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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
disregarded due to major methodological deficiencies
Study period:
21 days
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: No standard study protocol, relevant data not published, no clinical observations, no organ weights and no complete histopathological evaluation.

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1994
Report Date:
1994

Materials and methods

Principles of method if other than guideline:
Repeated dose toxicity study. No standard study protocol, no clinical observations, no organ weights and no complete histopathological examination, relevant data not published, treatment on 5 days per week for 3 weeks.
GLP compliance:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): gallium arsenide
no further data

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
male Wistar albino rats
- Source: Defence Research and Development Establishment
- Weight: 120 g
- Age: 5-6 weeks
- Acclimation period: 7 days

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: phosphate buffer 0.1 M, pH 6.5
Details on oral exposure:
- Justification for use and choice of vehicle (if other than water):
suspended in vehicle and delivered within 5 min. from buffer addition to ensure "that a minimal amount of GaAs would be in soluble form at the time of administration."
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
21 days
Frequency of treatment:
5 days per week
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 50, 100, 200 mg/kg bw.
Basis:
actual ingested
No. of animals per sex per dose:
10
Control animals:
yes
Positive control:
no

Examinations

Observations and examinations performed and frequency:
body weight not recorded
Other examinations:
Biochemical parameters were evaluated in brain, plasma, blood:
- Glutathione (GSH)
- Acetylcholinesterase (AChE)
- Delta-aminolevulinic acid dehydratase (ALAD)
- Dopamine (DA)
- Homovanillic acid (HVA)
- 5-Hydroxytryptamine (5-HT)
- 5-Hydroxyindoleacetic acid (5-HIAA)
- Norepinephrine (NE)
Measurement of Arsen in brain using atomic absorption spectrophotometer
some histopathological evaluation of brain

Results and discussion

Results of examinations

Clinical signs:
not specified
Mortality:
not specified
Body weight and weight changes:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
effects observed, treatment-related
Description (incidence and severity):
Blood ALAD, ZZP: decreased 100 and 200 mg/kg bw. , Blood GSH, S-GOT and S-GPT: increased 200 mg/kg bw.
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

brain tissue activities:      

100 mg/kg bw: increased: GSH

200 mg/kg bw.: increased: ALAD, GSH, MDA, ALP

Arsen content (µg per 100 ml blood per g tissue):

                    Blood              Brain                   

control:                            0.03                   n.d.             

50 mg GaAs/kg bw.        1.47                   0.11

100 mg GaAs/kg bw.         4.93                  0.19

200 mg GaAs/kg bw.       12.41                  0.39

Applicant's summary and conclusion

Executive summary:

Groups of 10 male Wistar rats were administered an oral dosage of 0, 50, 100 and 200 mg GaAs/kg bw for 21 days on 5 days a week.

50 mg GaAs/kg bw.: increased AChE in the brain (but no dose-related effects)

100 mg GaAs/kg bw.: decreased blood ALAD, brain ALAD, increased: brain AChE (but no dose-related effects)

200 mg GaAs/kg bw.: decreased blood ALAD, brain ALAD, increased: brain DA, brain NE, brain HVA, brain 5 -HIAA, blood GSH, Brain GSH, AChE (but no dose-related effects). Arsen contents of brain and blood dose-related.

No standard study protocol used, relevant data not published, no organ weights and no sufficient histopathological evaluation. The study is of limited relevance for the evaluation of GaAs as such because the substance was mixed in solvent phosphate buffer prior to administration in order to achieve soluble GaAs.