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Toxicological information

Acute Toxicity: oral

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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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
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

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:
No adverse observations
Body weight:
All animals showed expected gain in body weight over the study period.
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).