Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study not carried out in accordance with current guidelines or GLP, but appears scientifically acceptable and well reported.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1978
Report Date:
1978

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
A single acute oral administration of ammonium hexachloroplatinate was given to rats (first main study) at 500 mg/kg bw (the highest dose causing no deaths in a range-finding study). As a high mortality rate was recorded at this level, a second main study was carried out at 200 mg/kg bw.
GLP compliance:
not specified
Test type:
fixed dose procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): ammonium hexachloroplatinate
- Substance type: yellow powder
- Physical state: solid
- Lot/batch No.: 57662

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Olac, Shaw Farm, Blackthorn, Bicester, Oxon
- Age at study initiation: “Young adult”
- Weight at study initiation: 175-320 g
- Fasting period before study: Overnight fast
- Housing: 5 rats (of one sex) in polypropylene cages
- Diet (e.g. ad libitum): ad libitum rodent diet 41B supplied by Pilsbury Ltd, Birmingham
- Water (e.g. ad libitum): ad libitum

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
vegetable oil
Details on oral exposure:
Dose administration was by a single peroral injection using a metal cannula. Test material administered in 10 mL vegetable oil.
Doses:
In the range-finding study, male and female rats were administered 25, 50, 200, 500 or 2000 mg/kg bw. In the first main study rats were administered 500 mg/kg bw, and in the second main study 200 mg/kg bw
No. of animals per sex per dose:
One rat/sex (range-finding study) and ten rats/sex (for the main studies)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Immediately after dosing, 4 hours after dosing, and daily for 14 days.
- Necropsy of survivors performed: yes
Statistics:
Acute oral median lethal dose (LD50)

Results and discussion

Preliminary study:
In the range-finding study, both rats died at 2000 mg/kg bw, but no deaths were seen at 500 mg/kg bw and below.
Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
approximate LD50
Effect level:
200 mg/kg bw
Sex:
male
Dose descriptor:
approximate LD50
Effect level:
> 200 - < 500 mg/kg bw
Sex:
female
Dose descriptor:
approximate LD50
Effect level:
< 200 mg/kg bw
Mortality:
In the range-finding study both rats died at 2 g/kg bw within 24 hrs of dosing; no deaths were seen at any other dose level. In the first main study, 4 male and 4 female rats died at 500 mg/kg bw within 3 days of administration. Therefore a second main study was performed at 200 mg/kg bw. At this level, 4 females died within 24 hrs; the remaining 6 animals (including 5 males) survived the 14-day observation period.
Clinical signs:
Not reported.
Body weight:
Not reported.
Gross pathology:
In the six surviving rats receiving 200 mg/kg bw, pale kidneys were seen in one male and one female rat; no abnormalities were detected in the other 4 males following a macroscopic examination.

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category III
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of ammonium hexachloroplatinate is approximately 200 mg/kg bw in rats. Four of five females, but none of five males, died after a single oral dose at this level, suggesting that the LD50 in females maybe somewhat lower than this.
Executive summary:
The acute toxicity of ammonium hexachloroplatinate was investigated in a well-conducted study Sprague-Dawley rats. Initially, rats (1/sex/group)received the test material via oral gavage at doses of 25, 50, 200, 500 or 2000 mg/kg bw. Both rats died at the top dose within 24 hours; no deaths were seen at the lower doses. Subsequently, 5 rats/sex received the test material at a dose of 500 mg/kg bw (the highest dose causing no deaths in the range-finding study) by stomach tube. As 4 rats of each sex died within 3 days of administration of the test material at this dose, a second main study (again involving 5 rats/sex) was performed at 200 mg/kg bw. At this level, 4 females died within 24 hours, whilst the remaining animals survived the 14-day observation period.

 

Of the surviving animals at 200 mg/kg bw, pale kidneys were observed in one male and one female; no gross abnormalities were detected in the other 4 animals. The study authors conclude that the acute oral LD50 of ammonium hexachloroplatinate in the rat is "likely to be in the region of 200 mg/kg bw", and classed the test substance according to Hodge and Sterner (1943) as "moderately toxic". Four of five females, but none of five males, died after a single oral dose of 200 mg/kg bw, suggesting that the LD50 in females may be somewhat below 200 mg/kg bw and in males is greater than 200 mg/kg bw (but less than 500 mg/kg bw). The possible sensitivity of females to ammonium hexachloroplatinate in this test system was not discussed by the study authors.

 

Based on the results of this study, the test material should be classified for acute oral toxicity (category 3) according to EU CLP criteria (EC 1272/2008).