ERGOT ALKALOIDS

Overview

Chemical Names

Ergot alkaloids

Functional Class

Food Contaminant
MYCOTOXIN

Evaluations

Evaluation year: 2021

Comments:

The Committee established a group ARfD of 0.4 µg/kg bw per day. The Committee established a group TDI for the sum of total ergot alkaloids in the diet at the same value as the group ARfD of 0.4 µg/kg bw per day.

Intake:

The Committee noted that some estimates of the mean (0.46–0.47 µg/kg bw per day) and high percentile (0.56–0.86 µg/kg bw per day) chronic dietary exposure in children and some estimates of the high percentile acute dietary exposure in children (0.65–0.98 µg/kg bw per day) and in adults (0.49 µg/kg bw per day) exceeded the EAs group health-based guidance value (HBGV), and that this may indicate a human health concern.

Tolerable Intake:

TDI of 0.4 µg/kg bw per day

Meeting:

Report:

TRS 1036-JECFA91/12

Tox Monograph:

FAS 82-JECFA 91/57

Toxicological study

Pivotal Study:

The Committee identified the pharmacological effect of ergometrine maleate on the uterus, causing uterine contractions in humans during late pregnancy and postpartum, as the critical effect for the evaluation of ergot alkaloids (EAs) in the diet. The Committee established an acute reference dose (ARfD), based on the following considerations: 1. The lowest oral therapeutic dose of 0.2 mg ergometrine maleate (equivalent to 2.5 µg/kg bw, expressed as ergometrine) is considered a pharmacological effect level in the most sensitive individuals, i.e. those with high absorption. 2. Of the EAs that have been used as drugs, ergometrine is known to have the highest potency for uterine contractions and its uterotonic effect increases towards the end of pregnancy. effect level at the therapeutic dose (LOEL) to a NOEL, the Committee took into consideration that the data relate to a short-lived, reversible, pharmacological effect, seen within a very sensitive subpopulation (women in late pregnancy or postpartum). A UF of 2 was considered appropriate for extrapolating from a pharmacological LOEL to a NOEL. To derive an ARfD from a NOEL based on human data, in the absence of additional information, the default UF would normally be 10. However, for a substance that reversibly interacts with specific receptors, as is the case here, with a pharmacological effect that is predominantly dependent on its maximum plasma concentration (i.e. Cmax), a UF for toxicokinetic differences is considered unnecessary. The Committee therefore applied the UF of 3.16 to cover possible interindividual toxicodynamic differences. Applying a composite UF of 6.3 (2 × 3.16) results in an acute reference dose of 0.4 µg ergometrine/kg bw (2.5 ÷ 6.3 = 0.4).