Chronic toxicity and carcinogenicity studies of chromium picolinate monohydrate administered in feed to F344/N rats and B6C3F1 mice for 2 years

Abstract

Trivalent chromium (Cr(III)) has been proposed to be an essential element, which may increase sensitivity to insulin and thus participate in carbohydrate and lipid metabolism. Humans ingest Cr(III) both as a natural dietary constituent and in dietary supplements taken for weight loss and antidiabetic effects. Chromium picolinate (CP), a widely used supplement, contains Cr(III) chelated with three molecules of picolinic acid and was formulated in an attempt to improve the absorption of Cr(III). In order to examine the potential for CP to induce chronic toxicity and carcinogenicity, the NTP conducted studies of the monohydrate form (CPM) in groups of 50 male and female F344/N rats and B6C3F1 mice exposed in feed to concentrations of 0, 2,000, 10,000 or 50,000 ppm for 2 years; exposure concentrations were selected following review of the data from NTP 3-month toxicity studies. Exposure to CPM did not induce biologically significant changes in survival, body weight, feed consumption, or non-neoplastic lesions in rats or mice. In male rats, a statistically significant increase in the incidence of preputial gland adenoma at 10,000 ppm was considered an equivocal finding. CPM was not carcinogenic to female rats or to male or female mice.

Occupational exposure to hexavalent chromium and cancers of the gastrointestinal tract: A meta-analysis

“…One objective of this study was to provide information that could contribute to a cancer risk assessment of ingested Cr(VI), and to that end, it is important to compare occupational exposures with those that induced tumors in the recent NTP rodent cancer bioassays [6] and potential drinking-water exposures among humans. While the current occupational exposure limit in the U.S. is 5 mg/m 3 , it was lowered from 50 mg/m 3 in 2006.…”

“…Whether Cr(VI) poses a cancer hazard from ingestion exposures in humans is an important public health question because a substantial proportion of the public is routinely exposed to low levels of Cr(VI) in drinking water. For example, low levels of Cr(VI) exist in at least one-third of California's drinking-water supply [6]. An important consideration in cancer risk assessment is whether cancers observed in rodents are relevant to human exposures, and epidemiologic findings for GI cancers among Cr(VI)-exposed workers can contribute to a weight of evidence (WOE) analysis for cancer risk assessment.…”

“…Cancer risk assessment for Cr(VI) has traditionally addressed only inhalation exposures [1][2][3][4][5]. However, the observation in a recent National Toxicology Program (NTP) study of increased rates of oral-cavity tumors in rats and small intestine tumors in mice administered Cr(VI) in drinking water at concentrations ranging from 20 to 180 mg/L [6] suggests that an increased risk of gastrointestinal (GI) tract cancers may exist among humans exposed to Cr(VI). Whether Cr(VI) poses a cancer hazard from ingestion exposures in humans is an important public health question because a substantial proportion of the public is routinely exposed to low levels of Cr(VI) in drinking water.…”

Mechanistic Insights from the NTP Studies of Chromium

“…Over a concentration range of 100 to 10,000 mg/plate, no evidence of mutagenicity was observed in S. typhimurium strains TA100 and TA98 or E. coli strain WP2 uvrA pKM101 following exposure to CPM, with or without exogenous metabolic activation. In addition, no increase in the frequency of micronucleated erythrocytes was observed in male B6C3F1 mice administered CPM (80-50,000 ppm) in feed for 3 months (Stout, Nyska, et al 2009). In female mice, however, a small increase in micronucleated erythrocytes was judged to be equivocal.…”

“…up to 50,000 ppm in the diet (Stout, Nyska, et al 2009;NTP 2010). The lack of an effect on body weight following exposure to CPM in these studies is notable because CP has been marketed as a dietary supplement for weight loss.…”