Toxicity and carcinogenicity of riddelliine following 13 weeks of treatment to rats and mice

Chan, Po-Chuen; Mahler, Joel F.; Bucher, John R.; Travlos, Gregory S.; Reid, Jon B.

doi:10.1016/0041-0101(94)90368-9

Cited by 46 publications

(67 citation statements)

References 17 publications

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“…Riddelliine induced signifi cant elevations in UDS in rat liver (Mirsalis, 1987;Mirsalis et al, 1993). UDS was also detected in hepatocytes cultured from male and female rats and mice following 5 or 30 days of riddelliine treatment by gavage (Chan, 1993;Chan et al, 1994;NTP, 2003). Four PAs or PA metabolites, senecionine, retrorsine, seneciphylline and 19-OH-senecionine, along with four alkenals, trans-4-OH-2-hexenal, trans-4-OH-2-nonenal, nonenal and hexenal, were measured in primary cultures of rat hepatocytes using the UDS test.…”

Section: Unscheduled Dna Synthesismentioning

confidence: 98%

“…The liver is the main carcinogenic target. However, tumors induced by PAs also were found in lung, kidney, skin, bladder, brain and spinal cord, pancreatic islets and adrenal gland (Allen et al, 1975;Brandange et al, 1970;Chan et al, 1994;Cook et al, 1950;Furuya et al, 1976;Harris and Chen, 1970;Hirono et al, 1976Hirono et al, , 1977Hirono et al, , 1978Hirono et al, , 1979Hirono et al, , 1983Johnson et al, 1978;Kuhara et al, 1980;Mattocks and Cabral, 1982;Mori et al, 1984;Peterson et al, 1983;Rao et al, 1983;Rao and Reddy, 1978;Schoental, 1975;Schoental and Cavanagh, 1972;Schoental et al, 1954Schoental et al, , 1970Schoental et al, , 1971Schoental and Head, 1957;Shumaker et al, 1976;Reddy, 1972, 1974;Williams, 1970). Despite no clear evidence that PAs induce tumors in humans, the frequent occurrence of primary liver tumors in the natives of Central Africa and South Africa has been associated with the consumption of traditional medicinal PA-containing plants (Pavlica and Samuel, 1970;Schoental, 1968;Schoental and Coady, 1968;Williams et al, 1967).…”

Section: Carcinogenicity and Hepatotoxicitymentioning

confidence: 99%

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Genotoxicity of pyrrolizidine alkaloids

Chen

Mei

2010

J of Applied Toxicology

181

133

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Section: Unscheduled Dna Synthesismentioning

confidence: 98%

Section: Carcinogenicity and Hepatotoxicitymentioning

confidence: 99%

Genotoxicity of pyrrolizidine alkaloids

Chen

Mei

2010

J of Applied Toxicology

181

133

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“…per day and B 6 C 3 F 1 mice at 0, 0.33, 3.3 or 25 mg/kg b.w. per day 5 days per week for 10 weeks before mating for both sexes, continuing through gestation and lactation for the females (Chan et al, 1994). Female rats and mice in the top dose groups had prolonged oestrus.…”

Section: Developmental and Reproductive Toxicitymentioning

confidence: 99%

“…Riddelliine (92 % riddelliine, 5 % retrorsine, 1.3 % seneciphylline) has been investigated by the NTP in F344/N rats and B6C3F1 mice exposed by gavage (5 days/week) for 2, 13 and 105 weeks (NTP, 1993;Chan et al, 1994;Chan et al, 2003;NTP 2003). In the 2-week study, groups of five male and five female rats and mice were dosed with 0, 0.33, 1.0, 3.3, 10, or 25 mg per kg body weight.…”

Section: Repeated Dose Toxicitymentioning

confidence: 99%

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Scientific Opinion on Pyrrolizidine alkaloids in food and feed

