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EC number: 240-973-0 | CAS number: 16919-58-7
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian cell study: DNA damage and/or repair
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 01 May 2020 - 09 Jul 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 01 May 2020 - 09 Jul 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- 29 July 2016
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian erythrocyte micronucleus test
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Lot/batch number of test material: AI2707.
- Expiration date of the lot/batch: 25 August 2020 (from CoA).
- Purity: 99%.
- Purity test date: CoA issued 22 January 2020.
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature, protected from light.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None.
- Final preparation of a solid: Test item was suspended in corn oil.
FORM AS APPLIED IN THE TEST (if different from that of starting material)
: Suspension. - Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- The Wistar Han rat was the species and strain of choice because it is a readily available rodent which is commonly used for genotoxicity testing, with documented susceptibility to a wide range of toxic items. Moreover, historical control background data has been generated with this strain.
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: 6 weeks.
- Weight at study initiation: 150 ± 7.8 g (Mean body weight ± SD).
- Assigned to test groups randomly: Yes.
- Fasting period before study: No.
- Housing: Up to 5 animals of the same sex and in the same dosing group were housed together.
- Diet: Commercial pellets ad libitum, except during designated procedures.
- Water: Tap water, ad libitum.
- Acclimation period: At least 6 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C.
- Humidity (%): 40 to 70%.
- Air changes (per hr): ≥ 10.
- Photoperiod: 12 hrs light/12 hrs dark, except during designated procedures.
IN-LIFE DATES:
From: Approx. 20 Mar 2020 (6 weeks before experimental start date).
To: 10 Jun 2020. - Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: corn oil.
- Source of vehicle: Fagron Farmaceuticals, Capelle a/d IJssel, the Netherlands.
- Justification for choice of solvent/vehicle: corn oil is a widely used standard vehicle for in vivo animal experiments.
- Concentration of test material in vehicle: analytical verification confirmed that the measured test item concentrations in vehicle were 109%, 103% and 108% of the nominal values for group 2, group 3 and group 4 (i.e. 37.5, 75 and 105 mg/kg(bw) respectively). Accuracy and homogeneity (coefficient of variation ≤ 10%) of the test item in vehicle was confirmed.
- Amount of vehicle (if gavage or dermal): 10 mL/kg bw
- Stability of test item in vehicle: stability of test item suspended in vehicle demonstrated for 4 hours at room temperature under normal laboratory conditions(sufficient for the dosing of all test animals), after which unused test item formulations were discarded. - Duration of treatment / exposure:
- Three consecutive days.
- Frequency of treatment:
- Daily.
- Post exposure period:
- Tissue samples taken 3 - 4 hours after administration of final dose.
- Dose / conc.:
- 37.5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 75 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 150 mg/kg bw/day (actual dose received)
- Remarks:
- Test item-related mortality was observed in a preliminary dose range finding study in which three male and three female rats received three consecutive daily doses of 200 mg/kg bw, and one animal of each sex received 300 mg/kg bw/day. Clinical signs of toxicity (ataxia, lethargy, hunched posture, rough coat and diarrhoea) were observed at 150 mg/kg bw/day, which was determined to be the maximum tolerated dose.
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Cyclophosphamide.
- Route of administration: Gavage.
- Doses / concentrations: A single dose of 19 mg/kg bw, dissolved in physiological saline. - Tissues and cell types examined:
- Bone marrow from the femur.
- Details of tissue and slide preparation:
- The femurs were flushed with foetal calf serum and the cell suspension centrifuged. The supernatant was removed and a drop of the remaining cell suspension was spread across a clean slide and fixed with methanol. The slides were automatically stained with Giemsa using the Wright Stain Procedure.
The number of micronucleated polychromatic erythrocytes was initially counted in at least 4000 polychromatic erythrocytes (with a maximum deviation of 5%).Slides were scored at a magnification of 1000x.
The ratio of polychromatic to normochromatic erythrocytes was determined by counting and differentiating at least the first 1000 erythrocytes at the same time. Micronuclei were only counted in polychromatic erythrocytes. - Evaluation criteria:
- The test item was considered positive if all of the following criteria were met:
a) at least one treatment group showed a statistically significant increase in frequency of micronucleated polychromatic erythrocytes.
b) the increase was dose related.
c) the results were outside the 95% confidence limits of the historical control data.
If none of the above criteria were met, and bone marrow exposure to the test item occurred, the substance was considered negative.
