Diamminedichloropalladium

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

16 March 2012 - 10 August 2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study, to GLP. Occasional deviations from protocol were not considered to impact the integrity or outcome of the study.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

occasional humidity variations outwith protocol limits and daily-post dose observations made less frequently than protocol required were not considered to impact the integrity or outcome of the study

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Diamminedichloropalladium

EC Number:

238-269-3

EC Name:

Diamminedichloropalladium

Cas Number:

14323-43-4

Molecular formula:

Cl2H6N2Pd

IUPAC Name:

Diamminedichloropalladium

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Diamminedichloropalladium
- Substance type: Technical product
- Physical state: Dark yellow/orange powder
- Analytical purity: Not specified
- Impurities (identity and concentrations): Not specified
- Composition of test material, percentage of components: 50.33% palladium content; <10% Ir, Sb and Si; 6% Rh; <5% Pt, Mn and Sn; 3% Cu; <2% Ru, Au, Ag, Al, Co, Fe, Mg, Pb and Zn; <1% Ca, Cr and Ni
- Purity test date: Not specified (composition tested on 14 December 2011)
- Lot/batch No.: 11011
- Expiration date of the lot/batch: 31 October 2012
- Formulation stability under test conditions: At least 9 days at ambient temperature in the dark; actually used within 2 hours of preparation
- Storage condition of test material: Ambient temperature, in the dark
- Other: Supplier - Heraeus Precious Metals GmbH & Co., Heraeusstr. 12-14, 63450 Hanau, Germany

Test animals

Species:

rat

Strain:

other: Sprague-Dawley Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, Margate, UK
- Age at study initiation: 8-12 weeks old
- Weight at study initiation: 222.9-250.0 g
- Fasting period before study: overnight
- Housing: In groups of 3 (except when reduced by mortality) in appropriately sized solid-bottomed polycarbonate cages with stainless steel mesh tops, suspended on movable racks
- Bedding: wood shavings
- Diet: ad libitum PMI Nutrition International Certified Rodent Diet No. 5CR4 (14% protein)
- Water: ad libitum from the public supply
- Acclimation period: At least 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): daily average temperatures approx 20-21
- Humidity (%): range of daily average relative humidity approx. 43-49%; on several occasions humidity was intermittently below 40%, the actual minimum humidity was approx. 22% but, on that day, the daily mean humidity was approx. 43%
- Air changes (per hr): Minimum of 10
- Photoperiod (hrs dark / hrs light): 12 hrs dark/12 hrs light

IN-LIFE DATES: From: 27 March 2012 To: 10 April 2012

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: high viscosity hydroxypropyl methylcellulose in Milli-Q water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 30 and 200 mg/mL
- Amount of vehicle (if gavage): 0.5% (w/v)
- Justification for choice of vehicle: Not given
- Lot/batch no. (if required): DT200527
- Purity: Not given

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg bw

DOSAGE PREPARATION (if unusual): A weighed amount of hydroxypropyl methylcellulose (HPMC) was blended with a measured volume of Milli-Q water. The blender was rinsed with more Milli-Q water and the vehicle was then made up to a final volume in a volumetric flask. The required amount of test item was weighed into a mortar bowl and approx. 70% of the vehicle gradually added and the mixture homogenized then transferred to a suitable container that held the remaining 30% of vehicle. Formulations were magnetically stirred until an orange-coloured formulation was obtained. Analysis of prepared formulations with regard to stability, concentration and homogeneity was not conducted however, examination of the formulation records indicated that all preparations had been prepared correctly.

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: The starting dose was selected following review of the documentation of the test item supplied by the Sponsor

Doses:

300 and 2000 mg/kg bw

No. of animals per sex per dose:

6 females/low dose, 3 females/high dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals observed daily for clinical effects (although signs seen in all Group 1 animals were not recorded on days 5 and 6 and only recorded for 2 of the animals on day 13), twice daily for viability, and body weights recorded before dosing on day 1 and on days 8 and 15 for the low dosed animals and daily until day 9 and on days 13 and 15 for the survivors of th ehigh-dose group .
- Necropsy of survivors performed: yes (all animals were necropsied)
- Necropsy parameters: examination of cranial, thoracic and abdominal organs and tissues
- Other examinations performed: clinical signs, body weight, other: mortality/moribundity

Statistics:

No formal statistical analysis was conducted.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: CL not applicable

Mortality:

There were no deaths amongst animals treated at a dose of 300 mg/kg bw. However 2 of the 3 animals were euthanised on days 9 and 13 with 2000 mg/kg bw.

Clinical signs:

other: All animals treated with 300 mg/kg bw displayed subdued behaviour for a short period after dosing. Full recovery was seen within 3 hours. At 2000 mg/kg bw, all animals displayed subdued behaviour, laboured breathing, piloerection and partial closure of

Gross pathology:

There were no macroscopic abnormalities at 300 mg/kg bw.

At 2000 mg/kg bw, lesions to the stomachs of all 3 animals were noted and included thickening of the non-glandular stomach and abnormal (black) stomach contents in one animal, distention of the stomach and filing with brown liquid in another, and distention of the stomach, dark pink discolouration of the glandular serosa, black discolouration of the glandular mucosa, thickening of the glandular stomach and thinness of the non-glandular stomach in the third animal. Other macroscopic abnormalities included pale discolouration of the lobes of the lungs in one animal and abnormal (green) contents of the oesophagus and dark red dicolouration of the pancreas in another.

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an OECD Test Guideline 423 study, to GLP, the acute oral LD50 of diamminedichloropalladium was determined to be between 300 and 2000 mg/kg bw

Executive summary:

In an acute oral toxicity test, conducted according to OECD Test Guideline 423 and to GLP, groups of 6 and 3 female rats were given a single oral intubation of 300 and 2000 mg/kg bw, respectively, and observed for 14 days.

No deaths were reported in any of the 6 animals at the lower dose and there were no effects on body weight gain and no macroscopic abnormalities. At 2000 mg/kg bw, unscheduled deaths were reported in 2 (euthanasia on days 9 and 13, respectively) of the 3 animals, with all animals showing overt signs of toxicity and (likely local) effects in the non-glandular stomach.

The acute oral median lethal dose (LD50) of diamminedichloropalladium was determined to be between 300 and 2000 mg/kg bw. Based on the results of this study, diamminedichloropalladium should be classified for acute oral toxicity (category 4) according to EU CLP criteria (EC 1272/2008).