Registration Dossier

Diss Factsheets

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
17 December 2002 to 23 January 2003
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study (OECD, EU, EPA), to GLP, on the dihydrate, with minor deviations (dose level and humidity) that are not considered to affect the validity of the study.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2003
Report date:
2003

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
starting dose 200mg/kg bw (not 300 mg/kg bw) and humidity up to 6% below the minimum level recommended.
Qualifier:
according to guideline
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
yes
Remarks:
starting dose 200mg/kg bw (not 300 mg/kg bw) and humidity up to 6% below the minimum level recommended.
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Reference substance 002
Cas Number:
10102-05-3
Constituent 2
Reference substance name:
Palladium(II) nitrate dihydrate
Cas Number:
32916-07-7
Molecular formula:
2NO3.Pd.2H2O
IUPAC Name:
Palladium(II) nitrate dihydrate
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)nitrate dihydrate
- Substance type: orange-brown powder
- Physical state: solid
- Analytical purity: 40.1% (+/- 0.1%) palladium
- Impurities (identity and concentrations): no data [but see gentox study, with same batch no]
- Purity test date: no data [see gentox study, with same batch no]
- Lot/batch No.: 2403/02-02
- Expiration date of the lot/batch: 21 October 2003
- Stability under test conditions: no data
- Storage condition of test material: room temperature in dark
- Other: [Please note that the dihydrate has a different CAS RN (32916-07-7) to the anhydrous form (10102-05-3)]

Test animals

Species:
rat
Strain:
other: Wistar strain Crl(Wl) 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: females 168-173 g (200 mg/kg bw)
males 241-252 g (200 mg/kg bw)
females 208-238 g (2000 mg/kg bw)
- 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:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20 or 200 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg bw
- Purity: tissue culture grade

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

DOSAGE PREPARATION (if unusual):

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no data

Doses:
male and female: 200 mg/kg bw
female: 2000 mg/kg bw
No. of animals per sex per dose:
3 of each sex at 200 mg/kg bw
3 females at 2000 mg/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed twice daily. Weighed at start of study and day 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
no data

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 200 - < 2 000 mg/kg bw
Remarks on result:
other: CL not determined
Sex:
male
Dose descriptor:
LD50
Effect level:
> 200 mg/kg bw
Remarks on result:
other: CL not determined
Mortality:
All three females dosed at 2000 mg/kg died or were sacrificed due to distress, one on day 1, and two on day 2 after dosing.
Clinical signs:
200 mg/kg bw:
females had a hunched posture (lasting 2-3 days); uncoordinated movements (lasting 2 days); piloerection (from 4 hr to 1 day); salivation (lasting 2 hr); one animal had noisy breathing (lasting 4 hr).
males exhibited a hunched posture (lasting 1 day).

2000 mg/kg bw:
lethargy and hunched posture occurred within 2 hr and remained until death. In the two animals that survived until day 2, swelling of the abdomen occurred within 2 hr in one animal and by 1 day in the second; by day 1or 2 chromodacryorrhoea was seen around the snout and forelegs; yellow discolouration of the urine and yellow staining of the genital region was apparent by day 1 or 2; piloerection occurred by 2 hr; slow breathing was seen by day 2.
Body weight:
200 mg/kg bw:
females: 168-173 g before treatment; 217-235 g on day 14. Mean body weight gain 54 g
males: 241-252 g before treatment; 360-376 g on day 14. Mean body weight gain 122 g

2000 mg/kg bw:
females: 208-238 g before treatment; 205-231 g at death on day 1 or 2. Body weight loss 8 g.
Gross pathology:
No gross abnormalities were detected at 200 mg/kg bw. At 2000 mg/kg bw, the stomachs of two animals contained blood and perforations were seen in the glandular musocae. In all three animals the glandular mucosae showed either dark red or black discolouration. The caecal contents in two animals were dark red. Dark red foci were apparent in the thymus of one animal.
Other findings:
No other findings were reported

- Potential target organs: gastrointestinal tract

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
An acute oral LD50 value of >200 mg/kg bw and < 2000 mg/kg bw was determined in male and female rats.
Executive summary:

Palladium(II)nitrate dihydrate was studied for acute toxicity after single oral administration in rats. The test substance, available as an orange-brown powder, was given as an aqueous solution at a dose of 200 mg/kg bw to groups of three male and three female rats. A further group of three females received a dose of 2000 mg/kg bw.

 

At the higher dose one animal died within 24 hr and the remaining two animals were sacrificed due to distress on day 2 after dosing. Lethargy and hunched posture was evident within 2 hr of treatment. The two females surviving until day 2 showed abdominal swelling, chromodacryorrhoea around the snout and forelegs, yellow discolouration of the urine, yellow staining of the genital region, piloerection and slow breathing. At necropsy, all three females exhibited dark red or black discolouration of the glandular mucosa. In two animals the stomach contained blood, the glandular mucosa was perforated and the caecal contents were dark red. Dark red foci were apparent in the thymus of one animal.

 

A hunched posture and uncoordinated movements, lasting 2-3 days, and piloerection, lasting from 4 hr to 1 day, were evident in females treated with 200 mg/kg bw. One female also had noisy breathing, lasting 4 hr. In males dosed at 200 mg/kg bw the only clinical sign was hunched posture lasting for 1 day. All animals survived the 14 day observation period and at necropsy no abnormalities were evident in the rats dosed at 200 mg/kg bw.

 

An acute oral LD50value of >200 mg/kg bw and < 2000 mg/kg bw was determined in male and female rats.