Dipotassium hexachloropalladate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The administration and the pre- and post- observation periods were between 27 June and 09 August 1989.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study, conducted to OECD guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Remarks:

No significant deviations

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Reference substance 003

Cas Number:

16919-73-6

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Potassium hexachloropalladate (IV)
- Substance type: Red powder
- Physical state: Solid
- Analytical purity: 26.8% Pd
- Purity test date: Apparently 07 July 1989
- Lot/batch No.: 041368
- Expiration date of the lot/batch: no data
- Stability under test conditions: Stable
- Storage condition of test material: Kept desiccated in a closed container in a fridge

Test animals

Species:

rat

Strain:

other: Bor: WISW (SPFCpb)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co. KG., D-4799 Borchen
- Age at study initiation: 8 weeks (males); 9 weeks (females)
- Weight at study initiation: 152-210 g (males); 136-167 g (females)
- Fasting period before study: 16 hours
- Housing: 1 rat/cage in type II Macrolon cages
- Diet (e.g. ad libitum): ad libitum standard diet ssniff R “Special diet for rats”, supplied by ssniff Spezialfutter GmbH, D-4770 Soest
- Water (e.g. ad libitum): ad libitum from Stadtwerke Beilefeld (Municipal Works)
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.5-22.5
- Humidity (%): 40-70
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): 12/12 (6 am- 6 pm: artificial lighting; 6 pm-6 am: “natural light-dark-rhythm”)

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

peanut oil

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 46.4, 68.1 or 100 mg/ml.
- Amount of vehicle (if gavage): 21.5 ml
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): Batch 5479, supplied by H. Lamotte, D-2800 Bremen
- Purity: no data

Doses:

Rats were administered 1000, 1470 or 2150 mg/kg bw in 21.5 ml/kg bw.

No. of animals per sex per dose:

Five rats/sex/dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days (a single animal was observed for 21 days because of reduced body weight at 14 days)
- Frequency of observations and weighing: Observed for 4-6 hours after administration, then once daily; weighed at the beginning and at 7 and 14 days (or after death; a single animal was weighed at 21 days); deaths recorded twice daily, except on Saturdays, Sundays and national holidays when they were only counted once.
- Necropsy of survivors performed: yes
- Other examinations performed: external appearance, “body orifices”, thoracic and abdominal body cavities and their contents, histopathology of the lungs, clinical signs, body weight.

Statistics:

Acute oral median lethal dose (LD50)

Results and discussion

Preliminary study:

Not applicable

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 448 mg/kg bw

95% CL:

> 1 234 - < 1 696

Remarks on result:

other: Probit analysis

Effect levels 2

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 1 358 mg/kg bw

95% CL:

> 924 - < 1 882

Remarks on result:

other: Probit analysis

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 1 562 mg/kg bw

95% CL:

> 1 123 - < 2 249

Remarks on result:

other: Probit analysis

Mortality:

Two males in the mid-dose group died 6 days after administration; all high-dose males died within 7 days. Four females in the mid-dose group died within five days of administration; all high-dose females died within 3 days.

Clinical signs:

Slightly reduced movement, diarrhoea, red nasal discharge and “sunken sides” were seen in some of the females given 1000 mg/kg bw. At 1470 and 2150 mg/kg bw, more obvious signs of neurotoxicity than reduced movement were reported (restrained gait, tremor, reduced muscle tone), along with other general signs of toxicity (including piloerection, strenuous respiration yellow nasal discharge and, in the high dose group only, red-discoloured urine). In males, slightly reduced movement was reported in two animals given 1000 mg/kg bw. Higher doses caused similar neurotoxic and general toxicity symptoms as those seen in females (but included loss of righting reflex, reduced body temperature and black discolouration of the faeces).

Body weight:

Reduced body weight gain was reported in three females given 1000 mg/kg bw, and in one female and two males given 1470 mg/kg bw.

Gross pathology:

Effects on the digestive organs (glandular stomach, forestomach, intestine and liver) consistent with a local irritant effect were reported in mid- and high-dose males and females. A slightly diminished spleen was noted in one mid-dose male, and one mid-dose female exhibited a foam-filled trachea. Abnormalities in the lungs (dark red, puffy, emphysematous appearance and dark red discolouration or spotting) were seen in high-dose male and female animals; dark red spotting in the lungs was also seen in mid-dose females.

Other findings:

- Histopathology: Lung congestion was reported in males given 2150 mg/kg bw and in females given 1470 and 2150 mg/kg bw.

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, conducted according to OECD guidelines, the acute oral LD50 of dipotassium hexachloropalladate in the rat has been calculated as approximately 1400 mg/kg bw.

Executive summary:

In a GLP study conducted according to OECD Test Guideline 401, five rats/sex/group were treated with 1000, 1470 or 2150 mg/kg bw dipotassium hexachloropalladate by stomach tube, and observed for 14 days (although one animal was observed for 21 days).

 

Two males and four females in the mid-dose group died within six days; all animals in the high-dose group died within seven days. Toxic effects included neurotoxicity, local irritant effects on the digestive organs and lung damage.

 

The study authors calculate (using probit analysis) that the acute oral median lethal dose (LD50) is 1562 mg/kg bw in male rats (95% CI 1123-2249 mg/kg bw), 1358 mg/kg bw in female rats (95% CI 924-1182 mg/kg bw) and 1448 mg/kg bw for both sexes combined (95% CI 1234-1696 mg/kg bw).

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