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Description of key information

Assessment of the acute oral toxicity of indium trichloride (InCl3) in Kiss, CiToxLAB Hungary Ltd., 2012:
As no mortality was observed in Group 1 (three Wistar rats treated at a dose level of 2000mg/kg), a confirmatory group (Group 2) was treated at the same dose level. Mortality was observed in one animal in the confirmatory group, therefore no further testing was required according to OECD 423 and Commission Regulation(EC) No 440/2008 of 30 May2008, B.1.tris.
Under the conditions of this study, the acute oral LD50value of the test item Indium trichloride was found to be above 2000 mg/kg bw in female Wistar CRL:(WI) rats

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:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
GLP compliance:
yes (incl. QA statement)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sandhofer Weg 7, D-97633 Sulzfeld
- Weight at study initiation (g): 196 – 217 g
- Housing: 3 animals / cage (Type II polypropylene/polycarbonate)
- Diet: ssniff® SM R/M-Z+H "Autoclavable complete feed for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany, ad libitum
- Water: tap water from municipal supplies, as for human consumption, ad libitum.
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 3
- Humidity (%): 30-70 %
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
A single oral gavage administration was followed by a fourteen-day observation period. On the night before treatment, the animals were fasted. The food but not water was withheld during an overnight period. Animals were weighed just before treatment. The test item was administered by oral gavage in the morning. The food was returned 3 hours after the treatment.

Doses:
2000mg/kg
No. of animals per sex per dose:
6
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:

Clinical Observations: performed at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.

Body Weight Measurement: body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly after.

Necropsy:
Macroscopic examination was performed on all animals. Surviving animals were sacrificed by exsanguination under pentobarbital anaesthesia (Euthasol® 40 %; Lot: 11B15 6; Expiry date: January 2014; Produced by: AST Beheer B.V. Oudewater Netherlands (Produlab Pharma, Raamsdonksveer)). After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.



Statistics:
none
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Indium trichloride resulted in mortality at 2000 mg/kg bw (1/6 on Day 4).
Clinical signs:
other: Treatment with Indium trichloride caused decreased activity (6/6), hunched back (6/6), piloerection (6/6), and death (1/6). All surviving animals fully recovered and were symptom free from Day 6 until the end of the observation period.
Gross pathology:
Necroscopy:
Macroscopic findings:
Found dead animal:
Dark/red discoloration of the non-collapsed lungs, thymus, mandibular and lung-associated lymph nodes, and fur at the perinasal area were found at necropsy.
Surviving animals:
No macroscopic observations were noted in remaining surviving animals terminated on Day 14.


Other findings:
none

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)
Executive summary:

The purpose of this study was to assess the acute oral toxicity of indium trichloride (InCl3).

As no mortality was observed in Group 1 (three Wistar rats treated at a dose level of 2000mg/kg), a confirmatory group (Group 2) was treated at the same dose level. Mortality was observed in one animal in the confirmatory group, therefore no further testing was required according to OECD 423 and CommissionRegulation(EC) No 440/2008of30 May2008, B.1.tris.

Under the conditions of this study, the acute oral LD50value of the test item Indium trichloride was found to be above 2000 mg/kg bw in female Wistar CRL:(WI) rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
In conclusion of the identified LD 50 differences between the two indium chloride acute oral toxicity studies (Kiss 2012; Szakmary et al 2001), differences in the vehicles used provide the most plausible explanation differences in the observed toxicity and the level at which it became apparent. In Szakmary et al 2001, the addition of Tween 80 to distilled water as a surfactant may have inhibited the body’s own natural detoxification apparatus in the form of P-gp resulting in increased uptake and therefore toxicity. If the use of Tween 80 led to an overestimation of toxicity, the defined LD50 of 1983 mg/kg may be conservative in comparison to the same study repeated in the absence of Tween 80.
Given the relative closeness of these two LD50 values (1983 mg/kg vs >2000 mg/kg) despite a possible overestimation of toxicity due to the use of Tween 80, it is possible that a repeat study using an aqueous media that does not contain a known inhibitory surfactant of P-gp may provide an LD50 of >2000 mg/kg.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because the substance is classified as corrosive to the skin
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:
the study does not need to be conducted because the substance is classified as corrosive to the skin
Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

From the available acute oral toxicity data, the results of the rat study on InCl3 (Szakmary et al 2001, supporting study) were considered inconclusive for classification (LD50= 1983 mg/kgbw) due to the inclusion of 5% Tween 80 as a surfactant in the dose vehicle (destilled water). Tween 80 has been shown to inhibit the body's own natural detoxification process in the form of the permeability glycoprotein (P-gp) found on the apical/luminal membrane of intestinal cells (Zhang et al 2003). The use of Tween 80 may therefore have caused an overestimation of toxicity making the study unreliable for classification purposes. Therefore, the study was repeated under the standard conditions of the recently more used Acute Oral Toxicity-Acute Toxic Class Method (OECD Guideline 423). The LD50 of this recent study was clearly >2000 mg/kgbw (Kiss 2012).



Justification for classification or non-classification

Based on the results of the available acute oral rat study, indium trichloride does not require classification for acute oral 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.


There are no available data on which to evaluate acute inhalation and dermal toxicity as the substance is corrosive.

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