Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 April 1995 - 8 November 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study carried out according to GLP and OECD guideline 401 (current at 1995).

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1995
Report Date:
1995

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Potassiumhexachloroplatinate(IV)

- Substance type:
- Physical state: Powder
- Analytical purity: >99.9%
- Impurities (identity and concentrations):
- Composition of test material, percentage of components:
- Isomers composition:
- Purity test date:
- Lot/batch No.: 8833 / June 23, 1994
- Expiration date of the lot/batch:

- Stability under test conditions: According to sponsor, the test substance was stable throughout the experimental period
- Storage condition of test material: Closed container in refrigerator
- Other:

Test animals

Species:
rat
Strain:
other: Wistar-Unilever (HsdCpb:Wu)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, D-33176 Borchen
- Age at study initiation: Males 8-9 weeks; Females 9-10 weeks
- Weight at study initiation: Males 166-218 g; Females 140-170 g
- Fasting period before study: Approx. 16 hours before treatment
- Housing: Macrolon cages, type II
- Diet (e.g. ad libitum): Standard diet ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days before administration

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 43-64
- Air changes (per hr): not stated
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
1%
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 21.5 - 100 mg/ml (males and females)
- Amount of vehicle (if gavage): 4.64 ml/kg bw
- Justification for choice of vehicle: not stated
- Lot/batch no. (if required): E 114 30100
- Purity: not stated

MAXIMUM DOSE VOLUME APPLIED: 4.64 ml/kg bw

DOSAGE PREPARATION (if unusual): Test substance was suspended in the vehicle immediately before dosing using a homogenizer
Doses:
100, 215 or 464 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Continously for first 4 - 6 hours, and then once daily. Body weights recorded at the beginning and also 7 and 14 days after administration, or after death of the animals on days 2 - 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology (kidneys)
Statistics:
Probit analysis

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
195 mg/kg bw
95% CL:
>= 142 - <= 268
Sex:
male
Dose descriptor:
LD50
Effect level:
184 mg/kg bw
95% CL:
>= 85.1 - <= 357
Sex:
female
Dose descriptor:
LD50
Effect level:
212 mg/kg bw
95% CL:
>= 105 - <= 423
Mortality:
10/10 at 464 mg/kg bw dose
4/5 males at 215 mg/kg bw dose
3/5 females at 215 mg/kg bw dose

Time of death: 5/sex between 6-24 h post-dose of 464 mg/kg bw. 215 mg/kg bw dose: 1, 2 and 1 males died on days 2, 3 and 5, respectively; females, 1,1 and 1 died 6-24 h and days 2 and 3, respectively.
Clinical signs:
Onset of symptoms only reported as occurring 1.5 hr - 4 days after treatment.

Deceased animals:
464 mg/kg bw: hypokinesia, diarrhoea, sunken sides, stilted, restrained and staggered gait, tremor, clonic convulsions, tonic convulsions of the hind legs, sunken sides.

215 mg/kg bw: hypokinesia, diarrhoea, sunken sides, stilted, restrained and staggered gait, tremor, sunken sides, piloerection.

Surviving animals:
215 mg/kg bw: sunken sides. Animals recovered within 3-4 days.

100 mg/kg bw: Unspecific signs of distress sunken sides, stilted or restrained gait.
Gross pathology:
464 mg/kg bw: males - glandular stomach reddened and/or hardened walls (5), yellow deposit in glandular mucosa (5), small intestine filled with fluid (3) lung beige discolouration (1).
Females - glandular stomach reddened and/or hardened walls (5), yellow deposit in glandular mucosa (5), Stomach (3) or small intestine (4) filled with fluid, non-collapsed lung (1).
215 mg/kg bw: males - glandular stomach reddened and/or hardened walls (4), small intestine (1), bladder (1) and thoracic cavity (2) filled with fluid, pale kidneys (2), stomach yellow content (1). Females - glandular stomach reddened and/or hardened walls (3), small intestine (2) and thoracic cavity (1) filled with fluid.
Other findings:
Microscopic findings: 5/sex showed marked necrosis and degeneration of the proximal renal tubules at 464 mg/kg bw, and 3 males and 1 female at 215 mg/kg bw. Minimal to marked changes in proximal tubules in 1 male and 2 females at 215 mg/kg bw and 3/sex at 100 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of potassium hexachloroplatinate was determined to be 195 mg/kg bw in rats.
Executive summary:

The acute toxicity of potassium hexachloroplatinate was investigated in Sprague-Dawley rats, in an OECD Test Guideline 401 study, conducted according to GLP. Animals (5/sex/group) were administered the test substance (as a suspension in 1% carboxymethylcellulose) by oral gavage at doses of 100, 215 or 464 mg/kg bw, and observed for up to 14 days.

 

All animals died at the top dose, while 4 males and 3 females died at 215 mg/kg bw. Deaths occurred 1 to 5 days after administration. No mortality was observed in the low dose groups. Toxic effects included hypokinesia, stilted, staggered and restrained gait, tremor, diarrhoea, and sunken sides. Additionally, clonic and tonic convulsions and piloerection were detected. Individual animals showed loss of muscle tone and righting, pain and corneal reflexes, red crusted nose, or prolapse of penis. Microscopic examination of the kidneys revealed severe to very severe acute necrosis and degeneration of the proximal tubules at the highest two doses. The acute oral LD50 was determined (using probit analysis) to be 184 mg/kg bw in male rats (95% CI 85.1-357 mg/kg bw), 212 mg/kg bw in females (95% CI 105-423 mg/kg bw) and 195 mg/kg bw for both sexes combined (95% CI 142 -268 mg/kg bw).

 

Based on the results of this study, the test material should be classified for acute oral toxicity (category 3) according to EU CLP criteria (EC 1272/2008).