BfR | Annual Report 2013
44
Based on animal experiments, the carcinogenic effect of certain unsatu-
rated PAs like lasiocarpine, monocrotaline and riddelline can be seen as
validated and a corresponding risk considered to exist for humans. For
other PAs like isatidine, jacobine, retrorsine, seneciphylline, senkirkine
and petasitenine, animal studies using the compound itself or its active
metabolites also indicate a carcinogenic effect, but in these cases the
data are incomplete. PAs that showed to be carcinogenic in animal ex-
periments also exhibited mutagenic effects in genotoxicity testing. The
estimated value for the lowest dose that causes a cancer incidence of
not more than 10 % with 95-percent certainty (benchmark dose lower
confidence limit 10 %, BMDL 10) is 0.073 mg/kg BW/day. This figure
was derived from a carcinogenicity study using lasiocarpin based on
the findings for male rats.
PA research I: bioavailability and molecular effect mechanisms
A number of PAs showed carcinogenic and mutagenic effects in ani-
mal experiments, but the molecular mechanisms of PA effects on the
human organism are not yet fully understood. The BfR is conducting
molecular biology analyses (transcriptomics) to determine the effect
mechanisms of PA toxicity in humans. These analyses are designed
to show how PAs effect the gene expression of xenobiotic-metabo-
lising enzymes in primary human hepatocytes and human cell lines.
So-called transport analyses with selected PAs supply information on
oral bioavailability. The findings point to structure-dependent trans-
port via the intestinal barrier. The suspected cause is seen as being
interactions of the individual PAs with transport proteins (MDR1 for
example). The research project can help to identify biomarkers that
can be used to develop an hepatic
in-vitro
test system for the sensi-
tive detection of PAs.
To better assess the potential health risks,
the BfR carried out a research project to
measure the concentrations of unsaturated
pyrrolizidine alkaloids in herbal teas and teas.
>>
Some pyrrolizidine alkaloids showed carcinogenic
and mutagenic properties in animal experiments, but
the effect mechanisms on the human organism are
not yet fully understood.