2011

EFS2

226

130

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The European Food Safety Authority (EFSA) was asked by the European Commission to deliver a scientific opinion on pyrrolizidine alkaloids (PA) in food and feed. PAs are toxins exclusively biosynthesised by plants. To date, approximately 600 different PAs are known. Results for 13,280 bulk honey and 1324 retail honey samples were provided to EFSA by one Member State and 351 feed samples were provided by a second Member State. The EFSA Panel on Contaminants in the Food Chain (CONTAM Panel) performed estimates of both acute and chronic exposure to PAs through honey for three different age groups. Although there might be other sources of PA exposure, due to lack of data the CONTAM Panel was not able to quantify dietary exposure from food other than honey. A number of PAs were identified as being of particular importance for food and feed. Based on the present knowledge of metabolism, activation, DNA adduct-formation, genotoxicity and carcinogenicity, the CONTAM Panel concluded that 1,2-unsaturated PAs may act as genotoxic carcinogens in humans. Therefore, the CONTAM Panel decided to apply the Margin of Exposure (MOE) approach. A benchmark dose lower confidence limit for a 10 % excess cancer risk (BMDL 10 ) of 70 µg/kg b.w. per day for induction of liver haemangiosarcomas by lasiocarpine in male rats was calculated as the reference point for comparison with the estimated dietary exposure. The CONTAM Panel concluded that there is a possible health concern for those toddlers and children who are high consumers of honey. There is generally a low risk of PA poisoning in livestock and companion animals in the EU as most PA poisonings reported recently are due to accidental exposure. © European Pyrrolizidine alkaloids in food and feedEFSA Journal 2011;9(11):2406 2 SUMMARYFollowing a request from the European Commission, the Panel on Contaminants in the Food Chain (CONTAM Panel) was asked to deliver a scientific opinion on the risks to human and animal health related to the presence of pyrrolizidine alkaloids (PA) in food and feed. PAs are toxins exclusively biosynthesised by plants. They are typical plant secondary metabolites against herbivores. It has been estimated that approximately 6000 plant species world wide, representing 3 % of all flowering plants, may contain pyrrolizidine alkaloids. PAs are mainly found in the distantly related angiosperm families of the Boraginaceae (all genera), Asteraceae (tribes Senecioneae and Eupatorieae) and Fabaceae (genus Crotalaria). The PA-content of plant material depends on a large number of factors (species, plant organ, harvest, storage, extraction procedures). Reported contents vary from trace amounts up to 19 % based on dry weight. The name pyrrolizidine is the chemical description of two-fused 5-membered rings with a nitrogen atom at the bridgehead. This motif is the central structure of a variety of PAs. PAs generally consist of an amino alcohol which is referred to as necine or necine base and an acid part which is called a necic acid. Most of the known PAs are este...

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Application ofDNAMicroarray in Studies of Herbal Dietary Supplements

Guo

Fuscoe²,

et al. 2009

General, Applied and Systems Toxicology

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Herbal dietary supplements are used extensively worldwide and the consumption has dramatically increased in the United States in recent years. Although side effects of many herbal dietary supplements have been reported, safety assurance has not been addressed adequately and toxicological data on most herbal dietary supplements are lacking. To address the issue of human health protection, there are currently more than 30 herbal dietary supplements or active ingredients under study by the US National Toxicology Program (NTP). Herbal products often exhibit great variability in quality because of different processing methods, cultivation conditions, and harvest time, as well as the strain and species differences. Authentication of plant species used for preparation of herbal dietary supplements is a critical step of safety assurance. Botanical extracts differ from drugs in that they are mixtures of many active constituents. At present, there are no well‐established methodologies for evaluating the toxicity or determining the toxic mechanisms of herbal plant extracts due to the complexity of chemical components. In this chapter, we describe the applications of DNA microarray for plant authentication and mechanistic studies of herbal dietary supplements.

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Toxicity and carcinogenicity of riddelliine following 13 weeks of treatment to rats and mice

Cited by 46 publications

References 17 publications

Genotoxicity of pyrrolizidine alkaloids

Genotoxicity of pyrrolizidine alkaloids

Scientific Opinion on Pyrrolizidine alkaloids in food and feed

Application ofDNAMicroarray in Studies of Herbal Dietary Supplements

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