Diammonium hexachloroiridate

Endpoint summary

Description of key information

 The acute median lethal oral dose (LD50) to rats of Diammonium Hexachloroiridate was demonstrated to be between 300 and 2000 mg/kg body weight.

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:

20 July - 12 Aug 2020

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Version / remarks:

v 17 December 2001

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 bis (Acute Oral Toxicity - Fixed Dose Procedure)

Version / remarks:

v 30 May 2008

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

fixed dose procedure

Limit test:

no

Specific details on test material used for the study:

100% purity

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

Wistar Han
Females were nulliparous and non-pregnant
age at beginning of treatment: 8 - 12 weeks
Acclimatization:At least 5 days prior to the start of dosing under test conditions after health examination. Only animals without any visible signs of illness were used for the study.

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

different test item concentrations were prepared individually
Test substance formulations were freshly prepared on the day of dosing, issued at room temperature and administered as soon as possible (within 4 hours of preparation)
Homogeneity of the test item in vehicle was maintained during treatment using a magnetic stirrer.
Grinding of the test item in a mortar was used to formulate the test item
The test item was administered at a constant dose volume of 10 mL/kg body weight
Feed: 2018C Teklad Global 18% protein rodent diet (certified), ad libitum (except for overnight fasting prior to dosing; diet was returned immediately after dosing was complete)
Water: tap water, ad libitum
The temperature in the animal room was between approximately 20 to 26°C instead of 20 to 24°C for several hours on several days due to insufficient capacity of the air conditioning system during a summer heat wave. This deviation to the study plan, however, does not affect the validity of the study.

Doses:

In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the initial starting dose, since a severe toxicity which may necessitate humane euthanasia was not expected at this dose level.
Since no toxicity was evident at this dose level, a single rat was dosed at 2000 mg/kg.
Two single animals were treated, sequentially, as follows:
Dose level (mg/kg) Concentration (mg/mL) Dose volume (mL/kg) Number of rats
Female
300 30 10 1
2000 200 10 1

Due to mortality and signs of systemic toxicity at a dose level of 2000 mg/kg, an additional group of animals (n=4) was treated at 300 mg/kg:
Dose level (mg/kg) Concentration (mg/mL) Dose volume (mL/kg) Number of rats
Female
300 30 10 4
A total of five animals were therefore treated at a dose level of 300 mg/kg in the study.

No. of animals per sex per dose:

5 female test animal at 300 mg/kg, 1 animal at 2000 mg/kg

Control animals:

no

Details on study design:

Clinical observations and inspections for morbidity / mortality were performed at least three times within the first six hours after application (i.e., 30 minutes and 1 hour, 2 hours and 4 hours after dosing on day 0), thereafter at least once daily for 14 days. All surviving animals were observed for 14 days after dosing.
The nature and severity, where appropriate, of the clinical signs and the time were recorded at each observation for all individual animals. If applicable, the time of death/humane kill was recorded as precisely as possible. Observations included changes in the skin and fur, eyes and mucous membranes, and respiratory, circulatory, autonomic and central nervous system, and somatomotor activity and behavior pattern. Particular attention was directed to the observation of tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma.
Body weights were recorded on Day 0 (prior to dosing), Day 7, and 14, or (if applicable) at death (unscheduled).
A gross necropsy was performed on all animals that died or were humanely killed during the study (if applicable) and at the end of the in-life part. Any macroscopic abnormalities were recorded. Routinely no organs or tissues were retained.

Statistics:

The test item is classified according to Annex 3 of the OECD Guidelines for Testing of Chemicals No. 420 ‘Acute Oral Toxicity – Fixed Dose Procedure’ (adopted 17 December 2001) as shown in the Flow Chart in Annex 2.
Evaluation of data includes the identification of the number of animals that died during the study (or that were killed for humane reasons), and determination of the nature, severity, onset and duration of the toxic effects. If possible, the signs of toxic effects of evident toxicity are described. Evident toxicity refers to the toxic effects of sufficient severity that administration of the next higher dose level could result in development of severe signs of toxicity and probable mortality. Effects on body weights and abnormalities noted at necropsy were identified.
Using the mortality data obtained, an estimate of the acute oral median lethal dose (LD50) of the test item was made.

