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EC number: 257-471-2 | CAS number: 51850-20-5
- 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
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (LLNA)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Although the study is not a conventional guideline study, it is well-conducted and scientifically acceptable.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 011
- Report date:
- 2011
Materials and methods
- Principles of method if other than guideline:
- The primary aim of the study was to evaluate the allergenic potential of the test substance and to determine its ability to cause allergic sensitization of the respiratory tract. Following analysis of lymphocyte proliferation using a standard local lymph node assay (LLNA) protocol cytokine fingerprinting was undertaken to explore respiratory sensitizing potential. Repeated topical exposure of BALB/c strain mice to chemical respiratory allergens, or contact allergens, has been shown to provoke characteristic cytokine secretion profiles consistent with the divergent activation of discreet T cell subpopulations. Cytokine profiles were compared with the recognised respiratory sensitizers Trimellitic anhydride (TMA) and Ammonium hexachloroplatinate (AHCP), as well as the known contact sensitizer 2,4-Dinitrochlorobenzene (DNCB) and the non-sensitizer Tetraammine platinum dichloride (TPC).
- GLP compliance:
- no
- Remarks:
- Non-standard guideline study conducted at academic institution
- Type of study:
- mouse local lymph node assay (LLNA)
Test material
- Reference substance name:
- Hexahydroxyplatinic acid
- IUPAC Name:
- Hexahydroxyplatinic acid
- Reference substance name:
- Diaquatetrahydroxyplatinum
- EC Number:
- 257-921-8
- EC Name:
- Diaquatetrahydroxyplatinum
- Cas Number:
- 52438-26-3
- IUPAC Name:
- 52438-26-3
- Test material form:
- solid - liquid: suspension
- Details on test material:
- - Name of test material (as cited in study report): Hexahydroxyplatinic acid (HHPA)
- Analytical purity: records of test compound characterisation, including purity, were held by the sponsor
- Other: All test preparations were fine suspensions of HHPA in DMF after sonification for 15 mins
Constituent 1
Constituent 2
In vivo test system
Test animals
- Species:
- mouse
- Strain:
- Balb/c
- Sex:
- not specified
Study design: in vivo (LLNA)
- Vehicle:
- dimethylformamide
- Concentration:
- 40% and 80% in LLNA; 80% for cytokine fingerprinting
- No. of animals per dose:
- 4/group in LLNA; 3/group for cytokine fingerprinting
- Details on study design:
- Using a standard LLNA protocol, mice (4/group) received 25 ul of chemical [80% or 40% HHPA in DMF, or DMF alone] on the dorsum of both ears on days 0, 1 and 2. Five days after the initiation of treatment, draining lymph nodes were isolated, pooled on a treatment group basis and a single cell suspension prepared. Total cellularity per lymph node was recorded. Cells (in quintuplicate) were cultured at 107 cells/ml for 24 hr in the presence of radiolabelled thymidine (2 uCi). Culture was terminated by automated cell harvesting and thymidine incorporation measured by beta-scintillation counting.
Results and discussion
- Positive control results:
- Details on positive and negative control results for the cytokine fingerprinting assay are presented below under Any other information on results incl tables
In vivo (LLNA)
Resultsopen allclose all
- Parameter:
- SI
- Remarks on result:
- other: See results, below
- Parameter:
- other: disintegrations per minute (DPM)
- Remarks on result:
- other: Full details on results are presented below under Any other information on results incl. tables
Any other information on results incl. tables
HHPA displayed some activity in the modified LLNA, with 80% HHPA/DMF achieving a combined stimulation index (SI) of 5.7. Full results are given below:
Treatment |
Cellularity (cells/lymph node x 106) |
Thymidine incorporation (dpm) |
Combined Stimulation Index (SI) |
80% HHPA/DMF |
5.5 |
8570 |
5.7 |
40% HHPA/DMF |
7.3 |
6285 |
5.4 |
DMF |
4.25 |
1953 |
1 |
In the 13 -day cytokine fingerprinting assay, total cellularity per lymph node was recorded as a measure of immune activation. Topical exposure to the positive control substances TMA and DNCB induced marked increases in lymph node cellularity. AHCP induced a more modest increase in lymph node cellularity, whereas TPC and HHPA were without marked effects on lymph node cell (LNC) numbers. Full results are given below:
Treatment |
Cellularity (cells/lymph node x 106) |
10% TMA/AOO |
13.5 |
1% DNCB/AOO |
14.3 |
5% AHCP/DMF |
11.5 |
5% TPC/DMF |
4 |
80% HHPA/DMF |
4 |
Type 2 cytokine IL-4 results are presented below. LNCs isolated from the known skin sensitizer DNCB treated mice expressed very low levels of IL-4, whilst treatment with the respiratory sensitizer TMA resulted in relatively vigorous IL-4 expression. Exposure to AHCP (also known to be a respiratory sensitizer) also induced the production of IL-4, albeit at lower levels than that provoked by TMA. Treatment with 80% HHPA (or 5% of the non-sensitizer TPC), however, stimulated very low levels of IL-4 production:
Treatment |
IL-4 (pg/ml) |
10% TMA/AOO |
668 |
1% DNCB/AOO |
73 |
5% AHCP/DMF |
213 |
5% TPC/DMF |
11 |
80% HHPA/DMF |
20 |
In the analysis of additional type 2 cytokines (IL-5, IL-10, IL-13) and type 1 cytokines (IL-12, IFN-gamma), LNCs derived from TPC-treated animals expressed relatively low levels of all cytokines with the exception of (type 1) IL-12. DNCB exhibited a selective type 1 cytokine profile with relatively vigorous IFN-gamma production and IL-12 expression, but relatively low levels of type 2 cytokines IL-5, IL-10 and IL-13. TMA-activated LNCs expressed a type 2 cytokine profile with relatively high levels of IL-5, IL-10 and IL-13, but low levels of the type 1 cytokines. A similar type 2 pattern of cytokine expression was recorded following topical exposure to AHCP. For HHPA-activated LNCs, levels of type 2 cytokines were below the limit of detection and the cytokine profile was similar to the non-sensitizing TPC.
