Ascaridole

In brief

What ascaridole is

Take a flat six-membered ring of carbon atoms. Throw a two-atom bridge across it, from one side to the other, so that the ring is forced into a rigid cage instead of a flexible hoop. Put a methyl group on one of the two bridgehead carbons and an isopropyl group on the other, and leave one double bond in the longer path between them. Now make that bridge out of two oxygen atoms bonded to each other rather than out of carbon. That is ascaridole ¹.

The oxygen-oxygen bond is the whole of its character. A bond between two oxygen atoms is called a peroxide; when it is tied into a ring system so that it cannot simply fall off the end of a molecule, it is called an endoperoxide. Peroxide bonds are weak compared with the carbon-carbon and carbon-oxygen bonds around them, and weak in a specific way: hand one an electron and it breaks, leaving behind a fragment with an unpaired electron, which is a free radical ¹⁷. Everything in the rest of this page follows from that sentence.

The molecule occurs naturally as a racemate, an equal mixture of its two mirror-image forms, in both of the plants that make most of it ². It is a colorless liquid when pure, and it has a close relative, isoascaridole, which is the same atoms rearranged into a different structure, formed when ascaridole is heated and often reported alongside it in plant oils ^13,36. Papers call the molecule itself (Z)-ascaridole or cis-ascaridole; the two labels describe the same geometry, and a percentage published for ascaridole may or may not include isoascaridole, which is one reason figures from different laboratories are hard to compare ³⁶. The name comes from Ascaris, the large roundworm of the human intestine, against which the parent oil was used.

Finding it, drawing it, and making it

The oil came first and the molecule second. Oil of chenopodium, distilled from the fruit and half-dried tops of American wormseed, was already an article of commerce in Baltimore and Illinois when chemists set about finding what in it killed worms ¹⁹. By 1932 the answer was settled enough for the Calcutta School of Tropical Medicine to write it down plainly: the anthelmintic properties of the oil are due to a chemical compound, ascaridole, present at 40 to 70 percent in various samples ¹⁹. Who first separated the compound from the oil and named it ascaridole, after Ascaris, could not be established from any source opened for this page: the early chemical papers are not indexed in PubMed, and the 2025 systematic review that is this page's anchor for the chemistry carries no account of the structure's elucidation ¹. Otto Wallach, who spent his career mapping the terpenes and won the 1910 Nobel Prize in Chemistry for that work, is commonly credited with establishing the structure. The prize and the terpene work are not in doubt; the attribution of ascaridole's structure to him is supported by no source read for this page, and is set down here as unverified. The earliest work this page can date from a source it has read is E. K. Nelson's, published in 1920, and that is about distillation rather than structure ¹⁹.

The practical problem in those years was that the molecule did not survive its own extraction. E. K. Nelson, working at the United States Bureau of Chemistry, found that the chief active ingredient was unstable and decomposed gradually on boiling with water, and concluded that the distillation had to be run fast, with steam at high pressure, with the condenser kept warm and the warm distillation water discarded ¹⁹. Russell confirmed it from the other direction: a good flow of steam gave an oil that passed every United States Pharmacopoeia requirement and contained a high percentage of ascaridole, while slower distillation and lower steam pressure lowered the oil's specific gravity ¹⁹. The active principle of the world's leading worm medicine could be destroyed by the heat used to obtain it.

In 1944 Günther Schenck and Karl Ziegler made ascaridole in the other direction, and in doing so invented a reaction. Alpha-terpinene, which sits in the same plant oils as ascaridole, is a conjugated diene: two double bonds in a row. Shine light on a dye in the presence of ordinary oxygen and the dye passes its energy to the oxygen molecule, lifting it into an excited state called singlet oxygen; singlet oxygen then adds across both ends of the diene in one step, closing the peroxide bridge ¹⁵. It was the first preparative photosensitized addition of singlet oxygen across a diene, the reaction that still carries Schenck's name, and it is still taught as a classic. It was not the first endoperoxide made with light: ergosterol peroxide had been prepared by dye-sensitized photo-oxygenation sixteen years earlier, which is why the priority claim here is for the reaction and not for the class of product. Eighty years later it remains the reaction chemists reach for when they want to prove a new catalyst makes singlet oxygen ^38,39,40.

The plant's own route is different and stranger. Johnson and Croteau found a soluble iodide peroxidase in wormseed fruit and leaf that converts alpha-terpinene to ascaridole, working best in acid conditions with hydrogen peroxide and iodide present ². Compounds that trap superoxide or quench singlet oxygen did not block it, which argues the enzyme is not simply generating singlet oxygen and letting Schenck's reaction happen; the authors proposed a peroxide transfer initiated by enzyme-generated iodine ². Modern chemists have gone partway back toward the enzyme: an immobilized dye-decolorizing peroxidase has been used to generate singlet oxygen and synthesize ascaridole without a photochemical dye ⁴¹.

• Gas chromatography with mass spectrometrySeparates an essential oil into its constituents and identifies each by its fragmentation pattern, which is how every modern figure for ascaridole content is produced ^3,36.Quantifying ascaridole, its heat-rearranged twin isoascaridole, and the precursor alpha-terpinene in plant oils and commercial products.Good for identity and relative proportion; the better studies report (Z)-ascaridole and its heat-rearrangement product isoascaridole as separate peaks, 29.7 and 13.0 percent in one wormseed oil, rather than one combined figure ³⁶.Heat in the injector can convert ascaridole to isoascaridole, so the ratio reported partly reflects the instrument; nuclear magnetic resonance was needed to settle which isomer boldo oil actually contains ⁴².
• Electron paramagnetic resonance with spin trappingDetects unpaired electrons. A trap molecule binds a fleeting radical into a stable adduct whose spectrum names the kind of radical formed ¹⁷.The only direct way to show that ascaridole's bridge has opened inside a living cell, and to test what opens it.Definitive for the presence and broad class of radical; it identified secondary alkyl and carbon-centered radicals and showed iron dependence ¹⁷.It cannot say which molecules in the cell the radicals then attack, which is why the actual targets remain unknown ²⁹.
• Patch testing with ascaridoleDilute ascaridole is applied to the skin under an occlusive patch and read after several days to diagnose allergic contact dermatitis ²².Working out whether a reaction to tea tree oil or another essential oil is an allergy to this specific molecule.In 319 patients with eczema, positive reactions rose with test concentration, from 1.4 percent at 1 percent to 5.5 percent at 2 percent and 7.2 percent at 5 percent; among the 250 of them who were also tested with oxidized tea tree oil, every positive reaction to the oil came with a positive reaction to ascaridole ²².Irritant and doubtful reactions rise with concentration too, so too strong a test produces false positives; 2 percent was the concentration recommended ²².
• Physical constants of the oilThe historical method. The United States Pharmacopoeia specified a density range, a solubility in dilute alcohol and an optical rotation range for the oil, and a batch outside them was rejected ¹⁹.Quality control in the era when oil of chenopodium was a listed medicine.It caught gross adulteration and under-distillation; Indian oil failed the specification and did contain less ascaridole, 46 percent against 65 percent in American oil ¹⁹.A set of bulk physical properties cannot measure the active molecule, and the toxicity of different stocks varied considerably whatever the constants said ¹⁹.

Where it occurs, and how much of it there is

Ascaridole's main home is the fruit of American wormseed, where it is 60 to 80 percent of the volatile oil, and its second home is the leaf of the Chilean boldo tree, where it is a smaller component ². Chile exports around two thousand tons of boldo leaf a year as a traditional herbal product ⁴². No comparable figure exists for wormseed, which is gathered as a weed and used as a dietary condiment as well as a medicine ⁴³, so which of the two plants delivers more ascaridole to more people is not known.

Neither figure can be assumed for any particular sample, and this is the most practically important fact about the molecule. In boldo, the ascaridole content is under genetic control: it was highest in northern Chilean populations and differed between groups of seedlings sharing one parent, and most of the variation was inherited rather than caused by the growing conditions, so where the leaf was harvested sets the dose ⁷. Published Chilean boldo oils have ranged from about 9 percent ascaridole to about 51 percent ^42,44. In wormseed the same spread appears for different reasons. Three Ecuadorian populations analyzed in 2026 ran from about 3 to 11 percent ascaridole, with the differences tracking soil pH, metals and organic matter ³. Three oils from the same plant material, handled differently before distillation, ranged from about 30 to 47 percent ⁴⁵. And a Bulgarian population analyzed in 2026 turned out to be something else entirely: a thymol and carvacrol chemotype, with oxygenated monoterpenes making up 56.79 percent of the oil, thymol 19.45 percent and carvacrol 14.30 percent among fifty-three constituents identified, a profile the authors note differs markedly from the ascaridole-rich chemotypes commonly reported. Ascaridole is not among the constituents they report, although the paper states no limit of detection for it ⁴.

The molecule also turns up well outside those two plants. It is a major constituent of the leaf oil of Croton pulegiodorus from northeastern Brazil, at 23.18 percent in one sample and 27.57 percent in another ^8,46, and one of the main constituents of the leaf oil of Croton regelianus from the same region ⁹. It dominates the oil of dwarf Labrador tea harvested near the treeline in northern Quebec at about 65 percent, a composition never before attributed to that species ¹¹. It reaches about 35 percent in marsh rosemary from Poland and swings between about 7 and 14 percent across the growing season in the same species in Lithuania ^10,47. It has been reported for the first time in a wormwood relative from Kashmir, mostly as isoascaridole ¹³, and in the flower and leaf but not the stem of a yarrow ¹².

One source is not a plant at all. Tea tree oil contains alpha-terpinene but no ascaridole when freshly distilled. Left in a bottle exposed to light and air, the alpha-terpinene oxidizes, and within days peroxides climb from under 50 to over 500 parts per million and ascaridole and isoascaridole appear, neither of which had ever been reported in that oil before ¹⁴. Schenck's reaction, running slowly on a bathroom shelf.

The thirty years it was the best drug in the world

Baumler and Fribourg brought the oil into Europe in 1881 for hookworm and the results were not encouraging; the oil had already been used against roundworm and had not become popular, because of the toxic and sometimes fatal effects produced in some cases ¹⁹. What changed was the work of Schüffner and Verwoerd in Sumatra in 1913, who gave it in 3 cubic centimeter doses with castor oil and chloroform and got results superior to thymol and betanaphthol, the standards of the day ¹⁹. The First World War did the rest: supplies of santonin and thymol fell, and the oil came rapidly into use ¹⁹.

The numbers that made its reputation are worth reading in the original, because they are not estimates but worm counts. Samuel Darling's Malaya Board, working in 1915 and 1916 under the Colonial Office and the Rockefeller Foundation, treated prisoners in the Federated Malay States, washed every stool for seventy-two hours, counted the worms expelled, then gave a second confirmatory course to count what the first had missed ²¹. Against hookworm, three hourly doses of the oil totaling 3 cubic centimeters removed 98.9 percent of worms in 17 valid cases; two treatments of a half-dose regimen removed 99.03 percent in 39 cases ²¹. In a head-to-head comparison at moderate doses, the oil removed 96.15 percent against 88.6 percent for thymol, 46.9 percent for a eucalyptus and chloroform mixture, and 26.7 percent for betanaphthol ²¹. In a small necropsy series of six patients who had received the maximum course and later died of unrelated disease, 99.4 percent of worms had been removed ²¹. These are the best efficacy data ever produced for this drug, and they were obtained in imprisoned colonial subjects: every man was dosed a second time so that the first dose could be scored, and nothing in the paper records that any of them consented or could have refused ²¹.

