Palladium

Endpoint summary

Description of key information

No relevant acute oral, dermal or inhalation toxicity data were identified with palladium.
The substance is considered to fall withing the scope of the read-across category 'Palladium, palladium monoxide and Palladium dihydroxide'. In an acute oral toxicity study, groups of male Sprague-Dawley rats were administered palladium monoxide by stomach tube and observed for 14 days. Using the prescribed statistical method, the acute oral median lethal dose (LD50) was found to exceed 4.9 g/kg bw. Via a weight-of-evidence argumentation, the registrants consider it justified to avoid in vivo testing for acute toxicity(oral) for this substance (as exemplified in ECHA Guidance R.7a Figure 7.4-4) and consider the substance of low acute hazard via the oral route with an assumed LD50>2000 mg/kg(bw). Based on this experimental evidence, palladium is considered to have an LD50>2000 mg/kg(bw).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Conducted prior to standard OECD/EU test guidelines and GLP. While there is somewhat limited reporting of methods and results, the study appears scientifically acceptable.

Qualifier:

no guideline followed

Principles of method if other than guideline:

In the lethal dose experiments, male Sprague-Dawley rats received the tested palladium salt by gavage and were observed through a 14-day period. The LD50 values were calculated by the method of Litchfield and Wilcoxon. The exact dosing strategy is unclear and no details on pathological assessment are given.

GLP compliance:

no

Remarks:

(prior to GLP)

Test type:

other: No data

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 100-110 g
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): Presumably ad libitum
- Water (e.g. ad libitum): Presumably ad libitum
- Acclimation period: 1-1.5 weeks

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: gavage

Vehicle:

not specified

Details on oral exposure:

No data

Doses:

No data

No. of animals per sex per dose:

No data

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: No data
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: No data

Statistics:

The LD50 values were calculated by the method of Litchfield and Wilcoxon.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 4 900 mg/kg bw

Based on:

test mat.

Remarks on result:

other: CL was not determined

Mortality:

Palladium salts often kill 4-10 days after administration. An LD50 of >40 mmol/kg bw, using a molecular weight of approximately 122.42 g/mol, equates to >4896.8 mg/kg bw.

Clinical signs:

other: No data

Gross pathology:

No data

Other findings:

No data

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

In an acute oral toxicity study, an LD50 of greater than 4.9 g/kg bw was reported in male rats gavaged with palladium monoxide, and observed for up to 14 days.

Executive summary:

In an acute oral toxicity study, groups of male Sprague-Dawley rats were administered palladium monoxide by stomach tube and observed for 14 days. Using the prescribed statistical method, the acute oral median lethal dose (LD50) was found to exceed 4.9 g/kg bw.

Based on the results of this study, palladium monoxide should not be classified for acute oral toxicity according to EU CLP criteria (EU 1272/2008).

Reference 2

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Conducted prior to standard OECD/EU test guidelines and GLP. While there is somewhat limited reporting of methods and results, the study appears scientifically acceptable.

Justification for type of information:

Substance considered to fall within the scope of the read-across category 'Palladium, Palladium monoxide and Palladium dihydroxide'

Reason / purpose for cross-reference:

read-across source

Qualifier:

no guideline followed

Principles of method if other than guideline:

In the lethal dose experiments, male Sprague-Dawley rats received the tested palladium salt by gavage and were observed through a 14-day period. The LD50 values were calculated by the method of Litchfield and Wilcoxon. The exact dosing strategy is unclear and no details on pathological assessment are given.

GLP compliance:

no

Remarks:

(prior to GLP)

Test type:

other: No data

Limit test:

no

Species:

rat

Strain:

Sprague-Dawley

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: No data
- Age at study initiation: 4-5 weeks
- Weight at study initiation: 100-110 g
- Fasting period before study: No data
- Housing: No data
- Diet (e.g. ad libitum): Presumably ad libitum
- Water (e.g. ad libitum): Presumably ad libitum
- Acclimation period: 1-1.5 weeks

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: gavage

Vehicle:

not specified

Details on oral exposure:

No data

Doses:

No data

No. of animals per sex per dose:

No data

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: No data
- Necropsy of survivors performed: No data
- Other examinations performed: clinical signs, body weight,organ weights, histopathology, other: No data

Statistics:

The LD50 values were calculated by the method of Litchfield and Wilcoxon.

Sex:

male

Dose descriptor:

LD50

Effect level:

> 4 900 mg/kg bw

Based on:

test mat.

Remarks on result:

other: CL was not determined

Mortality:

Palladium salts often kill 4-10 days after administration. An LD50 of >40 mmol/kg bw, using a molecular weight of approximately 122.42 g/mol, equates to >4896.8 mg/kg bw.

Clinical signs:

other: No data

Gross pathology:

No data

Other findings:

No data

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study, an LD50 of greater than 4.9 g/kg bw was reported in male rats gavaged with palladium monoxide, and observed for up to 14 days.

