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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
23 June 1997 to 15 July 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Conducted according to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

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)
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: tetramine platinum hydrogencarbonate
- Substance type: Technical product
- Physical state: Solid (powder)
- Analytical purity: > 99.9%
- Purity test date: 1997-02-19
- Lot/batch No.: 02/95
- Expiration date of the lot/batch: 1999-12-31
- Stability under test conditions: Stable throughout study according to sponsor
- Storage condition of test material: Stored dry at < 30oC in closed container

Test animals

Species:
rat
Strain:
other: HsdCpb: WU
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, D-33176 Borchen
- Age at study initiation: males 7 weeks; females 9 weeks
- Weight at study initiation: males 156-166 g; females 151-173 g
- Fasting period before study: 16 hours
- Housing: 1 animal/Macrolon cage, type II; soft wood granulate bedding
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5-21.6
- Humidity (%): 41-73
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hrs dark / 12 hrs light

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
Trade name TylopurR C 1000 P; 0.5% aqueous CMC: trade name Tylose
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 215 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: test substance given as a suspension
- Lot/batch no. (if required): E 114 30100

DOSAGE PREPARATION: test substance suspended immediately before dosing using a homogenizer and magnetic stirrer
Doses:
2150 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: Continuous observations for 4-6 hr after dosing, then once per day. Weighed at start of study and day 7 and 14 (or after death if this occurred earlier).
- Necropsy of survivors performed: yes
Statistics:
Not applicable, LD50 higher than the dose administered

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 150 mg/kg bw
Mortality:
One male and one female died on days 5 and 6, respectively.
Clinical signs:
other: Surviving animals: Males (n=4): 2 had no symptoms, 2 showed slightly reduced movement, staggered gait and sunken sides (lasting 1-4 days). Females (n=4): 4 had diarrhoea, 2 had staggered gait, 2 had sunken sides, 1 had reduced movement. Deceased animals
Gross pathology:
No gross abnormalities detected.
Other findings:
No other findings reported

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral LD50 value of tetraammineplatinum hydrogen carbonate was determined to exceed 2150 mg/kg bw in male and female rats.
Executive summary:

In an acute oral toxicity test, conducted in accordance with OECD Test Guideline 401 (withdrawn in 2002) and to GLP, HsdCpb: WU rats (5/sex) were gavaged with tetraammineplatinum hydrogen carbonate (as a suspension in aqueous carboxymethyl cellulose) at a limit dose of 2150 mg/kg bw and observed for 14 days.

 

Three males showed reduced movement, staggered gait and sunken sides starting 75 minutes after dosing and lasting until day 1 or 4 after dosing. One of these males additionally showed clonic convulsions, diarrhoea, piloerection, stilted gait, red crusted nose and emaciation, and subsequently died (on day 5 after dosing). The other two males showed no signs of toxicity during the observation period.

 

All females exhibited diarrhoea, and some showed staggered and/or stilted gait, reduced movement and sunken sides. These effects were evident from 90 minutes after dosing, and lasted for 6 days or, in one animal, until death (on day 6).

 

The acute oral LD50 value was therefore determined to exceed 2150 mg/kg bw in male and female rats.

 

Based on the results of this study, tetraammineplatinum hydrogen carbonate does not require classification for acute oral toxicity according to EU CLP criteria (EC 1272/2008).