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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 234-576-1 | CAS number: 12012-35-0
- 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
Toxicity to reproduction
Administrative data
- Endpoint:
- reproductive toxicity, other
- Remarks:
- 3 months exposure
- Type of information:
- read-across based on grouping of substances (category approach)
- Adequacy of study:
- supporting study
- Study period:
- October 2001 - August 2004
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Justification for type of information:
- Justification in section 13 read-across analogue approach
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 2 010
Materials and methods
- Principles of method if other than guideline:
- Groups of 10 male and 10 female rats were fed diets containing 0, 2,000, 10,000, or 50,000 ppm chromium picolinate monohydrate (equivalent to average daily doses of approximately 160, 800, or 4,240 mg chromium picolinate monohydrate/kg body weight to males and 160, 780, or 4,250 mg/kg to females) for 14 weeks.
Test material
- Reference substance name:
- Chromium picolinate monohydrate
- Cas Number:
- 27882-76-4
- Molecular formula:
- C18H14CrN3O7,H2O
- IUPAC Name:
- Chromium picolinate monohydrate
- Test material form:
- solid: particulate/powder
Constituent 1
- Specific details on test material used for the study:
- Chromium picolinate monohydrate was obtained from TCI America (Portland, OR) in one lot (OGJ01) and from Sigma-Aldrich (St. Louis, MO) in one lot (CHESS0204DFCI). Lot OGJ01 was used in the 3-month studies. Identity, purity, and stability analyses were performed by the analytical chemistry laboratory. Reports on analyses performed in support of the chromium picolinate monohydrate studies are on file at the National Institute of Environmental Health Sciences.
Tested lot of the chemical, a reddishpurple crystalline powder, were identified as chromium picolinate monohydrate by infrared and proton nuclear magnetic resonance spectroscopy, X-ray diffraction, and electrospray ionization-mass spectrometry (EI-MS).
The moisture contents of lots were determined using Karl Fischer titration. Purity of the test chemical was determined by elemental analyses, proton-induced X-ray emission (PIXE) spectroscopy), inductively coupled plasma-atomic emission spectroscopy (ICP-AES), high - performance liquid chromatography (HPLC) with diode-array detection (HPLC-DAD), UV detection (HPLC-UV), or ICPmass spectrometric detection (HPLC-ICP-MS).
The results of Karl Fischer titration for water content, elemental analyses for carbon, hydrogen, and nitrogen, and ICP-AES analysis for total chromium were all consistent with the theoretical values for chromium picolinate monohydrate. PIXE analysis indicated the absence of significant metallic impurities and a total chromium content of 117% of the theoretical value.
HPLC-DAD revealed a major component at 96%, one impurity at 2.1%, and five additional impurities at greater than or equal to 0.1% each. HPLC-UV by one system followed by HPLC-ICP-MS indicated that the maximum concentrations of free (uncomplexed) Cr(III) or Cr(VI) were less than 0.025%. The overall purity of the lot was determined to be greater than 96%. In an attempt to identify the impurities indicated by HPLC-DAD in the tested lot, preparations of chromium:picolinate complexes were made and analyzed using HPLC-DAD by a second system and HPLC-EI-MS. The results were inconclusive due to insufficient assay sensitivity and lack of authentic reference standards; however, these analyses provided evidence that the impurities in the test chemical were probably chromium:picolinate complexes, although the exact structures and ratios were uncertain.
Stability studies of the bulk chemical were performed using ICP-AES and HPLC-UV. These studies indicated that chromium picolinate monohydrate was stable as a bulk chemical for at least 2 weeks when stored in sealed amber glass containers at temperatures up to 60° C. To ensure stability, the bulk chemical was stored at room temperature, protected from light, in sealed plastic buckets.
Periodic reanalyses of the bulk chemical were performed during the 3-month studies using HPLC-UV, and no degradation of the bulk chemical was detected.
Test animals
- Species:
- rat
- Strain:
- other: F244/N
- Details on species / strain selection:
- Male and female F344/N rats were obtained from Taconic Farms, Inc. (Germantown, NY) for use in the study. Rats and mice were quarantined for 12 days before the beginning of the studies.
