Registration Dossier

Administrative data

Endpoint:
in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
Remarks:
Type of genotoxicity: chromosome aberration
Type of information:
experimental study
Adequacy of study:
key study
Study period:
first exposure was on 7 March 1989; last exposure in June 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP toxicity study conducted under the US National Toxicology Program (NTP). Study performed according to guideline OECD 474.Results reported within NTP Toxicology and Carcinogenesis Studies of Gallium Arsenide.
Cross-reference
Reason / purpose:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
2000
Reference Type:
publication
Title:
The in vivo erythrocyte micronucleus test: Measurement at steady state increases assay efficiency and permits integration with toxicity studies.
Author:
MacGregor, J T; Wehr, C M; Henika, P R; Shelby, M D
Year:
1990
Bibliographic source:
Fundam. Appl. Toxicol. 14, 513-522.

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
Deviations:
yes
Remarks:
; no positive control is reported
Principles of method if other than guideline:
The genetic toxicity of gallium arsenide was assessed by testing the ability of the chemical to increase the frequency of micronucleated erythrocytes in mouse peripheral blood.
GLP compliance:
yes
Type of assay:
micronucleus assay

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): gallium arsenide
- Physical state: solid, dark gray to black, fine powder
- Analytical purity: >98%
- Lot/batch No.: M051988
- Stability under test conditions: gallium arsenide was found to be stable for 2 weeks at temperatures up to 60°C when stored protected from light.
- MMAD: 0.9 - 1.3 µm
- Origin: the analytical chemistry laboratory, Midwest Research Institute (Kansas City, MO) obtained gallium arsenide from Johnson Matthey, Inc. (Ward Hill, MA) and prepared the single lot.
No further details are given.

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: mice were obtained from Simonsen Laboratories (Gilroy, CA)
- Age at study initiation: approximately 7 weeks old on the first day of the studies
- Assigned to test groups randomly: yes, under following basis: Animals were distributed randomly into groups of approximately equal initial mean body weights.
- Housing: mice were housed individually
- Diet: ad libitum; NIH-07 open formula pelleted diet
- Water: ad libitum
- Acclimation period: Animals were quarantined for 20 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): ~23
- Humidity (%): 55 +/- 15
- Air changes: 15/hour
- Photoperiod: 12 hours dark/light cycle
No further details are given.

Administration / exposure

Route of administration:
inhalation: aerosol
Vehicle:
- Vehicle(s)/solvent(s) used: air
Details on exposure:
TYPE OF INHALATION EXPOSURE: whole body

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: The study laboratory designed the stainless-steel inhalation exposure chambers so that uniform vapor concentrations could be maintained throughout the chambers when catch pans were in place. The total active mixing volume of each chamber was 1.7 m³.
- Method of holding animals in test chamber:
- System of generating particulates/aerosols: The gallium arsenide aerosol generation and delivery system had five basic components: a flexible-brush dust feed mechanism developed at the study laboratory, a Trost Model GEM-T air-impact mill, a cyclone separator, an aerosol charge neutraliser, and an aerosol distribution system. The flexible-brush dust feed mechanism employed a hopper into which the dry powder was poured. The hopper was reloaded with additional gallium arsenide at regular intervals throughout each day's exposure period. Aerosol passed through the charge neutraliser into the distribution line. At each chamber location, a vacuum pump drew aerosol from the distribution line into the chamber inlet, where the aerosol was further diluted with HEPA-filtered air to the appropriate concentration.
- Temperature, humidity in air chamber: 23-25°C, 55% +/- 15%
- Air change rate: 15 air changes per hour
- Method of particle size determination: The particle size distribution in each chamber was determined during pre-study testing and monthly during the 14-week study using a Mercer-style seven-stage impactor. The stages (glass coverslips lightly sprayed with silicone) were analysed by ICP/MS. The relative mass collected on each stage was analysed by probit analysis. The mass median aerodynamic particle diameter and the geometric standard deviation of the sample were estimated. The mass median aerodynamic particle diameter ranged from 0.8 to 1.6 µm.

TEST ATMOSPHERE
- Brief description of analytical method used: Chamber aerosol concentrations were monitored with real-time aerosol monitors (RAMs) that used a pulsed-lightemitting diode in combination with a silicon detector to sense light scattered over a forward angular range of 45° to 95° by particles traversing the sensing volume. The instrument responds to particles 0.1 to 20 µm in diameter; the geometric diameter of gallium arsenide aerosol approached the minimum of this range.
- Samples taken from breathing zone: no data
Duration of treatment / exposure:
14 weeks
Frequency of treatment:
6 hours plus T90 (12 minutes) per day, 5 days per week
Post exposure period:
none
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
0.1 mg/m³
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
1.0 mg/m³
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
10 mg/m³
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
37 mg/m³
Basis:
nominal conc.
Remarks:
Doses / Concentrations:
75 mg/m³
Basis:
nominal conc.
No. of animals per sex per dose:
10 male and 10 female mice were exposed to particulate aerosols of gallium arsenide.
Control animals:
yes, sham-exposed
Positive control(s):
no

Examinations

Tissues and cell types examined:
At the end of the 14-week study, peripheral blood samples were obtained from male and female mice.
Details of tissue and slide preparation:
CRITERIA FOR DOSE SELECTION: no data

TREATMENT AND SAMPLING TIMES ( in addition to information in specific fields): No further details are reported.

DETAILS OF SLIDE PREPARATION: Smears were immediately prepared and fixed in absolute methanol. The methanol-fixed slides were stained with acridine orange and coded.

METHOD OF ANALYSIS: Slides were scanned to determine the frequency of micronuclei in 2000 normochromatic erythrocytes (NCEs) in each of 9 or 10 animals per exposure group.

OTHER: A detailed discussion of this assay is presented by MacGregor et al. (1990).
Evaluation criteria:
Statistical as well as biological factors are considered. No further details are given.
Statistics:
The frequency of micronucleated cells among NCEs was analysed by a statistical software package that tested for increasing trend over exposure groups with a one-tailed Cochran-Armitage trend test, followed by pairwise comparisons between each exposure group and the control group. In the presence of excess binomial variation, as detected by a binomial dispersion test, the binomial variance of the Cochran-Armitage test was adjusted upward in proportion to the excess variation. In the micronucleus test, an individual trial is considered positive if the trend test P value is less than or equal to 0.025 or if the P value for any single exposed group is less than or equal to 0.025 divided by the number of exposure groups.

Results and discussion

Test results
Sex:
male/female
Genotoxicity:
negative
Toxicity:
not examined
Vehicle controls valid:
not specified
Negative controls valid:
not examined
Positive controls valid:
not specified
Additional information on results:
No further details are given.

Applicant's summary and conclusion

Conclusions:
Interpretation of results (migrated information): negative
Gallium arsenide induced no increase in the frequency of micronucleated erythrocytes in peripheral blood of male or female mice exposed by inhalation for 14 weeks.
Executive summary:

Particulate gallium arsenide was evaluated for toxicity and genotoxicity in a 14 -week study in male and female B6C3F1 mice, with whole body inhalation (0.1 to 75 mg/m³) as the route of exposure.Male and female mice were examined for frequency of micronucleated NCEs.

No increases over the control frequencies were noted in mice of either gender.