Hexachloroiridic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 July 1988 – 2 August 1988

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study, to GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexachloroiridic acid

EC Number:

241-012-8

EC Name:

Hexachloroiridic acid

Cas Number:

16941-92-7

Molecular formula:

Cl6Ir.2H

IUPAC Name:

hexachloroiridium(2-);hydron

Test material form:

solid: crystalline

Details on test material:

- Name of test material (as cited in study report): chloroiridic acid
- Molecular formula (if other than submission substance): H2IrCl6.6H2O
- Substance type: brown crystals
- Physical state: solid
- Analytical purity: 38.5% Ir
- Lot/batch No.: 6767
- Storage condition of test material: room temperature
- Other: soluble in water, strongly acidic

Test animals

Species:

rat

Strain:

other: Wistar Bor: WISW (SPFTNO)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co. KG, D-4799 Borchen
- Age at study initiation: males 7 weeks, females 9 weeks
- Weight at study initiation: males 132-160 g, females 130-154 g
- Fasting period before study: 16 hrs before treatment
- Housing: 1 rat / macrolon type II cage
- Diet: ad libitum standard diet, ssniff R “special diet for rats” supplied by ssniff Spezialfutter GmbH, D-4770 Soest
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-22
- Humidity (%): 50-65 (for 10 hrs up to 70%)
- Photoperiod: artificial lighting from 6 am – 6 pm, “natural light-dark-rhythm” from 6 pm – 6 am

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 21.5 – 46.4 mg/ml
- Amount of vehicle (if gavage): 21.5 ml/kg

MAXIMUM DOSE VOLUME APPLIED: 21.5 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: none given

Doses:

Male and female rats were administered 464, 681 or 1000 mg/kg bw, based on the water containing trade product.

No. of animals per sex per dose:

Five rats/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: behaviour and general condition was observed continuously for the first 4-8 hrs after administration and then once daily, mortality was checked twice daily and once on Saturdays, Sundays and national holidays, body weights recorded 7 and 14 days after administration or after death on days 2-14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

The acute oral median lethal dose (LD50) values and the slopes of the dose mortality curves for male rats and for both sexes were determined, together with 95% confidence intervals by probit analysis. For the females, because of a very steep course of the dose-lethality curve, the LD50 value could only be estimated graphically.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

LD50

Effect level:

827 mg/kg bw

95% CL:

586 - 1 371

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

560 mg/kg bw

Remarks on result:

other: CL not determined

Effect levels 3

Sex:

male/female

Dose descriptor:

LD50

Effect level:

690 mg/kg bw

95% CL:

584 - 816

Mortality:

All deaths occurred between 3 and 24 hrs after administration. All of the females in the mid- and high-dosed groups died, together with 4 of the high-dosed and 1 of the mid-dosed males. No deaths of either sex were recorded at the low-dose.

Clinical signs:

other: Clinical signs of intoxication occurred from 12 minutes up to more than 6 hrs after application and lasted for 1 to 12 days or until death. They included slight to severe hypokinesia, stilted gait, slight to moderate tremor, moderate to severe clonic conv

Gross pathology:

At necropsy of deceased animals, the abdominal cavity was filled with an aqueous liquid. All animals showed thickening, grey or red staining and/or ulceration of the mucosa of the stomach and, in one male, it was covered with black material. The mucous membranes of the small intestine and cecum were thickened, discoloured grey or red and their surface was rough and the content of the intestine was partially brown discoloured or liquid. The seminal vesicles were diminished in one male and red spots were seen on the pancreas in two mid-dosed animals.

Other findings:

- Histopathology: Microscopic examination of the intestines and pancreas was conducted in rats of the low- and mid-dosed groups. Increased mixed inflammatory cell infiltration of the intestinal mucosa was noted in 2 animals, one of those also showing focal glandular and lymphoid hyperplasia of Peyer’s patch. Mixed inflammatory cell infiltration of the peritoneal fatty tissue was seen in three animals and in one, acute focal haemorrhages were reported in the duodenum, jejunum and pancreas.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LD50) of hexachloroiridic acid in the male and female rat is 690 mg/kg bw with 95% confidence limits of 584-816. When considering each sex individually, the LD50 for males is 827 mg/kg bw (95% CI 586-1371) and for females, estimated graphically, is 560 mg/kg bw.

Executive summary:

In an OECD Test Guideline 401 acute oral toxicity study, to GLP, groups of 5 male and 5 female rats were administered 464, 681 or 1000 mg hexachloroiridic acid/kg bw by stomach tube and observed for 14 days.

Clinical signs of toxicity appeared between 12 minutes and 6 hours after administration and lasted for 1-12 days or until death. Deaths were recorded between 3 and 24 hrs after dosing, with all females at the mid- and top-dose levels and 1 and 4 males at the mid- and top-dose levels respectively dying. Necropsy and microscopic examination revealed effects on the abdominal cavity, stomach, intestine, seminal vesicles and/or pancreas.