The incidence of micronuclei was assessed in 4000 polychromatic erythrocytes per animal. - Statistics:
- ToxRat Professional v 3.2.1 (ToxRat Solutions® GmbH, Germany) was used for statistical
analysis of the data.
A test item is considered positive in the micronucleus test if all of the following criteria are
met:
a) At least one of the treatment groups exhibits a statistically significant (one-sided,
p < 0.05) increase in the frequency of micronucleated polychromatic erythrocytes
compared with the concurrent negative control
b) The increase is dose related when evaluated with a trend test.
c) Any of the results are outside the 95% control limits of the historical control data range.
A test item is considered negative in the micronucleus test if:
a) None of the treatment groups exhibits a statistically significant (one-sided, p < 0.05)
increase in the frequency of micronucleated polychromatic erythrocytes compared with
the concurrent negative control.
b) There is no concentration-related increase when evaluated with a trend test.
c) All results are within the 95% control limits of the negative historical control data range. - Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- yes
- Remarks:
- One high-dose animal died after the first dose, and was replaced by an additional animal. Clinical signs of toxicity were observed in the high-dose group: hunched posture (4/5 animals), lethargy (5/5 animals) and diarrhoea (1/5 animals).
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Platinum was quantifiable in plasma samples from high-dose (150 mg/kg bw/day) satellite animals 1, 3, 6 and 12 hours after completing the second day of treatment. Moreover, platinum was quantifiable in plasma samples from all high-dose animals taken at necropsy approximately 3 hours after the third dose. Therefore it was confirmed that the bone marrow was exposed to the test item. No test item was detected in the animals dosed with vehicle.
No statistically significant increase in the frequency of micronucleated polychromatic erythrocytes was observed.
Treated animals showed no decrease in the PCE:NCE ratio, indicating a lack of toxicity to the bone marrow. - Conclusions:
- Diammmonium hexachloroplatinate did not cause an increase in the number of micronucleated polychromatic erythrocytes in the bone marrow of rats administered up to 150 mg/kg bw/day by gavage on three consecutive days. As such, and as platinum was detected in the plasma of the test animals, diammonium hexachloroplatinate was concluded to be non-genotoxic in vivo.
- Executive summary:
The in vivo clastogenicity and aneugenicity of diammonium hexachloroplatinate, as evaluated by its ability to induce micronuclei in polychromatic erythrocytes, was assessed in a study following OECD 474 and according to GLP. Male Wistar rats (5/group) were given gavage doses of 37.5, 75 or 150 mg/kg bw/day of the test item on three consecutive days, or a vehicle control. The concurrent positive control group received a single dose of cyclophosphamide. Bone marrow was harvested from the femurs and assessed for micronuclei.
There was no increase in the number of micronucleated polychromatic erythrocytes in any treatment group. On that basis, diammonium hexachloroplatinate was concluded to be non-genotoxic under the conditions of this assay.
Mean Number of Micronucleated Polychromatic Erythrocytes and Ratio of Polychromatic/Normochromatic Erythrocytes | ||||||||
group | treatment | Dose (mg/kg body weight) | animal number | Number of micronucleated polychromatic erythrocytes (number per animal) | Number of micronucleated polychromatic erythrocytes (mean +/- SD) (1,2) | ratio polychromatic/ normochromatic erythrocytes (mean +/- SD) (1,3) | ||
1 | vehicle control | 0 | 1 | 4 | 4.6 | ± 1.1 | 1.11 | ± 0.16 |
2 | 5 | |||||||
3 | 3 | |||||||
4 | 5 | |||||||
5 | 6 | |||||||
2 | test item | 37.5 | 6 | 0 | 1.6 | ± 1.7 | 1.22 | ± 0.06 |
7 | 0 | |||||||
8 | 2 | |||||||
9 | 2 | |||||||
10 | 4 | |||||||
3 | test item | 75 | 11 | 0 | 2.4 | ± 1.5 | 1.18 | ± 0.18 |
12 | 2 | |||||||
13 | 3 | |||||||
14 | 4 | |||||||
15 | 3 | |||||||
4 | test item | 150 | 16 | 2 | 3.2 | ± 2.2 | 1.0 | ± 0.08 |
17 | 0 | |||||||
18 | 4 | |||||||
19 | 5 | |||||||
21 | 5 | |||||||
6 | Cyclophosphamide | 19 | 29 | 8 | 10.8 | ± 1.8 (4) | 0.91 | ± 0.07 |
30 | 12 | |||||||
31 | 12 | |||||||
32 | 10 | |||||||
33 | 12 |
Legend
(1) Five animals per treatment group.