Type 2 cytokines |
IL-5 (pg/ml) |
IL-10 (pg/ml) |
IL-13 (pg/ml) |
||||||
Treatment |
96 hr |
120 hr |
144 hr |
96 hr |
120 hr |
144 hr |
96 hr |
120 hr |
144 hr |
10% TMA/AOO |
289 |
335 |
576 |
594 |
822 |
1019 |
872 |
1043 |
1423 |
1% DNCB/AOO |
209 |
165 |
65 |
47 |
55 |
22 |
164 |
136 |
27 |
5% AHCP/DMF |
98 |
175 |
98 |
101 |
129 |
187 |
75 |
142 |
99 |
5% TPC/DMF |
ND* |
<10 |
<10 |
ND* |
<10 |
<10 |
ND* |
<10 |
<10 |
80% HHPA/DMF |
ND* |
<10 |
<10 |
ND* |
<10 |
<10 |
ND* |
<10 |
<10 |
*not done - insufficient cells
Type 1 cytokines |
IL-12 (pg/ml) |
IFN-gamma (pg/ml) |
||||
Treatment |
96 hr |
120 hr |
144 hr |
96 hr |
120 hr |
144 hr |
10% TMA/AOO |
108 |
110 |
104 |
389 |
321 |
398 |
1% DNCB/AOO |
187 |
201 |
209 |
1225 |
1241 |
1130 |
5% AHCP/DMF |
97 |
86 |
86 |
93 |
126 |
116 |
5% TPC/DMF |
ND* |
154 |
152 |
ND* |
16 |
<10 |
80% HHPA/DMF |
ND* |
132 |
138 |
ND* |
<10 |
<10 |
*not done - insufficient cells
Total serum IgE concentrations are presented below:
|
IgE concentration (ng/ml) |
||
Treatment |
No 1 |
No 2 |
No 3 |
10% TMA/AOO |
1864 |
1230 |
966 |
5% AHCP/DMF |
654 |
1354 |
2937 |
5% TPC/DMF |
49 |
36 |
14 |
80% HHPA/DMF |
59 |
47 |
ND* |
*not done - mouse terminated early due to lymphoproliferative disorder, not compound related.
TMA and AHCP resulted in marked increases in total serum IgE concentration compared with the negative control platinum TPC. There was no marked elevation in total serum IgE following topical exposure to HHPA.
Applicant's summary and conclusion
- Interpretation of results:
- not sensitising
- Remarks:
- Migrated information Criteria used for interpretation of results: expert judgment
- Conclusions:
- Hexahydroxyplatinic acid (HHPA) at high concentrations demonstrated a mild sensitisation response using a conventional Local Lymph Node Assay (LLNA) (40% and 80% HHPA in DMF gave a Stimulation Index (SI) of 5.4 and 5.7, respectively). However, the more sophisticated detailed cytokine fingerprinting assay indicated that it was not a significant skin or respiratory sensitiser, demonstrating a cytokine profile similar to that of the recognised non-sensitiser tetraammineplatinum dichloride.
- Executive summary:
Hexahydroxyplatinic acid (HHPA) was subjected to a modified LLNA, combined with a detailed cytokine fingerprinting assay, to evaluate its allergenic potential, particularly with regard to its ability to cause sensitisation of the respiratory tract.
Mice (4/group) received a 25 μL application of HHPA (concentrations of 40% or 80% HHPA in DMF, or DMF alone) on the dorsum of both ears on three consecutive days. Five days after the initiation of treatment, cell proliferation in the local lymph nodes was measured by incorporation of radiolabelled thymidine.
Subsequently, a standard 13-day cytokine fingerprinting assay was undertaken, involving mice (3/group) exposed to 80% HHPA in DMF. Additional groups of mice were treated with ammonium hexachloroplatinate (AHCP) (a respiratory sensitising platinum salt; positive control), tetraammineplatinum dichloride (TPC) (a non-sensitising platinum salt; negative control), as well as the reference respiratory allergen trimellitic anhydride (TMA) or the reference contact allergen 2,4 -dinitrochlorobenzene (DNCB). Animals received 50 μL of test chemical on both shaved flanks on day 0 and day 5, followed by a further dose of 25 μL of chemical on the dorsum of both ears on days 10, 11 and 12.
In the LLNA, the observed Stimulation Index (SI) values were 5.4 and 5.7 at 40 and 80%, respectively, demonstrating a mild sensitisation response. However, the more sophisticated detailed cytokine fingerprinting assay indicated that the test material was not a significant skin or respiratory sensitiser. Type 1 and type 2 cytokine profiles were compared with those of the known respiratory sensitisers TMA and AHCP, the contact sensitizer DNCB, and the known non-sensitiser TPC. HHPA failed to stimulate vigorous type 2 cytokine production, indicating a lack of respiratory sensitising potential, and demonstrated a cytokine profile similar to that of the non-sensitiser TPC. Type 1 cytokine IFN-gamma was below the limit of detection, and IL-12 was not elevated above normal background values, based on historical vehicle controls.
Overall, the results suggest that HHPA is not a significant skin or respiratory tract sensitiser. It is recommended that a lack of skin sensitising potential be confirmed using a standard in vivo assay for skin sensitisation using guinea-pigs.
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