Diammineplatinum(II) nitrite

Endpoint summary

Description of key information

In a guideline study, to GLP, the acute oral LD50 of diammineplatinum dinitrite was determined to be around 5000 mg/kg bw in rats (Berthold, 1989).

No relevant acute dermal or inhalation toxicity data were identified.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

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.

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

Test type:

standard acute method

Limit test:

yes

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

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.

Sex:

male

Dose descriptor:

approximate LD50

Effect level:

5 000 mg/kg bw

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.

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).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

5 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No relevant human acute toxicity data were identified.

Diammineplatinum dinitrite was tested for its acute oral toxicity in rats, according to OECD Test Guideline 401. The test item was administered by gavage 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 (Berthold, 1989).

 

No acute dermal or inhalation toxicity data were identified, or are required at this tonnage.

Justification for classification or non-classification

Based on the results of the available and reliable acute oral rat study, diammineplatinum dinitrite does not require classification for acute oral toxicity according to EU CLP criteria (EC 1272/2008).

 

No clear evidence of specific target organ toxicity was noted. As such, classification for STOT-SE is not considered appropriate.