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EC number: 222-357-3 | CAS number: 3444-17-5
- 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
Basic toxicokinetics
Administrative data
- Endpoint:
- basic toxicokinetics in vivo
- Type of information:
- read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- data from handbook or collection of data
- Remarks:
- collection of data
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 010
Materials and methods
- Objective of study:
- absorption
- distribution
- excretion
- metabolism
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Study was conducted in parallel of a 2-year oral carcinogenicity study. The purposes of this study is to determine the absorption of chromium picolinate into the systemic circulation, and the fate of both the chromium and the picolinate parts of chromium picolinate.
- GLP compliance:
- yes
Test material
- Reference substance name:
- Chromium picolinate monohydrate
- Cas Number:
- 27882-76-4
- Molecular formula:
- C18-H12-Cr-N3-O6.H2-O
- IUPAC Name:
- Chromium picolinate monohydrate
- Test material form:
- solid
- Details on test material:
- Nonradiolabeled chromium picolinate was obtained from Spectrum Quality Products, Inc. (Gardena, CA - USA) in one lot (NG0569).
Radiolabeled chromium picolinate, labeled with 14C at multiple sites in the aromatic rings, was synthesized by Wizard Laboratories (West Sacramento, CA) at a specific activity of 52.0 mCi/mmole of chromium picolinate (17.3 mCi/mmole of each of the three picolinate ligands). The [14C]-chromium picolinate was supplied as a neat solid and its radiochemical purity was determined by HPLC.
Constituent 1
- Radiolabelling:
- yes
- Remarks:
- 14C for picolinate anion
Test animals
- Species:
- rat
- Strain:
- Fischer 344
- Sex:
- male
- Details on test animals or test system and environmental conditions:
- origin: Charles River Laboratories, Inc. (Raleigh, NC - USA)
acclimation period: at least one week
feed: Certfied Purina Rodent Chow #5002 and tap water ad libitum
housing: standard polycarbonate cages until they are used for an experiment, then individual glass metabolism chambers
body weight at initiation of the study: 206 - 233 grams
age at initiation of the study: 58 - 71 days old
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: water or propylene glycol
- Duration and frequency of treatment / exposure:
- single dose
Doses / concentrationsopen allclose all
- Dose / conc.:
- 15.3 mg/kg bw (total dose)
- Remarks:
- A dose formulation of [14C]-chromium picolinate dissolved in propylene glycol at a concentration of 2.84 mg (33.6 μCi) chromium picolinate per gram of dose preparation was prepared.
- Dose / conc.:
- 17.4 mg/kg bw (total dose)
- Remarks:
- A slurry of [14C]-chromium picolinate was prepared in water at an activity of 9.93 μCi per mg chromium picolinate.
- No. of animals per sex per dose / concentration:
- 4 male rats per dose
- Control animals:
- no
- Details on study design:
- Urine and feces were collected until excretion was essentially complete (52 hours) and analyzed for total radiolabel by LSS and chromium. Exhaled organic volatiles and CO2 were collected for 24 and 48 hours, respectively. The animals were sacrificed at 52 hours postdosing. The
following tissues were collected: adipose (two sites), bladder, blood, brain, heart, kidney, liver, lung, muscle (two sites), skin (ear), spleen, testis, stomach (with contents), small intestine (with contents), large intestine (with contents), and cecum (with contents). The collected tissues were stored at approximately –20° C until analyzed for total radiolabel by tissue solubilization followed by LSS. Aliquots of the 8- and 24-hour urine collections were analyzed for chromium picolinate and metabolites by HPLC/LSS.
Results and discussion
Toxicokinetic / pharmacokinetic studies
- Details on distribution in tissues:
- 15.3 mg/kg oral Dose of [14C]-Chromium Picolinate in Propylene Glycol to rats:
Less than 1% of 14C dose was found in tissues after 52 hours (adipose, bladder, blood, brain, heart, kidney, liver, lung, muscle, skin, spleen, testis, gastrointestinal tract).
