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Description of key information

In an OECD Test Guideline 425 study, to GLP, the acute oral LD50 value of palladium di(4-oxopent-2-en-2-oate) was estimated to be 2000 mg/kg bw (Matting, 2013).

In a limit test conducted according to OECD Test Guideline 402, and to GLP, the acute dermal LD50 in rats of palladium di(4-oxopent-2-en-2-oate) following 24-hr skin contact was more than 2000 mg/kg bw (Matting, 2014).

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:
27 August to 23 October 2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: OECD guideline study, to GLP.
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
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
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
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

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

 

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.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
2 000 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:
18 February to 6 March 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study performed to GLP.
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))
Qualifier:
according to guideline
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/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: "Young adult rats"
- Weight at study initiation: 200-254 g
- Fasting period before study: No data
- Housing: Individually in polypropylene/polycarbonate cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20.4-22.7
- Humidity (%): 31-45%
- Air changes (per hr): 15-20
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 12 February 2014 To: 4-6 March 2014
Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: No data
- % coverage: About 10%
- Type of wrap if used: Sterile gauze pad covered in a patch with an adhesive hypoallergenic plaster. The entire trunk of the animal was wrapped in a semi-occlusive plastic wrap

REMOVAL OF TEST SUBSTANCE
- Washing (if done): With water (at body temperature) at the end of the exposure period
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: No data
- For solids, paste formed: Dampened with water
Duration of exposure:
24 hours
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations at 1 and 5 hours after treatment, then once daily. Body weight recorded just before treatment (day 0) and on study days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, skin irritation, body weight
Statistics:
Not performed
Preliminary study:
Not performed
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: No mortalities seen
Mortality:
No deaths were seen.
Clinical signs:
At 2000 mg/kg bw, the test item caused slightly decreased activity and a hunched back in four animals (2 females and 2 males) and piloerection in one male. All animals were symptom free from 10 days after the treatment until the end of the observation period.
Body weight:
Body weight loss was seen in 1 male (-3 g) and two females (-48 and -29 g) between days 0 and 7. Animals gained weight for the remainder of the study.
Gross pathology:
No adverse findings observed.
Other findings:
- Other observations: Yellowish staining was observed on the treated skin in all animals after treatment.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a limit test conducted according to OECD Test Guideline 402, and to GLP, the acute dermal LD50 in rats of palladium di(4-oxopent-2-en-2-oate) following 24-hr skin contact was more than 2000 mg/kg bw .
Executive summary:

In a limit test performed in accordance with OECD Test Guideline 402 and to GLP, young Wistar rats (5/sex) were given a 24-hour semi-occlusive application of palladium di(4-oxopen-2-en-2-oate) at 2000 mg/kg bw (dampened with water to ensure good contact with the skin). Animals were observed for 14 days after treatment for deaths, as well as changes in body weight and clinical signs of toxicity. At necropsy, any gross abnormalities were reported.

 

No deaths were seen over the 14-day observation period; the acute dermal LD50 was determined to be more than 2000 mg/kg bw. Based on the results of this study, classification for acute dermal toxicity under the EU CLP regulation would not be required for the test compound.

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 palladium 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. Based on the results of this acute oral rat study, palladium di(4-oxopen-2-en-2-oate) should cautiously be classified for acute oral toxicity (category 4) according to EU CLP criteria (EC 1272/2008).

In a limit test performed in accordance with OECD Test Guideline 402 and to GLP, young Wistar rats (5/sex) were given a 24-hour semi-occlusive application of palladium di(4-oxopen-2-en-2-oate) at 2000 mg/kg bw (dampened with water to ensure good contact with the skin). Animals were observed for 14 days after treatment for deaths, as well as changes in body weight and clinical signs of toxicity. At necropsy, any gross abnormalities were reported. No deaths were seen over the 14-day observation period; the acute dermal LD50 was determined to be more than 2000 mg/kg bw (Matting, 2014). Based on the results of this study, classification for acute dermal toxicity under the EU CLP regulation is not required.

 

No relevant 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, to GLP, and the only acute oral toxicity study available

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

Justification for classification or non-classification

Based on the results of the available acute oral rat study, palladium di(4-oxopent-2-en-2-oate) 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 palladium di(4-oxopent-2-en-2-oate).

 

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