Darling also recorded the species difference, which matters because it says something about how the drug reached the worm: 96.8 percent of Necator americanus were removed by the first treatment against 76.6 percent of Ancylostoma duodenale, and resistance rose with the size of the worm ²¹. Soper reported the same asymmetry from the other side, finding carbon tetrachloride better against pure Necator infection and chenopodium better for Ascaris, with Ancylostoma infections best cleared by a combination of the two weighted toward chenopodium ¹⁹.

And Darling wrote down, in 1919, the sentence that explains everything that happened next. In using a vermicide, he said, one is employing a drug poisonous to man as well as to the worm, and the object should be to narcotize the worms and expel them together with the administered vermicide as rapidly as possible to prevent injury to the host ²¹. The purgative given after the dose, and the insistence that several stools be passed within two or three hours of it, existed to get the poison out of the patient before it was absorbed ²¹. The light meal the night before and the milk in the morning had the opposite purpose. Darling withheld food in order to exert the maximum toxic effect on the worms, because food or chyme in the stomach and small intestine seemed to lock up or absorb some of the chenopodium and leave a smaller portion to reach them; he also found that the purge given before treatment could, in some circumstances, be omitted without altering the result very much ²¹.

What the bridge does, and why iron decides

The first clean piece of evidence that the peroxide bridge is the active feature came in 1990 and was almost accidental. Ascaridole arrested the growth of Plasmodium falciparum in culture at very low concentrations, and the authors tested cineole alongside it as a control: the same carbon skeleton with a single bridging oxygen, an epoxide, instead of two. Cineole was totally inactive at identical concentrations ⁵⁰. Twenty-seven years later the same comparison was run in Leishmania with 1,4-cineole and gave the same answer, with the added detail that the peroxide-free analogue produced no detectable radicals and had no selectivity between parasite and host cell ¹⁷.

The activation step has been worked out in some detail. In cell-free systems, reduction by ferrous iron gives secondary alkyl radical intermediates, confirmed by trapping them and by gas chromatography showing that isopropyl groups are lost from ascaridole during the process ¹⁷. The reaction is driven either by small iron complexes or by hemin together with a thiol reducing agent such as cysteine ¹⁷. In living Leishmania, carbon-centered radicals appear in the presence of ascaridole, an iron chelator suppresses them, and cysteine increases them ¹⁷. Ascaridole also shifts the redox balance of the parasite's labile iron pool toward the oxidized state, which is the fingerprint of iron having donated electrons into something ^17,52.

Here the comparison with artemisinin becomes informative rather than decorative. Both molecules need the same kind of activation, but they prefer different activators. Ascaridole binds heme less tightly than artemisinin does and shifts the loose iron pool more, which points to small-molecule iron as its main activator; artemisinin behaves as though heme is its main activator, and in Leishmania, inhibitors of heme oxygenase antagonized artemisinin and raised its inhibitory concentration by orders of magnitude ^17,52. In the malaria parasite the heme dependence of artemisinin is firmly established: it is activated by heme rather than free ferrous iron, which is why it is most potent against the stages busy digesting hemoglobin, and why parasites with mutant Kelch13 proteins that bind heme less tightly activate less drug and survive ^53,54,55. Nothing equivalent has been worked out for ascaridole in Plasmodium.

What happens after activation is less well understood than the activation itself, and the honest summary is in the 2024 review: the precise targets of the toxic free radicals remain open-ended ²⁹. The best-characterized downstream picture is from Leishmania donovani, where ascaridole raised reactive oxygen species, started lipid peroxidation and depleted thiols, failed to raise mitochondrial superoxide and barely affected respiration, and instead inhibited glycolysis, with loss of membrane potential, depletion of adenosine triphosphate, the molecule every cell spends as energy, cell cycle arrest and an apoptosis-like death following ³⁰. In an earlier study in a different Leishmania species the mitochondrial effects did appear, but only on prolonged incubation and only when iron was available to activate the compound, which fits the same model with a slower clock ⁵⁶.

The poisoning: what it damaged, and in whom

The toxicology of ascaridole is not a modern inference from animal studies. It is a clinical literature, written by the doctors who were using the drug, and it is unusually consistent about which organs fail. The brain comes first: vomiting, then depressed consciousness, then seizures. Then the liver and the kidneys. And, peculiarly, the inner ear ^26,33,34.

The best-documented single case is a Mexican report from 1996, and it is worth setting out in full because it is the one instance where the dose received was measured rather than guessed. A child of two years and nine months was given the volatile oil on the advice of a traditional healer, in a total quantity of 40 milliliters. The course was vomiting, deep coma, seizures, dilated pupils, breathing that stopped, acid accumulating in the blood, collapse of the circulation and death; the electroencephalogram showed a diffuse encephalopathy and imaging showed severe brain swelling. At necropsy there was brain swelling and neuronal death, pneumonia, enteritis, inflammation around the bile ducts, mild pancreatitis and death of the kidney tubules. Chemical analysis of the actual oil administered found ascaridole at 39 milligrams per milliliter, so the 40 milliliters given carried about 1,560 milligrams of it. For a child of that age the dose formerly used in medicine would have been about 60 milligrams, so the child received roughly twenty-six times a therapeutic dose; and 1,560 milligrams is 56 percent above the 1,000 milligrams that the authors cite as the dose reported lethal in people ²⁶. That 1,000-milligram figure is the only human lethal dose anywhere in this literature, and it is the number against which every animal median lethal dose on this page should be read. The plant in this case was Chenopodium graveolens, a relative of American wormseed rather than the same species; the oil was sold and given as oil of epazote, and the authors describe ascaridole as the main active compound of the chenopodium herbs generally ²⁶.

That is one case, but the pattern it shows recurs. Three patients treated for roundworm with the oil died of liver damage, reported in 1951 ²⁷. The same year produced a sixteen-page review of childhood poisoning by the oil, a case report in the Journal of Pediatrics, and a case of toxic hepatitis with kidney shutdown treated by exchange transfusion, in which the patient's blood is drawn off and replaced with donor blood to wash the poison out ^28,33,49. A poisoning report had appeared in the Journal of the American Medical Association in 1946 ⁴⁸, and the interaction with castor oil, used as the purgative in some regimens, drew its own paper in 1947 ⁵⁷. Hearing loss after poisoning with the oil was reported as late as 1968 ³⁴, and Juul and Vraa-Jensen had already published electrobiological and histological studies of ascaridole's action on the inner ear in 1947, which makes the ear one of the few organs studied with the purified molecule rather than the oil ³⁵.

The modern animal numbers are consistent with that history and come from oils rather than the pure compound. An ascaridole-rich Croton leaf oil had a median lethal dose by mouth in mice of 460.42 milligrams per kilogram, with changes in blood counts and biochemistry at lower doses and alterations in liver and kidney on histology, although the blood tests that usually reveal such injury, the liver enzymes called transaminases together with urea and creatinine, the waste products the kidney clears, stayed near control values and both the comet and micronucleus tests for genetic damage were negative ⁸. A 2026 study of the same oil applied to the skin found no deaths, no irritation and no histological damage, but unexplained falls in red cells, hematocrit, hemoglobin, white cells and platelets at an intermediate dose that did not recur at the highest dose, and a significant fall in serum aspartate aminotransferase, one of those liver enzymes, in every treated group without any matching change on histology ⁴⁶. A 2023 Moroccan study put the median lethal dose of all three oils it tested, one of them a wormseed oil in which ascaridole was 17.7 percent, at 500 milligrams per kilogram of body weight in rats, and placed them in acute-toxicity category four: a band for substances harmful by mouth rather than acutely lethal, and not the most severe band of the scale the authors used ⁵⁸. None of these figures is a measurement of ascaridole. They are measurements of mixtures in which ascaridole is one component among dozens, and the 2025 review's complaint that nobody has established a safety profile for the purified molecule applies to toxicology as much as to efficacy ¹.

The oil, the tea, and which one does the killing

A reasonable person reading the preceding section would conclude that the traditional herb must be dangerous. The experimental answer is more interesting than that, and it cuts against the molecule.

In 2004 a group at McMaster University separated the question properly. They made the traditional water infusion, measured how well it killed nematodes, then pulled the ascaridole out of it into hexane and tested the parts. Almost 90 percent of the nematode-killing activity of the infusion was due to a water-loving component that was not ascaridole. Synthetic ascaridole and the ascaridole extracted from the infusion both reduced stimulated contractions of rat gut muscle at the concentrations needed to kill the worm; the infusion itself, and the ascaridole-free residue left after extraction, had no detectable effect on gut muscle at worm-killing concentrations ⁵¹. The conclusion the authors drew is the one the data support: the traditional infusion is safer than the plant's essential oil, and it is not ascaridole that makes the infusion work.

That finding has a sharp edge, because the modern deaths come from the infusion, not the oil. Two children died within twelve hours in a Rabat emergency department after drinking the plant as a fever remedy, one a five-month-old with toxic encephalopathy and one a ten-year-old with severe gastroenteritis and dehydration ⁵⁹. A four-year-old girl given repeated high-dose infusions for fever arrived with impaired consciousness four hours after ingestion and died of multi-organ failure ⁶⁰. The infusion is safer than the oil at equivalent use; it is not safe, and repeated concentrated doses in a small child are not equivalent use.

A commercial analysis of ten boldo products makes the same point in a different plant. Fifty-three compounds were identified in the essential oils of the samples but only twelve in the volatile fraction of the infusions made from them, and every one of the oils was highly cytotoxic, with estimated lethal concentrations below 200 parts per million; the study reports no such figure for the teas made from the same products, and the contrast it does report is that the teas had the better antioxidant capacity, because that activity sits in the non-volatile fraction that distillation leaves behind ²⁴. Distillation is not concentration of a herb. It is the selection of one chemical class out of it, and for these plants the class selected is the dangerous one.

Boldo: the one place ascaridole is still swallowed on purpose

Boldo is a Chilean tree whose leaf has been drunk for digestive and liver complaints for a long time and is exported at around two thousand tons a year ⁴². Its leaf oil contains ascaridole, and ascaridole is one of the four chemical markers, with p-cymene, 1,8-cineole and the alkaloid boldine, used to confirm that a commercial boldo sample is genuine ²⁴. Boldo is the one preparation in which ascaridole is still swallowed deliberately as a medicine inside a regulatory framework. It is not the only deliberate exposure. The wormseed infusion is still drunk as a home fever remedy, as the deaths in the preceding section show, and the leaf of the same plant is used as a dietary condiment, with its oil used as a natural antioxidant in food processing ⁴³, in quantities nobody has measured for ascaridole content. What boldo has that the others do not is a regulator's judgment about which preparation may be sold.

