National Toxicology Program

National Toxicology Program
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Abstract for TR-556 - Chromium Picolinate Monohydrate (CASRN 27882-76-4)

ABSTRACT

TR-556
Toxicology and Carcinogenesis Studies of Chromium Picolinate Monohydrate (CAS No. 27882-76-4) in F344/N Rats and B6C3F1 Mice (Feed Studies)

 

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Abstract

Chemical Formula: C18H12CrN3O6⋅H2O -- Molecular Weight: 436

Chromium picolinate monohydrate is the commercially available form of chromium picolinate. Chromium picolinate is one of a number of compounds that contain chromium in the trivalent state (Cr III), which is the predominant form of chromium in nature. Humans ingest Cr III in food and dietary supplements. The major uses of Cr III in the chemical and manufacturing industries include production of chromium pigments and leather tanning. Chromium picolinate was nominated by the National Cancer Institute and a private individual for testing based on the potential for widespread consumer exposure from use as a dietary supplement. Male and female F344/N rats and B6C3F1 mice were exposed to chromium picolinate monohydrate (95% to 96% pure) in feed for 3 months or 2 years. Genetic toxicology studies with chromium picolinate monohydrate were conducted in Salmonella typhimurium, Escherichia coli, and mouse peripheral blood erythrocytes. Genetic toxicology studies with chromium picolinate were conducted in S. typhimurium and rat bone marrow erythrocytes.

3-MONTH STUDY IN RATS

Groups of 10 male and 10 female rats were fed diets containing 0, 80, 240, 2,000, 10,000, or 50,000 ppm chromium picolinate monohydrate (equivalent to average daily doses of approximately 7, 20, 160, 800, or 4,240 mg chromium picolinate monohydrate/kg body weight to males and 6, 20, 160, 780, or 4,250 mg/kg to females) for 14 weeks. All rats survived to the end of the study. Mean body weights and feed consumption of all exposed groups of males and females were similar to those of the control groups throughout the study. No exposure-related lesions occurred in males or females.

3-MONTH STUDY IN MICE

Groups of 10 male and 10 female mice were fed diets containing 0, 80, 240, 2,000, 10,000, or 50,000 ppm chromium picolinate monohydrate (equivalent to average daily doses of approximately 17, 50, 450, 2,300, or 11,900 mg chromium picolinate monohydrate/kg body weight to males and 14, 40, 370, 1,775, or 9,140 mg/kg to females) for 14 weeks. All mice survived to the end of the study. Mean body weights and feed consumption of all exposed groups were similar to those of the control groups throughout the study. No exposure-related lesions occurred in male or female mice.

2-YEAR STUDY IN RATS

Groups of 50 male and 50 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 90, 460, or 2,400 mg/kg to males and 100, 510, or 2,630 mg/kg to females) for 105 weeks. Survival of all exposed groups of males and females was similar to that of the control groups. Mean body weights and feed consumption of exposed groups of males and females were generally similar to those of the controls throughout the study. The incidence of preputial gland adenoma was significantly increased in males exposed to 10,000 ppm and exceeded the historical control ranges.

2-YEAR STUDY IN MICE

Groups of 50 male and 50 female mice were fed diets containing 0, 2,000, 10,000, or 50,000 ppm chromium picolinate monohydrate (equivalent to average daily doses of approximately 250, 1,200, or 6,565 mg/kg to males and 240, 1,200, or 6,100 mg/kg to females) for 105 weeks. Survival of all exposed groups of males and females was similar to that of the control groups. Mean body weights of exposed groups of males were generally similar to those of the controls throughout the study; mean body weights of 50,000 ppm females were 10% less than the control group at 1 year, but similar to the control group at 2 years. Feed consumption by exposed groups of males and females was similar to that by the controls throughout the study. No neoplasms or nonneoplastic lesions were attributed to exposure to chromium picolinate monohydrate.

GENETIC TOXICOLOGY

In the standard screening assays conducted by the NTP, chromium picolinate monohydrate showed no clear evidence of genotoxicity. It was not mutagenic in Salmonella typhimurium strains TA98 or TA100 or Escherichia coli strain WP2 uvrA/pKM101 when tested with or without exogenous metabolic activation (S9). No increase in the frequency of micronucleated normochromatic erythrocytes was observed in male B6C3F1 mice administered chromium picolinate monohydrate in feed for 3 months. A small increase in micronucleated normochromatic erythrocytes was seen in female mice at the highest exposure concentration tested, and the results in female mice were considered equivocal.

Additional genotoxicity testing was conducted with chromium picolinate (not the monohydrate form of the compound), and results were also negative. No induction of gene mutations was observed in two independent studies conducted in several strains of S. typhimurium with and without S9. No induction of micronucleated polychromatic erythrocytes was observed in bone marrow of male F344/N rats treated with chromium picolinate by oral gavage three times at 24-hour intervals.

CONCLUSIONS

Under the conditions of these 2-year feed studies there was equivocal evidence of carcinogenic activity of chromium picolinate monohydrate in male F344/N rats based on an increase in the incidence of preputial gland adenoma. There was no evidence of carcinogenic activity of chromium picolinate monohydrate in female F344/N rats or in male or female B6C3F1 mice exposed to 2,000, 10,000, or 50,000 ppm.

Synonyms: Chromium 2-pyridine-carboxylate; chromium tripicolinate; chromium tris (picolinato)-; chromium, tris (2-pyridinecarboxylato-N(1), O(2))-(9CI); picolinate acid, chromium salt
Trade name: Chromax®



 

 

Summary of the 2-Year Carcinogenesis and Genetic Toxicology Studies of Chromium Picolinate Monohydrate and Genetic Toxicology Studies of Chromium Picolinate
  Male
F344/N Rats
Female
F344/N Rats
Male
B6C3F1 Mice
Female
B6C3F1 Mice
Concentrations in feed 0, 2,000, 10,000, 50,000 ppm 0, 2,000, 10,000, 50,000 ppm 0, 2,000, 10,000, 50,000 ppm 0, 2,000, 10,000, 50,000 ppm
Body weights Exposed groups similar to control group Exposed groups similar to control group Exposed groups similar to control group 50,000 ppm group was 10% less than the control group at 1 year, but similar to the control group at 2 years
Survival rates 37/50, 36/50, 35/50, 28/50 36/50, 35/50, 36/50, 40/50 46/50, 43/50, 38/50, 45/50 45/50, 44/49, 44/50, 39/50
Nonneoplastic effects None None None None
Neoplastic effects None None None None
Equivocal findings Preputial gland: adenoma (1/50, 1/50, 7/50, 4/50) None None None
Level of evidence of carcinogenic activity Equivocal evidence No Evidence No Evidence No Evidence
Genetic toxicology for chromium picolinate monohydrate
Assay Results
Salmonella typhimurium and Escherichia coli gene mutations: Negative in strains TA98 and TA100 with and without S9; negative in Escherichia coli strain WP2 uvrA/pKM101 with and without S9
Micronucleated erythrocytes
Mouse peripheral blood in vivo:
Negative in males; equivocal in females
Genetic toxicology for chromium picolinate
Assay Results
Salmonella typhimurium gene mutations: Negative in strains TA97, TA98, TA100, TA102, TA104, and TA1535 with and without S9
Micronucleated erythrocytes
Male rat bone marrow in vivo:
Negative

Date: June 2010

Pathology Tables, Survival and Growth Curves from NTP 2-year Studies

Target Organs & Incidences from 2-year Studies

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