Diammineplatinum(II) nitrite

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

6 March 1989 to 11 April 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD and EU), and conducted according 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

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Diammineplatinum(II) nitrite

EC Number:

238-203-3

EC Name:

Diammineplatinum(II) nitrite

Cas Number:

14286-02-3

Molecular formula:

H6N4O4Pt

IUPAC Name:

diiminodinitroplatinumbis(ylium)

Details on test material:

- Name of test material (as cited in study report): Dinitrodiammine-platinum(II)
- Substance type: yellow powder
- Physical state: solid
- Analytical purity: no data
- Lot/batch No.: 6734
- Stability under test conditions: stable throughout experimental period
- Storage condition of test material: kept refrigerated with a drying agent

Test animals

Species:

rat

Strain:

other: Bor: WISW (SPFCpb)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Breeder; Winklemann Versuchstierzucht GmbH & Co. KG., D-4799 Borchen
- Age at study initiation: Males 7-9 weeks, females 10 weeks
- Weight at study initiation: Males 130-204 g, females 144-162 g
- Fasting period before study: 16 hours
- Housing: Macrolon cages, type II (one animal/cage)
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5-23
- Humidity (%): 40-70
- Photoperiod (hrs dark / hrs light): 12 hrs natural light-dark-rhythm (6 pm to 6 am) / 12 hrs artificial lighting

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% aqueous tylose suspension; Tylose(R)

Details on oral exposure:

Males were administered about 2.15 or 5.11 g/kg bw, at a concentration of 147 and 348 mg/ml, respectively. For the females, only one dose level of 5.11 g/kg bw was administered, at a concentration of 348 mg/ml.

Doses:

2.15 or 5.11 g/kg bw

No. of animals per sex per dose:

Five/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: For behaviour and general toxicity, the animals were observed continuously for the first 4 to 6 hrs after administration, and then once daily. Mortality was checked twice daily, and the body weights recorded at the beginning, and then at 7 and 14 days after administration.
- Necropsy of survivors performed: yes

Statistics:

The LD50 was determined by rational estimation for male rats. For female rats a limit test was conducted.

Results and discussion

Effect levels

Effect levels 1

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

5 000 mg/kg bw

Effect levels 2

Sex:

female

Dose descriptor:

approximate LD50

Effect level:

> 5 110 mg/kg bw

Mortality:

Deaths occurred in two males at 5.11 g/kg bw on day seven after administration

Clinical signs:

other: Piloerection was seen between days 2 and 11 after treatment (or until death), in all 5 male and 5 female rats in the high dose groups only.

Gross pathology:

No abnormalities reported following a macroscopic examination, although a dark red discolouration of the intestine was seen in the two males that died at the top dose.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In a GLP guideline study, the acute oral LD50 of dinitrodiammine-platinum(II) was determined to be about 5 g/kg bw in rats.

Executive summary:

In an OECD Test Guideline 401 study, dinitrodiammine-platinum(II) was administered by stomach tube to groups of male rats at 2.15 and 5.11 g/kg bw and to 5 female rats at the higher dose only.

Two males died at the top dose seven days after administration. No other deaths were reported in the 14 day observation period. LD50 values were determined to be about 5 g/kg bw in males and above 5.11 g/kg bw in females. All dose groups exhibited reductions in body weight or growth after the first week of observation. Piloerection was seen in all rats in the high dose groups, but not in males given the lower dose. No abnormalities were seen following macroscopic examination, although a dark red discolouration of the intestine was seen in the two deceased males receiving the top dose.

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