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Administrative data

Description of key information

In an OECD Test Guideline 421 reproductive/developmental toxicity screening study, to GLP, in rats with tetraammineplatinum dinitrate, the general systemic toxicity NOAEL for females was 250 mg/kg bw/day on the basis of reduced growth at the highest tested dose (1000 mg/kg bw/day). No adverse effects were observed in males at any dose (Hansen, 2015).

 

No repeated dose toxicity studies by the inhalation or dermal route were identified, or are required.

 

 

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
250 mg/kg bw/day
Study duration:
subacute
Species:
rat
Quality of whole database:
Overall, good-quality database which meets REACH Standard Information Requirements.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Mode of Action Analysis / Human Relevance Framework

No data identified.

Additional information

No relevant human data were identified.

 

No specific repeated dose toxicity studies were identified for tetraammineplatinum dinitrate, or are required at this tonnage (1-10 tpa).

 

In an OECD Test Guideline 421 reproductive/developmental toxicity study, conducted according to GLP, rats (12/sex/group) received a solution of tetraammineplatinum dinitrate by gavage at doses of 0, 50, 250 or 1000 mg/kg bw/day for at least 28 days (males were dosed for 28 days in total, while females received treatment for a longer period of time [incorporating the gestation period and proceeding up until post-partum day 3, test day 40-47]). This reproductive and developmental screening assay has some limitations compared to a standard repeated dose assay for assessing general systemic toxicity (e.g. no haematology, clinical chemistry or urinalysis; histopathology was limited to the high dose group). The only clinical sign of toxicity was a significantly reduced body weight in high-dose females at the end of the study on post-partum day 4. No adverse effects were observed in males at any dose. There was no impact on food consumption in males or females. Thus, the NOAEL for general toxicity was deemed to be 250 mg/kg bw/day (Hansen, 2015).

Justification for classification or non-classification

No adverse systemic effects were seen in the reliable guideline reproductive/developmental screening assay on tetraammineplatinum dinitrate. The reduced growth seen at the highest tested dose (1000 mg/kg bw/day) in females alone is not considered sufficient for classification as STOT-RE. As such, the results of this study indicate that classification as STOT-RE is not required, according to EU CLP criteria (EC 1272/2008).