Registration Dossier
Registration Dossier
Data platform availability banner - registered substances factsheets
Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.
The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.
Diss Factsheets
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: - | CAS number: -
- 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 somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- other: experimental study used as Weight of Evidence
- Adequacy of study:
- weight of evidence
- Study period:
- 26 Feb 2020 - 30 Apr 2020
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Justification for type of information:
- In vivo genotoxicity data for similar Pt compounds are taken as weight-of-evidence to consider Pt concentrate P as non-genotoxic (see WoE argumentation in Section 13).
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
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 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
Test material
- Reference substance name:
- Tetraammineplatinum dichloride
- EC Number:
- 237-706-5
- EC Name:
- Tetraammineplatinum dichloride
- Cas Number:
- 13933-32-9
- Molecular formula:
- Cl.1/2H12N4Pt
- IUPAC Name:
- Tetraammineplatinum dichloride
Constituent 1
- Specific details on test material used for the study:
- SOURCE OF TEST MATERIAL
- Lot/batch number of test material: 9005305492.
- Expiration date of the lot/batch: 07 January 2021.
- Purity test date: CoA issued 26 November 2019.
STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: In refrigerator (2 - 8 °C)
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: 138 ± 8.4 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: Not specified.
To: 09 Apr 2020.
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- -Vehicle(s)/solvent(s) used: corn oil (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 100, 104 and 106% of the nominal values for group 2, group 3 and group 4 (i.e. 250, 500 and 1000 mg/kg(bw)/d), respectively. Accuracy and homogeneity (coefficient of variation
≤ 10%) of the test item in vehicle was confirmed. "
- Amount of vehicle (if gavage or dermal): The dosing volume was 10 mL/kg body weight
- Stability of test item in vehicle: Analysis of Group 2 and Group 4 formulations after storage yielded a relative difference of ≤ 10% of the initial mean sample concentration results. The formulations were found to be stable during storage at room temperature under normal laboratory light conditions for at least 4 hours (which exceeded the time between preparation and use of formulations). - 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.:
- 250 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- Remarks:
- Maximum tolerable dose. In a preliminary dose-range finding study, 12 animals (group 1: 1 male and 1 female, group 2: 3 males and 3 females, Group 3: 1 male and 3 females) were dosed via oral gavage with 2000, 1000 and 1500 mg/kg body weight (groups 1, 2 and 3, respectively). Mortality and severe toxicity were observed at doses of 1500 and 2000 mg/kg/day. These doses were therefore considered to be higher than the MTD. A dose of 1000 mg/kg/day was assumed to be the MTD.
- 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.
Examinations
- 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.
- Evaluation criteria:
- 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.
The incidence of micronuclei was assessed in at least 4000 polychromatic erythrocytes per animal.
A micronucleus test is considered acceptable if it meets the following criteria:
a) The concurrent negative control data are considered acceptable for addition to the
laboratory historical control database
b) The concurrent positive controls should induce responses that are compatible with those
generated in the historical positive control database and produce a statistically significant
increase compared with the concurrent negative control. The positive control data was
analyzed by the Welch t test (inhomogeneous variances, one-sided, p < 0.05).
c) The appropriate number of doses and cells has been analysed.
d) The criteria for the selection of the highest dose are consistent with those described in the
OECD 474 guideline - Statistics:
- ToxRat Professional v 3.2.1 (ToxRat Solutions® GmbH, Germany) was used for statistical
analysis of the micronucleus test data.
Results and discussion
Test results
- Key result
- Sex:
- male
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Positive controls validity:
- valid
- Additional information on results:
- Confirmation of exposure:
Platinum was quantifiable in plasma samples from high-dose (1000 mg/kg/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 3-4 hours after the third dose. Therefore it was confirmed that the animals were 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. A slight increase was seen in all treatment groups that was within the 95% limits of the historical control data.
Treated animals showed no decrease in the PCE:NCE ratio, indicating a lack of toxicity to the bone marrow.
Characterisation data indicating whether micronuclei contain whole or fragmented chromosomes have not been generated since the in vivo MN assay was clearly negative. Moreover, this characterisation is no requirement in the OECD474 guidance.
Any other information on results incl. tables
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 | 0 | 2,0 | ± 1,6 | 1,24 | ± 0,14 |
2 | 1 | |||||||
3 | 3 | |||||||
4 | 4 | |||||||
5 | 2 | |||||||
2 | test item | 25 | 6 | 3 | 2,2 | ± 0,8 | 1,17 | ± 0,23 |
7 | 2 | |||||||
8 | 3 | |||||||
9 | 1 | |||||||
10 | 2 | |||||||
3 | test item | 50 | 11 | 4 | 2,6 | ± 1,9 | 1,16 | ± 0,19 |
12 | 0 | |||||||
13 | 2 | |||||||
14 | 5 | |||||||
15 | 2 | |||||||
4 | test item | 100 | 16 | 2 | 2,6 | ± 0,9 | 1,06 | ± 0,28 |
17 | 2 | |||||||
18 | 3 | |||||||
19 | 4 | |||||||
20 | 2 | |||||||
6 | Cyclophosphamide | 19 | 26 | 38 | 66,8 | ± 36,1 (4) | 0,53 | ± 0,30 |
27 | 31 | |||||||
28 | 74 | |||||||
29 | 69 | |||||||
30 | 122 | |||||||
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 (Welch t test, P < 0.001). |
Dose-response relationship & statistics |
Micronucleus test (Evaluation of 4000 cells) |
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 Welsh t-test |
Distribution historical control data from experiments performed between November 2016 and November 2019. | ||||
negative control data | positive control data | |||
mean number of micronucleated cells per 4000 cells | 3.9 | 45.2 | ||
Standard deviation | 1.0 | 31.8 | ||
number of observations | 29 | 29 | ||
lower control limit (95% control limits) | 2* | -17 | ||
upper control limit (95% control limits) | 6 | 108 | ||
legend: * Rounded value; unrounded value is 1.895 |
Applicant's summary and conclusion
- Conclusions:
- Tetraammineplatinum dichloride did not induce an increase in micronucleated polychromatic erythrocytes in rats administered up to 1000 mg/kg bw/day by gavage on three consecutive days.
- Executive summary:
The in vivo clastogenicity of tetraammineplatinum dichloride, 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 250, 500 or 1000 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 a slight but not statistically significant increase in micronucleated polychromatic erythrocytes in all treatment groups, but the incidences fell within the 95% limits of the historical control data. On that basis, tetraammineplatinum dichloride was concluded to be non-genotoxic under the conditions of this assay.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.