(2) At least 4000 polychromatic erythrocytes were evaluated with a maximum deviation of 5%.
(3) The ratio was determined from at least the first 1000 erythrocytes counted.
(4) Significantly different from corresponding control group (Students t test, P < 0.001).
Dose-response relationship & statistics:
Test Item (comparison with the corresponding vehicle control group by using the Dunnett’s test): no significant differences
positive control: p-value (one sided) <0.001, significantly different from the corresponding vehicle control group by using the Student t-test
Distribution historical control data from experiments performed between June 2017 and June 2020. | |||
negative control data | positive control data | ||
mean number of micronucleated cells per 4000 cells | 3.6 | 44.6 | |
Standard deviation | 1.4 | 29.9 | |
number of obsevations | 41 | 38 | |
lower control limit (95% control limits) | 1 | -14 | |
upper control limit (95% control limits) | 6 | 103 |
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 020
- Report date:
- 2020
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 489 (In vivo Mammalian Alkaline Comet Assay)
- Version / remarks:
- 29 July 2016.
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian comet assay
Test material
- Reference substance name:
- Diammonium hexachloroplatinate
- EC Number:
- 240-973-0
- EC Name:
- Diammonium hexachloroplatinate
- Cas Number:
- 16919-58-7
- Molecular formula:
- Cl6Pt.2H4N
- IUPAC Name:
- diammonium hexachloroplatinate
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Physical description: Orange Powder
- Batch Number: YS1
- Storage and Handling: stored at room temperature in the dark
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Lot/batch number of test material: AI2707.
- Expiration date of the lot/batch: 25 August 2020 (from CoA).
- Purity: 99%.
- Purity test date: CoA issued 22 January 2020.
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature, protected from light.
TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None.
- Final preparation of a solid: Test item was suspended in corn oil.
FORM AS APPLIED IN THE TEST (if different from that of starting material)
: Suspension.
Test animals
- Species:
- rat
- Strain:
- Wistar
- Details on species / strain selection:
- The Wistar Han rat was the species and strain of choice because it is a readily available rodent which is commonly used for genotoxicity testing, with documented susceptibility to a wide range of toxic items. Moreover, historical control background data has been generated with this strain.
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: 6 weeks.
- Weight at study initiation: 150 ± 7.8 g (Mean body weight ± SD).
- Assigned to test groups randomly: Yes.
- Fasting period before study: No.
- Housing: Up to 5 animals of the same sex and in the same dosing group were housed together.
- Diet: Commercial pellets ad libitum, except during designated procedures.
- Water: Tap water, ad libitum.
- Acclimation period: At least 6 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 to 24°C.
- Humidity (%): 40 to 70%.
- Air changes (per hr): ≥ 10.
- Photoperiod: 12 hrs light/12 hrs dark, except during designated procedures.
IN-LIFE DATES:
From: Approx. 20 Mar 2020 (6 weeks before experimental start date).
To: 10 Jun 2020.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle(s)/solvent(s) used: corn oil.
- Source of vehicle: Fagron Farmaceuticals, Capelle a/d IJssel, the Netherlands.
- Justification for choice of solvent/vehicle: corn oil is a widely used standard vehicle for in vivo animal experiments.
- Concentration of test material in vehicle: analytical verification confirmed that the measured test item concentrations in vehicle were 109%, 103% and 108% of the nominal values for group 2, group 3 and group 4 (i.e. 37.5, 75 and 105 mg/kg(bw) respectively). Accuracy and homogeneity (coefficient of variation ≤ 10%) of the test item in vehicle was confirmed.
- Amount of vehicle (if gavage or dermal): 10 mL/kg bw
- Stability of test item in vehicle: stability of test item suspended in vehicle demonstrated for 4 hours at room temperature under normal laboratory conditions(sufficient for the dosing of all test animals), after which unused test item formulations were discarded. - Duration of treatment / exposure:
- Three consecutive days.
- Frequency of treatment:
- Daily.
- Post exposure period:
- Tissue samples taken 3 - 4 hours after administration of final dose.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 37.5 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 75 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 150 mg/kg bw/day (actual dose received)
- Remarks:
- Test item-related mortality was observed in a preliminary dose range finding study in which three male and three female rats received three consecutive daily doses of 200 mg/kg bw, and one animal of each sex received 300 mg/kg bw/day. Clinical signs of toxicity (ataxia, lethargy, hunched posture, rough coat and diarrhoea) were observed at 150 mg/kg bw/day, which was determined to be the maximum tolerated dose.