How much ascaridole a boldo drinker takes in is not knowable from the label. Reported ascaridole in Chilean boldo oils runs from about 9 percent to about 51 percent ^42,44, and the trait is heritable and varies by provenance within Chile, being highest in northern populations ⁷. Nuclear magnetic resonance on one commercial sample showed the ascaridole present was mainly the cis isomer ⁴². Against that variability sits the finding that the infusion carries only a small fraction of the oil's volatile load: fifty-three compounds were identified in the oils of ten commercial samples and only twelve in the volatile fraction of the infusions made from them ²⁴.

Regulators have drawn the line between the two preparations rather than trying to set a safe concentration. The European traditional-use framework for boldo covers the leaf and aqueous preparations of it, not the distilled essential oil ²⁵. That monograph could not be opened for this page, so its scope is reported here as this page's reading of a document it has not read, and no numerical limit on ascaridole is taken from it; no European instrument that this page could reach sets a maximum ascaridole content for boldo, and the line appears to be drawn between preparations instead. The practical effect is that boldo leaf tea remains a legal traditional herbal product in Europe while boldo oil is not sold for internal use. The published toxicology gives the obvious ground for treating the two differently, whatever ground the regulator gave: the oil carries the ascaridole and the volatile load, and the infusion carries very little of either ²⁴. The toxicity figures go as far as this: every commercial boldo oil tested had a median lethal concentration below 200 parts per million, which, on the conventional cut-off for that assay, the authors classed as highly cytotoxic, and the study reports no corresponding figure for the teas made from the same products ²⁴.

Boldo oil's other modern life is as a pesticide, where its ascaridole is an asset. An ascaridole-enriched fraction prepared from boldo leaf oil, raising the content from 31.4 to 89.5 percent, was about twice as potent as the parent oil against mosquito larvae, which is a direct demonstration that ascaridole carries the activity ⁶¹. Boldo oil was toxic to filariasis-vector mosquito larvae and houseflies and less toxic to a non-target water flea than a conventional synthetic insecticide, and it barely inhibited acetylcholinesterase, the enzyme that clears the nerve signal acetylcholine from a junction so that the nerve can fire again. Blocking that enzyme is how organophosphate and carbamate insecticides kill: the signal never switches off. Boldo oil, at least, is not doing that, so whatever it does to insects it does some other way ⁴². It also inhibits seed germination and seedling growth in weeds ⁴⁴ and kills blowfly larvae, pupae and adults, though in that study the authors attributed the effect to several constituents acting together rather than to ascaridole alone ⁶².

The allergen nobody meant to make

Most people who meet ascaridole in 2026 meet it in a cosmetic, and nobody put it there. Tea tree oil contains alpha-terpinene and no ascaridole when it is freshly distilled. Bjorn Hausen's group stored tea tree oil on a window sill and watched: within four days peroxides rose from under 50 to more than 500 parts per million, p-cymene climbed from 2 to 11.5 percent, alpha- and gamma-terpinene and terpinolene fell by half, and ascaridole and isoascaridole appeared, having never before been reported in that oil ¹⁴. Freshly distilled oil was a very weak sensitizer in guinea pigs; the oxidized oil was about three times stronger ¹⁴.

The clinical consequence is now well mapped. Tea tree oil has caused more published allergic reactions than any other essential oil since the first cases in 1991, and positive patch test rates in routine testing range from 0.1 to 3.5 percent ²³. Ascaridole is the first of six constituents that the standard review names as the probable major sensitizers, the others being terpinolene, alpha-terpinene, 1,2,4-trihydroxymenthane, alpha-phellandrene and limonene; the review's own wording is that these appear to be the major sensitizers, and the list is not a ranking ²³. Hausen's original series makes the same point against over-attribution: all eleven tea-tree-sensitive patients reacted strongly to alpha-terpinene and terpinolene as well as to ascaridole ¹⁴. Patients reacting to both the oil and ascaridole have been reported ⁶³, and the concentration at which ascaridole should be tested was settled by a study of 319 patients with eczema: positive reactions rose from 1.4 percent at a test concentration of 1 percent to 5.5 percent at 2 percent and 7.2 percent at 5 percent, but irritant and doubtful reactions rose too, especially at the highest concentration, and the recommendation was to test at 2 percent ^22,64. Among the 250 of those patients who were also tested with oxidized tea tree oil at 5 percent, every positive reaction to the oil came with a positive reaction to ascaridole ²².

The immunology confirms that this is allergy and not simple irritation, and it confirms the mechanism is the same one that works in parasites. Ascaridole caused full maturation of human monocyte-derived dendritic cells, raising three surface proteins the cell uses to switch on T cells, called CD86, CD80 and CD40, and one it uses to stick to them, CD54, and releasing four inflammatory messenger proteins: interleukin-1 beta, tumor necrosis factor alpha, interleukin-6 and interleukin-8. CD stands for cluster of differentiation, the numbering system for these surface markers; the first three are costimulatory molecules and the fourth is an adhesion molecule. Irritants do not do this ²⁰. Ascaridole reacted with cysteine-containing peptides but not lysine-containing ones, and when it was first treated with iron to force the radical, that peptide reactivity far exceeded that of ascaridole itself, with increased induction of the stress-response gene heme oxygenase 1, this last step shown in THP-1 cells, a leukemia cell line used as a stand-in for dendritic cells rather than in the primary human cells used earlier in the same study ²⁰. A separate chemical study then identified a substituted cyclohexenone among the breakdown products of the radical route, naming at least one of the electrophilic species that binds skin protein ³⁷.

So the mechanism that makes ascaridole a candidate antiparasitic and the mechanism that makes it a contact allergen are the same reaction: iron opens the bridge, radicals form, and whatever protein is nearest gets modified. In a parasite the nearest protein belongs to the parasite. In skin it belongs to the patient.

The modern laboratory work, and what each study can and cannot support

Since about 1990 ascaridole has had a second life as a research compound, and the literature is easy to overstate. The 2025 systematic review is blunt about why: almost all of it concerns crude essential oils rather than the isolated molecule, no comprehensive safety profile exists, and no clinical study of the purified compound is reported in it ¹. With that caveat, what has been shown is worth setting out precisely, because some of it is genuinely striking and some of it points the other way.

Against Leishmania, the evidence is the deepest. Leishmania is a single-celled parasite spread by the bite of a sandfly; depending on the species it causes either slow skin ulcers that scar, or a disease of the spleen, liver and bone marrow that kills if it is not treated. The drugs for it are old, toxic and failing, which is why a new mechanism attracts attention. Ascaridole was the most active single component of wormseed oil against the parasite in culture, though the whole oil had the better selectivity index ⁶⁵. In Leishmania donovani it half-inhibited the promastigote, the slender swimming form that lives in the sandfly and grows in culture, at 2.47 micromolar, and the amastigote, the round form that lives inside a human cell and is the one that has to be killed to cure a patient, at 2.00 micromolar, while the concentration that killed half of a macrophage cell line was 41.47 micromolar and half of mouse peritoneal macrophages 37.58 micromolar, which is a selectivity window of about seventeen- to nineteen-fold ³⁰. Combined with carvacrol at a one to four ratio it was synergistic in culture and reduced lesion size and parasite load in mice given injections into the lesion ⁶⁶.

Against Leishmania amazonensis amastigotes, ascaridole half-inhibited growth at 11.5 micromolar, against 15.0 to 19.2 micromolar for artemisinin, artemether and artesunate and 30.1 micromolar for meglumine antimoniate, the standard antimonial drug, so in that comparison ascaridole was the more potent endoperoxide ³². In the mouse half of the same study, ascaridole reduced lesion size and parasite load about as well as artemisinin, artesunate and the antimonial did ³². The authors nonetheless recommended artemisinin for further work, on the ground that it would be useful where parasites resist antimonials; they published selectivity indexes for the artemisinins, above 13 for artemisinin, 6 for artemether, 11 for artesunate and 1 for dihydroartemisinin, but none for ascaridole ³². Note also that the 11.5 micromolar measured here and the 2.00 micromolar reported in Leishmania donovani differ nearly six-fold: they come from different species, different laboratories and different readouts, and nobody has reconciled them ^30,32. And in the one study that gave the whole oil and the purified components side by side in live animals, at 30 milligrams per kilogram injected into the lesion every four days for fourteen days, the oil prevented lesion development and beat the standard drug while the purified components, ascaridole among them, had no measurable effect, and an artificial mixture of the pure components killed the mice within three days ³¹. That result and the ascaridole arm of the artemisinin comparison point opposite ways in the same disease and the same mouse strain, and the disagreement is unexplained ^31,32.

Against Plasmodium falciparum, the work is entirely in culture and there is not much of it. Ascaridole arrested development at 0.05 micromolar over three days, with no parasites visible at 0.1 micromolar. At lower concentrations the effect fell mainly on the trophozoite, the stage at which the parasite sits inside a red blood cell feeding and growing, while the younger ring stage was only marginally affected, though those ring-stage parasites did not go on to develop normally either ⁵⁰. Isolated ascaridole from a northern Labrador tea oil gave half-maximal inhibitory concentrations of 147.3 nanomolar against the drug-sensitive 3D7 strain and 104.9 nanomolar against the Dd2 strain, and the oil's activity was less than half the isolated compound's, which assigns the activity to ascaridole ¹¹. Against that sits a third result, pointing the same way as the leishmaniasis reversal: in a 2013 panel of the whole oil and its purified components, only the whole oil acted on Plasmodium falciparum, and purified ascaridole did not ⁶⁵. Three studies in culture, two finding purified ascaridole potent and one finding it inactive, are the whole of the evidence for malaria. No animal study of ascaridole in malaria has been published, and the three culture studies do not agree.

Against Trypanosoma cruzi, the parasite that causes Chagas disease, the single direct measurement is unflattering to ascaridole. Kiuchi's group isolated four monoterpene hydroperoxides from the same plant and tested all five compounds against the epimastigote stage: ascaridole came in at 23 micromolar, while the four hydroperoxides ranged from 0.8 to 3.1 micromolar, making them seven to nearly thirty times more potent ⁶⁷. The epimastigote is the form found in the insect vector, not the form that infects people, which limits what the figures mean. In a separate panel, only the whole oil and not purified ascaridole showed activity against Trypanosoma brucei, which causes African sleeping sickness ⁶⁵.

Against cancer cells, there is one study of the purified molecule and it is modest. Ascaridole had half-maximal inhibitory concentrations of 6.3 to 18.4 micrograms per milliliter in a leukemia and a colon cancer cell line, and in mice carrying sarcoma 180 it inhibited tumor growth by 33.9 percent at 10 milligrams per kilogram and 33.3 percent at 20 milligrams per kilogram, with organs only weakly affected on histology ⁹. The ceiling at a third, and the failure to improve when the dose doubled, are as informative as the effect. Two other studies are often cited as anticancer evidence and should not be: one found that a seed extract whose largest constituent was ascaridole slowed migration and invasion of a liver cancer cell line, but the authors' own analysis pointed to three other compounds as the likely actives ⁶⁸; the other found that wormseed oil killed a normal human liver cell line through the mitochondrial apoptosis pathway at concentrations in the same range reported against tumor cells ⁴³.

