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EC number: 246-356-2 | CAS number: 24613-89-6
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics
- Type of information:
- migrated information: read-across based on grouping of substances (category approach)
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- The EU RAR contains summaries of literature studies performed to various designs and reoprted to different standards, and also incorporates the older UK HSE review (1986). However the information as a whole is consistent and is considered to provide adequate information to illustrate the basic toxicokinetics of Cr (VI) compounds.
Data source
Reference
- Reference Type:
- review article or handbook
- Title:
- European Union Risk Assessment Report: chromium trioxide, sodium chromate, sodium dichromate, ammonium dichromate, potassium dichromate
- Author:
- European Chemicals Bureau
- Year:
- 2 005
- Bibliographic source:
- 3rd Priority List; Volume 53
Materials and methods
- Objective of study:
- other: The reviewed studies cover all aspects of toxicokinetics
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- The EU RAR summarises the results of a number of studies performed to various designs. Studies were performed to investigate all aspects of the toxicokinetics of CR (VI) compounds in various species.
- GLP compliance:
- not specified
- Remarks:
- Older published studies: assumed not to be GLP compliant
Test material
- Reference substance name:
- Chromium trioxide
- EC Number:
- 215-607-8
- EC Name:
- Chromium trioxide
- Cas Number:
- 1333-82-0
- Molecular formula:
- CrO3
- IUPAC Name:
- chromium trioxide
- Reference substance name:
- Sodium dichromate
- EC Number:
- 234-190-3
- EC Name:
- Sodium dichromate
- Cas Number:
- 10588-01-9
- Molecular formula:
- Cr2H2O7.2Na
- IUPAC Name:
- sodium dichromate
- Reference substance name:
- Sodium chromate
- EC Number:
- 231-889-5
- EC Name:
- Sodium chromate
- Cas Number:
- 7775-11-3
- Molecular formula:
- CrH2O4.2Na
- IUPAC Name:
- disodium dioxido(dioxo)chromium
- Reference substance name:
- Potassium dichromate
- EC Number:
- 231-906-6
- EC Name:
- Potassium dichromate
- Cas Number:
- 7778-50-9
- Molecular formula:
- Cr2H2O7.2K
- IUPAC Name:
- potassium dichromate
- Details on test material:
- Various Cr (VI) compounds were used in the reviewed studies. Absorption into the body of the different water-soluble Cr (VI) salts is very similar, and once absorbed, dissociation in aqueous media means that the toxicokinetics of Cr(VI) in the different salts is essentially identical. Toxicokinetic data obtained experimentally using different water soluble Cr (VI) compounds can therefore be extrapolated to all compounds in this group.
Constituent 1
Constituent 2
Constituent 3
Constituent 4
- Radiolabelling:
- other: Radiolabelling was used in some of the reviewed studies
Test animals
- Species:
- other: various
- Strain:
- other: various
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Various studies were reviewed that used rats, mice, guinea pigs and rabbits.
Administration / exposure
- Route of administration:
- other: various
- Vehicle:
- water
- Duration and frequency of treatment / exposure:
- The studies summarised in the EU RAR are of various designs.
Doses / concentrations
- Remarks:
- Doses / Concentrations:
The studies summarised in the EU RAR are of various designs.
- No. of animals per sex per dose / concentration:
- The studies summarised in the EU RAR are of various designs.
- Control animals:
- not specified
Results and discussion
- Preliminary studies:
- A number of the reviewed studies could be considered to be preliminary in nature (i.e. non GLP- or guideline compliant), however these are summarised in the relevant sections below.
Toxicokinetic / pharmacokinetic studies
- Details on absorption:
- Following inhalation or intratracheal instillation of highly water-soluble Cr (VI) compounds, approximately 20-30% of the chromium dose was rapidly absorbed into the bloodstream, apparently much of this still in the hexavalent state. Some chromium was also removed from the lung by mucociliary clearance into the gastrointestinal tract. The residual chromium remaining in the lung was cleared much more slowly, with significant amounts remaining in the lung for several weeks. In animals, gastrointestinal uptake of chromium following oral administration of highly-soluble Cr (VI) was generally poor due to reduction of Cr (VI) to Cr (III) in stomach. When food was given ad libitum, only 1-3% of orally administered Cr (VI) was absorbed in rats and mice; the amount increased if food had been withdrawn for 16-48 hours. In contrast, one study reported at least 18% absorption in unstarved guinea pigs receiving potassium chromate orally.