- No. of animals per sex per dose:
- 5
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- Ethyl methanesulphonate.
- Route of administration: Gavage.
- Doses / concentrations: 200 mg/kg bw, dissolved in physiological saline, administered twice.
Examinations
- Tissues and cell types examined:
- Cells were isolated from the liver, glandular stomach, duodenum and kidney.
- Details of tissue and slide preparation:
- Minced liver or kidney tissue was added to collagenase and dissolved in HBSS (saline). This suspension was shaken and centrifuged. The cell pellet was resuspended in HBSS and kept on ice prior to preparation of the slides.
Tissue from the glandular stomach and duodenum was stored on ice in "mincing buffer incomplete" (HBSS + EDTA). The surface epithelium of both the glandular stomach and duodenum was discarded as it contains a high proportion of apoptotic cells which distort the comet analysis. The cells, suspended in the buffer, were filtered though a 100 µm cell strainer and stored on ice prior to preparation of the slides.
Low melting point agarose was added to the cell suspensions and layered on a pre-coated comet slide (Trevigen), which was then incubated for 10 - 21 minutes in the refrigerator. Three slides per tissue were prepared.
Slides were kept overnight in the refrigerator, immersed in pre-chilled lysis solution. After rinsing, the slides were placed in freshly-prepared alkaline solution; electrophoresis was performed for 20 minutes (stomach and duodenum) or 30 minutes (liver and kidney). Following another rinse, the slides were immersed in absolute ethanol and allowed to dry, before staining with SYBR Gold fluorescent dye. - Evaluation criteria:
- 150 comets were examined per sample using an IV image analysis system. Only horizontal comets, oriented with the head on the left and the tail on the right, were scored. Cells that showed overlap or were not sharp were not scored.
A test item was considered positive if all of the following criteria were met:
a) at least one treatment group demonstrated a statistically significant increase in % tail intensity vs. control.
b) the increase was dose-related.
c) any of the results were outside the 95% confidence limits of the historical control data.
If none of the above criteria were met, and direct or indirect evidence supportive of exposure of, or toxicity to, the target tissues was demonstrated, the test item was considered negative. If the data precluded making a conclusion of clearly positive or negative, the result was concluded as equivocal. - Statistics:
- ToxRat Professional v 3.2.1 (ToxRat Solutions® GmbH, Germany) was used for statistical
analysis of the comet assay data .
A test item is considered positive in the comet assay if all of the following criteria are met:
a) At least one of the treatment groups exhibits a statistically significant (one-sided, p <
0.05) increase in percentage Tail Intensity is detected compared with the concurrent
negative control.
b) The increase is dose related when evaluated with a trend test.
c) Any of the results are outside the 95% control limits of the historical control data range.
A test item is considered negative in the comet assay if:
a) None of the treatment groups exhibits a statistically significant (one-sided, p < 0.05)
increase in percentage Tail Intensity is detected compared with the concurrent negative
control.
b) There is no concentration-related increase when evaluated with a trend test.
c) All results are within the 95% control limits of the negative historical control data range.
Results and discussion
Test resultsopen allclose all
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- Kidney: no statistically significant increase in % tail intensity. cfr table under section 'Any other information on results incl. tables'
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- Liver: no statistically significant increase in % tail intensity. cfr table under section 'Any other information on results incl. tables'
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- Glandular stomach: no statistically significant increase in % tail intensity. cfr table under section 'Any other information on results incl. tables'
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Remarks:
- Duodenum: no statistically significant increase in % tail intensity. cfr table under section 'Any other information on results incl. tables'
- Toxicity:
- yes
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- One high-dose animal died after the first dose, and was replaced by an additional animal. Clinical signs of toxicity were observed in the high-dose group: hunched posture (4/5 animals), lethargy (5/5 animals) and diarrhoea (1/5 animals).
Platinum was quantifiable in plasma samples from high-dose (150 mg/kg bw/day) satellite animals 1, 3, 6 and 12 hours after completing the second day of treatment. Moreover, platinum was quantifiable in plasma samples from all high-dose animals taken at necropsy approximately 3 hours after the third dose. Therefore it was confirmed that there was systemic exposure to the test item. No test item was detected in the animals dosed with vehicle.