Two activities the 2025 systematic review lists are not supported by any test of the purified molecule, and should be read with that in mind. The review reports antimicrobial activity ¹; but in the one panel that tested purified ascaridole against bacteria and fungi, neither the oil nor ascaridole was active ⁶⁵, and what antimicrobial activity has been published belongs to whole oils, in which thymol and carvacrol are the constituents with the established antibacterial record ⁴. The review also reports anti-inflammatory activity ¹. The 2026 Bulgarian study measured that as inhibition of albumin denaturation, a cell-free bench test in which a protein is heated and the substance is scored on how much of the unfolding it prevents, and obtained half-inhibiting concentrations of 67.0 to 77.0 micrograms per milliliter for the whole oil, comparable to ibuprofen in the same assay; but that oil reported no ascaridole among its constituents, so the result cannot be attributed to this molecule ⁴. The only 2025 work pointing at ascaridole itself as an anti-inflammatory is computational: a network pharmacology and molecular docking study of Rhododendron tomentosum, the marsh rosemary that appears earlier on this page under its older name Ledum palustre, ranked ascaridole among four constituents predicted to bind five target proteins involved in inflammation and cell proliferation ⁶⁹. Docking predicts binding inside software. It is not evidence of an effect in a cell, let alone in a person.

A further pair of findings sits outside the endoperoxide story altogether, and both are worth knowing because they show the molecule is not a one-trick reagent. Inhaled ascaridole reduced locomotor activity in caffeine-excited mice and prolonged barbiturate-induced sleep by 42 percent, and a benzodiazepine-receptor antagonist reversed the effect, implicating the system that uses gamma-aminobutyric acid, the brain's main calming signal, rather than radical chemistry ⁷⁰. And cis-ascaridole does inhibit insect acetylcholinesterase, the nerve-signal enzyme described in the boldo section above: a conventional neurotoxic mechanism with nothing to do with the peroxide bridge, and one that sits awkwardly beside the finding that boldo oil barely inhibits the same enzyme ^42,71.

Why it has no clinical use, and what replaced it

Ascaridole left medicine for two separate reasons, and it is worth keeping them apart. The first was that something cheaper arrived: Maurice Hall discovered the anthelmintic properties of carbon tetrachloride in 1921, and by 1932 carbon tetrachloride cost about Rs 2-8-0 a pound against Rs 32 a pound for oil of chenopodium, an order of magnitude, which made mass treatment campaigns possible that the oil could not support ¹⁹. The second was the dying, which is set out above ^26,27,28,33.

What replaced it is a different class of drug entirely, and the comparison explains why nobody is coming back. The benzimidazoles, albendazole and mebendazole, bind the worm's tubulin and starve it, a target the host's own tubulin binds poorly, which gives them the therapeutic window ascaridole never had. In the current pooled evidence, single-dose albendazole and mebendazole reduce roundworm egg output by about 95.5 and 98.7 percent respectively, with cure rates of 91.3 and 92.8 percent ⁷⁴. For hookworm, albendazole reaches an egg reduction rate of about 93.4 percent and a cure rate of 78.3 percent ⁷⁴. Those modern figures are not the same measurement as Darling's. An egg reduction rate is the percentage fall in the number of worm eggs counted in stool, and a cure rate is the percentage of patients in whom no eggs can be found afterward; Darling counted the worms themselves. The two cannot be set directly against each other, and the choice of stool test alone moves apparent efficacy by a wide margin: in the 2025 emodepside trials, efficacy measured by polymerase chain reaction was lower than efficacy measured by the older Kato-Katz smear for every drug and every dose ⁷⁵.

That is not a story of unqualified success, and the gaps are real. All four recommended drugs perform poorly against whipworm, mebendazole managing a cure rate of only about 42 percent, and albendazole's egg reduction rate against whipworm fell measurably between 1995 and 2015, from about 72.6 percent to about 43.4 percent, which the authors flag as a concern about emerging resistance ⁷⁶. The response has been combinations: albendazole with ivermectin, albendazole with oxantel pamoate, mebendazole with ivermectin and tribendimidine with oxantel pamoate all outperform albendazole alone against whipworm ⁷⁷. Since 2025 there is also a new drug rather than a new combination. Emodepside, a cyclooctadepsipeptide that acts on a worm potassium channel the host does not share, has been through dose-finding randomized trials at six single doses from 5 to 30 milligrams against 400 milligrams of albendazole, and gave higher cure rates than albendazole against both whipworm and roundworm ⁷⁵.

The point for ascaridole is that the gap is being filled with new combinations of selective drugs, not by reviving an unselective one. A modern revival would have to clear hurdles the old oil never faced: a defined purified substance, a reproducible dose, an established safety profile, and demonstrated superiority over a drug that cures nine roundworm infections in ten. The 2025 review states the position without embellishment: therapeutic application faces limitations, mainly due to the scarcity of studies evaluating the compound in isolation, and rigorous preclinical and clinical studies with purified ascaridole would be needed before any claim could be made ¹.

There is one more practical obstacle, though it should be stated at the strength the evidence supports. What is documented is about the oil. Chopra and Mukherji recorded in 1932 that oil of chenopodium has no definite boiling point and that heated to 100 degrees Celsius in air it explodes with great violence, and Nelson found the active principle decomposed gradually on boiling with water, which is why the historical distillation had to be run fast with the condenser kept warm ¹⁹. For the purified molecule the modern picture is more moderate: the sensitization literature calls ascaridole a fairly stable endoperoxide at room temperature ²⁰, and it is handled routinely in laboratories, although peroxides as a class are treated as heat- and shock-sensitive and are not distilled hard. A substance whose parent oil cannot be heated is not impossible to manufacture, but it is one more cost against a benefit nobody has demonstrated.

Its second life: a reagent, a benchmark and a pesticide

Ascaridole did not disappear from science when it left medicine. It moved sideways into two fields where its reactivity is a feature rather than a hazard.

The first is photochemistry, where Schenck's reaction has become the standard proof that a new catalyst makes singlet oxygen. If alpha-terpinene goes in and ascaridole comes out, singlet oxygen was present; if p-cymene comes out instead, the oxidation went by a radical route through superoxide. A 2025 series of porphyrin metallacages showed this fork with unusual clarity: changing only the single metal atom at the center of the porphyrin switched the product between the two, cobalt favoring superoxide and p-cymene, zinc favoring singlet oxygen and ascaridole, with nickel and copper doing both ⁷⁸. The same test has been used to characterize dye-functionalized cage molecules that bind the substrate and raise conversion up to twenty-eight-fold ⁷⁹, titanium-oxo complexes as a homogeneous alternative to titanium dioxide ⁸⁰, perovskite nanocrystals carrying dyes ³⁹, a zirconium tungstate solid catalyst ⁴⁰, a zirconium-substituted polyoxometalate that reached a 90 percent ascaridole yield ³⁸, and enzymes in place of dyes ⁴¹. It has even served as the model reaction for scaling gas-liquid photochemistry to production rates, reaching 92 percent conversion in a spinning disc reactor ¹⁶.

The second is pest control, where ascaridole's indiscriminate reactivity is exactly what is wanted and the selectivity problem is much smaller. Bioassay-guided fractionation identified (Z)-ascaridole as the active insecticidal constituent of wormseed oil against the maize weevil, several times more potent than the crude oil by both fumigation and contact ⁷³, and the same against German cockroaches ³⁶. Boldo oil fractionated to 89.5 percent ascaridole was about twice as potent as the parent oil against mosquito larvae ⁶¹. An ascaridole-rich marsh rosemary oil killed mosquitoes, moths and houseflies, was not toxic to earthworms, only moderately toxic to water fleas, and showed high inhibitory concentrations against human keratinocytes and fibroblasts with no DNA damage on the comet assay ¹⁰. And wormseed oil kills the freshwater snails that carry schistosomiasis along with the fluke's free-swimming stage, although it was lethal to zebrafish at a lower concentration than it killed the snails, which the authors state frankly as a limit on its field use ^5,81. Herbicidal use has a 2025 entry of its own. In a comparison of three Chenopodium species, the shoot essential oils suppressed the germination and seedling growth of two weeds more strongly than leachates or decaying residues did, and in the Chenopodium ambrosioides oil the principal component was ascaridole, at 8.87 percent ⁶. That 8.87 percent is worth noticing for a second reason: it is one more sample in which the molecule the plant is famous for is a minor constituent.

The pattern across both fields is the same. Where you want a molecule that reacts hard with whatever is nearby, ascaridole is excellent. Where you need it to tell one cell from another, it is not.

2023 to 2026, verified

The most consequential recent publication is the first systematic review devoted to ascaridole, published in Fitoterapia in November 2025 ¹. Its conclusions are not a promotional summary. It describes the broad spectrum of activity reported, proposes that reactive oxygen generation through activation of the peroxide group is the common mechanism and that this is artemisinin-like, and then states that therapeutic application faces limitations, mainly because so few studies have evaluated the isolated compound, and that rigorous preclinical and clinical work with purified ascaridole would be needed to establish a safety profile and validate it as a therapeutic candidate ¹. That is the honest state of the field in 2026: an interesting mechanism, almost no evidence about the molecule itself, and nothing in humans. A second 2025 review, of the source plant's oils and extracts rather than of the molecule, arrives at the same place by a different route: a wide therapeutic range reported, including nematocidal, schistosomicidal and antimalarial activity, and the authors' own conclusion that much research is still required to understand the mechanisms and to evaluate safety and efficacy in clinical trials ⁸². Its method is worth stating, because it is now a common one: of 814 records retrieved from one database, a natural-language-processing tool clustered the titles and abstracts and cut the set by 86.73 percent, so that review rests on what an automated screen kept ⁸².

The 2024 review of natural endoperoxides as antileishmanials adds the clearest statement of why the approach might work and where it stops. Leishmania lacks catalase and a selenium-dependent glutathione peroxidase, so its antioxidant defense is weak and endoperoxides exploit that; artemisinin and ascaridole create a redox imbalance, inhibit glycolytic function rather than oxidative phosphorylation, depolarize the mitochondrial membrane and deplete adenosine triphosphate; and the precise targets of the toxic radicals remain open-ended ²⁹.

The newest chemical surveys are a useful corrective to any assumption that the plant delivers a standard dose. Three Ecuadorian populations of the source plant ranged from about 3 to 11 percent ascaridole with the differences correlating with soil pH, heavy metals and organic matter, and the oil yields were low throughout ³. A Bulgarian population of the same species turned out to be a thymol and carvacrol chemotype, with oxygenated monoterpenes at 56.79 percent of the oil, thymol at 19.45 percent and carvacrol at 14.30 percent among fifty-three constituents identified; ascaridole is not among the constituents they report, although no limit of detection is stated for it, and the authors note that the profile differs markedly from the ascaridole-rich chemotypes in the literature ⁴. A 2025 study from Argentine Patagonia adds another population and another kind of result. The oil of a local Dysphania ambrosioides, known there as paico, was dominated by ascaridole at 34.87 percent; against Varroa destructor, the mite that is the worst parasite of managed honeybees, it was significantly repellent, and against the bees themselves it reduced the survival of adults and of larvae at low concentrations. Of the three Patagonian oils tested, the one whose major constituent was alpha-pinene, and which carried no ascaridole, returned a selectivity index between mite and bee above 100 and was the one the authors put forward as a usable acaricide; the two carrying ascaridole and the sesquiterpene esquelenone returned 25 and 3.1 ⁸³. The margin problem follows the molecule out of medicine and into the hive.

