Diammonium hexachloropalladate

Endpoint summary

Description of key information

In a GLP study, similar to OECD guidelines, an acute oral LD50 of 1226 mg/kw bw was reported in rats gavaged with diammonium hexachloropalladate, and observed for up to 14 days (Dreher, 1989).

No acute inhalation or dermal toxicity data were identified.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

15 September 1989 – 11 October 1989

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted according to a company standard protocol designed to comply with the recommendations of OECD Guideline No. 401 and EEC Directive 84/449/EEC.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Qualifier:

equivalent or similar to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Bantin & Kingman Ltd, Grimston, Aldborough, Hull UK
- Age at study initiation: approx. 5-8 weeks
- Weight at study initiation: males 120-146 g, females 120-136 g
- Fasting period before study: over night
- Housing: groups of up to 5/sex in solid-floor polypropylene cages with sawdust bedding
- Diet: ad libitum Rat and Mouse Expanded Diet No. 1 supplied by Special Diet Services Limited, Witham, Essex, UK
- Water: ad libitum
- Acclimation period: minimum of 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-24
- Humidity (%): 54-64
- Air changes (per hr): approx. 15/hr
- Photoperiod (hrs dark / hrs light): 12 hours light and 12 hours dark

Route of administration:

oral: gavage

Vehicle:

other: 1% methyl cellulose

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 50, 100, 300 and 500 mg/ml in range-finding study; 100.0, 144.2, 208.0 and 300.0 mg/ml in main study
- Amount of vehicle (if gavage): 10 ml/kg bw
- Justification for choice of vehicle: no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: 10 ml/kg bw

DOSAGE PREPARATION (if unusual): Test material freshly prepared, as required.

Doses:

500, 1000, 3000 and 5000 mg/kg bw in the range finding study; 1000, 1442, 2080 and 3000 mg/kg bw in the main study

No. of animals per sex per dose:

1/sex/dose in the range-finding study; 5/sex/dose in the main study

Control animals:

no

Details on study design:

- Duration of observation period following administration: 5 days for range-finding study; 14 days for main study
- Frequency of observations and weighing: in the main study: observed 1 and 4 hrs after dosing and once daily thereafter for 14 days; bodyweights recorded on the day of treatment (day 0) and on days 7 and 14, or at death
- Necropsy of survivors performed: in main study: yes
- Other examinations performed: in main study: clinical signs, body weight

Statistics:

Acute oral median lethal dose (LD50) and 95% confidence limits were calculated using the method of Thompson, 1947.

Preliminary study:

In the preliminary range-finding study, all animals survived a dose of up to 1000 mg/kg bw, while both died at 3000 mg/kg bw and above, indicating that the oral LD50 lies between 1000 and 3000 mg/kg bw.

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 226 mg/kg bw

Based on:

test mat.

95% CL:

1 044 - 1 438

Sex:

male

Dose descriptor:

LD50

Effect level:

1 147 mg/kg bw

Based on:

test mat.

95% CL:

809 - 1 627

Sex:

female

Dose descriptor:

LD50

Effect level:

1 292 mg/kg bw

Based on:

test mat.

95% CL:

1 116 - 1 496

Mortality:

All deaths were noted 1-9 days after treatment. All of the animals at the top two dose levels and 4 male and 4 female rats at 1442 mg/kg bw died. Only one male and no female deaths were recorded at the lowest dose level.

Clinical signs:

other: Animals at all dose levels showed hunched posture, piloerection, pallor of the extremities, emaciation and red/brown staining around the snout. A decrease in respiration rate was noted in one female given 1000 mg/kg bw, 11 days after treatment. Incidents

Gross pathology:

No abnormalities were found amongst the low dosed animals. Thickening and sloughing of the glandular gastric epithelium and sloughing of the non-glandular gastric epithelium were seen in the animals which survived exposure to 1442 mg/kg bw. Amongst the animals which died during the study following exposure to 1442 mg/kg bw or above, abnormally red lungs, dark liver, pale kidneys, severe or very severe haemorrhage, ulceration, thickening and sloughing of the glandular gastric epithelium, haemorrhage and sloughing of the non-glandular gastric epithelium and haemorrhage of the small and large intestines were noted. The non-glandular gastric epithelium was also distended or greatly distended with fluid.

Interpretation of results:

Toxicity Category IV

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In a GLP study, similar to OECD guidelines, an acute oral LD50 of 1226 mg/kg bw was reported in rats gavaged with ammonium hexachloropalladate (IV), and observed for up to 14 days.

Executive summary:

In a standard acute oral toxicity study (to GLP), groups of five male and five female rats were administered 1000, 1442, 2080 or 3000 mg/kg bw of ammonium hexachloropalladate (IV) by stomach tube and observed for 14 days.

All animals in the top two dose levels and 4 males and 4 females given 1442 mg/kg bw died. Only one male in the lowest dose group died. Clinical signs of toxicity appeared immediately following administration in all dose groups and lasted for up to 8 days. Reductions in body weight gain or loss of body weight were noted amongst the survivors and gross pathological examination revealed effects on the lungs, liver, kidneys, glandular gastric epithelium, non-glandular gastric epithelium and the small and large intestines of animals treated with 1442 mg/kg bw or above. Using the prescribed statistical method, the acute oral median lethal dose (LD50) and 95% confidence limits were found to be 1226 (1044-1438) mg/kg bw for all animals combined, 1147 (809-1627) mg/kg bw for males and 1292 (1116-1496) mg/kg bw for females.

Based on the results of this study, ammonium hexachloropalladate (IV) should be classifed for acute oral toxicity (Cat. 4) according to EU CLP criteria (EU 1272/2008).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 226 mg/kg bw

Quality of whole database:

Overall, good-quality database which meets REACH Standard Information Requirements.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No human data were identified for acute exposure.

In a standard acute oral toxicity study (to GLP), groups of five male and five female rats were administered diammonium hexachloropalladate at 1000, 1442, 2080 or 3000 mg/kg bw by stomach tube and observed for 14 days. All animals in the top two dose levels died, as did 4 rats/sex given 1442 mg/kg bw. Only one male in the lowest dose group died. Clinical signs of toxicity appeared immediately following administration in all dose groups and lasted for up to 8 days. Reductions in growth or body weight were noted amongst the survivors and gross pathological examination revealed effects on the lungs, liver, kidneys, glandular gastric epithelium, non-glandular gastric epithelium and the small and large intestines of animals treated with 1442 mg/kg bw or above. Using the prescribed statistical method, the acute oral median lethal dose (LD50) and 95% confidence limits were found to be 1226 (1044-1438) mg/kg bw for all animals combined, 1147 (809-1627) mg/kg bw for males and 1292 (1116-1496) mg/kg bw for females (Dreher, 1989).

No acute inhalation toxicity data were identified. However, the compound is not expected to reach the lungs in appreciable quantities (based on respiratory tract deposition modelling data). Thus, inhalation will not be a significant route of exposure. Similarly, no acute dermal toxicity data were identified. However, skin contact during production and/or use is expected to be negligible.

Justification for selection of acute toxicity – oral endpoint
GLP study, similar to OECD guidelines, and the only acute oral toxicity study available.

Justification for classification or non-classification

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

No clear evidence of specific target organ toxicity was noted. As such, classification for STOT-SE is not considered appropriate.