Any other information on results incl. tables
Group mean % tail DNA for the different tissues analyses (mean and standard deviation) | ||
liver | tail intensity (%) | SD |
vehicle control | 4.54 | 0.63 |
test item 37.5 mg/kg | 4.70 | 0.74 |
test item 75 mg/kg | 4.28 | 0.79 |
test item 150 mg/kg | 3.76 | 0.23 |
EMS 200 mg/kg | 82.11* | 6.52 |
* significantly different (p<0.001) compared to corresponding vehicle control group | ||
duodenum | tail intensity (%) | SD |
vehicle control | 7.57 | 1.48 |
test item 37.5 mg/kg | 6.64 | 1.30 |
test item 75 mg/kg | 5.8 | 0.93 |
test item 150 mg/kg | 6.15 | 0.78 |
EMS 200 mg/kg | 46.84* | 4.76 |
* significantly different (p<0.001) compared to corresponding vehicle control group | ||
stomach | tail intensity (%) | SD |
vehicle control | 6.32 | 1.57 |
test item 37.5 mg/kg | 6.47 | 0.33 |
test item 75 mg/kg | 4.22 | 0.83 |
test item 150 mg/kg | 5.44 | 1.31 |
EMS 200 mg/kg | 53.24* | 4.73 |
* significantly different (p<0.001) compared to corresponding vehicle control group | ||
kidney | tail intensity (%) | SD |
vehicle control | 4.62 | 0.84 |
test item 37.5 mg/kg | 4.96 | 1.84 |
test item 75 mg/kg | 5.11 | 1.00 |
test item 150 mg/kg | 5.16 | 0.59 |
EMS 200 mg/kg | 86.05* | 4.45 |
* significantly different (p<0.001) compared to corresponding vehicle control group |
Historical data Comet assay Negative control | ||||
Liver | Duodenum | Stomach | Kidney | |
Tail Intensity (%) | Tail Intensity (%) | Tail Intensity (%) | Tail Intensity (%) | |
Males and Females | Males and Females | Males and Females | Males and Females | |
Mean | 2.4 | 4.3 | 3.5 | 9.1 |
SD | 1.6 | 2.0 | 1.8 | 7.9 |
n | 34 | 19 | 22 | 9 |
Lower control limit (95% control limits) | -0.8 | 0.3 | 0.0 | -6.3 |
Upper control limit (95% control limits) | 5.6 | 8.2 | 7.0 | 24.5 |
SD = Standard deviation | ||||
n = Number of observations | ||||
Kidney: Historical control data from experiments performed in Feb 2012 – June 2020 | ||||
Liver, Stomach, Duodenum: Historical control data from experiments performed in July 2017 – June 2020 | ||||
Historical data Comet assay Positive control (200 mg/kg bw EMS orally dosed for two consecutive days) | ||||
Liver | Duodenum | Stomach | Kidney | |
Tail Intensity (%) | Tail Intensity (%) | Tail Intensity (%) | Tail Intensity (%) | |
Males and Females | Males and Females | Males and Females | Males and Females | |
Mean | 87.7 | 45.4 | 55.3 | 83.3 |
SD | 6.7 | 12.1 | 11.6 | 11.8 |
n | 33 | 19 | 22 | 9 |
Lower control limit (95% control limits) | 74.5 | 21.7 | 32.6 | 60.2 |
Upper control limit (95% control limits) | 100.9 | 69.1 | 78 | 106.4 |
SD = Standard deviation | ||||
n = Number of observations | ||||
Kidney: Historical control data from experiments performed in Feb 2012 – June 2020 | ||||
Liver, Stomach, Duodenum: Historical control data from experiments performed in July 2017 – June 2020 |
Applicant's summary and conclusion
- Conclusions:
- When tested in the comet assay, diammonium hexachloroplatinate did not induce DNA damage in the liver, kidney, glandular stomach or duodenum of rats administered up to 150 mg/kg bw/day by gavage on three consecutive days. As such, and as platinum was detected in the plasma of the test animals, diammonium hexachloroplatinate was concluded to be non-genotoxic in vivo.
- Executive summary:
The potential for diammonium hexachloroplatinate to cause DNA damage was evaluated in a study following OECD 489 and according to GLP. Male Wistar rats (5/group) were given gavage doses of 37.5, 75 or 150 mg/kg bw/day of the test item on three consecutive days, or a vehicle control. The concurrent positive control group received two doses of EMS (200 mg/kg bw/day). Comet analyses were conducted on preparations of liver, glandular stomach, duodenum and kidney tissues.
There was no statistically significant increase in % tail intensity in the liver, kidney, glandular stomach or duodenum, indicating that the test item was not genotoxic to these tissues.
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