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Administrative data

Description of key information

In a guideline GLP study, the acute oral LD50 value of hexahydroxoplatinum(IV) acid was determined to exceed 2150 mg/kg bw (limit test) in rats (Berthold, 1995a).

 

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:
29 March-12 April 1995
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD Guideline, to GLP, with a minor deviation (humidity) that would not be expected to affect results
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
Relative humidity was below the protocol-stated range twice (for around 1 hour)
Qualifier:
according to
Guideline:
other: EEC Guideline 92/32/EEC
Deviations:
yes
Remarks:
Relative humidity was below the protocol-stated range twice (for around 1 hour)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
other: HsdCpb: WU
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan-Winkelmann GmbH, D-33176 Borchen
- Age at study initiation: 9 weeks (males); 10 weeks (females)
- Weight at study initiation: 218-225 g (males); 159-170 g (females)
- Fasting period before study: Approximately 16 hours
- Housing: Macrolon cages, type II
- Diet (e.g. ad libitum): ssniff R special diet for rats (ad libitum)
- Water (e.g. ad libitum): From Stadtwerke Halle (utility service provider), using an automatic drinking water system with drinking nipples or drinking bottles (ad libitum)
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-22
- Humidity (%): 34-61
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
CMC (carboxymethyl cellulose)
Remarks:
Aqueous CMC 0.5% (Registered trademark name Tylose; Tylopur C 1000 P)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 215 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg
- Justification for choice of vehicle: None given
- Lot/batch no. (if required): E 11430100
- Purity: No data

DOSAGE PREPARATION: Suspension, prepared using a homogenizer
Doses:
2150 mg/kg bw (males and females)
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: Observed continuously for 4-6 hours after administration; then once/day
- Necropsy of survivors performed: yes
- Other examinations performed: mortality and clinical signs (at least once/day), body weight (days 0, 7, 14)
Sex:
male/female
Dose descriptor:
LD0
Effect level:
> 2 150 mg/kg bw
Based on:
test mat.
Remarks on result:
other: CL not applicable
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 150 mg/kg bw
Based on:
test mat.
Remarks on result:
other: CL not applicable
Mortality:
None
Clinical signs:
Stilted gait (seen between 55 minutes and 1 day after administration) in 1 male and 3 females.
Sunken sides (seen between 55 minutes and 1 day after administration) in 1 male and 4 females.
Body weight:
No significant effects
Gross pathology:
No significant findings
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a guideline GLP study, the acute oral LD50 value of hexahydroxoplatinum(IV) acid was determined to exceed 2150 mg/kg bw (limit test) in rats.
Executive summary:

In a well-conducted acute oral toxicity test, conducted in accordance with OECD Test Guideline 401 and to GLP, HsdCpb: WU rats (5/sex) were gavaged with hexahydroxoplatinum(IV) acid (as a suspension in aqueous carboxymethyl cellulose) at a limit dose of 2150 mg/kg bw and observed for 14 days.

 

Transient clinical signs of stilted gait and sunken sides were apparent in some animals. No deaths were observed within the observation period. The oral LD50 (and indeed the LD0) was therefore determined to exceed 2150 mg/kg bw in male and female rats.

 

Based on the results of this study, no classification for acute oral toxicity is required 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.

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.

 

In a well-conducted acute oral toxicity test, conducted in accordance with OECD Test Guideline 401 and to GLP, HsdCpb: WU rats (5/sex) were gavaged with hexahydroxoplatinum(IV) acid (as a suspension in aqueous carboxymethyl cellulose) at a limit dose of 2150 mg/kg bw and observed for 14 days. Transient clinical signs of stilted gait and sunken sides were apparent in some animals. No deaths were observed within the observation period. The oral LD50 (and indeed the LD0) was therefore determined to exceed 2150 mg/kg bw in male and female rats (Berthold, 1995a)

 

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

 

Similarly, no acute dermal toxicity data were identified. However, skin contact during production and/or use is expected to be negligible.

Justification for classification or non-classification

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

 

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