Registration Dossier

Registration Dossier

Diss Factsheets

Administrative data

Description of key information

Assessment of the acute oral toxicity of indium in Asakura et al 2008:

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.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
not applicable
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
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

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)
Preliminary study:
a preliminary study was done in which no death were observed
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

none

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.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study technically not feasible
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
Justification for type of information:
REACH Annex XI (2) Testing is technically not possible:
- For an acute inhalation toxicity test , particle size distribution around 4µm is needed. Such a sample is not technically feasible to be prepared since In is a soft metal. Instead of trying to make smaller particle size <<20µm the material will stick together and result in bigger particles again.
- Indium powder ≤20µm is not marketed as such for industrial scale
- In is a soft metal and probably no exposure is possible because of no dust exposure, therefore: No inhalation exposure to indium metal at the workplace (REACH Annex XI(3) exposure considerations). This is supported by a dustiness test on dust fractions of 1g indium powder (20µm). It can be concluded from this dustiness test that: the tested sample is worst case and not marketed as such and showing very small dustiness values for the alveolar fraction. Therefore, it can be concluded that for industrial In metal shots no dust exposure is occurring, so there is no inhalation exposure to indium metal (reference: Final - Report on the determination of the dust generation tendency (“dustiness”) of Indium - Report No. GS 3 – 00 043 13, DMT GmbH & Co. KG)
Clinical signs:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
other:
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the results of the available acute oral rat study, indium does not require classification for acute oral toxicity according to EU CLP criteria (EC 1272/2008).


There are no available data on which to evaluate acute inhalation toxicity. However, acute inhalation toxicity can be considered low in view of no inhalation exposure to indium metal at the workplace. Therefore, indium does not require classification for acute inhalation toxicity according to EU CLP criteria (EC 1272/2008).


There are no available data on which to evaluate acute dermal toxicity. However, acute dermal toxicity can be considered low in view of the poor absorption by this route and the substance does not meet the criteria for classification as acute toxicity or STOT SE by the oral route. Therefore, indium does not require classification for acute dermal toxicity according to EU CLP criteria (EC 1272/2008)

No clear evidence of specific target organ toxicity was noted. As such, classification for STOT-SE is not considered appropriate.

 

EU Privacy Disclaimer

This website uses cookies to ensure you get the best experience on our websites.