). Compressed air was supplied to the dust generator at 30 psi. The aerosolized dust was then fed directly into the chamber through the dust outlet assembly.

An eight-stage Andersen Cascade Impactor was used to assess the particle size distribution of the test atmosphere. Samples were withdrawn from the breathing zone of the animals at two intervals. The filter paper collection stages were weighed before and after sampling to determine the mass collected upon each stage. The aerodynamic mass median diameter and geometric standard deviation were determined graphically using two-cycle logarithmic probit axes.
Analytical verification of test atmosphere concentrations:
no
Duration of exposure:
ca. 4 h
Remarks on duration:
The exposure period was extended beyond 4 hours to allow the chamber to reach equilibrium (T99). The times for 90 and 99% equilibration of the chamber atmosphere were 0.5 and 1.0 minute, respectively.
Concentrations:
gravimetric concentration: 5.16 mg/L
nominal chamber concentration: 22.64 mg/L
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
After establishing the desired generation procedures during pre-test trials, ten healthy rats (5/sex) were exposed to the test atmosphere for 4 hours. Chamber concentration and particle size distributions of the test substance were determined periodically during the exposure period. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days following exposure. Body weights were recorded prior to exposure and again on Days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice.
Statistics:
6 samples of the chamber atmosphere were measured. Average result: 5.16 +/- 0.25 mg/l.

Results and discussion

Preliminary study:
Pre-test exposure trial produced a chamber concentration of 5.20mg/L, while the Mass median aerodynamic diametre of the particles that were suspended was estimated to be 2.5μm, based on graphic analysis of the particle size distribution as measured with an Andersen Cascade Impactor.
Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.16 mg/L air
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: No deaths or adverse effects were observed at the exposure concentration of 5.16mg/l
Mortality:
None
Clinical signs:
other: 4 animals (1 male, 3 female) experienced nasal discharge (black). The male and one female only for Day 1 after removal from the chamber. The other two females until Day 2 after removal from the chamber.
Body weight:
All animals lost body weight on Day 1, but gained weight subsequently.
Gross pathology:
No gross abnormalities after necropsy.

Any other information on results incl. tables

Table 1: Pre-test exposure trials

 Trial No  Compressed Air Pressure (psi)  Compressed Air Volume (Lpm)  Compressed Mixing Air (Lpm)  Total Air Volume (Lpm)  Dust Generator Motor Setting Chamber Conc. (mg/l) Particle Size Sampled 
1  30   28.4  3.3  31.7  20.0  6.20  No
2 30  28.3  3.3  31.6  18.0  5.20  Yes

Table 2: Summary of particle size distribution

 Sample No  Time of sample (hours)  Collection Time (minutes)  Mass Median Aerodynamic Diametre (μm)  Geometric Standard Deviation
 1  1.5  1  2.4  2.11
 2  3.0  1  2.3  2.11

Applicant's summary and conclusion

Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The substance showed no toxic or other adverse effects after the exposure of ten rats to a concentration of 5.15mg/l. The substance is considered non-toxic for inhalatory exposure.
Executive summary:

An acute inhalation toxicity test was conducted with rats to determine the potential for Slags, Ferronickel-manufg., CAS No: 69012-29-9, to produce toxicity from a single exposure via the inhalation (nose-only exposure) route. Under the conditions of this study, the single exposure acute inhalation LC50 of the test substance is greater than 5.16 mg/L in male and female rats. After establishing the desired generation procedures during pre-test trials, ten healthy rats (5/sex) were exposed to the test atmosphere for 4 hours. Chamber concentration and particle size distributions of the test substance were determined periodically during the exposure period. The animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days following exposure. Body weights were recorded prior to exposure and again on Days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice.

All animals survived exposure to the test atmosphere. The gravimetric chamber concentration was 5.16 mg/L. Based on graphic analysis of the particle size distribution as measured with an Andersen Cascade Impactor, the mass median aerodynamic diameter was estimated to be 2.35 μm. Immediately following exposure, all animals appeared active and healthy. Apart from one male and three females that exhibited nasal discharge on Days 1 and/or 2, all rats continued to appear active and healthy over the 14-day observation period. There were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behavior. Although all rats lost body weight by Day 1, all animals gained weight over the entire study. No gross abnormalities were noted for the animals

when necropsied at the conclusion of the 14-day observation period.