Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 May 2006 to 24 May 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline study, to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2006
Report Date:
2006

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
yes
Remarks:
both sexes studied, only one dose tested, no data presented on histopathological results
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry, and Fisheries (JMAFF) Guidelines (2000), including the most recent revisions
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): platinum(2+)tetraammine(SP-4-1) diacetate
- Substance type: no data
- Physical state: white crystalline powder with lumps
- Analytical purity: 46.95% (Pt)
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: AP013/06
- Expiration date of the lot/batch: 20 March 2007
- Stability under test conditions: not indicated
- Storage condition of test material: at room temperature in the dark

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: body weight variation did not exceed +/- 20% of the sex mean
- Fasting period before study: no data
- Housing: individually
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.1 to 23.3
- Humidity (%): 36 to 68
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: no data

Administration / exposure

Type of coverage:
occlusive
Vehicle:
water
Remarks:
Milli-U
Details on dermal exposure:
TEST SITE
- Area of exposure: approximately 25 cm2 for males, and 18 cm2 for females
- % coverage: 10% total body surface
- Type of wrap if used: a dressing consisting of a surgical gauze patch (Surgy 1D) covered with aluminium foil and a Coban elastic bandage. Micropore tape was additionally used to fix the bandages in females.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): washed with water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight
- Constant volume or concentration used: no

VEHICLE
- Amount(s) applied (volume or weight with unit): no data
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
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: daily observations, weekly measurements of body weight
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight
Statistics:
No data

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortaility seen at limit dose
Mortality:
No mortality occurred
Clinical signs:
Hunched posture, chromoacryorrhoea, lethargy, shallow respiration and/or piloerection were noted in the majority of animals on days one and/or two. Treated skin showed general, focal or maculate erythema, scales, scabs, scars and/or necrosis during the observation period.
Body weight:
No body weight changes indicative of toxicity were observed.
Gross pathology:
Post mortem macroscopic examinations showed no abnormalities.
Other findings:
- Organ weights: no data
- Histopathology: no data
- Potential target organs: no data
- Other observations: no data

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In a guideline study, to GLP, the acute dermal LD50 value of tetraammineplatinum(II) diacetate, following 24-hour occlusive application in rats, was reported to exceed 2000 mg/kg bw.
Executive summary:

The acute dermal toxicity of tetraammineplatinum(II) diacetate was investigated in a protocol conducted according to OECD Test Guideline 402 and to GLP. The test substance was applied under occlusion to the skin of Wistar rats (5/sex) at a limit dose of 2000 mg/kg bw for 24 hours. After this period, dressings were removed and the skin was washed with water. Animals were then monitored over the next two weeks for mortality and any clinical signs of toxicity. After this period, any survivors were sacrificed, and subjected to gross necropsy.

No mortality occurred during the experiment, and no macroscopic abnormalities were found at post mortem. No body weight changes indicative of toxicity were observed. Clinical signs included hunched posture, bloody tears, lethargy, shallow respiration and piloerection. In the treated skin area, general, focal or maculate erythema, scales, scabs, scars and/or necrosis were apparent. Hence the acute dermal LD50 value of tetraammineplatinum(II) diacetate was determined to exceed 2000 mg/kg bw in rats.

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