Toxicology has continued on ascaridole-rich oils rather than on the molecule. The 2024 oral study of a Croton leaf oil in mice gave a median lethal dose of 460.42 milligrams per kilogram, found liver and kidney changes on histology without matching changes in transaminases, urea or creatinine, and found no genetic damage on either the comet or micronucleus test ⁸. Its 2026 companion applied the same oil to skin and found no deaths, no irritation and no histological change, but falls in red cells, in hematocrit, which is the share of blood volume made up of red cells, in hemoglobin, in white cells and in platelets at an intermediate dose that did not recur at the highest dose, an inconsistency the authors do not resolve, and a significant fall in serum aspartate aminotransferase in every treated group with no matching change on histology ⁴⁶. A 2023 study put a wormseed oil's median lethal dose in rats at 500 milligrams per kilogram ⁵⁸.

The 2025 chemistry is all about singlet oxygen, and none of that strand is about drugs ^16,78,79. The rest of 2025 is applied rather than clinical: a botanical acaricide trial in honeybee colonies ⁸³, a weed-suppression study ⁶, and one computational paper that models ascaridole against inflammatory proteins without touching a cell ⁶⁹. And no clinical trial of ascaridole appears anywhere in this period. A PubMed search for ascaridole across 2025 and 2026, run on 19 October 2026, returns ten records, none of them involving a human subject, and the 2025 systematic review, searching the whole literature, calls for clinical studies to be undertaken rather than reporting any ¹. A search of the trial registries would be needed to say that none is planned; what can be said is that none has been published. That is the single most important negative finding on this page.

What is still unknown

Nobody knows what ascaridole's radicals actually hit. The activation step is well characterized and the downstream consequences are measurable, but the target proteins have never been identified, and the 2024 review says so explicitly ²⁹. For artemisinin this question has been answered with chemical proteomics, which found more than a hundred parasite protein targets ⁵³; the equivalent experiment with ascaridole has not been done.

Nobody knows why the whole oil outperformed its purified components in living mice while ascaridole outperformed everything in the dish ^31,65, and the question is sharper because a second mouse experiment, in the same parasite and the same mouse strain, found ascaridole-treated animals comparable to the artemisinins and to the standard antimonial ³². The likeliest explanations are that minor constituents contribute, that the oil alters delivery into the infected cell, or that the purified components are simply too toxic at the doses required, and the synergy seen between ascaridole and carvacrol supports the first ⁶⁶. None of these has been tested as a hypothesis.

Nobody knows what the therapeutic window would be in a person. The best measured selectivity in culture is about seventeen- to nineteen-fold against macrophages ³⁰, which is narrow, and the historical clinical record suggests the real margin in a child was narrower still ²⁶. There is no pharmacokinetic study of ascaridole in humans at all.

Nobody knows whether ascaridole is carcinogenic. The only experiment is the 1992 study in Egyptian toads, where the oil induced hepatocellular carcinoma, the commonest form of primary liver cancer, in 23 percent of treated animals, with metastases in the kidneys of six, after an average latent period of 3.6 plus or minus 0.4 months ⁸⁴. An amphibian model with small numbers and no mammalian replication cannot settle the question in either direction, and the modern genotoxicity tests on ascaridole-rich oils were negative ⁸.

Nobody knows how much ascaridole people actually consume. Boldo leaf is exported at around two thousand tons a year ⁴², ascaridole content in the leaf is genetically variable and unlabeled ⁷, and the fraction carried into an infusion is small but unquantified for any commercial product ²⁴. The same is true of the ascaridole that forms spontaneously in aging tea tree oil, which is now the commonest route of exposure and is not measured on any label ^14,23. Two further gaps belong here. Nobody has measured what a person who eats the leaf as a dietary condiment takes in ⁴³. And this page could not establish whether ascaridole itself is named in the European Union's list of substances prohibited in cosmetic products: the legal texts were not reachable for this review and no source opened here states it, so the page makes no claim either way.

A note on the evidence itself. The PubMed records consulted for this page, last checked on 19 October 2026, carry no retraction notice and no expression of concern, which is a check only as good as PubMed's own flagging; the two sources that are not indexed in PubMed, Schenck and Ziegler's 1944 paper and the European monograph on boldo leaf, could not be checked at all and were not read for this page ^15,25. The interests behind the work are worth naming anyway, because they shape which questions get asked. A large share of the modern ascaridole literature is written for the agrochemical industry, looking for botanical insecticides, acaricides, molluscicides and herbicides, and those papers are interested in potency and in cost, not in selectivity toward a human patient ^10,42,73,81. Another share comes from the essential-oil and herbal-products trade, where the commercial question is whether a sample is genuine and saleable rather than whether it is safe ^7,24. The skin literature has a commercial interest of its own that should be named. The dendritic-cell study that establishes ascaridole as a true sensitizer rather than an irritant was co-authored from the Central Product Safety Department of the Procter and Gamble Company ²⁰, and the consumer-goods industry has a direct stake in which constituent of a cosmetic oil is identified as the allergen and at what concentration it is tested. That does not make the result wrong: the dendritic-cell data are the strongest evidence on this page that this is allergy and not irritation. It does mean the question asked was an industry question. The small body of genuinely pharmacological work on the molecule comes from a handful of academic groups in Havana, Vienna and Kolkata who have collaborated for two decades and who are, to their credit, the ones reporting the negative results ^17,31,32. No pharmaceutical company has an interest in ascaridole, which is one reason the clinical study that the 2025 review asks for has not been done and probably will not be ¹.

Where it connects

Sources

84 sources, numbered as they are cited. Every one was checked against PubMed or its publisher before it was cited here; the note under each says what it shows and what it does not.

1. 1
   Abadia ACM, Gnoatto SCB. Chemistry and biological properties of Ascaridole: A systematic review.Fitoterapia · 2025 · 188:106982doi:10.1016/j.fitote.2025.106982 · PMID 41213362

   The most recent systematic review of the molecule: an endoperoxide monoterpene with a peroxide bridge, drawn mainly from Dysphania ambrosioides, with antiparasitic, anticancer, antimicrobial and anti-inflammatory activity reported, a proposed reactive-oxygen mechanism through activation of the peroxide group, and the authors' own conclusion that almost no work has been done on the purified compound and none in people.

2. 2
   Johnson MA, Croteau R. Biosynthesis of ascaridole: iodide peroxidase-catalyzed synthesis of a monoterpene endoperoxide in soluble extracts of Chenopodium ambrosioides fruit.Arch Biochem Biophys · 1984 · 235(1):254-66doi:10.1016/0003-9861(84)90274-1 · PMID 6497393

   Enzyme work in plant extracts: ascaridole is 60 to 80 percent of the volatile oil of American wormseed fruit and a lesser component of boldo leaf oil; both plants make it as a racemate; a soluble iodide peroxidase converts alpha-terpinene to ascaridole. Quenchers of singlet oxygen did not block the plant reaction, which argues against singlet oxygen as the plant's route.

3. 3
   Blacio S, Gadvay K, Rivas K, et al. Impact of Soil Nutrients on Chemical Composition and Antioxidant Activities of Dysphania ambrosioides Essential Oil in Southern Ecuador.Plants (Basel) · 2026 · 15(3):373doi:10.3390/plants15030373 · PMID 41681538

   Three Ecuadorian populations of the source plant with ascaridole ranging from about 3 to 11 percent of the oil, the differences tracking soil pH, metals and organic matter. Evidence that the content of the active molecule is set partly by the ground the plant grows in.

4. 4
   Nacheva A, Bojilov D, Manolov S, et al. Chemical Composition and Biological Activity of Essential Oil from Dysphania ambrosioides from Bulgaria.Molecules · 2026 · 31(6):946doi:10.3390/molecules31060946 · PMID 41900046

   A 2026 analysis of the source plant from Bulgaria: a thymol and carvacrol chemotype, oxygenated monoterpenes 56.79 percent, thymol 19.45 percent, carvacrol 14.30 percent, 53 constituents identified, which the authors note differs markedly from the ascaridole-rich chemotypes in the literature. Ascaridole is not among the constituents reported, but the paper states no limit of detection for it, so this page records it as absent from the reported constituents rather than as measured and not detected. Also the source of the anti-inflammatory figures, measured as inhibition of albumin denaturation in a cell-free assay on the whole oil.

5. 5
   Ignacchiti MDC, de Queiroz VT, Martins IVF, et al. Chemical composition and effect of Dysphania ambrosioides (L.) Mosyakin & Clemants essential oil on Biomphalaria glabrata (D'Orbigny, 1835).Nat Prod Res · 2022 · 36(10):2595-2598doi:10.1080/14786419.2021.1910261 · PMID 33866878

   An oil that was 87 percent (Z)-ascaridole killed all the snails tested at ten parts per million within a day. A near-pure natural preparation of the molecule and the most potent snail-killing figure in this group of papers.

6. 6
   Al-Andal A, Radwan AM, Donia AM, Balah MA. Allelopathic pathways and impacts of Chenopodium species via leachates, decaying residues, and essential oils.PLoS One · 2025 · 20(4):e0321782doi:10.1371/journal.pone.0321782 · PMID 40299911

   Allelopathy of three Chenopodium species by three routes. The shoot essential oils were the most suppressive of weed germination and growth; ascaridole was the principal component of the Chenopodium ambrosioides oil at 8.87 percent, against carvacrol at 10.64 and 8.43 percent in the other two species.

7. 7
   Vogel H, Razmilic I, Muñoz M, Doll U, Martin JS. Studies of Genetic Variation of Essential Oil and Alkaloid Content in Boldo (Peumus boldus).Planta Med · 1999 · 65(1):90-1doi:10.1055/s-2006-960450 · PMID 17260243

   Why boldo's ascaridole content cannot be assumed from the label: the trait is under genetic control, highest in northern Chilean populations and heritable between half-sib families, so wild-harvested leaf varies by provenance.

8. 8
   Monteiro dos Santos PÉ, Cavalcanti de Barros M, Vieira de Barros A, et al. Acute oral toxicity and genotoxicity assessment of the essential oil from Croton pulegiodorus Baill (Euphorbiaceae) leaves in mice.Toxicon · 2024 · 251:108147doi:10.1016/j.toxicon.2024.108147 · PMID 39433261

   A modern dose-finding toxicity study of an ascaridole-rich oil in mice, giving the median lethal dose by mouth, the liver and kidney changes on histology, and negative comet and micronucleus tests.

