Diammonium hexachloropalladate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 September 1989 – 11 October 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to a company standard protocol designed to comply with the recommendations of OECD Guideline No. 401 and EEC Directive 84/449/EEC.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1989

Report date:

1989

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 001

Cas Number:

19168-23-1

Details on test material:

- Name of test material (as cited in study report): Ammonium hexachloropalladate (IV)
- Substance type: red coloured powder
- Physical state: solid
- Lot/batch No.: 042011
- Stability under test conditions: not determined
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bantin & Kingman Ltd, Grimston, Aldborough, Hull UK
- Age at study initiation: approx. 5-8 weeks
- Weight at study initiation: males 120-146 g, females 120-136 g
- Fasting period before study: over night
- Housing: groups of up to 5/sex in solid-floor polypropylene cages with sawdust bedding
- Diet: ad libitum Rat and Mouse Expanded Diet No. 1 supplied by Special Diet Services Limited, Witham, Essex, UK
- Water: ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24
- Humidity (%): 54-64
- Air changes (per hr): approx. 15/hr
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 1% methyl cellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50, 100, 300 and 500 mg/ml in range-finding study; 100.0, 144.2, 208.0 and 300.0 mg/ml in main study
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

DOSAGE PREPARATION (if unusual): Test material freshly prepared, as required.

Doses:

500, 1000, 3000 and 5000 mg/kg bw in the range finding study; 1000, 1442, 2080 and 3000 mg/kg bw in the main study

No. of animals per sex per dose:

1/sex/dose in the range-finding study; 5/sex/dose in the main study

Control animals:

no

Details on study design:

- Duration of observation period following administration: 5 days for range-finding study; 14 days for main study
- Frequency of observations and weighing: in the main study: observed 1 and 4 hrs after dosing and once daily thereafter for 14 days; bodyweights recorded on the day of treatment (day 0) and on days 7 and 14, or at death
- Necropsy of survivors performed: in main study: yes
- Other examinations performed: in main study: clinical signs, body weight

Statistics:

Acute oral median lethal dose (LD50) and 95% confidence limits were calculated using the method of Thompson, 1947.

Results and discussion

Preliminary study:

In the preliminary range-finding study, all animals survived a dose of up to 1000 mg/kg bw, while both died at 3000 mg/kg bw and above, indicating that the oral LD50 lies between 1000 and 3000 mg/kg bw.

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 226 mg/kg bw

Based on:

test mat.

95% CL:

1 044 - 1 438

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

1 147 mg/kg bw

Based on:

test mat.

95% CL:

809 - 1 627

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

1 292 mg/kg bw

Based on:

test mat.

95% CL:

1 116 - 1 496

Mortality:

All deaths were noted 1-9 days after treatment. All of the animals at the top two dose levels and 4 male and 4 female rats at 1442 mg/kg bw died. Only one male and no female deaths were recorded at the lowest dose level.

Clinical signs:

other: Animals at all dose levels showed hunched posture, piloerection, pallor of the extremities, emaciation and red/brown staining around the snout. A decrease in respiration rate was noted in one female given 1000 mg/kg bw, 11 days after treatment. Incidents

Gross pathology:

No abnormalities were found amongst the low dosed animals. Thickening and sloughing of the glandular gastric epithelium and sloughing of the non-glandular gastric epithelium were seen in the animals which survived exposure to 1442 mg/kg bw. Amongst the animals which died during the study following exposure to 1442 mg/kg bw or above, abnormally red lungs, dark liver, pale kidneys, severe or very severe haemorrhage, ulceration, thickening and sloughing of the glandular gastric epithelium, haemorrhage and sloughing of the non-glandular gastric epithelium and haemorrhage of the small and large intestines were noted. The non-glandular gastric epithelium was also distended or greatly distended with fluid.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a GLP study, similar to OECD guidelines, an acute oral LD50 of 1226 mg/kg bw was reported in rats gavaged with ammonium hexachloropalladate (IV), and observed for up to 14 days.

Executive summary:

In a standard acute oral toxicity study (to GLP), groups of five male and five female rats were administered 1000, 1442, 2080 or 3000 mg/kg bw of ammonium hexachloropalladate (IV) by stomach tube and observed for 14 days.

All animals in the top two dose levels and 4 males and 4 females given 1442 mg/kg bw died. Only one male in the lowest dose group died. Clinical signs of toxicity appeared immediately following administration in all dose groups and lasted for up to 8 days. Reductions in body weight gain or loss of body weight were noted amongst the survivors and gross pathological examination revealed effects on the lungs, liver, kidneys, glandular gastric epithelium, non-glandular gastric epithelium and the small and large intestines of animals treated with 1442 mg/kg bw or above. Using the prescribed statistical method, the acute oral median lethal dose (LD50) and 95% confidence limits were found to be 1226 (1044-1438) mg/kg bw for all animals combined, 1147 (809-1627) mg/kg bw for males and 1292 (1116-1496) mg/kg bw for females.

Based on the results of this study, ammonium hexachloropalladate (IV) should be classifed for acute oral toxicity (Cat. 4) according to EU CLP criteria (EU 1272/2008).