Dihydrogen tetrachloropalladate(2-)

Endpoint summary

Description of key information

In an OECD Test Guideline 423 study, to GLP, the acute oral LD50 value of dihydrogen tetrachloropalladate (solution) was determined to range between 200 and 2000 mg/kg bw following gavage administration in rats (van Huygevoort, 2003a).

No relevant acute dermal or inhalation toxicity data were identified. However, acute toxicity testing by a second route is not considered appropriate as dihydrogen tetrachloropalladate is considered corrosive to the skin.

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:

20 November 2002 to 18 December 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Guideline study (OECD, EU), to GLP

Qualifier:

according to guideline

Guideline:

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

Deviations:

yes

Remarks:

200 mg/kg bw dose instead of the recommended 300 mg/kg bw

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

yes

Remarks:

200 mg/kg bw dose instead of the recommended 300 mg/kg bw

GLP compliance:

yes

Test type:

acute toxic class method

Species:

rat

Strain:

other: Wistar strain Crl(WI) 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: males 254-269 g
females 157-183 g
- 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

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

VEHICLE
No vehicle. Test substance (in solution) was dosed undiluted as delivered by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 0.13 and 1.33 ml/kg bw (for 200 and 200 mg/kg bw dose, respectively)

Doses:

200 and 2000 mg/kg bw

No. of animals per sex per dose:

200 mg/kg bw 3/sex
2000 mg/kg bw 3 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: continuous on day of dosing, then daily
- Necropsy of survivors performed: yes

Statistics:

none

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:

2000 mg/kg bw all three females were sacrificed due to distress on day 1 after dosing.
200 mg/kg bw one male died on day 2; all 3 females survived.

Clinical signs:

other: 2000 mg/kg bw lethargy, hunched posture, uncoordinated movements, piloerection, quick breathing (lasting 1 hr), slow breathing (on day 1). In addition, individual animals exhibited ptosis and vomiting with red spots, hypothermia, rales and laboured breath

Gross pathology:

2000 mg/kg bw the glandular mucosa of the stomach was hardened and had a black discolouration. One female also showed a yellowish discolouration of the liver and a reddish, clear fluid in the abdominal cavity.

200 mg/kg bw no abnormal findings in animals that survived the observation period. The deceased male had a thickened glandular mucosa, gastro-intestinal tract distended with gas and dilation of the right kidney.

Other findings:

- Organ weights: not examined
- Histopathology: not examined
- Potential target organs: no data

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

In a GLP OECD Test Guideline 423 study, to GLP, the acute oral LD50 value of dihydrogen tetrachloropalladate (solution) was determined to range between 200 and 2000 mg/kg bw [expressed as compound dose] following gavage administration in rats.

Executive summary:

In a OECD Test Guideline 423 study, to GLP, dihydrogen tetrachloropalladate (solution) was studied for acute oral toxicity after single gavage administration in Wistar rats. The test substance was administered undiluted as a brown liquid at a dose [expressed as compound dose] of 200 mg/kg bw to both sexes (3/sex/dose) and at 2000 mg/kg bw to 3 females.

 

All females dosed at 2000 mg/kg bw were sacrificed due to distress on day 2 after dosing. Clinical signs showed lethargy, hunched posture, uncoordinated movements, piloerection, quick breathing (lasting 1 hr after dosing), slow breathing (on day 1). In addition, individual animals exhibited ptosis, vomiting with red spots, hypothermia, rales and laboured breathing. At 200 mg/kg bw all animals had hunched posture and rales; piloerection was observed in the females and one female also showed chromodacryorrhoea around the snout. Symptoms lasted between 1 and 7 days in females and 2 days in males. Necropsy of the females dosed at 2000 mg/kg bw showed hardening of the glandular mucosa of the stomach and a black discolouration. One female also exhibited a yellowish discolouration of the liver and a reddish, clear fluid in the abdominal cavity. No abnormal findings were evident in the animals dosed at 200 mg/kg bw and which survived the observation period. The deceased male at necropsy exhibited a thickened glandular mucosa, gastro-intestinal tract distended with gas and dilation of the right kidney.

 

Under the conditions of this test, an acute oral LD50 value for dihydrogen tetrachloropalladate solution was determined to range between 200 and 2000 mg/kg bw following gavage administration in rats. This is considered to approximate to a discriminating dose of 300 mg/kg bw. Based on the results of this acute oral rat study, dihydrogen tetrachloropalladate should be classified for acute oral toxicity (category 4) according to EU CLP criteria (EC 1272/2008).

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

discriminating dose

Value:

300 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 relevant acute toxicity human data were identified.

 

In an OECD Test Guideline 423 study, to GLP, dihydrogen tetrachloropalladate (solution) was studied for acute oral toxicity after single gavage administration in Wistar rats. The test substance was administered undiluted as a brown liquid at a dose of 200 mg/kg bw to both sexes (3/sex) and at 2000 mg/kg bw to 3 females. All females dosed at 2000 mg/kg bw were sacrificed due to distress on day 2 after dosing. Clinical signs included lethargy, hunched posture, uncoordinated movements, piloerection, quick breathing (lasting 1 hr after dosing) and slow breathing (on day 1). In addition, individual animals exhibited ptosis, vomiting with red spots, hypothermia, rales and laboured breathing. At 200 mg/kg bw all animals had hunched posture and rales; piloerection was observed in the females and one female also showed chromodacryorrhoea around the snout. Symptoms lasted between 1 and 7 days in females and 2 days in males. Necropsy of the females dosed at 2000 mg/kg bw showed hardening of the glandular mucosa of the stomach and a black discolouration. One female also exhibited a yellowish discolouration of the liver and a reddish, clear fluid in the abdominal cavity. No abnormal findings were evident in the animals dosed at 200 mg/kg bw that survived the observation period. The deceased male at necropsy exhibited a thickened glandular mucosa, gastro-intestinal tract distended with gas and dilation of the right kidney. Under the conditions of this test, an acute oral LD50 value for dihydrogen tetrachloropalladate solution was determined to be in the range between 200 and 2000 mg/kg bw following gavage administration in rats (van Huygevoort, 2003a). This is considered to approximate to a discriminating dose of 300 mg/kg bw. Based on the results of this acute oral rat study, dihydrogen tetrachloropalladate (solution) is classified for acute oral toxicity (category 4) according to EU CLP criteria (EC 1272/2008).

 

No relevant acute dermal or inhalation toxicity data were identified. However, acute toxicity testing by a second route is not considered appropriate as dihydrogen tetrachloropalladate (solution) is corrosive to the skin.

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

Justification for classification or non-classification

Based on the results of the available acute oral rat study, dihydrogen tetrachloropalladate (solution) is 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.