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Toxicological information

Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
no
Principles of method if other than guideline:
Not Applicable
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Nickel monoxide
EC Number:
215-215-7
EC Name:
Nickel monoxide
Cas Number:
1313-99-1
Molecular formula:
NiO
IUPAC Name:
Nickel (II) oxide
Details on test material:
- Name of test material (as cited in study report): Black Nickel oxide, Code: N105-PTL
- Physical state: black, solid
- Composition of test material, percentage of components: 96.4% nickel monoxide, other ingredients
- Solubility: Insoluble in cold water
- Stability under test conditions: Test substance was expected to be stable for the duration of testing.
- Storage condition of test material: The test substance was stored at room temperature and stored under nitrogen after initial testing.
- Other: Documentation ofthe methods ofsynthesis, fabrication, or derivation of the test substance is retained by

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Received from Ace Animals, Inc., Boyertown, PA on
- Age at study initiation: 8-9 weels
- Weight: males 257-277 grams and females 180-211 grams at experimental start.
- Housing: suspended stainless steel caging with mesh floors. Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet (e.g. ad libitum): ad libitum; Purina Rodent Chow #5012
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23ºC
- Humidity (%): 50-64%
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Mini Nose Only Inhalation Chamber, ADG Developments LTD
- Exposure chamber volume: liters
- Method of holding animals in test chamber: Animals were individuallyhoused in polycarbonate holding tubes which seal to the chamber with an "0" ring during exposure.
- Source and rate of air: Filtered air was supplied by an air compressor (JUN-AIR, Model #6-15) to the dust generator. Additional compressed mixing air, supplied 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.
- Method of conditioning air: The measurements inside the exposure tube were made with a Humidity-Temperature Indicator (Taylor, Model #5502) and room conditions were measured with a Temperature-Humidity Monitor (Dickson, Model #TH550). Temperature and relative humidity values were recorded every 15 minutes for the first hour of exposure and every 30 minutes thereafter.
- System of generating particulates/aerosols: The 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 DF 183 or 183A) and compressed to 5,000 lbs/in^2 using a lab press (Carver, Model C). The container was then fitted with a stainless steel cutting head (Model DF 1945S or 1935S) and cutting blade (ModelDF 1915S or 1905S). 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.
- Method of particle size determination: 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 during each exposure. 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.


TEST ATMOSPHERE
- Brief description of analytical method used: Gravimetric samples were withdrawn at six intervals from the breathing zone of the animals during each exposure. Samples were collected using 25 mm glass fiber filters (GF/B Whatman) in a filter holder attached by 1/4 inch tygon tubing to a vacuum pump (Reliance Electric, Model #G557X). Filterpapers were weighed before and after collection to determine the mass collected. This value was divided by the total volume of air sampled to determine tile chamber concentration. Sample airflows were measured using a Mass Flowmeter (Omega, Model #FMA-561O).
- Samples taken from breathing zone: yes

TEST ATMOSPHERE (if not tabulated)
- MMAD (Mass median aerodynamic diameter): 2.45 um
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Gravimetric samples were withdrawn at six intervals from the breathing zone of the animals during each exposure. Sample airflows were measured using a Mass Flowmeter.
Duration of exposure:
4 h
Concentrations:
5.15 mg/L (median aerodynamic diameter was estimated to be um)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: daily observations; weights taken at start of study, days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: daily observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directcd to observation of tremors, convulsions, salivation, diarrhea, and coma.
Statistics:
Not Applicable

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 5.15 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: All 10 animals survived the observation period, gained weight, and appeared active and healthy.
Mortality:
All animals survived the observational 14-day period.
Clinical signs:
other: Immediately following exposure and throughout the 14-day observation period all animals appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior.
Body weight:
All animals had gained weight in both dose groups by the end of the study.
Gross pathology:
No gross abnormalities were noted for any of the animals in either of the dose groups when necropsied at the conclusion of the 14-day observation period.
Other findings:
Not Applicable

Applicant's summary and conclusion

Interpretation of results:
other: no apparent toxicity at these dose levels
Conclusions:
Under the conditions of this study, the acute inhalation LC50 of the test substance is greater than 5.15 mg/L in male and female rats.