Triammonium hexachlororhodate

Endpoint summary

Key value for chemical safety assessment

Genetic toxicity in vitro

Description of key information

Ammonium hexachlororhodate was mutagenic in a bacterial reverse mutation assay using Salmonella typhimurium strains TA97a, TA98, TA100 and TA102 when tested in the presence and absence of a rat liver metabolic activation system (Bunger et al., 1996).

 

Evidence of DNA damage was observed when triammonium hexachlororhodate was tested in the absence of metabolic activation in a bacterial SOS chromotest (Lantzsch and Gebel, 1997).

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 stated

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Not to current international guidelines, but scientifically acceptable

Guideline:

other: Revised test protocol of Maron and Ames (1983)

Version / remarks:

The study differed principally from OECD TG471 in that only four bacterial strains were tested. The recommended strain TA1535 was ommitted.

Principles of method if other than guideline:

Bacterial reverse mutation assay. The study differed principally from OECD TG471 in that only four bacterial strains were tested. The recommended strain TA1535 was ommitted.

GLP compliance:

not specified

Type of assay:

bacterial reverse mutation assay

Species / strain / cell type:

S. typhimurium, other: TA97a, TA98, TA100 and TA102

Metabolic activation:

with and without

Metabolic activation system:

Sprague-Dawley rat liver, Induced with Phenobarbital and beta-naphthoflavone

Test concentrations with justification for top dose:

The test substance was dissolved in distilled water and diluted to 5-500 ug/plate [probably 10, 50, 100 or 500 ug/plate] in all four tester strains , in the absence or presence of (4% and 10%) S9. The number of revertant colonies on the plates were recorded after 48 hours of incubation in the dark at 37degC.

Negative solvent / vehicle controls:

yes

Remarks:

Distilled water

Positive controls:

yes

Positive control substance:

methylmethanesulfonate

Positive controls:

yes

Positive control substance:

other: 2-aminofluorene

Details on test system and experimental conditions:

METHOD OF APPLICATION: in agar (plate incorporation)

DURATION
- Exposure duration: 48 hr in dark

NUMBER OF REPLICATIONS: Tests done in duplicate and repeated at least three times

Evaluation criteria:

For the test substance to be considered mutagenic, a two-fold (or more) increase in the mean revertant numbers must be observed in the plates containing the test substanced compared to the spontaneous reversion rate.

Species / strain:

S. typhimurium, other: TA97a, TA98, TA100 and TA102

Metabolic activation:

with

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Species / strain:

S. typhimurium, other: TA97a, TA98 and TA102

Metabolic activation:

without

Genotoxicity:

positive

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Species / strain:

S. typhimurium, other: TA100

Metabolic activation:

without

Genotoxicity:

negative

Cytotoxicity / choice of top concentrations:

cytotoxicity

Vehicle controls validity:

valid

Additional information on results:

The test substance caused a 2- to 10-fold increase in revertants in all four tester strains (compared with spontaneous reversion rates), in the presence of S9. In the absence of S9, a 2- to 10-fold increase in reversion rates was seen in three tester strains, whereas in TA100 there was no evidence of a mutagenic effect. "The increase in reverse mutation rates in the samples that tested positive was dosage-dependent".

High doses of the metal compounds proved toxic to the tester strains", resulting in a thinning of the background bacterial lawn. Although no actual data were provided for ammonium hexachlororhodate, the minimum toxic dose for the rhodium salts was apparently 500 ug/plate.

Conclusions:

Interpretation of results (migrated information):
positive

Ammonium hexachlororhodate was mutagenic in a bacterial reverse mutation assay using Salmonella typhimurium strains TA97a, TA98, TA100 and TA102 when tested in the presence and absence of a rat liver metabolic activation system.

Executive summary:

In a bacterial reverse mutation assay,similar to OECD Test Guideline 471, ammonium hexachlororhodate was tested for mutagenic activity using Salmonella typhimurium strains TA97a, TA98, TA100 and TA102 in both the presence and absence of a metabolic activation system derived from phenobarbital and beta-naphthoflavone induced rat livers (S9). (The recommended strain TA1535 was omitted.) A mutagenic effect was seen in all four strains in the presence of metabolic activation and in all but strain TA100 in its absence.

 

In conclusion, the test substance was mutagenic in Salmonella typhimurium, in the presence and absence of metabolic activation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (positive)

Genetic toxicity in vivo

Description of key information

No data identified.

Endpoint conclusion

Endpoint conclusion:

no study available

Mode of Action Analysis / Human Relevance Framework

No data identified.

Additional information

In a bacterial reverse mutation assay,similar to OECD Test Guideline 471,ammonium hexachlororhodate was tested for mutagenic activity using Salmonella typhimurium strains TA97a, TA98, TA100 and TA102 in both the presence and absence of a metabolic activation system derived from phenobarbital and beta-naphthoflavone induced rat livers (S9).(The recommended strain TA1535 was omitted.)A mutagenic effect was seen in all four strains in the presence of metabolic activation and in all but strain TA100 in its absence. In conclusion, the test substance was mutagenic in Salmonella typhimurium, in the presence and absence of metabolic activation(Bunger et al., 1996).

 

In a non-guideline study, the ability of triammonium hexachlororhodate to induce DNA damage in the bacterium Escherichia coli (strain PQ37), in an SOS chromotest, was assessed (in the absence of a metabolic activation system). A maximum induction factor (IFmax, in the absence of cytotoxicity) of 35.25 was reported, indicating a genotoxic effect. In conclusion, the test substance showed an ability to induce DNA damage in a bacterial SOS chromotest in the absence of metabolic activation Lantzsch & Gebel, 1997).

No in vivo genotoxicity data were identified for triammonium hexachlororhodate.

 

In 2002, the Dutch Expert Committee on Occupational Standards (DECOS) reviewed the genotoxic and carcinogenic potential of rhodium and rhodium compounds. In its evaluation, the Committee found that several water-soluble rhodium (III) compounds were genotoxic in bacteria and in mammalian cells (DECOS, 2002). Based mainly on rhodium trichloride (in vitro and in vivo) data, the Committee was of the opinion that all water-soluble rhodium (III) compounds are a human health concern in regards to these endpoints.

 

 

References

DECOS (2002). Dutch Expert Committee on Occupational Standards, a committee of the Health Council of the Netherlands. Rhodium and compounds: Evaluation of the carcinogenicity and genotoxicity.

Justification for classification or non-classification

The weight-of-the evidence indicates that the water-soluble rhodium (III) compounds should be considered as potentially mutagenic and, as such, triammonium hexachlororhodate is self-classified for germ cell mutagenicity (category 2) according to EU CLP criteria (EC 1272/2008).