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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
Study period:
March 25, 1985 to April 8, 1985
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP guideline study with acceptable restrictions.
Cross-referenceopen allclose all
Reason / purpose:
reference to same study
Reason / purpose:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1985
Report Date:
1985

Materials and methods

Test guideline
Guideline:
other: not reported
Principles of method if other than guideline:
Principles of method not described. Details of test methods described throughout the following sections.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Nickel powder
- Physical state: powder
- Impurities (identity and concentrations): not specified
- Composition of test material, percentage of components: not specified
- Stability under test conditions: not specified
- Storage condition of test material: not provided

Test animals

Species:
rat
Strain:
other: Sprague-Dawley derived albino
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Inc., Wilmington, Massachusetts
- Age at study initiation: young adult (approximately 8 weeks of age)
- Weight at study initiation: 205-237 grams
- Fasting period before study: not reported
- Housing: Individually housed in wire mesh bottom cages. All housing and care conformed to the standards established in "Guide for the Care and Use of Laboratory Animals" DHEW Publication No. (NIH) 78-23.

- Diet (e.g. ad libitum): Food (NIH 07 Open Formula, certified rodent diet, Zeigler Brothers, Inc., Gardner, PA) was suppied fresh each week (ad libitum) except during the exposure period.

- Water (e.g. ad libitum): Fresh tap water was suppied each week (ad libitum) except during the exposure period.

- Acclimation period: Minimum of 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C) and Humidity (%): All animals were housed in environment-controlled rooms with temperature and relative humidity regulated as per "Guide for the Care and Use of Laboratory Animals".
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12 hour light-dark cycle


Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
whole body
Vehicle:
other: not applicable
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: A 128 L acrylic (plexiglass), portable chamber designed by the FDRL scientific staff.
- Exposure chamber volume: 128L
- Method of holding animals in test chamber: individually caged during exposure
- Source and rate of air: Transvector jet (Model 901, Vortec Corporation, Cincinnati, OH), 100 L/minute
- Method of conditioning air: An air treatment system (Charles Spengler and Associates, Cincinnati, OH) constructed of a glass fiber pre-filter, Micretain(r) HEPA filter, and an activated charcoal bank

- System of generating particulates/aerosols: NBS-II dust generator (BGI, Inc., Waltham, MA) using an air inlet port.
- Method of particle size determination: A multijet cascade impactor (Model 02-200, In-Tox Products, Albuquerque, Nl'1).
- Treatment of exhaust air: Vented via an air treatment system (Charles Spengler and Associates, Cincinnati, OH)
- Temperature in air chamber during exposure: 19oC (initial) , 23oC (final)
- Humidity in air chamber during exposure: 49% (initial) , 29% (final)
- Pressure in air chamber during exposure: not provided


TEST ATMOSPHERE
- Brief description of analytical method used: Test atmosphere temperature and relative humidity were taken at initiation, once during and at the conclusion of exposure, using a Taylor wet bulb/dry bulb hygrometer placed within the chamber. The instrument was modified so that chamber air was drawn over the wet bulb at the time of reading.

- Samples taken from breathing zone: no


VEHICLE: Not applicable

PARTICLE SIZE ANALYSIS
Particle size analysis was performed twice during the exposure using a multijet cascade impactor (Model 02-200, In-Tox Products, Albuquerque, Nl'1). Stages one to seven of the impactor were fitted with pre-weighed stainless steel impaction substrates. Stage eight (final filter stage) was fitted with a pre-weighed cellulose filter membrane (Gelman Type A/E, 47 mm, Triacetate, 99.7% efficient at 0.3 micrometers). Chamber air was drawn through the impactor at a rate of 20 L/minute. The change in weight (mg) of each substrate was determined subsequent to sampling. The cumulative percent of aerosol collected through each stage was determined.

EXPOSURE DETAILS
- Rationale for the selection of the exposure concentration: The nominal Nickel Powder exposure concentration was calculated by dividing the net weight of test article utilized (g) by total chamber airflow (L).

-The animals were exposed to nickel powder for 66 minutes. Six minutes were added to the 60 minute exposure period in order to allow the test system to reach 99% of the desired concentration (point of equilibration).

-During exposure, the animals were individually housed in wire-mesh cages. Following exposure, the animals remained in the chamber for at least six minutes. The chamber was maintained during these six minutes at the designated airflow rate of 100 L/minute using clean ambient air only. After the exposure, animals were individually housed.
Analytical verification of test atmosphere concentrations:
yes
Remarks:
Measurements were taken at initiation, once during and at the conclusion of exposure, using a Taylor wet bulb/dry bulb hygrometer placed within the chamber.
Duration of exposure:
1 h
Concentrations:
10.2 mg/l
No. of animals per sex per dose:
10
Control animals:
no
Details on study design:
PURPOSE OF STUDY
To evaluate the potential toxicity of a dust aerosol generated from Nickel Powder that is administered via inhalation to five male and five female Sprague-Dawley albino rats (randomly chosen from acclimated animals).

EXPOSURE DETAILS
- Rationale for the selection of the exposure concentration: The nominal Nickel Powder exposure concentration was calculated by dividing the net weight of test article utilized (g) by total chamber airflow (L).

-The animals were exposed to nickel powder for 66 minutes. Six minutes were added to the 60 minute exposure period in order to allow the test system to reach 99% of the desired concentration (point of equilibration).

-During exposure, the animals were individually housed in wire-mesh cages. Following exposure, the animals remained in the chamber for at least six minutes. The chamber was maintained during these six minutes at the designated airflow rate of 100 L/minute using clean ambient air only. After the exposure, animals were individually housed.


OBSERVATION DETAILS
- Duration of observation period following administration: 14 days

- Frequency of observations and weighing: animals were recorded periodically during exposure, subsequent to exposure on day one and twice daily for 14 additional days; body weights were recorded on days 1 (just prior to exposure), 8, and 15.

- Other examinations performed: observe for clinical signs of toxicity

-Necropsy of survivors performed: no
Statistics:
Not provided

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
male/female
Dose descriptor:
other: NOAEC
Effect level:
>= 10.2 mg/L air
Exp. duration:
66 min
Remarks on result:
other: No effects observed over a 14-day period post-exposure
Mortality:
No mortality was observed in any of the animals.  
Clinical signs:
other: No signs of toxicity were observed in any of the animals.  
Body weight:
No adverse effect on body weight was observed.
Gross pathology:
Not examined
Other findings:
The mean particle size of nickel powder could not be accurately determined. No particles were present in the first and second stage of the particle size impactor, indicating that nickel powder did not remain suspended in the test atmosphere. However, it cannot be concluded that the majority of particles generated with the test article were not less than 12 micrometers in size.

Any other information on results incl. tables

Nickel powder via inhalation by whole-body exposure failed to produce mortality or signs of toxicity.

Applicant's summary and conclusion

Executive summary:

STUDY RATED BY AN INDEPENDENT REVIEWER.

Summary of FDRL (1985)

Five male and five female rats were whole-body exposed for one hour to a dust aerosol, which was generated from nickel powder at the nominal concentration

of 10.2 mg/l. The animals were observed periodically during exposure and for 14 days following exposure. No mortality or signs of toxicity were observed.

The exposure duration in this study was too short compared with the Annex V method (4 h).