Dihydrogen tetrachloropalladate(2-)

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

20 November 2002 to 18 December 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD, EU), to GLP

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2003

Report date:

2003

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

200 mg/kg bw dose instead of the recommended 300 mg/kg bw

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

200 mg/kg bw dose instead of the recommended 300 mg/kg bw

GLP compliance:

yes

Test type:

acute toxic class method

Test material

Test material information

Constituent 1

Reference substance name:

Dihydrogen tetrachloropalladate(2-)

EC Number:

241-047-9

EC Name:

Dihydrogen tetrachloropalladate(2-)

Cas Number:

16970-55-1

Molecular formula:

Cl4Pd.2H

IUPAC Name:

dihydrogen tetrachloropalladate(2-)

Test material form:

other: liquid

Details on test material:

- Name of test material (as cited in study report): dihydrogen tetrachloropalladate(II)-solution
- Substance type: brown liquid
- Physical state: liquid
- Analytical purity: 99.95%
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: 47% of H2(PdCl4) in the solution
- Purity test date: no data
- Lot/batch No.: 4515932529
- Expiration date of the lot/batch: 12 September 2003
- Stability under test conditions: no data
- Storage condition of test material: room temperature in the dark

Test animals

Species:

rat

Strain:

other: Wistar strain Crl(WI) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Deutschland
Sulzfeld
Germany
- Age at study initiation: about 8 weeks
- Weight at study initiation: males 254-269 g
females 157-183 g
- Fasting period before study: overnight
- Housing: Macrolon cages, on sawdust
- Diet (e.g. ad libitum): conventional diet, ad libitum
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 3
- Humidity (%): 30-70
- Air changes (per hr): about 15
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
No vehicle. Test substance (in solution) was dosed undiluted as delivered by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 0.13 and 1.33 ml/kg bw (for 200 and 200 mg/kg bw dose, respectively)

Doses:

200 and 2000 mg/kg bw

No. of animals per sex per dose:

200 mg/kg bw 3/sex
2000 mg/kg bw 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: continuous on day of dosing, then daily
- Necropsy of survivors performed: yes

Statistics:

none

Results and discussion

Effect levels

Effect levels 1

Sex:

female

Dose descriptor:

LD50

Effect level:

> 200 - < 2 000 mg/kg bw

Remarks on result:

other: CL not determined

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

> 200 mg/kg bw

Remarks on result:

other: CL not determined

Mortality:

2000 mg/kg bw all three females were sacrificed due to distress on day 1 after dosing.
200 mg/kg bw one male died on day 2; all 3 females survived.

Clinical signs:

other: 2000 mg/kg bw lethargy, hunched posture, uncoordinated movements, piloerection, quick breathing (lasting 1 hr), slow breathing (on day 1). In addition, individual animals exhibited ptosis and vomiting with red spots, hypothermia, rales and laboured breath

Gross pathology:

2000 mg/kg bw the glandular mucosa of the stomach was hardened and had a black discolouration. One female also showed a yellowish discolouration of the liver and a reddish, clear fluid in the abdominal cavity.

200 mg/kg bw no abnormal findings in animals that survived the observation period. The deceased male had a thickened glandular mucosa, gastro-intestinal tract distended with gas and dilation of the right kidney.

Other findings:

- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: no data

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In a GLP OECD Test Guideline 423 study, to GLP, the acute oral LD50 value of dihydrogen tetrachloropalladate (solution) was determined to range between 200 and 2000 mg/kg bw [expressed as compound dose] following gavage administration in rats.

Executive summary:

In a OECD Test Guideline 423 study, to GLP, dihydrogen tetrachloropalladate (solution) was studied for acute oral toxicity after single gavage administration in Wistar rats. The test substance was administered undiluted as a brown liquid at a dose [expressed as compound dose] of 200 mg/kg bw to both sexes (3/sex/dose) and at 2000 mg/kg bw to 3 females.

 

All females dosed at 2000 mg/kg bw were sacrificed due to distress on day 2 after dosing. Clinical signs showed lethargy, hunched posture, uncoordinated movements, piloerection, quick breathing (lasting 1 hr after dosing), slow breathing (on day 1). In addition, individual animals exhibited ptosis, vomiting with red spots, hypothermia, rales and laboured breathing. At 200 mg/kg bw all animals had hunched posture and rales; piloerection was observed in the females and one female also showed chromodacryorrhoea around the snout. Symptoms lasted between 1 and 7 days in females and 2 days in males. Necropsy of the females dosed at 2000 mg/kg bw showed hardening of the glandular mucosa of the stomach and a black discolouration. One female also exhibited a yellowish discolouration of the liver and a reddish, clear fluid in the abdominal cavity. No abnormal findings were evident in the animals dosed at 200 mg/kg bw and which survived the observation period. The deceased male at necropsy exhibited a thickened glandular mucosa, gastro-intestinal tract distended with gas and dilation of the right kidney.

 

Under the conditions of this test, an acute oral LD50 value for dihydrogen tetrachloropalladate solution was determined to range between 200 and 2000 mg/kg bw following gavage administration in rats. This is considered to approximate to a discriminating dose of 300 mg/kg bw. Based on the results of this acute oral rat study, dihydrogen tetrachloropalladate should be classified for acute oral toxicity (category 4) according to EU CLP criteria (EC 1272/2008).