French pharmacovigilance survey evaluating the hepatic toxicity of coumarin

Andréjak, M.; Gersberg, Marta; Sgro, C; Decocq, Guillaume; Hamel, Jean-Dominique; Morin, Mario; Gras, Valérie

doi:10.1002/(sici)1099-1557(199808)7:1+<s45::aid-pds353>3.3.co;2-t

Cited by 24 publications

(7 citation statements)

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“…In addition, direct anti‐tumor activity was reported, and the substance was used to treat renal cell carcinoma and other tumors, with doses of up to 7000 mg daily 15. Some of the patients developed severe hepatotoxicity (toxic hepatitis, liver failure in a few cases) from a few weeks to 6 months after commencement of treatment 16–18. These observations led to these products being withdrawn from the market in several countries in the 1990s (Australia, Belgium, France and Canada) 18.…”

Section: Hazard Of Coumarinmentioning

confidence: 99%

Toxicology and risk assessment of coumarin: Focus on human data

Abraham

Wöhrlin

Lindtner

et al. 2010

Molecular Nutrition Food Res

234

143

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Coumarin is a secondary phytochemical with hepatotoxic and carcinogenic properties. For the carcinogenic effect, a genotoxic mechanism was considered possible, but was discounted by the European Food Safety Authority in 2004 based on new evidence. This allowed the derivation of a tolerable daily intake (TDI) for the first time, and a value of 0.1 mg/kg body weight was arrived at based on animal hepatotoxicity data. However, clinical data on hepatotoxicity from patients treated with coumarin as medicinal drug is also available. This data revealed a subgroup of the human population being more susceptible for the hepatotoxic effect than the animal species investigated. The cause of the high susceptibility is currently unknown; possible mechanisms are discussed. Using the human data, a TDI of 0.1 mg/kg body weight was derived, confirming that of the European Food Safety Authority. Nutritional exposure may be considerably, and is mainly due to use of cassia cinnamon, which is a popular spice especially, used for cookies and sweet dishes. To estimate exposure to coumarin during the Christmas season in Germany, a telephone survey was performed with more than 1000 randomly selected persons. Heavy consumers of cassia cinnamon may reach a daily coumarin intake corresponding to the TDI.

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Section: Hazard Of Coumarinmentioning

confidence: 99%

Toxicology and risk assessment of coumarin: Focus on human data

Abraham

Wöhrlin

Lindtner

et al. 2010

Molecular Nutrition Food Res

234

143

View full text Add to dashboard Cite

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“…Coumarin is a well-recognized rat hepatotoxicant in men and animals [13][14][15]. Coumarin can cause toxic effect through 3,4-epoxide intermediate, which may be responsible for its toxic effects.…”

Section: Discussionmentioning

confidence: 99%

Acute and Subchronic Oral Toxicities of Justicia pectoralis J. Extract in Wistar Rats

Lagarto¹,

Bueno²,

Guerra³

et al. 2009

TONPJ

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We have studied the acute and subchronic oral toxicities of Justicia pectoralis J hydroalcoholic extract in Wistar rats. In acute test, both sexes of adult Wistar rats were given single po dose of J. pectoralis extract at 2000 mg/kg. Following euthanasia 14 days later, mortality and signs of toxicity were not observed. In subchronic test, J. pectoralis extract was po administered to both sexes of Wistar rats at 10, 100 and 1000 mg/kg/day, 5 days per week for 90 days. The major toxicological endpoints examined included animal body weight, food intake, selected tissue weights, and histopathological examinations. In addition, we examined blood elements and blood chemistry. Of the blood elements, the blood clotting time was significantly affected in males and females after 90 days. For blood chemistry parameters, cholesterol, ALT, bilirubin, and urea were affected. Organs and tissues abnormalities were not observed in histopathological examination. These results indicate that the effects observed are low and include slight variations in blood clotting time and biochemical parameters.

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“…Figure 1. The major metabolic pathways in coumarin biotransformation 1 The structure of the glutathione conjugate, that was actually described by Vassallo et al (2003), had a double bond at C3-C4 and did not contain the hydroxyl group at C4. According to Vassallo (personal communication, 2004) the double bond was re-introduced with a loss of water during sample clean-up.…”

Section: Studies On Metabolismmentioning

confidence: 99%

“…against lymphoedema or other protein oedemas) compounds Casley-Smith, 1985, 1986;Koch et al, 1995;Beinssen,1994;Morrison and Welsby, 1995). Recently investigators concluded on the basis of their survey that there was a strong signal for potential hepatotoxicity of coumarin (likely due to the production of reactive metabolites in some patients exhibiting a coumarin-7-hydroxylase defiency) that caused the authority to withdraw coumarin from the market in France (Andrejak et al, 1998).…”

Section: Evaluation Of Additional Relevant Information On Coumarin Simentioning

confidence: 99%

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to Coumarin

2004

EFSA Journal

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French pharmacovigilance survey evaluating the hepatic toxicity of coumarin

Cited by 24 publications

References 0 publications

Toxicology and risk assessment of coumarin: Focus on human data

Toxicology and risk assessment of coumarin: Focus on human data

Acute and Subchronic Oral Toxicities of Justicia pectoralis J. Extract in Wistar Rats

Opinion of the Scientific Panel on food additives, flavourings, processing aids and materials in contact with food (AFC) related to Coumarin

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