Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
20 June 1988 to 3 August 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study, to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
- Name of test material (as cited in study report): Palladium(II)-acetate trimer
- Substance type: brown powder
- Physical state: solid
- Analytical purity: 47.15% palladium
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: no data
- Purity test date: no data
- Lot/batch No.: 6597
- Expiration date of the lot/batch: no data
- Stability under test conditions: stable throughout study period “according to sponsor”
- Storage condition of test material: room temperature
- Other:

Test animals

Species:
rat
Strain:
other: Wistar Bor:WISW
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Winkelmann Versuchstierzucht GmbH & Co. KG.
D-4799 Borchen
- Age at study initiation: 9-10 weeks
- Weight at study initiation: males 183-200 g
females 136-169 g
- Fasting period before study: 16 hr
- Housing: Macrolon cages; woodchip bedding
- Diet (e.g. ad libitum): conventional; ad libitum
- Water (e.g. ad libitum): tap water; ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.5-21
- Humidity (%): 45-65
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To:

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
peanut oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 110 or 237 mg/ml
- Amount of vehicle (if gavage): 21.5 ml/kg bw
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED:

DOSAGE PREPARATION (if unusual): test substance suspended in vehicle immediately before dosing using an homogenizer

Doses:
2370 and 5110 mg/kg bw
No. of animals per sex per dose:
5 females at 2370 mg/kg bw
5/sex at 5110 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: continuous observation for 4-8 hr, then once daily. Weighed before dosing and on days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: histopathology on heart and kidneys

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 110 mg/kg bw
Mortality:
At 5110 mg/kg bw, one female died on day 4
Clinical signs:
At 5110 mg/kg bw both sexes showed slight to severe hypokinesia, stilted gait, diarrhoea, sunken sides, piloerection, vocalization on handling, strenuous respiration. One male and two females also had a brown nasal discharge. Symptoms were recorded 30 min after dosing and lasted for up to 9 days. The female that died exhibited clonic convulsions, decreased muscle tone, loss of righting reflex and decreased body surface temperature.

At 2370 mg/kg bw all animals had diarrhoea and slight to moderate hypokinesia, 4 had sunken sides and individuals exhibited a stilted gait and piloerection.
Body weight:
2370 mg/kg bw: females: 136-146 g before treatment; 157-182 g on day 14. Mean body weight gain 31 g.

5110 mg/kg bw:
females: (n=4) 157-169 g before treatment; 180-205 g on day 14. Mean body weight gain 30 g (n=1)169 g before treatment; 154 g at death on day 4. Body weight loss 15 g.
males: 183-200 g before treatment; 238-273 g on day 14. Mean body weight gain 58 g
Gross pathology:
No gross abnormalities were detected in animals surviving to 14 days.
The deceased female had pale spots in the heart and kidneys and haemorrhages in the stomach.
Other findings:
- Histopathology: at 5110 mg/kg bw in some animals the kidneys showed single focal proximal tubular cell hyperplasia with some eosophilic material in the tubules. Minimal focal mononuclear cell infiltration was detected in the heart and kidneys of some animals.

The deceased rat exhibited acute single cell necroses in the heart, massive diffuse necroses of the proximal and distal renal tubular cells with deposition of eosinophilic material and massive storage of slightly basophilic material in proximal renal tubules.

At 2370 mg/kg bw one female showed minimal mononuclear cell infiltration and minimal focal interstitial nephritis. No abnormalities were detected in the heart.

- Potential target organs: heart and kidney
- Other observations:

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study, an LD50 of greater than 5110 mg/kg bw was reported in rats gavaged with palladium (II) acetate trimer, and observed for up to 14 days.
Executive summary:
The acute toxicity of palladium(II)-acetate trimer was assessed after single oral administration in rats, in a study conducted in accordance with OECD Test Guideline 401 and to GLP. The test substance, available as a brown powder, was given in peanut oil at a dose of 2370 mg/kg bw to females and at 5110 mg/kg bw to both sexes.

 

At 5110 mg/kg bw all animals had diarrhoea and exhibited slight to severe hypokinesia. Stilted gait, diarrhoea, sunken sides, piloerection, vocalization on handling and strenuous respiration were noted in some animals. One male and two females also had a brown nasal discharge. Symptoms were recorded 30 min after dosing and were reported to last for up to 9 days. One female exhibited clonic convulsions, decreased muscle tone, loss of righting reflex and decreased body surface temperature before death on day 4 after dosing.

 

At 2370 mg/kg bw all animals had diarrhoea and slight to moderate hypokinesia, 4 had sunken sides and individual animals exhibited a stilted gait and piloerection.

 

No gross abnormalities were evident at necropsy in the rats that survived the observation period. The deceased female had pale spots in the heart and kidneys and haemorrhages in the stomach.

 

Histological examination revealed single focal proximal tubular cell hyperplasia with some eosophilic material in the tubules of some animals dosed at 5110 mg/kg bw. Minimal focal mononuclear cell infiltration was detected in the heart and kidneys of some of these rats. The deceased rat exhibited acute single cell necroses in the heart, massive diffuse necroses of the proximal and distal renal tubular cells with deposition of eosinophilic material and massive storage of slightly basophilic material in proximal renal tubules.

 

At 2370 mg/kg bw one female showed minimal mononuclear cell infiltration and minimal focal interstitial nephritis. No abnormalities were detected in the heart in animals given this dose.

 

The acute oral LD50 value was found to exceed 5110 mg/kg bw (limit test).

 

Based on the results of this study, palladium (II) acetate should not be classified for acute oral toxicity according to EU CLP criteria (EC 1272/2008).