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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
27 August to 23 October 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline study, to GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
up-and-down procedure
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Palladium (II) di(4-oxopent-2-en-2-oate)
EC Number:
237-859-8
EC Name:
Palladium (II) di(4-oxopent-2-en-2-oate)
Cas Number:
14024-61-4
Molecular formula:
C10H14O4Pd
IUPAC Name:
palladium (II) di(4-oxopent-2-en-2-oate)
Test material form:
other: solution
Details on test material:
- Name of test material (as cited in study report): palladium (II) di(4-oxopent-2-en-2-oate)
- Substance type: no data
- Physical state: yellow solid
- Analytical purity: ~100%
- Impurities (identity and concentrations): platinum at 40 ppm; iridium, antimony and silicon at <10 ppm; rhodium at 6 ppm; manganese and tin at <5 ppm; ruthenium, gold, silver, aluminium, cobalt, copper, iron, magnesium, lead and zinc at <2 ppm; calcium, chromium and nickel at <1 ppm
- Composition of test material, percentage of components: 34.98% palladium
- Isomers composition: no data
- Purity test date: 29 May 2013
- Lot/batch No.: 21613
- Expiration date of the lot/batch: June 2014
- Stability under test conditions: no data
- Storage condition of test material: controlled room temperature (15-25°C, below 70% relative humidity), under inert gas

Test animals

Species:
rat
Strain:
other: RccHan:(WIST)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories S.r.l., S.Pietro al Natisone (UD), Zona Industriale Azzida, 57, 33040, Italy
- Age at study initiation: ~9-12 weeks
- Weight at study initiation: 166-203 g
- Fasting period before study: overnight
- Housing: individual caging (polypropylene/polycarbonate)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.2-24.7
- Humidity (%): 31-70
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: Reception from: 21 August to 18 September 2013. Necrospy from: 10 September to 23 October 2013

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Remarks:
distilled
Details on oral exposure:
VEHICLE
- Concentration in vehicle: various
- Amount of vehicle (if gavage): various
- Justification for choice of vehicle: commonly used solvent

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw (1.7-2.0 ml/animal)

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: LD50 expected to be between 300 and 2000 mg/kg bw
Doses:
550 or 2000 mg/kg bw
No. of animals per sex per dose:
550 mg/kg bw: 2 females
2000 mg/kg bw: 5 females
Control animals:
other: not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: checked for clinical signs at 30 minutes, then 1, 2, 3, 4 and 6 hours after dosing. Then checked once daily for 14 days. Body weight measured on days -1, 0 (start of experiment), 7 and 14. Body weight of dead animals recorded at necropsy.
- Necropsy of survivors performed: yes (gross pathology of the cranial, thoracic and abdominal cavities)
Statistics:
Not relevant

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 2 000 mg/kg bw
Based on:
test mat.
Remarks:
mortality
Remarks on result:
other: CL not determined.
Mortality:
Mortality was observed on days 1 and 12 in 2/5 animals receiving a single dose of palladium di(4-oxopent-2-en-2-oate) at 2000 mg/kg bw. No mortality was observed in the 2 animals treated with 550 mg/kg bw. See Table 1 in "any other information on results incl. tables" for details.
Clinical signs:
At 550 mg/kg bw, decreased activity and decreased general body tone was observed in one animal on days 2-5. The other animal remained symptom-free throughout the observation period.

At 2000 mg/kg bw, the test item caused decreased activity, hunched back and piloerection in all five animals. Additional observations at this dose level included vocalisation (2/5), liquid faeces (3/5), dyspnoea (1/5) and wasted appearance (4/5). Animals which survived were symptom-free from days 8, 9 or 12 until the end of the study.
Body weight:
All surviving animals showed body weight loss between Days 0 and 7 at the dose level of 2000 mg/kg bw.
Gross pathology:
Animals found dead:
Dark/red foci, found at the glandular mucosa of the stomach in 2/2 rats which were found dead, were considered to be potentially related to the administration of the test item. Other changes such as collapsed/non-collapsed lungs, dilatation of the stomach with gas, or clear liquid at the perinasal fur were regarded as agonal or post mortem.

Surviving animals (necropsy at day 14):
There were no macroscopic abnormalities in animals dosed at 550 mg/kg bw or in surviving rats dosed at 2000 mg/kg bw and terminated on Day 14.
Other findings:
No data

Any other information on results incl. tables

Table 1. Mortality of animals treated via gavage with palladium di(4-oxopent-2-en-2-oate)

Animal Number

Dosage

(mg/kg bw)

Dose volume (ml/animal)

Viability/Mortality

Short term

Long term

2903

550

1.7

Survived

Survived

2904

2000

1.9

Survived

Survived

2905

2000

1.9

Died

-

2906

550

2.0

Survived

Survived

3477

2000

1.7

Survived

Died

3478

2000

1.9

Survived

Survived

3479

2000

2.0

Survived

Survived

 

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity test (up and down procedure) on female rats, conducted to GLP and according to OECD Test Guideline 425, the LD50 for palladium di(4-oxopent-2-en-2-oate) was estimated to be 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of palladium (II) di(4-oxopent-2-en-2-oate) was assessed using the up and down procedure. The study was performed to GLP and according to OECD Test Guideline 425.

 

Female RccHan:(WIST) rats were treated with a single oral (gavage) dose of the test material (in distilled water) at 550 mg/kg bw (2 animals) or 2000 mg/kg bw (5 animals), before a 14-day observation period. Animals were checked for clinical signs of toxicity, and effects on body weight. Rats were subject to gross necropsy upon death or terminal killing.

 

Two of the five animals treated with 2000 mg/kg bw died, while neither of the two animals treated with 550 mg/kg bw died. Under the conditions of this study, the acute oral LD50 was estimated to be about 2000 mg/kg bw in female rats. The test compound would therefore be cautiously classified as Category 4 for acute toxicity via the oral route under the EU CLP regulation.