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Integration of mechanistic and pharmacokinetic information to derive oral reference dose and margin-of-exposure values for hexavalent chromium

In a newly published risk assessment¹, scientists integrated mode of action and toxicokinetic data to develop an RfD protective of both cancer and noncancer effects from oral exposure to hexavalent chromium. This video abstract highlights the publication resulting from this research. … Continue reading

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Ten factors for considering the mode of action of Cr(VI)-induced gastrointestinal tumors in rodents

Highlights: Hexavalent chromium, Cr(VI), induces intestinal tumors in mice. Eastmond enumerated 10 factors for determining a mutagenic mode of action. These 10 factors are used to assess the mode of action for Cr(VI). Analysis supports a non-mutagenic mode of action … Continue reading

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Assessment of the mutagenic potential of hexavalent chromium in the duodenum of big blue® rats

Highlights: An in vivo mutation assay informed by OECD Test Guideline 488 was conducted. Big Blue® (TgF344) rats were exposed to 180 ppm Cr(VI) in drinking water for 28 days. TgF344 rats were gavaged 20 mg/kg ENU on days 1, 2, 3, … Continue reading

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High-Throughput Screening Data Interpretation in the Context of In Vivo Transcriptomic Responses to Oral Cr(VI) Exposure

A recently published study by ToxStrategies scientists in Toxicological Sciences aimed to contribute to the understanding of Cr(VI) MOA by evaluating high-throughput screening (HTS) data and other in vitro data relevant to Cr(VI), and comparing these findings to robust in … Continue reading

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Reevaluation and Classification of Duodenal Lesions in B6C3F1 Mice and F344 Rats from 4 Studies of Hexavalent Chromium in Drinking Water

Abstract Thirteen-week and 2-year drinking water studies conducted by the National Toxicology Program (NTP) reported that hexavalent chromium (Cr(VI)) induced diffuse epithelial hyperplasia in the duodenum of B6C3F1 mice but not F344 rats. In the 2-year study, Cr(VI) exposure was … Continue reading

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Duodenal crypt health following exposure to Cr(VI): Micronucleus scoring, γ-H2AX immunostaining, and synchrotron X-ray fluorescence microscopy

Highlights: Micronuclei were assessed in crypts of Swiss roll duodenal sections from B6C3F1 mice. Oral gavage of 50 mg/kg cyclophosphamide significantly increased micronuclei. Cr(VI) in drinking water (up to 180 ppm) for 7 days did not increase micronuclei. Chromium was localized to … Continue reading

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