9. 9
   Bezerra DP, Marinho Filho JDB, Alves APNN, et al. Antitumor activity of the essential oil from the leaves of Croton regelianus and its component ascaridole.Chem Biodivers · 2009 · 6(8):1224-31doi:10.1002/cbdv.200800253 · PMID 19697341

   The only study to test purified ascaridole against tumor cells in culture and in an animal. Gives its inhibitory concentrations in two human cell lines and its tumor inhibition rates in the mouse sarcoma 180 model, which were around a third at both doses tested, with organs only weakly affected.

10. 10
    Benelli G, Pavela R, Cianfaglione K, et al. Ascaridole-rich essential oil from marsh rosemary (Ledum palustre) growing in Poland exerts insecticidal activity on mosquitoes, moths and flies without serious effects on non-target organisms and human cells.Food Chem Toxicol · 2020 · 138:111184doi:10.1016/j.fct.2020.111184 · PMID 32061727

    An ascaridole chemotype in a plant from a different family and a cold climate. Gives inhibitory concentrations in human keratinocytes and fibroblasts and a comet assay showing no DNA damage, which are among the few human-cell safety data for an ascaridole-rich oil.

11. 11
    Séguin JC, Gagnon D, Bélanger S, et al. Chemical Composition and Antiplasmodial Activity of the Essential Oil of Rhododendron subarcticum Leaves from Nunavik, Québec, Canada.ACS Omega · 2023 · 8(19):16729-16737doi:10.1021/acsomega.3c00235 · PMID 37214733

    An ascaridole-rich oil from a northern plant tested against two laboratory strains of Plasmodium falciparum in culture. Gives isolated ascaridole's own growth-inhibition figures and shows the oil's activity tracks its ascaridole content. In vitro only; no animal or human work.

12. 12
    Aminkhani A, Sharifi S, Ekhtiyari S. Achillea filipendulina Lam.: Chemical Constituents and Antimicrobial Activities of Essential Oil of Stem, Leaf, and Flower.Chem Biodivers · 2020 · 17(5):e2000133doi:10.1002/cbdv.202000133 · PMID 32239617

    Ascaridole and trans-isoascaridole among the main components of the flower oil of a yarrow, and present in the leaf but not the stem, which shows the molecule can be confined to particular organs of one plant.

13. 13
    Qadir M, Maurya AK, Waza AA, Agnihotri VK, Shah WA. Chemical composition, antioxidant and cytotoxic activity of Artemisia gmelinii essential oil growing wild in Kashmir valley.Nat Prod Res · 2020 · 34(22):3289-3294doi:10.1080/14786419.2018.1557178 · PMID 30618281

    Ascaridole and isoascaridole reported for the first time in a wormwood relative, with isoascaridole the larger of the two at about 30 percent. Shows the molecule turning up in the same genus that gives us artemisinin.

14. 14
    Hausen BM, Reichling J, Harkenthal M. Degradation products of monoterpenes are the sensitizing agents in tea tree oil.Am J Contact Dermat · 1999 · 10(2):68-77doi:10.1016/s1046-199x(99)90002-7 · PMID 10357714

    The paper that found ascaridole where nobody expected it. Tea tree oil left exposed to light and air formed peroxides, epoxides and endoperoxides within days, among them ascaridole and isoascaridole, neither previously reported in that oil; oxidized oil was about three times the sensitizer the fresh oil was.

15. 15
    Schenck GO, Ziegler K. Die Synthese des Ascaridols.Naturwissenschaften · 1944 · 32:157

    Primary document, not indexed in PubMed and not opened for this page: the first preparative photosensitized addition of singlet oxygen across a diene, made by adding singlet oxygen across alpha-terpinene; not the first endoperoxide prepared photochemically, since ergosterol peroxide was made by dye-sensitized photo-oxygenation in 1928. The chemistry it reports is confirmed by the modern work cited here, including the synthesis of ascaridole from alpha-terpinene used in the mitochondrial toxicology study.

16. 16
    Chaudhuri A, de Groot WFC, Schuurmans JHA, et al. Scaling Up Gas-Liquid Photo-Oxidations in Flow Using Rotor-Stator Spinning Disc Reactors and a High-Intensity Light Source.Org Process Res Dev · 2025 · 29(2):460-471doi:10.1021/acs.oprd.4c00458 · PMID 40012916

    An engineering paper using the alpha-terpinene to ascaridole photo-oxidation as its model reaction at production scale, reaching 92 percent conversion. Ascaridole's modern role is as a benchmark for singlet-oxygen chemistry rather than as a drug.

17. 17
    Geroldinger G, Tonner M, Hettegger H, et al. Mechanism of ascaridole activation in Leishmania.Biochem Pharmacol · 2017 · 132:48-62doi:10.1016/j.bcp.2017.02.023 · PMID 28263719

    The key mechanistic paper. Electron paramagnetic resonance spin-trapping detected carbon-centered radicals from ascaridole inside living Leishmania, blocked by an iron chelator and enhanced by cysteine. The analogue without the peroxide bridge, 1,4-cineole, produced no radicals and lost both potency and selectivity.

18. 18
    Monzote L, Stamberg W, Staniek K, Gille L. Toxic effects of carvacrol, caryophyllene oxide, and ascaridole from essential oil of Chenopodium ambrosioides on mitochondria.Toxicol Appl Pharmacol · 2009 · 240(3):337-47doi:10.1016/j.taap.2009.08.001 · PMID 19666043

    The host-side half of the mechanism, in rat liver mitochondria. Without added iron, ascaridole was the least toxic of the oil's three major components; with iron, carbon-centered radicals appeared, oxidative phosphorylation failed and lipid peroxidation began. Reduced hemin also activated it; mitochondrial cytochrome c did not. The ascaridole used was synthesized from alpha-terpinene.

19. 19
    Chopra RN, Mukherji B. Indian Chenopodium.Ind Med Gaz · 1932 · 67(1):5-7PMID 29010929

    Read in full from the PubMed Central scan. A pharmacology review from the Calcutta School of Tropical Medicine. Gives the oil's instability and violent decomposition on heating, ascaridole at 40 to 70 percent of samples, 46 percent in Indian versus 65 percent in American oil, the United States Pharmacopoeia physical specifications, Nelson's distillation finding, the 1881 European introduction, the 1913 Sumatra hookworm work, and the displacement by carbon tetrachloride after 1921.

20. 20
    Krutz NL, Hennen J, Korb C, et al. Activation of the Endoperoxide Ascaridole Modulates Its Sensitizing Capacity.Toxicol Sci · 2015 · 147(2):515-23doi:10.1093/toxsci/kfv148 · PMID 26185204

    The same iron chemistry seen in parasites, now in human immune cells. Ascaridole matured human dendritic cells, which irritants do not do, and treating it with iron first greatly increased its reactivity toward cysteine-containing peptides.

21. 21
    Darling ST. Recent Researches on Hookworm Infection in Indonesia.Ind Med Gaz · 1919 · 54(12):446-453PMID 29006654

    Read in full. The Rockefeller Foundation Malaya Board's own report of its 1915 to 1916 worm-count trials, with the head-to-head percentages of worms removed by oil of chenopodium against thymol, betanaphthol and a eucalyptus-chloroform mixture, the species difference between Necator and Ancylostoma, and the author's plain statement that a vermicide is a drug poisonous to the host as well as the worm. Note that the paper is internally inconsistent on its headline figure: the dosage table gives 98.9 percent for the three-dose course in 17 valid cases, while the text immediately beneath it reports 96.9 percent for the same regimen. The table value is the one used on this page. The trials were conducted in adult male prisoners, and the confirmatory design required every man to be dosed a second time.

22. 22
    Christoffers WA, Blömeke B, Coenraads PJ, Schuttelaar MLA. The optimal patch test concentration for ascaridole as a sensitizing component of tea tree oil.Contact Dermatitis · 2014 · 71(3):129-37doi:10.1111/cod.12199 · PMID 24645715

    Three hundred and nineteen patients with eczema patch tested at three concentrations of ascaridole. Gives the rise in positive reactions with concentration, the parallel rise in irritant and doubtful reactions, and the recommended testing concentration.

23. 23
    de Groot AC, Schmidt E. Tea tree oil: contact allergy and chemical composition.Contact Dermatitis · 2016 · 75(3):129-43doi:10.1111/cod.12591 · PMID 27173437

    The standard review. Positive patch test rates in routine testing ranged from 0.1 to 3.5 percent, fresh oil is a weak to moderate sensitizer, oxidation increases its potency, and ascaridole heads the list of the oil's major sensitizers.

24. 24
    de Souza WFM, Mariano XM, Isnard JL, et al. Evaluation of the volatile composition, toxicological and antioxidant potentials of the essential oils and teas of commercial Chilean boldo samples.Food Res Int · 2019 · 124:27-33doi:10.1016/j.foodres.2018.12.059 · PMID 31466647

    Ten commercial boldo products from Brazil. Ascaridole is one of four chemical markers of genuine boldo; fifty-three compounds were found in the oils but only twelve in the volatile fraction of the infusions, and every oil was highly cytotoxic, with estimated lethal concentrations below 200 parts per million. The paper does not report a corresponding lethality figure for the teas, and the only oil-versus-tea contrast it states is that the teas had the better antioxidant capacity; the assay organism is not named in the record consulted here. Still the clearest published evidence that the leaf infusion and the distilled oil are different exposures.

25. 25
    European Medicines Agency, Committee on Herbal Medicinal Products. Community herbal monograph on Peumus boldus Molina, folium.European Medicines Agency, Committee on Herbal Medicinal Products

    Regulator's document, not indexed in PubMed, and it could not be retrieved for this page: no document number, adoption date or revision date has been verified, which makes it the one source here that a reader cannot check from the citation. It is cited only for the point that the European traditional-use framework covers boldo leaf preparations and not boldo essential oil, and that point should be treated as unverified. No numerical limit on ascaridole is quoted from it, and no reason for the leaf-versus-oil distinction is attributed to it.

26. 26
    Montoya-Cabrera MA, Escalante-Galindo P, Meckes-Fisher M, et al. [Fatal poisoning caused by oil of epazote, Chenopodium graveolens].Gac Med Mex · 1996 · 132(4):433-7PMID 8964384

    The most completely documented single poisoning: a child given the oil by a traditional healer, with the clinical course, the necropsy organ findings and a chemical assay of the actual oil administered, which allows the ascaridole dose received to be calculated and compared with the dose formerly used in medicine.

27. 27
    Jelliffe DB. Oil of Chenopodium in the treatment of ascariasis; (report of three cases of fatal liver damage in African patients).J Trop Med Hyg · 1951 · 54(7):143-6PMID 24541284

    Three deaths from liver damage in patients treated for roundworm with the oil. PubMed holds the title and indexing only, with no abstract and no digital object identifier; cited for the existence and nature of the series, not for figures.

28. 28
    Agosto D. [Chenopodium oil poisoning in children].Acta Paediatr Lat · 1951 · 4(2):129-44PMID 14829264

    A sixteen-page 1951 review of childhood poisoning by the oil. Title and indexing only in PubMed; cited as evidence of how large the pediatric case literature had grown by that year, not for specific numbers.