Preliminary study:

In the absence of data regarding the toxicity of the test item, 300 mg/kg was chosen as the initial starting dose, since a severe toxicity which may necessitate humane euthanasia was not expected at this dose level. Since no toxicity was evident at this dose level, a single rat was dosed at 2000 mg/kg.
 
Two single animals were treated, sequentially, as follows:
Dose level (mg/kg) Concentration (mg/mL) Dose volume (mL/kg) Number of rats
Female
300 30 10 1
2000 200 10 1

Due to mortality and signs of systemic toxicity at a dose level of 2000 mg/kg, an additional group of animals was treated at 300 mg/kg

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

300 mg/kg: no deatjs
2000 mg/kg: One female (animal number 1) was found dead on day 1 after dosing

Clinical signs:

other: 300 mg/kg: There were no clinical signs of reaction to treatment throughout the study 2000 mg/kg: The animal was found dead in abdominal position, with secretion of Haderian glands, slimy/yellow stained anus, and partially closed eyes.

Gross pathology:

300 mg/kg: Animal 1 showed a white dot on spleen, animal 2 showed a cyst on the surface of the kidney, and animal 5 showed a hardened urinary bladder. The remaining animals did not show any abnormalies.
2000 mg/kg: Macrosopic examination of the animal which had died on test day 1 revealed a patchy liver, swollen pancreas, bloody stomach and substance residuals were stuck to stomach wall, swollen and bloodshot small intestines, and the caecum was slightly bloodshot.

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute median lethal oral dose (LD50) to rats of Diammonium Hexachloroiridate was demonstrated to be between 300 and 2000 mg/kg body weight.

Executive summary:

A GLP compliant study was performed (according to OECD420) to assess the acute oral toxicity of Diammonium Hexachloroiridate to the rat.

Following a sighting test at dose levels of 300 mg/kg b.w. and 2000 mg/kg b.w. in one female rat per dose group, a further group of four fasted females was given a single oral dose of Diammonium Hexachloroiridate, as a suspension in corn oil, at a dose level of 300 mg/kg body weight. Clinical signs and body weight development were monitored in all animals during the study. All animals were subjected to gross necropsy.

Mortality:The animal treated with a dose level 2000 mg/kg b.w. in the range finder was unexpectedly found dead on day 1 after application.

Clinical Observations:The animal treated with 2000 mg/kg b.w. was found dead in abdominal position, with secretion of Haderian glands, slimy/yellow stained anus, and partially closed eyes. The remaining animals (treated with 300 mg/kg b.w.) showed no signs of systemic toxicity.

Body Weight:Three animals treated with 300 mg/kg b.w. had lost weight on day 7 but showed weight gain thereafter until day 14. The remaining animals showed expected gains in body weight throughout the study period.

Necropsy:The animal treated with 2000 mg/kg b.w. showed a patchy liver, swollen pancreas, bloody stomach and substance residuals were stuck to the stomach wall, swollen and bloodshot small intestines, and the caecum was slightly bloodshot. Animal 1 treated with 300 mg/kg b.w. showed a white dot on the spleen, animal 2 treated with 300 mg/kg b.w. showed a cyst on the surface of the kidney, and animal 5 treated with 300 mg/kg b.w. showed a hardened urinary bladder.

The acute median lethal oral dose (LD₅₀) to rats of Diammonium Hexachloroiridate was demonstrated to be between 300 and 2000 mg/kg body weight. Diammonium Hexachloroiridate is included in Category 4 according to the Globally Harmonised System (GHS).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

300 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

The acute median lethal oral dose (LD50) to rats of Diammonium Hexachloroiridate was demonstrated to be between 300 and 2000 mg/kg body weight.

Justification for selection of acute toxicity – oral endpoint
Only relevant guideline study available.

Justification for classification or non-classification

The acute median lethal oral dose (LD50) to rats of Diammonium Hexachloroiridate was demonstrated to be between 300 and 2000 mg/kg body weight and places the substance into Acute toxicity hazard Category 4 [300 < ATE <=2000 mg/kg bw] under Regulation 1272/2008.