Executive summary:

In an acute oral toxicity study, groups of male Sprague-Dawley rats were administered palladium monoxide by stomach tube and observed for 14 days. Using the prescribed statistical method, the acute oral median lethal dose (LD50) was found to exceed 4.9 g/kg bw.

Based on the results of this study, palladium monoxide should not be classified for acute oral toxicity according to EU CLP criteria (EU 1272/2008).

The substance is considered to fall within the scope of the read-across category 'Palladium, Palladium monoxide and Palladium dihydroxide'

 

Reference 3

Endpoint:

acute toxicity: oral

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

Substance considered to fall within the scope of the read-across category 'Palladium, Palladium monoxide and Palladium dihydroxide'

Reason / purpose for cross-reference:

read-across source

Principles of method if other than guideline:

Weight-of-Evidence argumentation

GLP compliance:

no

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

Via a weight-of-evidence argumentation, the registrants consider it justified to avoid in vivo testing for acute toxicity(oral) for palladium dihydroxide (as exemplified in ECHA Guidance R.7a Figure 7.4-4) and consider the substance of low acute hazard via the oral route with an assumed LD50>2000 mg/kg(bw).

Executive summary:

Via a weight-of-evidence argumentation, the registrants consider it justified to avoid in vivo testing for acute toxicity(oral) for palladium dihydroxide (as exemplified in ECHA Guidance R.7a Figure 7.4-4) and consider the substance of low acute hazard via the oral route with an assumed LD50>2000 mg/kg(bw).

The substance is considered to fall within the scope of the read-across category 'Palladium, Palladium monoxide and Palladium dihydroxide'

 

Reference 4

Endpoint:

acute toxicity: oral

Type of information:

other: weight of evidence justification

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Principles of method if other than guideline:

Weight-of-Evidence argumentation

GLP compliance:

no

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Interpretation of results:

GHS criteria not met

Conclusions:

Via a weight-of-evidence argumentation, the registrants consider it justified to avoid in vivo testing for acute toxicity(oral) for this substance (as exemplified in ECHA Guidance R.7a Figure 7.4-4) and consider the substance of low acute hazard via the oral route with an assumed LD50>2000 mg/kg(bw).

Executive summary:

Via a weight-of-evidence argumentation, the registrants consider it justified to avoid in vivo testing for acute toxicity(oral) for this substance (as exemplified in ECHA Guidance R.7a Figure 7.4-4) and consider the substance of low acute hazard via the oral route with an assumed LD50>2000 mg/kg(bw).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

> 2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

exposure considerations

Justification for data waiving:

the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the physicochemical and toxicological properties suggest no potential for a significant rate of absorption through the skin

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

No relevant human or laboratory animal acute toxicity data were identified with palladium as test item. However, bioavailability considerations provide good support for the conclusion that palladium is associated with a low acute hazard potential and that substance specific acute toxicity studies can be waived.

 

Palladium is considered to be non-bioavailable following oral and dermal exposure, as evidenced by transformation/dissolution (Skaeff 2011 - cf. section 4.8) and bio-elution test data (Rodrigues 2012a,b,c,d,e - cf. section 7.12). Further, the existing in vivo skin irritation/sensitisation study (Arcelin, 1992), albeit somewhat limited in its assessment of general systemic effects, indicates a lack of acute systemic toxicity following dermal exposure (repeated 24-hr semi-occlusive skin contact). Moreover, skin contact during production and/or use is expected to be negligible and no general population exposure to palladium is anticipated.

 

The substance is considered to fall withing the scope of the read-across category 'Palladium, palladium monoxide and Palladium dihydroxide'. In an acute oral toxicity study, groups of male Sprague-Dawley rats were administered palladium monoxide by stomach tube and observed for 14 days. Using the prescribed statistical method, the acute oral median lethal dose (LD50) was found to exceed 4.9 g/kg bw. Via a weight-of-evidence argumentation, the registrants consider it justified to avoid in vivo testing for acute toxicity(oral) for this substance (as exemplified in ECHA Guidance R.7a Figure 7.4-4) and consider the substance of low acute hazard via the oral route with an assumed LD50>2000 mg/kg(bw). Based on this experimental evidence, palladium is considered to have an LD50>2000 mg/kg(bw).

 

It 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 (Selck and Parr 2012 a,b - cf section 4.5).

 

Since a substance is required to be bioavailable in order to induce systemic toxicity following acute exposure, palladium is not considered to pose an acute toxicity hazard. Finally, for animal welfare reasons, conducting new in vivo toxicity tests is considered a last resort. Consequently, no testing for acute toxicity of palladium is considered justified.

Justification for classification or non-classification

No acute toxicity data are available for palladium. However, such effects are not expected, based on a lack of bioavailability following exposure via the oral, dermal and inhalation routes, and read-across from palladium monoxide and palladium dihydroxide. As such, there is no evidence to classify palladium for acute toxicity according to EU CLP criteria (EC 1272/2008).