Diindium trioxide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

read-across based on grouping of substances (category approach)

Adequacy of study:

key study

Study period:

not applicable

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Justification for type of information:

Please refer for justification of read-across document in section 13

Data source

Reference

Reference Type:

publication

Title:

Oral toxicity of indium in rats: single and 28-day repeated administration studies.

Author:

Asakura K, Satoh H, Chiba M, Okamoto M, Serizawa K, Nakano M and Omae K

Year:

2008

Bibliographic source:

J Occup Health. 50(6):471-9

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Indium

EC Number:

231-180-0

EC Name:

Indium

Cas Number:

7440-74-6

Molecular formula:

In

IUPAC Name:

indium

Details on test material:

- Name of test material (as cited in study report): Indium
- Analytical purity: 99%
- Lot/batch No.: 67246G
- Stability under test conditions: stable based on the characteristics of indium
- Storage condition of test material: room temperature
- Other: particle diameter : M45 µm pass

Test animals

Species:

rat

Strain:

other: Crj: CD(SD) IGS rats (SPF)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan, Inc
- Age at study initiation: 5 wk
- Weight at study initiation: 125-145 g (male) and 116-130g (female)
- Fasting period before study: 18h
- Diet (ad libitum): pellet diet (MF, Oriental Yeast co, Ltd)
- Water (ad libitum): tap water irradiated by UV rays after passing through a 5µm filter
- Acclimation period: 6days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.2 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): 12 changes per hour
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: the dosing volume was set at 10mg/kg and the dose volume for individual animals was calculated based on the body weight measured just before dosing

DOSAGE PREPARATION (if unusual): done on the administration day

Doses:

2000mg/kg

No. of animals per sex per dose:

12

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: body weights of all animals were measured before dosing and on days 4, 8, and 15 (day of administration was designated as day 1)
- Necropsy of survivors performed: no
- Other examinations performed:
clinical signs: observed 5 times (shortly before dosing, and 0.5, 1, 3 and 5h after dosing) on the those day and thereafter once a day for 14 days
body weight: measured before dosing and on days 4, 8, and 15

Statistics:

Barlett's test: to test the homogeneity of the variances of the data
one way analysis of variance: used when to variances of the treatment group and the control group were homogenous; to analyze statistical significances in the numerical data (body weight, food consumption, hematology, blood chemistry, and organ weights)
Kruskal-Wallis test: used when to variances of the treatment group and the control group were heterogenous; to analyze statistical significances in the numerical data (body weight, food consumption, hematology, blood chemistry, and organ weights)
Dunnett's test or Dunnett-type ranksum test: to examine statistical significances in the data between groups
chi square test: to examine statistical significances in graded categorical data (urinalysis)

Results and discussion

Preliminary study:

a preliminary study was done in which no death were observed

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality observed

Clinical signs:

other: No abnormalities in clinical signs observed

Gross pathology:

Necroscopy:
no abnormalities observed

Other findings:

spontaneous changes: in one male of the 2000 mg/kg group pelvic dilatation of the kidneys was observed

Any other information on results incl. tables

none

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Tests done according to standard protocol. Good quality and considered useful for setting the reference value for acute oral toxicity (LD50>2000mg/kg)

Although this study represented an out of date test guideline as it was deleted on 17th December 2002 and replaced with the fixed dose (TG 420 [4]) and acute toxic class (OECD TG 425 [5]) methods, it meets in light of current test guidelines (i.e. TG 420) the minimum animal required of 5 animals (Asakura et al. used 12)
The preference within the current test guideline is that test substances are preferentially administered as an aqueous solution/suspension/emulsion followed in order of preference by a solution/suspension/emulsion in oil (e.g. corn oil) as used by Asakura et al).

Executive summary:

A limit study with Crj:CD (SD) IGS rats (SPF) was carried out according to OECD guideline no 401 to assess the oral LD50. No deaths and no abnormalities in clinical signs, body weights, and necropsy findings were observed for any of the animals. An LD50 value >2000mg/kg bw was reported.