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Administrative data

Description of key information

In an OECD guideline study, to GLP, an acute oral LD50 of 300-2000 mg/kg bw was determined following gavage administration of tetraammineplatinum(II) diacetate to female rats (Longobardi, 2004).

 

In an OECD guideline study, to GLP, the acute dermal LD50 of tetraammineplatinum(II) diacetate, following 24-hour occlusive application in rats, was reported to exceed 2000 mg/kg bw (Beerens-Heijnen, 2006).

 

No relevant acute inhalation toxicity data were identified (or are required).

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:
22 March - 28 April 2004
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, to GLP
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Italy S.r.l., 33049 San Pietro al Natisone (UD), Italy
- Age at study initiation: 6-8 weeks
- Weight at study initiation: 176-200 g
- Fasting period before study: overnight
- Housing: polycarbonate cage with a stainless steel mesh lid and floor (3 females/cage)
- Diet (e.g. ad libitum): ad libitum (commercial laboratory rodent diet)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 22 March 2004 To: 28 April 2004
Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 200 or 30 mg/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: No data
- Lot/batch no. (if required): No data
- Purity: No data

MAXIMUM DOSE VOLUME APPLIED: No data

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: All animals died at the initial dose
Doses:
300 and 2000 mg/kg
No. of animals per sex per dose:
3 females at 2000 mg/kg bw and 6 females at 300 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were observed 30 minutes, 2 and 4 hours after dosing and subsequently daily thereafter; animals were weighed on days 2, 8 and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology
Statistics:
Not conducted
Preliminary study:
Not applicable
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No CL calculated
Mortality:
2 animals died after dosing at 2000 mg/kg bw. The third animal was killed for humane reasons on day 2. No mortality occurred in the 6 animals dosed at 300 mg/kg bw.
Clinical signs:
Convulsions/tremors, a dirty appearance around the urogenital region, piloerection and pronation were observed in the surviving animal dosed at 2000 mg/kg bw. A dirty appearance around the urogenital region was also observed in three of the 6 animals dosed at 300 mg/kg bw. Complete recovery had occurred by day 4.
Body weight:
Slight body weight losses were observed on day 2 in some animals dosed at 300 mg/kg bw. Changes in body weight at the end of the study were within the normal range expected.
Gross pathology:
No abnormalities were observed in animals dosed at 300 mg/kg bw. The 2 animals found dead at 2000 mg/kg bw had abnormal stomach contents and one of them had abnormal contents and effects in the gastro-intestinal tract and colour abnormalities of the liver, brain and pituitary. In addition, external examination showed skin/fur staining around the muzzle and/or urogenital region.
Other findings:
No data
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In a guideline study, to GLP, an acute oral LD50 of 300-2000 mg/kg bw was determined following gavage administration of tetraammineplatinum(II) diacetate to female rats.
Executive summary:

The acute oral toxicity of tetraammineplatinum(II) diacetate to female rats was assessed in a study conducted according to OECD Test Guideline 423, and to GLP. A group of three animals received a single gavage dose of the test material at 2000 mg/kg bw. A further group of six animals received a dose of 300 mg/kg bw.

 

At the higher dose two animals died and the third was killed for humane reasons on day 2. Gross pathology of the deceased animals showed effects in the gastrointestinal tract as well as colour abnormalities of the liver, brain and pituitary. No mortality or significant signs of toxicity were observed in any of the animals dosed at 300 mg/kg bw. An acute oral LD50 value of >300 and < 2000 mg/kg bw was determined in female rats.

 

Based on the results of this acute oral rat study, tetraammineplatinum(II) diacetate should be classified for acute oral toxicity (category 4) according to EU CLP criteria (EC 1272/2008).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
discriminating dose
300 mg/kg bw
Quality of whole database:
Overall, good-quality database which meets REACH Standard Information Requirements.

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:
10 May 2006 to 24 May 2006
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Guideline study, to GLP
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
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
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
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
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).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Overall, good-quality database which meets REACH Standard Information Requirements.

Additional information

No relevant acute toxicity human data were identified.

 

The acute oral toxicity of tetraammineplatinum(II) diacetate to female rats was assessed in a study conducted according to OECD Test Guideline 423, and to GLP. A group of three animals received a single gavage dose of the test material at 2000 mg/kg bw. A further group of six animals received a dose of 300 mg/kg bw. At the higher dose two animals died and the third was killed for humane reasons on day 2. Gross pathology of the deceased animals showed effects in the gastrointestinal tract as well as colour abnormalities of the liver, brain and pituitary. No mortality or significant signs of toxicity were observed in any of the animals dosed at 300 mg/kg bw. An acute oral LD50 value of >300 and < 2000 mg/kg bw was determined in female rats (Longobardi, 2004).

 

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 (Beerens-Heijnen, 2006).

 

No acute inhalation toxicity data were identified. However, the compound is not expected to reach the lungs in appreciable quantities (based on vapour pressure data). Thus, inhalation will not be a significant route of exposure.

Justification for classification or non-classification

Based on the results of the available and reliable acute oral rat study, tetraammineplatinum(II) diacetate should be classified for acute oral toxicity (category 4) according to EU CLP criteria (EC 1272/2008).

 

No classification for acute dermal toxicity is required, based on the results of the available and reliable acute dermal rat study with tetraammineplatinum(II) diacetate.

 

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