Dermal absorption of highly water-soluble Cr (VI) compounds in guinea pigs varied between <1% and 4% of the applied aqueous dose, depending on the chromium concentration.
In humans, data from volunteer studies shows that chromium is poorly absorbed through the GI tract (2-9%) and intact skin. Diabetic patients may absorb up to 4 times more chromium through the GI tract than healthy individuals. - Details on distribution in tissues:
- Once absorbed, Cr (VI) appears to be widely distributed. A substantial proportion of Cr (VI) is absorbed by erythrocytes, and once inside the erythrocytes is rapidly reduced to Cr (III) by glutathione, becoming irreversibly boung to haemoglobin. Cr (VI) is also reduced to Cr (III) in plasma. Ascorbic acid, cysteine and cytochrome P450 enzymes can also reduce Cr (VI). Extra-cellular reduction to Cr (III) prevents cellular uptake.
In experimental animal studies, the level of chromium in most tissues decreased gradually from the first day post-exposure. However, the chromium content of the spleen showed a time-dependent increase over several weeks, due to clearance of senescent chromium-laden erythrocytes. Parenteral administration studies in pregnant rats (intravenous, intraperitoneal, subcutaneous) and mice (intravenous) using water-soluble 51Cr (VI) compoun ds have shown that radioactivity in the bloodstream can cross the placenta and be distributed within the embryo.
- Details on excretion:
- Inhaled Cr (VI) is excreted in similar amounts in the urine and faeces (in the range of 20-70% of administered dose). Following oral administration, excretion is largely in the faeces due to poor bioavailability. During the first 7 days following parenteral administration of readily water-soluble chromates, 35-60% of the chromium was excreted in the urine and 14-28% in the faeces.
Repeated daily exposure (inhalation, oral and s.c.) to highly-water soluble Cr (VI) compounds resulted in chromium accumulation in many organs and tissues. High levels were found in the lungs, spleen, dudodenum, kidneys, liver and testes following inhalation exposure.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- Cr (VI) is rapidly reduced in the gastrointestinal tract, in the plasma and intracellularly to Cr (III) by reaction with ascorbic acid, glutathione and by cytochrome P450. Following exposure to Cr (VI), chromium is excreted in the form of Cr (III) complexes with glutathione.
Any other information on results incl. tables
Information on the toxicokinetics of Cr (VI) compounds is available from numerous published studies in rats, mice, guinea pigs and rabbits and has been reviewed in the EU RAR. The RAR (2005) also incorporates studies previously reviewed by the UK Health & Safety Executive (1989).
Applicant's summary and conclusion
- Conclusions:
- Interpretation of results (migrated information): bioaccumulation potential cannot be judged based on study results
The comprehensive review of the available toxicokinetics studies in experimental animals and in humans adequately illustrates the basic toxicokinetics of Cr (VI) from water-soluble compounds. - Executive summary:
There is a good database available on the toxicokinetics of the chromium compounds under review, although there are relatively few human data. The available data indicate that the water-soluble Cr (VI) compounds covered are likely to behave in a similar manner in respect of toxicokinetics, and that the kinetic behaviour of these substances would be similar in those species studied, including humans. Following inhalation exposure, animal studies have shown that 20 - 30% of the administered Cr (VI) is absorbed via the respiratory tract. Highly water-soluble Cr (VI) is poorly absorbed via the gastrointestinal tract (only 2-9% of the dose was absorbed in human studies) due to reduction to the relatively poorly absorbed Cr (III). Only limited dermal absorption takes place through intact skin, with 1 -4% Cr (VI) from an aqueous solution crossing the skin in guinea pig studies. According to the results of animal testing, chromium derived from these compounds can remain in the lungs for several weeks after inhalation exposure and also becomes bound to haemoglobin in erythrocytes for the lifespan of the cells. Cr (VI) is reduced to Cr (III) after entering the body due to the influence of reducing agents, for example glutathione. Distribution is widespread even after a single dose and includes transfer of absorbed Cr (VI) across the placenta. Excretion occurs in urine and faeces. Repeated exposure leads to accumulation of chromium in several tissues, particularly the spleen because of the uptake of senescent erythrocytes.
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