Five male and five female rats and mice were randomly selected for parasite evaluation and gross observation of disease. Rats were approximately 5 to 6 weeks old at the beginning of the studies.
The health of the animals was monitored during the studies according to the protocols of the NTP
Sentinel Animal Program. - Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Rats were housed three (males) or five (females) per cage. Feed and water were available ad libitum.
Feed consumption was measured weekly for the first 13 weeks of the study and approximately monthly thereafter. Cages were changed and rotated twice weekly; racks were changed and rotated every 2 weeks.
Administration / exposure
- Route of administration:
- oral: feed
- Details on exposure:
- Groups of 10 male and 10 female rats were fed diets containing 0, 2,000, 10,000, or 50,000 ppm chromium picolinate monohydrate for 14 weeks. Additional groups of 10 male and 10 female clinical pathology study rats were exposed to the same concentrations for 3 weeks. Feed and water were available ad libitum.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Periodic analyses of the dose formulations of chromium picolinate monohydrate were conducted by the study laboratory using HPLC-UV by system E. During the 3-month studies, the dose formulations were analyzed at the beginning, midpoint, and end of the studies; all 35 dose formulations analyzed for tested animals were within 10% of the target concentrations. Animal room samples of these dose formulations were also analyzed; all 10 animal room samples for rats and eight of 10 for mice were within 10% of the target concentrations.
- Duration of treatment / exposure:
- Core studies: 14 weeks
Clinical pathology study: 3 weeks - Frequency of treatment:
- Observed twice daily; core study animals were weighed initially, weekly, and at the end of the studies; clinical findings were recorded weekly. Feed consumption by core study animals was recorded weekly by cage.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 ppm
- Dose / conc.:
- 2 000 ppm
- Dose / conc.:
- 10 000 ppm
- Dose / conc.:
- 50 000 ppm
- No. of animals per sex per dose:
- Core studies: 10 males and 10 females
Clinical pathology study: 10 male and 10 female rats
Examinations
- Parental animals: Observations and examinations:
- Clinical findings were recorded weekly for core study animals. Feed consumption by core study animals was recorded weekly by cage. Core study animals were weighed initially, weekly, and at the end of the studies.
- Oestrous cyclicity (parental animals):
- At the end of the 3-month studies, samples were collected for sperm motility and vaginal cytology evaluations on core study rats and mice exposed to 0, 2,000, 10,000, or 50,000 ppm. For 12 consecutive days prior to scheduled terminal sacrifice, the vaginal vaults of the females were moistened with saline, if necessary, and samples of vaginal fluid and cells were stained. Relative numbers of leukocytes, nucleated epithelial cells, and large squamous epithelial cells were determined and used to ascertain estrous cycle stage (i.e., diestrus, proestrus, estrus, and metestrus).
- Sperm parameters (parental animals):
- Male animals were evaluated for sperm count and motility at terminal sacrifice. The left testis and left epididymis were isolated and weighed. The tail of the epididymis (cauda epididymis) was then removed from the epididymal body (corpus epididymis) and weighed. Test yolk (rats) was applied to slides, and a small incision was made at the distal border of the cauda epididymis. The sperm effluxing from the incision were dispersed in the buffer on the slides, and the numbers of motile and nonmotile spermatozoa were counted for five fields per slide by two observers. Following completion of sperm motility estimates, each left cauda epididymis was placed in buffered saline solution.
Caudae were finely minced, and the tissue was incubated in the saline solution and then heat fixed at 65° C. Sperm density was then determined microscopically with the aid of a hemacytometer. To quantify spermatogenesis, the testicular spermatid head count was determined by removing the tunica albuginea and homogenizing the left testis in phosphate-buffered saline containing 10% dimethylsulfoxide. Homogenization-resistant spermatid nuclei were counted with a hemacytometer. - Statistics:
- Survival Analyses
The probability of survival was estimated by the product-limit procedure of Kaplan and Meier (1958) and is presented in the form of graphs. Animals found dead of other than natural causes or missing were censored from the survival analyses; animals dying from natural causes were not censored. Statistical analyses for possible dose-related effects on survival used Cox’s method for testing two groups for equality and Tarone’s life table test to identify dose-related trends. All reported P values for the survival analyses are two sided.
