Nickel(III) oxy hydroxide

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

May 29, 2009 - October 5, 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline Study

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2009

Report date:

2009

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

Test material information

Constituent 1

Reference substance name:

Nickel monoxide

EC Number:

215-215-7

EC Name:

Nickel monoxide

Cas Number:

1313-99-1

IUPAC Name:

oxonickel

Details on test material:

- Name of test material (as cited in study report): Green Nickel oxide, Code: NI26-PTL
- Physical state: dark grey powder (granules prior to grinding)
- Composition of test material, percentage of components: NiO green = 98%; CoO = 1.5%
- Expiration date of the lot/batch: Not Applicable
- Solubility: Insoluble in water
- Stability under test conditions: Test substance was expected to be stable for the duration oftesting.
- 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 Vale Inco Ltd. 200 Bay St. Royal Bank Plaza, Suite 1600, S. Tower, P.O. Box 70. Toronto, Ontario, CA. M5J 2K2.

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 May 19 and July21, 2009.
- Age at study initiation: 9-10 weeks
- Weight at study initiation: males 296-335 grams and females 204-230 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: 13 or 15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23°C
- Humidity (%): 58-78%
- 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: 6.7 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.
- Temperature, humidity, pressure in air chamber: 19-23°C, 58-78%, not applicable

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)
- Particle size distribution:
- MMAD (Mass median aerodynamic diameter): 2.35 um (low dose); 3.75 um (high dose)

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:

ca. 4 h

Concentrations:

0.183 mg/L (median aerodynamic diameter was estimated to be 2.35 um) and 5.08 mg/L (median aerodynamic diameter was estimated to be 3.75 um)

No. of animals per sex per dose:

5 males and 5 females per dose

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

Preliminary study:

The exposure procedures and atomization equipment used were based on the results of pre-test trial numbers 5 and 7. In each instance, the conditions ofgeneration were modified to achieve the targeted chamber concentration with a desirable particle size distribution.

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.08 mg/L air (analytical)

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 in both dose groups 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

Remarks:

Criteria used for interpretation of results: not specified

Conclusions:

Under the conditions of this study, the acute inhalation LC50 of the test substance is greater than 5.08 mg/L in male and female rats.

Executive summary:

Eurofins Product Safety Laboratory (EPSL) reported the findings of an independent test evaluating the acute inhalation toxicity of green nickel oxide as determined by the acute inhalation toxicity procedure in young male and female Sprague-Dawley albino rats (carried out according to OECD Test # 403 guidelines and using GLP standards). Green nickel oxide, Code: NI26-PTL and 98% pure, was aerosolized and concentrations were determined and maintained via gravimetric sampling from the breathing zone of the animals during each exposure. Prior to initiation of the full inhalation study, pre-test trials were conducted to establish generation procedures to achieve, to the extent possible, the targeted chamber concentration and desired particle size distribution [mass median aerodynamic diameter (MMAD) between 1.8 and 2.5 μm for the 0.18 mg/L dose level and between 1 and 4 um for the 5.0 mg/L dose level]. The estimated MMAD was 2.35 um (low dose) and 3.75 um (high dose). Five males and five females (ages 9-10 weeks old) were exposed nose-only to either 0.183 or 5.08 mg NiO/L air for 4 hours. All animals were observed for mortality during the exposure period. The animals were examined for signs of gross toxicity, and behavioral changes upon removal from the exposure chamber and at least once daily thereafter for up to 14 days. 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 directed to observation of tremors, convulsions, salivation, diarrhea, and coma. Body weights were measured prior to exposure, and then at days 7 and 14 of observation. All 10 animals in each dose group survived the observation period, gained weight, and appeared active and healthy. There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior. 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. Under the conditions of this study, the acute inhalation LC50 of the test substance is greater than 5.08 mg/L in male and female rats.