tetraammine platinum (II) hydrogen carbonate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

7 to 25 July 1989

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study

Remarks:

Guideline study (OECD, EU) to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Dates of QA inspection of systemic toxicity studies are 6, 14, 15 and 27 June 1989. General facilities audit performed on 29 June 1989. Therefore no specific QA inspections of this particular project were carried out.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

123439-82-7

Cas Number:

123439-82-7

IUPAC Name:

123439-82-7

Constituent 2

Reference substance name:

Tetraammine platinum hydrogencarbonate

IUPAC Name:

Tetraammine platinum hydrogencarbonate

Details on test material:

- Name of test material (as cited in study report): tetraammine platinum (II) hydrogen carbonate
- Substance type: Technical product
- Physical state: Solid (powder)
- Lot/batch No.: 038205
- Storage condition of test material: 4 deg C in refrigerator

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bantin and Kingman Ltd, Grimston, Aldborough, Hull, UK
- Age at study initiation: 5-8 weeks old
- Weight at study initiation: males 120-144 g; females 120-130 g
- Fasting period before study: overnight (plus 2 hr after dosing)
- Housing: 5/sex/solid-floor cage with sawdust bedding
- Diet: ad libitum conventional laboratory diet
- Water: ad libitum drinking water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-25
- Humidity (%): 68-78
- Air changes (per hr): approx 15
- Photoperiod: 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 20 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg

Doses:

200 mg/kg

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: observed 1 and 4 hr after dosing, then daily for 14 days. Body weights recorded prior to dosing and on days 7 and 14
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 200 - < 2 000 mg/kg bw

Mortality:

None

Clinical signs:

other: No adverse observations

Gross pathology:

No abnormalities

Other findings:

None

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 value of tetraammineplatinum(II) hydrogen carbonate in rats was determined to be >200 mg/kg bw (in the main study; 5/sex) but <2000 mg/kg bw (in the range-finder; 1 sex/dose). No evidence of systemic toxicity was observed at the limit dose of 200 mg/kg bw in the main study.

Executive summary:

The acute oral toxicity of tetraammineplatinum(II) hydrogen carbonate was investigated in an OECD Test Guideline 401 study, conducted to GLP. In a range-finding study, Sprague-Dawley rats (1/sex) were gavaged with the test material at 25, 200, 2000 or 5000 mg/kg bw. All four animals died at the top two doses. In the main study, rats (5/sex) were gavaged with the test material at a limit dose of 200 mg/kg bw and observed for 14 days.

 

There were no deaths in the main study and all animals showed expected gain in body weight over the study period. No abnormalities were noted at necropsy. The investigators stated that the acute oral LD50 value was therefore >200 mg/kg bw but <2000 mg/kg bw.

 

Based on the results of the range-finding study, tetraammineplatinum(II) hydrogen carbonate should be considered for classification for acute toxicity (category 4) according to EU CLP criteria (EC 1272/2008).