Spermatid & epididymal spermatozoal data, which have typically skewed distributions, were analyzed using the nonparametric multiple comparison methods of Shirley and Dunn. Jonckheere’s test was used to assess the significance of the dose-related trends and to determine whether a trend-sensitive test was more appropriate for pairwise comparisons than a test that does not assume a monotonic dose related trend
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- There were no clinical findings related to exposure to chromium picolinate monohydrate; reddish-colored feces of 50,000 ppm animals was believed to be due to excretion of the test article and was not considered a sign of toxicity.
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- no mortality observed
- Description (incidence):
- All rats survived to the end of the study
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Final mean body weights and body weight gains of all exposed groups were similar to those of the control groups.
- Food consumption and compound intake (if feeding study):
- no effects observed
- Description (incidence and severity):
- Dietary concentrations of 2,000, 10,000, and 50,000 ppm resulted in average daily doses of approximately 160, 800, and 4,240 mg chromium picolinate monohydrate/kg body weight to males and 160, 780, and 4,250 mg/kg to females.
- Food efficiency:
- no effects observed
- Description (incidence and severity):
- Feed consumption by exposed groups of males and females was generally similar to that by the controls throughout the study.
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- no effects observed
- Description (incidence and severity):
- There were minor sporadic changes in the hematology variables in rats. All changes were within physiological normal levels, none demonstrated an exposure relationship, and none were considered biologically important or toxicologically relevant.
- Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- There were minor sporadic changes in the clinical chemistry variables in rats. All changes were within physiological normal levels, none demonstrated an exposure relationship, and none were considered biologically important or toxicologically relevant.
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Description (incidence and severity):
- There were no significant changes in reproductive organ weights in male or female rats, in sperm par ameters in male rats, or in estrous cyclicity in female rats at any dose. No exposure-related lesions occurred in male or female rats.
- Histopathological findings: neoplastic:
- no effects observed
- Description (incidence and severity):
- There were no significant changes in reproductive organ weights in male or female rats, in sperm parameters in male rats, or in estrous cyclicity in female rats at any dose. No exposure-related lesions occurred in male or female rats.
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- no effects observed
- Description (incidence and severity):
- There were no significant changes in reproductive organ weights in male or female rats, in estrous cyclicity in female rats at any dose. No exposure-related lesions occurred in male or female rats.
- Reproductive function: sperm measures:
- no effects observed
- Description (incidence and severity):
- There were no significant changes in reproductive organ weights in male rats, in sperm parameters in male rats at any dose. No exposure-related lesions occurred in male or female rats.
- Reproductive performance:
- not specified
Effect levels (P0)
- Dose descriptor:
- NOAEC
- Effect level:
- >= 50 000 ppm
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- dermal irritation
- body weight and weight gain
- food consumption and compound intake
- food efficiency
- haematology
- clinical biochemistry
- organ weights and organ / body weight ratios
- gross pathology
- histopathology: non-neoplastic
- histopathology: neoplastic
- reproductive function (oestrous cycle)
- reproductive function (sperm measures)
- reproductive performance
- Remarks on result:
- not determinable due to absence of adverse toxic effects
Target system / organ toxicity (P0)
- Critical effects observed:
- not specified
Results: P1 (second parental generation)
General toxicity (P1)
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- not examined