29. 29
    Sarkar D, Monzote L, Gille L, Chatterjee M. Natural endoperoxides as promising anti-leishmanials.Phytomedicine · 2024 · 129:155640doi:10.1016/j.phymed.2024.155640 · PMID 38714091

    Review of the shared logic behind artemisinin and ascaridole: Leishmania lacks catalase and a selenium-dependent glutathione peroxidase, so its antioxidant defense is weak and endoperoxides exploit it. States plainly that the precise targets of the radicals remain unknown.

30. 30
    Sarkar D, De Sarkar S, Gille L, Chatterjee M. Ascaridole exerts the leishmanicidal activity by inhibiting parasite glycolysis.Phytomedicine · 2022 · 103:154221doi:10.1016/j.phymed.2022.154221 · PMID 35696799

    The most thorough single study of what ascaridole does to a parasite, in Leishmania donovani in culture. Gives the inhibitory concentrations against both parasite stages and against two kinds of host macrophage, from which the selectivity window can be read. Found the damage runs through glycolysis rather than mitochondrial respiration.

31. 31
    Monzote L, Pastor J, Scull R, Gille L. Antileishmanial activity of essential oil from Chenopodium ambrosioides and its main components against experimental cutaneous leishmaniasis in BALB/c mice.Phytomedicine · 2014 · 21(8-9):1048-52doi:10.1016/j.phymed.2014.03.002 · PMID 24768411

    The reversal that matters. In mice, the whole oil prevented lesion development and beat the standard antimonial drug, while the pure components, ascaridole among them, showed no effect, and an artificial mixture of the pure components killed the animals within three days.

32. 32
    Machín L, Nápoles R, Gille L, Monzote L. Leishmania amazonensis response to artemisinin and derivatives.Parasitol Int · 2020 · 80:102218doi:10.1016/j.parint.2020.102218 · PMID 33137506

    Head-to-head in culture and in mice. Ascaridole half-inhibited Leishmania amazonensis amastigotes at 11.5 micromolar against 15.0 to 19.2 micromolar for artemisinin, artemether and artesunate and 30.1 micromolar for meglumine antimoniate, and in the mouse arm ascaridole-treated animals were comparable to the artemisinins and to the antimonial. The authors still recommended artemisinin for further work, on the ground of usefulness where parasites resist antimonials; selectivity indexes are published for the artemisinins but not for ascaridole, so no safety-margin comparison can be drawn from this paper. The 11.5 micromolar here is nearly six times the 2.00 micromolar reported in Leishmania donovani by another group.

33. 33
    Sansone G, Cotellessa G. [Severe case of acute toxic hepatitis with hyperazotemia and renal block (Chenopodium oil poisoning) treated successfully by exchange transfusion].Minerva Pediatr · 1951 · 3(14):717PMID 14940869

    A case of combined liver and kidney failure from the oil, treated with exchange transfusion. Title and indexing only in PubMed; cited for the organ pattern it names in its title.

34. 34
    Kociolek G, Sulkowski W, Starzyński Z, Zolnowski Z. [Toxic damage to hearing during poisoning with chenopodium oil].Otolaryngol Pol · 1968 · 22(5):737-9PMID 5751714

    A case of hearing loss after poisoning with the oil, published two decades after the drug had largely gone. Title and indexing only in PubMed.

35. 35
    Juul A, Vraa-Jensen G. On the effect of ascaridole on the inner ear: electrobiological and histological studies on the localization of the cochlear microphone effect.Acta Pharmacol Toxicol (Copenh) · 1947 · 3(1):51-72doi:10.1111/j.1600-0773.1947.tb02637.x · PMID 20270058

    The laboratory counterpart to the deafness reports, and one of the few studies of the purified molecule's effect on a specific organ. PubMed holds title and indexing only; cited for the fact that the inner ear was studied as a target of ascaridole itself, not of the whole oil.

36. 36
    Zhu WX, Zhao K, Chu SS, Liu ZL. Evaluation of Essential Oil and its Three Main Active Ingredients of Chinese Chenopodium ambrosioides (Family: Chenopodiaceae) against Blattella germanica.J Arthropod Borne Dis · 2012 · 6(2):90-7PMID 23378965

    Gives the oil's composition with (Z)-ascaridole and isoascaridole quantified separately, and shows (Z)-ascaridole was the most potent of the constituents against cockroaches by both fumigation and topical application.

37. 37
    Chittiboyina AG, Avonto C, Khan IA. What Happens after Activation of Ascaridole? Reactive Compounds and Their Implications for Skin Sensitization.Chem Res Toxicol · 2016 · 29(9):1488-92doi:10.1021/acs.chemrestox.6b00157 · PMID 27513446

    Identifies a substituted cyclohexenone as a reactive electrophilic product formed when ascaridole breaks down by a radical route, which gives a chemical identity to at least one of the species that binds skin protein.

38. 38
    Maksimchuk NV, Puiggalí-Jou J, Zalomaeva OV, et al. Resolving the Mechanism for H2O2 Decomposition over Zr(IV)-Substituted Lindqvist Tungstate: Evidence of Singlet Oxygen Intermediacy.ACS Catal · 2023 · 13(15):10324-10339doi:10.1021/acscatal.3c02416 · PMID 37560188

    Uses the formation of ascaridole from alpha-terpinene as the diagnostic test for singlet oxygen, reaching a 90 percent yield after optimization. An example of ascaridole serving as a chemical indicator rather than a product of interest.

39. 39
    Cortés-Villena A, Bellezza D, Cunha C, et al. Engineering Metal Halide Perovskite Nanocrystals with BODIPY Dyes for Photosensitization and Photocatalytic Applications.J Am Chem Soc · 2024 · 146(21):14479-14492doi:10.1021/jacs.3c14335 · PMID 38572736

    A nanocrystal-dye hybrid whose usefulness the authors demonstrate by oxidizing alpha-terpinene to ascaridole through singlet oxygen; cited as one more instance of the reaction serving as a standard test.

40. 40
    Evtushok VY, Ivanchikova ID, Zalomaeva OV, et al. Heterogeneous H2O2-based selective oxidations over zirconium tungstate α-ZrW2O8.Dalton Trans · 2024 · 53(4):1528-1540doi:10.1039/d3dt03495j · PMID 38164099

    A solid catalyst in which the appearance of ascaridole from alpha-terpinene is taken as the signature that singlet oxygen is involved. Cited for that diagnostic use.

41. 41
    Ingenbosch KN, Quint S, Dyllick-Brenzinger M, et al. Singlet-Oxygen Generation by Peroxidases and Peroxygenases for Chemoenzymatic Synthesis.Chembiochem · 2021 · 22(2):398-407doi:10.1002/cbic.202000326 · PMID 32798264

    Enzymes, rather than dyes, used to make the singlet oxygen; an immobilized dye-decolorizing peroxidase was then used to synthesize ascaridole. A modern echo of the plant peroxidase route.

42. 42
    Pavela R, Benelli G, Petrelli R, et al. Exploring the Insecticidal Potential of Boldo (Peumus boldus) Essential Oil: Toxicity to Pests and Vectors and Non-target Impact on the Microcrustacean Daphnia magna.Molecules · 2019 · 24(5):879doi:10.3390/molecules24050879 · PMID 30832296

    Gives boldo oil's composition with ascaridole at about 9 percent, mostly as the cis isomer by nuclear magnetic resonance, and notes that around 2000 tons of boldo leaf are exported from Chile each year as a herbal medicinal product.

43. 43
    Wang XY, Hao JM, Ren QR, et al. Cytotoxicity and Apoptosis Induced by Chenopodium ambrosioides L. Essential Oil in Human Normal Liver Cell Line L02 via the Endogenous Mitochondrial Pathway Rather Than the Endoplasmic Reticulum Stress.Int J Environ Res Public Health · 2021 · 18(14):7469doi:10.3390/ijerph18147469 · PMID 34299918

    Important for reading the anticancer literature honestly: the oil killed a normal human liver cell line at concentrations in the same range as those reported against tumor cells, through the mitochondrial apoptosis pathway.

44. 44
    Verdeguer M, García-Rellán D, Boira H, et al. Herbicidal activity of Peumus boldus and Drimys winterii essential oils from Chile.Molecules · 2011 · 16(1):403-11doi:10.3390/molecules16010403 · PMID 21221059

    A Chilean boldo oil in which ascaridole was the single largest component at about 51 percent, far above the usual figure, and which inhibited seed germination and seedling growth of two weeds at every concentration tested. Shows how widely boldo's ascaridole content ranges.

45. 45
    Monzote L, Nance MR, García M, Scull R, Setzer WN. Comparative chemical, cytotoxicity and antileishmanial properties of essential oils from Chenopodium ambrosioides.Nat Prod Commun · 2011 · 6(2):281-6PMID 21425695

    Three oils from the same plant handled differently before distillation: ascaridole ranged from about 30 to 47 percent, antiparasitic activity was unchanged, but toxicity to host cells differed, so handling changed the safety margin without changing the potency.

46. 46
    Santos PÉMD, Barros MC, Freitas TP, et al. Assessment of acute dermal toxicity of Croton pulegiodorus Baill. leaf essential oil in mice.Toxicon · 2026 · 272:108992doi:10.1016/j.toxicon.2026.108992 · PMID 41519205

    The 2026 companion study, by skin rather than by mouth: no deaths and no skin irritation, but blood-count changes at an intermediate dose that the authors could not explain and that did not follow the dose upward.

47. 47
    Judzentiene A, Budiene J, Svediene J, Garjonyte R. Toxic, Radical Scavenging, and Antifungal Activity of Rhododendron tomentosum H. Essential Oils.Molecules · 2020 · 25(7):1676doi:10.3390/molecules25071676 · PMID 32260539

    Eight oils from one species across a growing season, with ascaridole isomers reaching about 7 to 14 percent in three of them and absent from the rest. Evidence that ascaridole content in a single plant population swings with the time of year.

48. 48
    Guyton WL. Poisoning due to oil of chenopodium.J Am Med Assoc · 1946 · 132:330doi:10.1001/jama.1946.02870410018006a · PMID 20997219

    A poisoning report in the Journal of the American Medical Association while the drug was still in wide use. Title and indexing only in PubMed.

49. 49
    Brant CH, Haire SD, Stumpe AR. Oil of chenopodium poisoning.J Pediatr · 1951 · 39(6):742-4doi:10.1016/s0022-3476(51)80240-3 · PMID 14898405

    A 1951 pediatric case report. Title and indexing only in PubMed; cited as one of the cluster of reports from that single year.

50. 50
    Pollack Y, Segal R, Golenser J. The effect of ascaridole on the in vitro development of Plasmodium falciparum.Parasitol Res · 1990 · 76(7):570-2doi:10.1007/BF00932563 · PMID 2217117

    The first test of ascaridole against the malaria parasite, in culture only. Also the cleanest evidence that the peroxide bridge is what acts: cineole, the same skeleton with an epoxide in place of the peroxide, was inactive at the same concentrations.

