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Administrative data

Description of key information

In an OECD guideline study, the acute oral LD50 of tetraamminepalladium hydrogen carbonate in female rats was reported to be 933 mg/kg bw (Allen, 1995a).


In an OECD guideline study, to GLP, the acute dermal LD50 of tetraamminepalladium hydrogen carbonate was found to be greater than 2000 mg/kg bw, as no deaths occurred at this limit dose (Allen, 1997a).


No relevant acute inhalation 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:
No data
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: OECD guideline study. However, potential deviations could not be fully assessed as the study report appears to have some pages omitted. On closely-related surrogate.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
not specified
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
not specified
GLP compliance:
not specified
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: no data
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: animals were fasted, but no details on duration of fasting period
- Housing: no data
- Diet (e.g. ad libitum): no data
- Water (e.g. ad libitum): no data
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%):no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data
Route of administration:
oral: unspecified
Vehicle:
arachis oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: no data
- Amount of vehicle (if gavage): no data
- Justification for choice of vehicle: no data
- Lot/batch no. (if required): no data
- Purity: no data

MAXIMUM DOSE VOLUME APPLIED: no data

DOSAGE PREPARATION (if unusual): no data
Doses:
0.5, 1 and 2 g/kg bw
No. of animals per sex per dose:
Five females/dose, a group of 5 males also treated at 2 g/kg bw
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed 30 minutes, 1, 2, 4 hours, and then daily and weighed at day 0, 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Statistics:
Acute oral median lethal dose (LD50) and 95% confidence limits of the test material were calculated by the method of Thompson W.R.
Preliminary study:
In the range finding study, one male and one female received 2 g/kg bw. The male was found dead two days after dosing, the female had no signs of systemic toxicity at day 5 after dosing. Hunched posture, lethargy and pilo-erection were seen in both animals, and ptosis and occasional body tremours were also noted in the male.
Sex:
female
Dose descriptor:
LD50
Effect level:
933 mg/kg bw
Based on:
test mat.
95% CL:
664 - 1 310
Mortality:
In the main study, all 5 male and 5 female rats receiving 2 g/kg bw died by day 3, whilst 3 of 5 females died at 1 g/kg bw on days 4 to 6. No deaths were seen in the females receiving 0.5 g/kg bw.
Clinical signs:
Hunched posture, lethargy, decreased respiratory rate, laboured respiration and emaciation were commonly noted in all dose groups during the study. Pilo-erection and ptosis were noted in animals dosed with 1 g/kg bw and above. Ataxia was seen in females dosed with 1 g/kg bw (and higher) and distended abdomen noted at 0.5 and 1 g/kg bw, and in males given 2 g/kg bw. Incidents of diarrhoea, noisy or gasping respiration, red/brown staining around the mouth and snout and occasional body tremours were also noted with isolated incidents of tiptoe or splayed gait, dehydration and increase salivation. Surviving animals had no signs of systemic toxicity within 1 to 9 days after dosing.
Body weight:
Surviving animals showed an “acceptable gain in bodyweight during the study”, except for one female administered 0.5 g/kg bw and one female given 1 g/kg bw who showed a body weight loss during the first and second week, respectively.
Gross pathology:
Haemorrhagic or abnormally red lungs, dark liver, dark or pale kidneys, gaseous distention of the stomach, dark, hardened or thickened gastric mucosa and haemorrhage of the small intestine were noted at necropsy of animals that died during the study. Sloughing of the non-glandular epithelium of the stomach with a raised limiting edge were noted in females receiving 0.5 and 1 g/kg bw killed at the end of the study period. Two female rats were found cannibalised, therefore necropsy was noted performed.
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In an OECD guideline study, the acute oral LD50 of tetraamminepalladium hydrogen carbonate in the female rat was reported to be 933 mg/kg bw .
Executive summary:

The acute oral toxicity of tetraamminepalladium hydrogen carbonate was assessed in rats, in a study conducted according to OECD Test Guideline 401.

In the range finding study, one male and one female rat received a single dose of 2000 mg /kg bw by oral gavage. The male was found dead two days after dosing whereas the female had no signs of systemic toxicity at day 5.

Therefore, in the main study, groups of 5 females were administered 500, 1000 or 2000 mg/kg bw of the test material and a group of 5 male rats received 2000 mg/kg bw. All 10 rats receiving 2000 mg/kg bw died by day 3 of the observation period, whilst 3 of 5 females receiving 1000 mg/kg bw died on days 4 to 6. No deaths were seen in the low dose females, following the 14-day observation period. The study authors conclude that the acute oral median lethal dose (LD50) of the test material in females rats is 933 mg/kg bw. “No significant difference in toxicity was noted between male and female animals”.