17.4 mg/kg oral Dose of [14C]-Chromium Picolinate to rats as an Aqueous Slurry:
Less than 1% of the 14C dose administered was found in the non-gastrointestinal tract tissues at 48 hours; the gastrointestinal tract tissues and contents contained 0.15% of the administered radioactivity.
- Details on excretion:
- The rats dosed orally with [14C]-chromium picolinate dissolved in propylene glycol excreted an average of 53% of the 14C dose in urine, 39% in feces, and 1.5% as CO2 in breath in 24 hours. No measurable dose was collected as volatiles in breath. An additional 8% of the 14C dose was excreted during the collections at 48 and 52 hours.
An average of 1.25% ± 0.24% and 97.5% ± 7.4% of the chromium dose was excreted in urine and feces, respectively, in 48 hours.
An average of 49.0% ± 1.2% the 14C dose received was excreted in 24 hours as N-picolinoylglycine.
An average of 1.9% ± 0.4% and 1.1% ± 0.7% of the 14C dose received was excreted in 24 hours as picolinic acid and chromium picolinate, respectively.
The rats dosed orally with [14C]-chromium picolinate water slurry excreted an average of 41% of the 14C dose in urine, 47% in feces, and 1.4% as CO in breath in 24 hours. An additional 4% of the 14 2 C dose was excreted during the collections at 48 hours.
An average of 1.53% ± 0.51% and 97.6% ± 7.4% of the chromium dose was excreted in urine and feces, respectively, in 48 hours.
Metabolite characterisation studies
- Metabolites identified:
- yes
- Details on metabolites:
- Only a single radiolabeled metabolite (Ur1) was excreted in rat urine following an oral dose of [14C]-chromium picolinate. This metabolite was isolated and purified by HPLC. No apparent decomposition was observed during the purification process. Analysis of the isolated and purified metabolite for total chromium showed that Ur1 does not contain chromium. A sample of Ur1 that would have contained 75 μg-Eq/L of chromium based on the chromium/14C ratio in chromium picolinate was found to contain less than 10 μg/L chromium (the limit of quantitation of the method).
Any other information on results incl. tables
The poor bioavailability of chromium III, even though it has been proposed to be an essential element, is well
known. The poor bioavailability is little improved when chromium is complexed with picolinic acid or similar
complexing agents. Chromium picolinate has low water solubility. The rate of dissolution of the solid complex
could be slow enough to affect bioavailability. One of the goals of these studies was to establish the effect of
formulation on bioavailability. Propylene glycol was found to be a good solvent for the complex allowing
comparison of bioavailability of a homogenous formulation to an aqueous slurry. Comparing total chromium
excreted in urine following dosing with either the solution or slurry reveals little difference in rats.
A second question these studies sought to answer was the form of chromium in circulation. The analysis of urine
revealed that about 1% of the administered chromium picolinate is excreted unchanged in the urine of rats. Analysis of blood 1 hour following a 17.4 mg/kg oral dose indicated a concentration of 31 ng chromium picolinate/g of blood. At this same time the total radioactivity in blood was 290 ng-Eq of chromium picolinate, so no more than 10% of the chromium in the blood was associated with picolinate.
Picolinic acid represents about 83% of the mass of chromium picolinate. The fate of this part of the complex has
received little attention. Excretion of picolinate-derived radioactivity in rats is about equally divided between urine
and feces. Excretion of chromium, however, is nearly 100% in feces. This implies that much of the picolinate is
absorbed without the chromium attached. The major urinary metabolite is a glycine conjugate of picolinic acid.
Picolinic acid is cleared rapidly in rats with elimination being primarily by conjugation with glycine. There is little evidence for accumulation of picolinate-derived material in tissues. Less than 1% of the administered radioactivity remains in tissues after 48 hours.
Applicant's summary and conclusion
- Conclusions:
- Based on study results, the Chromium picolinate shows no bioaccumulation potential in rats tissue.
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