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Administrative data

Description of key information

The acute oral LD50 value of tetraammineplatinum dichloride was reported to exceed 15.1 g/kg bw in rats (Jones, 1977a).
In rats, the acute dermal LD50 value (24-hour semi-occlusive application) for tetraammineplatinum hydrogen carbonate was >2000 mg/kg bw (Allen, 1977).
No relevant acute 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:
supporting study
Study period:
Not stated
Reliability:
4 (not assignable)
Rationale for reliability incl. deficiencies:
other: Only a 1-page study report, no data on guideline/GLP
Qualifier:
no guideline followed
Principles of method if other than guideline:
5 rats/sex were given a single oral dose of tetrammine platinous chloride at 15.1 g/kg bw, and observed for mortality.
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
- Name of test material (as cited in study report): tetrammine platinous chloride.
- Substance type: white powder
- Physical state: solid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data
- Other: Sponsor’s code no. CB 13
Species:
rat
Strain:
not specified
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: “young adult”
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: To:

Route of administration:
oral: unspecified
Vehicle:
not specified
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: no data

DOSAGE PREPARATION (if unusual): no data

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose:

Doses:
15.1 g/kg bw
No. of animals per sex per dose:
5/sex
Control animals:
no
Details on study design:
- Duration of observation period following administration: no data
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no data
- Other examinations performed: no data

Preliminary study:
1/sex dosed at 0.001, 0.05, 0.5 or 15 g/kg bw. No deaths, no other findings reported.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 15 100 mg/kg bw
Mortality:
None
Clinical signs:
No data
Body weight:
No data
Gross pathology:
No data
Other findings:
No data

Interpretation of results:
GHS criteria not met
Conclusions:
According to a brief report, the acute oral LD50 value for tetrammine platinous chloride in rats is >15.1 g/kg bw.


Executive summary:

In a brief report of an acute oral toxicity test, in which 5 rats/sex were given a single oral dose of tetrammine platinous chloride at 15.1 g/kg bw, there were no deaths. The acute oral LD50 is therefore >15.1 g/kg bw. No other findings were reported (but the extent of examination and observation is unclear).

The study report notes that, according to the tabulation of toxicity classes incorporated in the American NFPA No. 704M labelling system, the acute oral LD50 of CB 13 is likely to fall within Class 0 – “relatively harmless”.

Based on the results of this study, tetraammineplatinum dichloride 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
15 100 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9 to 23 January 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Conducted according to GLP
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: Sprague-Dawley CD (Crl : CD ® BR)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Limited
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: males 209-236 g; females 206-227 g.
- Fasting period before study: none
- Housing: Housed individually during the 24-hr exposure period, then in groups of five by sex in suspended polypropylene cages on woodflakes
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 41-55
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hrs dark/ 12 hrs light
Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: back and flanks
- % coverage: 10% of total body surface area
- Type of wrap if used: surgical gauze and self-adhesive bandage, secured with “Blenderm” latex- free, hypoallergenic, surgical tape.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with cotton wool moistened in distilled water
- Time after start of exposure: 24 hr

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: yes, powder moistened with distilled water

VEHICLE
- Amount(s) applied (volume or weight with unit): not stated
Duration of exposure:
24 hr
Doses:
2000 mg/kg bw

No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observed at 0.5, 1, 2 and 4 hrs after dosing, then daily for 14 days; weighed before treatment then weekly for 2 weeks.
- Necropsy of survivors performed: yes
- Other examinations performed: behavioural and clinical signs, body weight changes.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
None
Body weight:
Nine of the 10 rats showed normal gain in body weight. One female lost weight during the first week and then showed expected weight gain in second week.
Gross pathology:
No abnormalities
Other findings:
- Other observations: No dermal reactions, including erythema and oedema, were seen during the 14-day period.
Interpretation of results:
GHS criteria not met
Conclusions:
In rats, the acute dermal LD50 value (24-hour semi-occlusive application) for tetrammine platinum (II) hydrogen carbonate was >2000 mg/kg bw.
Executive summary:

An acute dermal toxicity test was conducted in the Sprague-Dawley CD strain rat, in accordance with OECD Test Guideline 402 and to GLP. Ten rats (five males and five females) were given a single 24-hour, semi-occluded dermal application of tetraammineplatinum hydrogen carbonate to intact skin at a dose level of 2000 mg/kg bw. The animals were observed for 14 days after the day of treatment and were then killed for gross pathological examination.

 

There were no deaths, and no signs of systemic toxicity or skin irritation during the study. All rats showed the expected increase in body weight during the study except for one female which showed body weight loss during the first week only. No abnormalities were noted at necropsy.

 

The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was >2000 mg/kg bw.

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

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw

Additional information

No relevant human acute toxicity data were identified.

 

In a brief report of an acute oral toxicity test, no deaths were reported following administration of a single oral dose of tetraammineplatinum dichloride at 15.1 g/kg bw, to a group of 5 rats/sex. The acute oral LD50 is therefore>15.1 g/kg bw. No other findings were reported (Jones, 1977a).

 

In an OECD Test Guideline 402 study, rats (5/sex) were given a single 24-hour, semi-occluded dermal application of tetraammineplatinum hydrogen carbonate to intact skin at a dose level of 2000 mg/kg bw. The animals were observed for 14 days after the day of treatment and were then killed for gross pathological examination. There were no deaths, and no signs of systemic toxicity or skin irritation during the study. All rats showed the expected increase in body weight during the study except for one female which showed body weight loss during the first week only. No abnormalities were noted at necropsy. The acute dermal median lethal dose (LD50) of the test material in the Sprague-Dawley CD strain rat was >2000 mg/kg bw (Allen, 1997).

Tetraammineplatinum hydrogen carbonate is considered to fall within the scope of the read-across category "tetraammineplatinum(II) salts". See section 13 in IUCLID for full read-across justification report.

 

No acute inhalation toxicity data were identified, or are required at this tonnage (1-10 tpa).


Justification for selection of acute toxicity – oral endpoint
Brief study report, but the only acute oral study available; sufficient to support the lack of classification for the compound.

Justification for selection of acute toxicity – dermal endpoint
OECD guideline study, and the only acute dermal study available.

Justification for classification or non-classification

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

 

Based on the results of the available and reliable acute dermal rat study with tetraammineplatinum hydrogen carbonate, tetraammineplatinum dichloride does not require classification for acute dermal 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.