Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
22 March - 28 April 2004
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:
2004
Report Date:
2004

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Platinum (2+) tetraammine diacetate
- Substance type: No data
- Physical state: white powder
- Analytical purity: No data
- Impurities (identity and concentrations): No data
- Composition of test material, percentage of components: Platinum (2+) tetraammine diacetate (48.8% Platinum)
- Isomers composition: Not applicable
- Purity test date: 20 February 2004
- Lot/batch No.: GB340
- Expiration date of the lot/batch: 11 February 2005
- Stability under test conditions: no data
- Storage condition of test material: ambient temperature in a desiccator

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy S.r.l., 33049 San Pietro al Natisone (UD), Italy
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 176-200 g
- Fasting period before study: overnight
- Housing: polycarbonate cage with a stainless steel mesh lid and floor (3 females/cage)
- Diet (e.g. ad libitum): ad libitum (commercial laboratory rodent diet)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 22 March 2004 To: 28 April 2004

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 or 30 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: No data

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: All animals died at the initial dose
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
3 females at 2000 mg/kg bw and 6 females at 300 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed 30 minutes, 2 and 4 hours after dosing and subsequently daily thereafter; animals were weighed on days 2, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology
Statistics:
Not conducted

Results and discussion

Preliminary study:
Not applicable
Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No CL calculated
Mortality:
2 animals died after dosing at 2000 mg/kg bw. The third animal was killed for humane reasons on day 2. No mortality occurred in the 6 animals dosed at 300 mg/kg bw.
Clinical signs:
Convulsions/tremors, a dirty appearance around the urogenital region, piloerection and pronation were observed in the surviving animal dosed at 2000 mg/kg bw. A dirty appearance around the urogenital region was also observed in three of the 6 animals dosed at 300 mg/kg bw. Complete recovery had occurred by day 4.
Body weight:
Slight body weight losses were observed on day 2 in some animals dosed at 300 mg/kg bw. Changes in body weight at the end of the study were within the normal range expected.
Gross pathology:
No abnormalities were observed in animals dosed at 300 mg/kg bw. The 2 animals found dead at 2000 mg/kg bw had abnormal stomach contents and one of them had abnormal contents and effects in the gastro-intestinal tract and colour abnormalities of the liver, brain and pituitary. In addition, external examination showed skin/fur staining around the muzzle and/or urogenital region.
Other findings:
No data

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In a guideline study, to GLP, an acute oral LD50 of 300-2000 mg/kg bw was determined following gavage administration of tetraammineplatinum(II) diacetate to female rats.
Executive summary:

The acute oral toxicity of tetraammineplatinum(II) diacetate to female rats was assessed in a study conducted according to OECD Test Guideline 423, and to GLP. A group of three animals received a single gavage dose of the test material at 2000 mg/kg bw. A further group of six animals received a dose of 300 mg/kg bw.

 

At the higher dose two animals died and the third was killed for humane reasons on day 2. Gross pathology of the deceased animals showed effects in the gastrointestinal tract as well as colour abnormalities of the liver, brain and pituitary. No mortality or significant signs of toxicity were observed in any of the animals dosed at 300 mg/kg bw. An acute oral LD50 value of >300 and < 2000 mg/kg bw was determined in female rats.

 

Based on the results of this acute oral rat study, tetraammineplatinum(II) diacetate should be classified for acute oral toxicity (category 4) according to EU CLP criteria (EC 1272/2008).