Based on the results of this study, tetraamminepalladium hydrogen carbonate should be classified for acute oral toxicity (category 4) according to EU CLP criteria (EU 1272/2008).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
933 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

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
9 January 1997 to 23 January 1997
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Guideline study, to GLP, on closely-related surrogate
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd, Margate, Kent
- Age at study initiation: 8-12 weeks
- Weight at study initiation: Males-219-244 g; Females-206-236 g
- Fasting period before study: No data
- Housing: Individually during exposure period; groups of five (by sex) for the remainder of the test
- Diet (e.g. ad libitum): Ad libitum
- Water (e.g. ad libitum): Ad libitum
- Acclimation period: Minimum 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21 deg C
- Humidity (%): 41-55%
- Air changes (per hr): 15/hour
- Photoperiod (hrs dark / hrs light): 12 hours continuous light followed by 12 hours continuous dark

IN-LIFE DATES: From: 9 January 1997 To: 23 January 1997
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: Shorn skin
- % coverage: 10% of total body surface area
- Type of wrap if used: A piece of surgical gauze was placed over the treatment area and semi-occluded with a piece of self-adhesive bandage which was further secured with a piece of Blenderm wrapped around each end

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Treated skin and surrounding hair were wiped with cotton wool moistened with distilled water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Concentration (if solution): Not applicable
- Constant volume or concentration used: yes
- For solids, paste formed: Test material was moistened with distilled water prior to use

VEHICLE
- Amount(s) applied (volume or weight with unit): Not applicable
- Concentration (if solution): Not applicable
- Lot/batch no. (if required): Not applicable
- Purity: Not applicable
Duration of exposure:
24-hour
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Toxicity-0.5, 1, 2 and 4 hours after dosing and subsequently once daily; Weighing-Day 0, 7 and 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: erythema and eschar formation, oedema formation
Statistics:
Using the mortality data obtained, an estimate of the acute dermal median lethal dose (LD50) of the test material was made
Preliminary study:
Not applicable
Sex:
male
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: CL not applicable
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: CL not applicable
Mortality:
There were no deaths in any of the 10 animals throughout the course of the study
Clinical signs:
No signs of systemic toxicity were noted during the study
Body weight:
All animals showed an expected gain in bodyweight during the study, except for 2 females which showed body weight loss or no gain in bodyweight during the first week and subsequently showed expected gain in bodyweight during the second week
Gross pathology:
No abnormalities were noted at necropsy
Other findings:
- Organ weights: No data
- Histopathology: No data
- Potential target organs: No data
- Other observations: No signs of skin irritation were noted during the study
Interpretation of results:
GHS criteria not met
Conclusions:
In a OECD guideline study, to GLP, the acute dermal LD50 of tetrammine palladium hydrogen carbonate was found to be greater than 2000 mg/kg bw.
Executive summary:

The acute dermal toxicity of tetrammine palladium hydrogen carbonate was evaluated in an OECD Test Guideline 402 study, conducted according to GLP. The test material was applied to the shorn skin of Sprague-Dawley CD rats (5/sex), under a semi-occlusive covering, and removed (by gentle washing) after 24 hr.

There were no signs of systemic toxicity, mortality or pathological findings during the 14-day observation period. Therefore, the acute dermal median lethal dose (LD50) of the test material was found to be greater than 2000 mg/kg bw.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Overall, good-quality database which meets REACH Standard Information Requirements.

Additional information

No relevant acute toxicity human data were identified.

 

The acute oral toxicity of tetraamminepalladium hydrogen carbonate was assessed in rats, in a study conducted according to OECD Test Guideline 401. In the range finding study, one male and one female rat received a single dose of 2000 mg/kg bw by oral gavage. The male was found dead two days after dosing whereas the female had no signs of systemic toxicity at day 5. Therefore, in the main study, groups of 5 females were administered 500, 1000 or 2000 mg/kg bw of the test material and a group of 5 male rats received 2000 mg/kg bw. All 10 rats receiving 2000 mg/kg bw died by day 3 of the observation period, whilst 3 of 5 females receiving 1000 mg/kg bw died on days 4 to 6. No deaths were seen in the low dose females, following the 14-day observation period. The study authors conclude that the acute oral median lethal dose (LD50) of the test material in female rats is 933 mg/kg bw. “No significant difference in toxicity was noted between male and female animals” (Allen, 1995a).

 

The acute dermal toxicity of tetraamminepalladium hydrogen carbonate was evaluated in an OECD Test Guideline 402 study, conducted according to GLP. The test material was applied to the shaved skin of rats (5/sex), under a semi-occlusive covering, and removed (by gentle washing) after 24 hr. There were no signs of systemic toxicity or mortality during the 14-day observation period, and no adverse pathology was found. Therefore, the acute dermal LD50 of the test material was found to be greater than 2000 mg/kg bw (Allen, 1997a). 

Tetraamminepalladium hydrogen carbonate is considered to fall within the scope of the read-across category "tetraamminepalladium salts". See IUCLID section 13 for full read-across justification report.

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.



Justification for selection of acute toxicity – oral endpoint
OECD guideline study, with limitations, and the only acute oral toxicity study available.

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

Justification for classification or non-classification

Based on the results of the available and reliable acute oral rat study with tetraamminepalladium hydrogen carbonate, tetraamminepalladium dichloride should be classified for acute oral toxicity (category 4) according to EU CLP criteria (EC 1272/2008).

 

No classification for acute dermal toxicity is required, based on the results of the available and reliable acute dermal rat study with tetraamminepalladium hydrogen carbonate.

 

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