Aristolochic Acid

Danger

H301 (100%): Toxic if swallowed [Danger Acute toxicity, oral]

P264, P270, P301+P316, P321, P330, P405, and P501 (click each P-code to see the statement)

Aggregated GHS information provided per 44 reports by companies from 6 notifications to the ECHA C&L Inventory.

The carcinogenic and mutagenic effects associated with the binding of metabolites of ingested aristolochic acid (AA) to DNA have been extensively described in vitro and in vivo, resulting in the classification of AA as a genotoxic carcinogen. AA-derived DNA adducts in renal cortical and urothelial tumor tissue of patients with documented BEN, associated with the dominance of the A:T to T:A transversions in the p53 tumor suppressor gene mutational spectrum. (A15444) AA is a nephrotoxic and carcinogenic compound, which has been demonstrated to be genotoxic and mutagenic both in vitro and in vivo. Toxicity and carcinogenicity of the nephrotoxic compound aristolochic acid between rodents and humans suggest a species-dependent mechanism of action. AA had a comparable effect on the cell cycle in primary human and porcine cells and the rat NRK-52E cell line following 48 h exposure, also corroborated by the reduced 3H-thymidine incorporation in NRK-52E cells. In addition, DNA unwinding, suggestive of enhanced DNA damage, was observed in primary porcine cells. (A15445)

Aristolochic acid

Group 1: Carcinogenic to humans

Volume 82: (2002) Some Traditional Herbal Medicines, Some Mycotoxins, Naphthalene and Styrene

2012

2008

NB Overall evaluation upgraded to Group 1 based on mechanistic and other relevant data

Aristolochic acids are absorbed after oral exposure. They are metabolized to aristolactams, which are further metabolized to a cyclic N-acylnitrenium ion, a re-active intermediateforming adducts with purine bases (adenine and guanine) in DNA (dA-AAI, dG-AAI, dA-AAII, and dG-AAII). A number of cytosolic and microsomal enzymes (CYP1A1, CYP1A2, NADPH:CYP reductase, prostaglandin H synthase, DT-diaphorase, xanthine oxidase, cyclooxygenase, and NAD(P)H:quinone oxidore-ductase) are capable of bioactivating aristolochic acids to the reactive form.

Substances that increase the risk of NEOPLASMS in humans or animals. Both genotoxic chemicals, which affect DNA directly, and nongenotoxic chemicals, which induce neoplasms by other mechanism, are included.

Chemical agents that increase the rate of genetic mutation by interfering with the function of nucleic acids. A clastogen is a specific mutagen that causes breaks in chromosomes.

Aristolochic acids are a family of carcinogenic, mutagenic, and nephrotoxic compounds commonly found in the Aristolochiaceae family of plants, including Aristolochia and Asarum (wild ginger), which are commonly used in Chinese herbal medicine. Aristolochic acid I is the most abundant of the aristolochic acids and is found in almost all Aristolochia species.