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- not examined
- Histopathological findings: neoplastic:
- no effects observed
Reproductive function / performance (P1)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- not examined
Target system / organ toxicity (P1)
- Critical effects observed:
- not specified
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Target system / organ toxicity (F1)
- Critical effects observed:
- not specified
Results: F2 generation
General toxicity (F2)
- Clinical signs:
- not examined
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- not examined
- Body weight and weight changes:
- not examined
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- not examined
- Histopathological findings:
- not examined
- Other effects:
- not examined
Developmental neurotoxicity (F2)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F2)
- Developmental immunotoxicity:
- not examined
Any other information on results incl. tables
Summary of Reproductive Tissue Evaluations for Male Rats in the 3-Month Feed Study of Chromium Picolinate Monohydrate (a)
0 ppm | 2000 ppm | 10000 ppm | 50000 ppm | |
n | 10 | 10 | 10 | 10 |
Weights (g) | ||||
Necropsy body wt | 326 ± 8 | 329 ± 6 | 319 ± 5 | 316 ± 9 |
L. Cauda epididymis | 0.2265 ± 0.0427 | 0.1862 ± 0.0045 | 0.1823 ± 0.0062 | 0.1781 ± 0.0073 |
L. Epididymid | 0.4582 ± 0.0088 | 0.4404 ± 0.0109 | 0.4440 ± 0.0129 | 0.4494 ± 0.0157 |
L. Testis | 1.5000 ± 0.0340 | 1.4757 ± 0.0216 | 1.4756 ± 0.0272 | 1.4635 ± 0.0337 |
Spermatid Mesasurement | ||||
Spermatid heads (10^7/g testis) | 109.47 ± 4.91 | 111.75 ± 3.94 | 100.41 ± 3.45 | 120.74 ± 7.93 |
Spermatid heads (107/testis) | 147.13 ± 6.02 | 151.50 ± 7.63 | 133.25 ± 4.47 | 158.63 ± 11.27 |
Epididymal spermatozoal measurements | ||||
Sperm motility (%) 7 0.09 ± 0.91 | 72.34 ± 2.11 | 71.22 ± 1.33 | 70.86 ± 0.82 | 70.09 ± 0.91 |
Sperm (10^7/g cauda epididymis) | 625.59 ± 62.68 | 576.71 ± 33.76 | 570.01 ± 32.04 | 595.47 ± 26.03 |
Sperm (10^7/cauda epididymis) | 120.41 ± 4.68 | 106.90 ± 5.78 | 102.78 ± 5.08 | 106.03 ± 6.29 |
a Data are presented as mean ± standard error. Differences from the control group are not significant by Dunnett’s test (body and tissue
weights) or Dunn’s test (spermatid and epididymal spermatozoal measurements).
Estrous Cycle Characterization for Female Rats in the 3-Month Feed Study of Chromium Picolinate Monohydrate (a)
0 ppm | 2000 ppm | 10000 ppm | 50000 ppm | |
Number weighed at necropsy | 10 | 10 | 10 | 10 |
Necropsy body wt (g) | 189 ± 4 | 190 ± 4 | 188 ± 4 | 190 ± 3 |
Proportion of regular cycling females (b) | 6/8 | 7/10 | 8/9 | 10/10 |
Estrous Cycle length (days) | 4.94 ± 0.47 (c) | 4.75 ± 0.21 | 4.44 ± 0.15 (d) | 5.00 ± 0.31 |
Estrous stages (% of cycle) | ||||
Diestrus | 51.7 | 38.3 | 38.3 | 44.2 |
Proestrus | 6.7 | 12.5 | 14.2 | 7.5 |
Estrus | 25.8 | 33.3 | 30.0 | 30.0 |
Metestrus | 15.8 | 15.8 | 17.5 | 18.3 |
a Necropsy body weights and estrous cycle length data are presented as mean ± standard error. Differences from the control group are not
significant by Dunnett’s test (body weight), Dunn’s test (estrous cycle length), or Fisher’s exact test (proportion of regular cycling females).
By multivariate analysis of variance, exposed females do not differ significantly from the control females in the relative length of time spent
in the estrous stages.
b Number of females with a regular cycle/number of females cycling
c Estrous cycle was longer than 12 days or unclear in 2 of 10 animals.
d Estrous cycle was longer than 12 days or unclear in 1 of 10 animals.
Applicant's summary and conclusion
- Conclusions:
- There were no significant changes in reproductive organ weights in male or female rats, in sperm parameters in male rats, or in estrous cyclicity in female rats at any dose.
No exposure-related lesions occurred in male or female rats. - Executive summary:
Based on the SMVCE results, the reproductive organ weights, and the histopathology of the reproductive organs, there was no evidence of toxicity to the reproductive system in these 3-month studies in rats and mice. Chromium picolinate is marketed as a dietary supplement primarily for weight loss in humans; however, no effect on body weight was observed in rats in the present studies.
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.