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Administrative data

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

No reliable genotoxicity data for palladium monoxide were identified.

In a limited dominant lethal mutation assay, no evidence of genotoxicity was seen following a single subcutaneous injection of powdered palladium oxide [oxidation state not clear] to male mice prior to mating with untreated females (Arnold et al., 1975).

Palladium dichloride was not mutagenic in a good-quality bacterial reverse mutation (Ames) assay when tested up to the limit of toxicity in the presence and absence of metabolic activation (Mortelmans et al., 1986).

Link to relevant study records
Reference
Endpoint:
in vitro gene mutation study in bacteria
Remarks:
Type of genotoxicity: gene mutation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
Not reported
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Good quality study, limited reporing. Similar to procedure described in OECD Test Guideline 471 (bacterial reverse mutation test) but compliance to current guidelines would have required an additional bacterial strain to detect certain oxidising mutagens and cross-linking agents (i.e. TA102 and/or E.coli).
Qualifier:
no guideline followed
Principles of method if other than guideline:
Similar procedure to OECD guideline 471:bacterial reverse mutation test, although only four strains of bacteria were tested. Current guidelines recommend an additional bacterial strain is tested to detect certain oxidising mutagens and cross-linking agents (i.e. TA102 and/or E.coli).
GLP compliance:
not specified
Type of assay:
bacterial reverse mutation assay
Target gene:
Histidine
Species / strain / cell type:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Metabolic activation system:
Aroclor 1254-induced rat and hamster liver S-9 (10%)
Test concentrations with justification for top dose:
0
0.3 ug/plate (without metabolic activation only)
1.0 ug/plate (without metabolic activation only)
3.0 ug/plate (with and without metabolic activation)
10.0 ug/plate (with and without metabolic activation)
33.0 ug/plate (with and without metabolic activation)
100 ug/plate (with metabolic activation only)
333 ug/plate (with metabolic activation only; complete toxicity seen)
Vehicle / solvent:
Distilled water
Untreated negative controls:
no
Negative solvent / vehicle controls:
yes
True negative controls:
no
Positive controls:
yes
Positive control substance:
9-aminoacridine
sodium azide
other: 4-nitro-o-phenylenediamine; 2-aminoanthracene
Details on test system and experimental conditions:
METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Preincubation period: 20 min at 37 deg C
- Exposure duration: 48 hr at 37 deg C

Cytotoxicity assessed by observation of background lawn.

Plates were examined for the presence of precipitate.

Three plates per dose level were evaluated.
Evaluation criteria:
Revertant colonies counted.
Evaluation criteria were those used by Haworth et al. (1983):
Mutagenic response - a dose-related, reproducible increase in the number of revertants over background (even if the increase is less than two-fold)
Non-mutagenic response - no increase in the number of revertants is elicited
Questionable response - when there is an absence of a clear-cut, dose-related increase in revertants; when the dose-related increases in the number of revertants are not reproducible; when the response is of insufficient magnitude to support a determination of mutagenicity
Statistics:
Not reported (but revertants were reported as: mean +/-SEM).
Species / strain:
S. typhimurium TA 1535, TA 1537, TA 98 and TA 100
Metabolic activation:
with and without
Genotoxicity:
negative
Cytotoxicity / choice of top concentrations:
cytotoxicity
Vehicle controls validity:
valid
Untreated negative controls validity:
not applicable
Positive controls validity:
valid
Remarks on result:
other: all strains/cell types tested
Remarks:
Migrated from field 'Test system'.
Conclusions:
Interpretation of results (migrated information):
negative

Palladium dichloride was not mutagenic in a good-quality bacterial reverse mutation (Ames) assay when tested up to the limit of toxicity in the presence and absence of metabolic activation.
Executive summary:

In a good quality study, similar to procedure described in OECD Test Guideline 471, palladium dichloride was tested up to the limit of toxicity in a bacterial reverse mutation assay in four strains of Salmonella typhimurium (TA98, TA100, TA1535 and TA1537), in the presence and absence of a S9 mammalian metabolic activation system. [Current guidelines recommend an additional bacterial strain to detect certain oxidising mutagens and cross-linking agents (i.e. TA102 and/or E.coli).]

The maximum doses tested were 33 ug/plate in the absence of S9 and 333 ug/plate in its presence (where complete cytotoxicity was seen; the next-lowest tested dose was 100 ug/plate). There was no convincing evidence of a mutagenic effect, and no dose response in any of the strains tested, either in the presence or absence of S9.

In conclusion, under the conditions of this study, palladium dichloride was not mutagenic to four strains of S. typhimurium, tested up to the limit of toxicity, in the presence and absence of S9.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed (negative)

Genetic toxicity in vivo

Description of key information

No in vivo gentoxicity data were identified or are required at this tonnage.

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

No reliable genotoxicity data for palladium monoxide were identified.

In a limited (non-guideline, pre-GLP) study, palladium oxide [oxidation state not clear] was tested for its ability to induce heritable genetic damage (usually indicative of chromosome aberrations) in a dominant lethal mutation assay in albino mice. Single subcutaneous injections of powdered material (100 mg as the metal) in saline (1 ml) were given to 10 males before housing with 3 untreated, virgin females/week for 6 consecutive weeks. The percentage of implants that resulted in early foetal deaths (in utero) did not differ from those measured in saline-treated controls. In conclusion, a mutagenic effect (indicative of chromosome aberrations) was not indicated for palladium oxide under the conditions of this limited dominant lethal mutation assay in mice (Arnold et al., 1975). It is worth noting, that the study has several deviations (e.g. inappropriate route, single dose, no positive control) and does not meet the acceptance criteria listed in the current OECD Test Guideline (478).

In a good quality study, similar to the procedure described in OECD Test Guideline 471, palladium dichloride was tested up to the limit of toxicity in a bacterial reverse mutation assay in four strains of Salmonella typhimurium (TA98, TA100, TA1535 and TA1537), in the presence and absence of a S9 mammalian metabolic activation system. [Current guidelines recommend an additional bacterial strain to detect certain oxidising mutagens and cross-linking agents (i.e. TA102 and/or E. coli).] The maximum doses tested were 33 µg/plate in the absence of S9 and 333 µg/plate in its presence (where complete cell death occurred; the next-lowest tested dose was 100 µg/plate). There was no convincing evidence of a mutagenic effect, and no dose response in any of the strains tested, either in the presence or absence of S9. In conclusion, under the conditions of this study, palladium dichloride was not mutagenic to four strains of S. typhimurium, tested up to the limit of toxicity, in the presence and absence of S9 (Mortelmans et al., 1986).

 

Palladium dichloride is considered to fall within the scope of the read-across category "uncomplexed and partially-complexed palladium compounds". See section 13 for full justification report.

Justification for classification or non-classification

No evidence of genotoxic activity has been seen with palladium dichloride in a reliable in vitro bacterial mutagenicity assay. In support, no evidence of genotoxicity was seen in a limited dominant lethal mutation assay with palladium monoxide. As such, classification of palladium monoxide for germ cell mutagenicity is not warranted, according to EU CLP criteria (EC 1272/2008).