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Toxicological information

Acute Toxicity: other routes

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Administrative data

Endpoint:
acute toxicity: other routes
Type of information:
experimental study
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No guideline study, sufficient data for evaluation but no quality assurance data of used analytical methods given

Data source

Reference
Reference Type:
publication
Title:
Different Acute Effects of Orally and Intratracheal Administeration of Disodium Arsenate and Gallium Arsenide on Heme Synthesis in Rats
Author:
Kondo M, Ichikawa I.
Year:
1994
Bibliographic source:
Applied Organometallic Chemistry, Vol. 8, 215-221 (1994)
Report Date:
1994

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study examined the effects of gallium arsenide exposure. Male Wistar rats received gallium arsenide suspensions at doses of 0, 200 or 400 mg/kg via a single intratracheal instillation.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): gallium arsenide (purity 99.999% obtained from Alfa Products (Danvers, MA, USA) and prepared by the method of Yamaouchi et al..
- Molecular formula: GaAs
No further information on the test material was stated.

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS: male SPF Jcl:Wistar rats
- Weight at study initiation: 200 - 220 g
No further information on the test animals was stated.

Administration / exposure

Route of administration:
other: intratracheal
Vehicle:
other: physiological saline
Details on exposure:
Five rats in each group were assigned to treatment groups to recieve 0.2 or 0.4 g of GaAs per cm³ physiological saline per kg body weight as a single intratracheal dose.
Doses:
0, 200 and 400 mg/kg bw.
No. of animals per sex per dose:
5
Control animals:
yes
Details on study design:
The animals were anesthetized with ether 16 h after administration of the compound and their blood was collected in heparinized plastic tubes from the vein of the right axilla. The hematocrit value was determined via capillary tube methods. Liver and kidney after perfusion through the portal vein were carefully removed, rinsed in cold saline, blotted and weighed.
Enzyme preparation and assay from bone marrow cells and blood:
Bone marrow cells from the femora of rats were collected and suspended in saline. The cells were precipitated by centrifugation at 3000 g for 10 min, washed twice with cold saline, hemolyzed by adding 2 cm³ of ice-cold water. Isotonicity was restored by adding 9 % NaCl solution, and the hemolysate was centrifugated at 48800 g for 30 min at 4 °C. The supernatant was used for assay of delta-aminolevulinic acid (ALA) dehydratase and porphobilinogen deaminase. The precipitate was washed 2 or 3 times with cold saline to exclude hemoglobin. The washed precipitate was homogenized in 1.0 cm³ of 0.25 M sucrose solution and used to determine delta-aminolevulinate synthase activity.
Whole-blood lysates were also used for assay of the enzymes.
Enzyme preparation from liver, kidney, and spleen:
Liver and kidneys were homogenized in 0.25 M sucrose solution. The mitochondria and supernatant fractions were prepared from the homogenate by centrifugation at 800 g for 10 min, 10000 g for 15 min, and 105000 g for 1 h, successively. The mitochondrial fraction was further washed twice with 0.25 M sucrose, resuspended in the same solution and used for assay of delta-aminolevulinate synthase. The 105000 g supernatant fraction was used for the assay of delta-aminolevulinate dehydratase and porphobilinogen deaminase activity.
Further method description:
Protein was determinde by the method of Lowry et al. (1951) with minor modification (Kondo et al., 1980). Colorimetric dertermination of ALA in kidney tissue was carried out on equal volumes of the supernatant fractions. The fractions pooled from 5 rats in each group were deproteinized with trichloroacetic acid using ion-exchange resins. Erythrocyte porphyrins were determined by the method reported previously (Kondo and Hirosawa, 1988)
Statistics:
The means and SD were calculated and the statistical significance of differences between the treated and the control groups was determined using Student's t-test.

Results and discussion

Effect levels
Sex:
male
Dose descriptor:
LD0
Effect level:
> 400 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No lethality at 400 mg/kg bw after single intratracheal instillation.
Mortality:
no
Clinical signs:
no data
Body weight:
no dose related changes

Any other information on results incl. tables

No lethality at 200 and 400 mg/kg bw after single intratracheal instillation.

Applicant's summary and conclusion

Conclusions:
16 hours after a single intratracheal administration of 200 or 400 mg/ kg bw. a possible biological effect of GaAs was seen with the delta-aminolevulinate dehydratase activity in the peripheral blood.
Executive summary:

Male Wistar rats received gallium arsenide suspensions at doses of 0, 200 or 400 mg/kg via a single intratracheal instillation.

No significant differences to the control group were seen with:

bone marrow cells delta-amonolevulinate dehydratase and porphobilinogen deaminase, peripheral blood porphobilinogen deaminase, erythrocytes content of coproporphin, free coproporphin, and zinc-protoporphyrin, liver and kidney delta-aminolevulinate dehydratase and porphobilinogen deaminase and kidney delta-aminolevulinate synthase.

Differences with no correlation to dosage or strongly differing standard deviations were observed with:

body weight, hematocrit, bone marrow activity of delta-aminolevulinate synthase and rat liver activity of delta-aminolevulinate synthase.

These differences have to be interpreted as merely statistical effects and do not indicate biological differences.

Possible biological effects of GaAs were seen the delta-aminolevulinate dehydratase activity in the peripheral blood with and without addition of dithiothreitol and zinc.

No standard test system and/or no guideline followed, especially no positive control. Methods not validated, therefore reliable with restrictions.