51. 51
    MacDonald D, VanCrey K, Harrison P, et al. Ascaridole-less infusions of Chenopodium ambrosioides contain a nematocide(s) that is(are) not toxic to mammalian smooth muscle.J Ethnopharmacol · 2004 · 92(2-3):215-21doi:10.1016/j.jep.2004.02.018 · PMID 15138003

    The experiment that separates the worm-killing from the molecule. Almost all the nematode-killing activity of a water infusion came from something other than ascaridole, and the ascaridole-free residue did not disturb rat gut muscle at worm-killing concentrations, while ascaridole did.

52. 52
    Geroldinger G, Tonner M, Quirgst J, et al. Activation of artemisinin and heme degradation in Leishmania tarentolae promastigotes: A possible link.Biochem Pharmacol · 2019 · 173:113737doi:10.1016/j.bcp.2019.113737 · PMID 31786259

    Compares the two endoperoxides directly. Low-temperature electron paramagnetic resonance showed ascaridole shifted the redox state of the parasite's loose iron pool more than artemisinin did, which is the evidence that the two molecules are activated by different iron sources.

53. 53
    Wang J, Lin Q. Chemical proteomics approach reveals the direct targets and the heme-dependent activation mechanism of artemisinin in Plasmodium falciparum using an artemisinin-based activity probe.Microb Cell · 2016 · 3(5):230-231doi:10.15698/mic2016.05.503 · PMID 28357359

    For the comparison molecule, not for ascaridole: artemisinin is activated by heme rather than free ferrous iron, binds many parasite proteins at once, and is far more potent against the stages that are digesting hemoglobin.

54. 54
    Quadros HC, Silva MCB, Moreira DRM. The Role of the Iron Protoporphyrins Heme and Hematin in the Antimalarial Activity of Endoperoxide Drugs.Pharmaceuticals (Basel) · 2022 · 15(1):60doi:10.3390/ph15010060 · PMID 35056117

    Review of endoperoxide activation chemistry: the reduced iron form of heme activates these drugs and the oxidized form does not, and the drug-heme adducts that result are themselves toxic to the parasite even though they no longer carry a peroxide bond.

55. 55
    Rahman A, Tamseel S, Dutta S, et al. Artemisinin-resistant Plasmodium falciparum Kelch13 mutant proteins display reduced heme-binding affinity and decreased artemisinin activation.Commun Biol · 2024 · 7(1):1499doi:10.1038/s42003-024-07178-2 · PMID 39538019

    How resistance to an endoperoxide arises in the malaria parasite: mutant Kelch13 proteins bind heme less tightly, so less drug is activated. Included because it shows the activation step, which ascaridole shares, is the step evolution attacks.

56. 56
    Monzote L, Geroldinger G, Tonner M, et al. Interaction of ascaridole, carvacrol, and caryophyllene oxide from essential oil of Chenopodium ambrosioides L. with mitochondria in Leishmania and other eukaryotes.Phytother Res · 2018 · 32(9):1729-1740doi:10.1002/ptr.6097 · PMID 29672979

    Separates the oil's components by target and by time course: ascaridole had no immediate effect on the parasite's electron transport chain, and only on prolonged incubation, with iron available, did superoxide rise and mitochondrial coupling fail.

57. 57
    Guevara R. Toxicity of oil of chenopodium when administered together with castor oil.J Philipp Med Assoc · 1947 · 23(6):259-67PMID 20265137

    On the interaction that worried clinicians: the oil given together with castor oil. Title and indexing only in PubMed; cited for the existence of the concern, which is why saline purgatives replaced oily ones in the worm regimens.

58. 58
    Ez-Zriouli R, ElYacoubi H, Imtara H, et al. Chemical Composition, Antioxidant and Antibacterial Activities and Acute Toxicity of Cedrus atlantica, Chenopodium ambrosioides and Eucalyptus camaldulensis Essential Oils.Molecules · 2023 · 28(7):2974doi:10.3390/molecules28072974 · PMID 37049738

    A wormseed oil with alpha-terpinene at 53.4 percent and ascaridole at 17.7 percent, and a rat median lethal dose of 500 milligrams per kilogram for all three oils studied, which the authors place in acute-toxicity category four. Category four is not a high-toxicity band: it is the band for substances harmful by mouth rather than acutely lethal, and this page states it that way rather than in the authors' phrasing.

59. 59
    Badinga LPCL, Mekaoui N, Karboubi L, Dakhama BSB. [M'khinza-related intoxication: about two observations].Pan Afr Med J · 2018 · 31:18doi:10.11604/pamj.2018.31.18.15987 · PMID 30918546

    Two children who died within twelve hours of drinking the plant as an infusion for fever, reported from a pediatric emergency department in Rabat. Evidence that the modern poisonings come from the herb as a home remedy, not from the pharmaceutical oil.

60. 60
    Elhaddadi H, Hamami A, Elouali A, Babakhouya A, Rkain M. A Fatal Case Report of Chenopodium ambrosioides L. (M'khinza) Intoxication.Cureus · 2024 · 16(5):e60351doi:10.7759/cureus.60351 · PMID 38883026

    A four-year-old girl given repeated high-dose infusions of the plant for fever, admitted with impaired consciousness four hours after ingestion and dying of multi-organ failure. The most recent documented death, and it is from the infusion rather than the oil.

61. 61
    de Castro DSB, da Silva DB, Tibúrcio JD, et al. Larvicidal activity of essential oil of Peumus boldus Molina and its ascaridole-enriched fraction against Culex quinquefasciatus.Exp Parasitol · 2016 · 171:84-90doi:10.1016/j.exppara.2016.10.008 · PMID 27815127

    Boldo oil fractionated to raise ascaridole from 31.4 to 89.5 percent; the enriched fraction was about twice as potent against mosquito larvae, which is direct evidence that ascaridole carries the oil's insecticidal activity.

62. 62
    Viana TS, Dias RF, Vianna ACS, Moreira RFA, Aguiar VM. Evaluation of Chilean Boldo Essential Oil as a Natural Insecticide Against Chrysomya megacephala (Diptera: Calliphoridae).J Med Entomol · 2020 · 57(5):1364-1372doi:10.1093/jme/tjaa051 · PMID 32198519

    Boldo oil tested against a blowfly at three life stages. The authors attribute the toxicity to several constituents acting together or synergistically, ascaridole among them, rather than to ascaridole alone, and found the pupa the most resistant stage.

63. 63
    Christoffers WA, Blömeke B, Coenraads PJ, Schuttelaar MLA. Co-sensitization to ascaridole and tea tree oil.Contact Dermatitis · 2013 · 69(3):187-9doi:10.1111/cod.12086 · PMID 23948040

    Case report of patients reacting to both. Title and indexing held by PubMed with no abstract; cited for the clinical association it names.

64. 64
    Bakker CV, Blömeke B, Coenraads PJ, Schuttelaar ML. Ascaridole, a sensitizing component of tea tree oil, patch tested at 1% and 5% in two series of patients.Contact Dermatitis · 2011 · 65(4):240-1doi:10.1111/j.1600-0536.2011.01948.x · PMID 21906073

    The earlier of the two Groningen patch-test reports. Title and indexing held by PubMed with no abstract; cited for the existence of the two-concentration comparison that the later study settled.

65. 65
    Monzote L, García M, Pastor J, et al. Essential oil from Chenopodium ambrosioides and main components: activity against Leishmania, their mitochondria and other microorganisms.Exp Parasitol · 2013 · 136:20-6doi:10.1016/j.exppara.2013.10.007 · PMID 24184772

    Ascaridole was the most active single component against Leishmania in culture, but the whole oil had the better selectivity index. Only the whole oil, not ascaridole alone, acted on Plasmodium falciparum and Trypanosoma brucei in this panel, and nothing in the panel acted on bacteria or fungi.

66. 66
    Pastor J, García M, Steinbauer S, et al. Combinations of ascaridole, carvacrol, and caryophyllene oxide against Leishmania.Acta Trop · 2015 · 145:31-8doi:10.1016/j.actatropica.2015.02.002 · PMID 25697866

    Ascaridole with carvacrol was strongly synergistic against Leishmania amazonensis in culture and reduced lesion size and parasite load in mice given intralesional injections. Spin-trapping in the same paper showed carvacrol damps the carbon-centered radical signal from iron-activated ascaridole, which complicates the simple radical story.

67. 67
    Kiuchi F, Itano Y, Uchiyama N, et al. Monoterpene hydroperoxides with trypanocidal activity from Chenopodium ambrosioides.J Nat Prod · 2002 · 65(4):509-12doi:10.1021/np010445g · PMID 11975490

    The one direct measurement of ascaridole against Trypanosoma cruzi, and it is unflattering: four companion monoterpene hydroperoxides from the same plant were far more potent against the epimastigote stage than ascaridole itself. Epimastigotes are the insect-gut form, not the form that infects people.

68. 68
    Huang J, Hao J, Nie J, et al. Possible Mechanism of Dysphania ambrosioides (L.) Mosyakin & Clemants Seed Extract Suppresses the Migration and Invasion of Human Hepatocellular Carcinoma Cells SMMC-7721.Chem Biodivers · 2023 · 20(3):e202200768doi:10.1002/cbdv.202200768 · PMID 36694378

    A seed extract whose largest single constituent was ascaridole slowed migration and invasion of a liver cancer cell line in culture. The authors' own network and transcriptome analysis pointed to three other compounds, not ascaridole, as the likely actives.

69. 69
    Xiao SP, Xie B, Li LM, et al. [Chemical constituents, biological activity evaluation of Rhododendron tomentosum, and mechanisms of its anti-inflammatory, antioxidant, and anti-rheumatoid arthritis activities based on network pharmacology and molecular docking technology].Zhongguo Zhong Yao Za Zhi · 2025 · 50(18):5198-5216doi:10.19540/j.cnki.cjcmm.20250607.201 · PMID 41507718

    In Chinese with an English abstract. Gas chromatography with mass spectrometry of the leaf and young-branch oils of marsh rosemary, then network pharmacology and molecular docking: ascaridole was one of four constituents, with lupeol, procyanidin B2 and terpinen-4-ol, predicted to bind five target proteins. Computational prediction only; no cell or animal experiment on ascaridole itself.

70. 70
    Dougnon G, Ito M. Role of Ascaridole and p-Cymene in the Sleep-Promoting Effects of Dysphania ambrosioides Essential Oil via the GABAergic System in a ddY Mouse Inhalation Model.J Nat Prod · 2020 · 84(1):91-100doi:10.1021/acs.jnatprod.0c01137 · PMID 33325703

    An effect of ascaridole that has nothing to do with the peroxide bridge's radical chemistry: inhaled ascaridole reduced activity in excited mice and lengthened barbiturate sleeping time, and a benzodiazepine-receptor antagonist blocked it. Mouse inhalation model only.

71. 71
    Almadiy AA. Chemical profile, mosquitocidal, and biochemical effects of essential oil and major components of Dysphania ambrosioides against Culex quinquefasciatus Say.Environ Sci Pollut Res Int · 2020 · 27(33):41568-41576doi:10.1007/s11356-020-10137-z · PMID 32691320

    Names cis-ascaridole by its systematic bicyclic name and shows it inhibits insect acetylcholinesterase, a mechanism entirely separate from the peroxide bridge.

72. 72
    Zamilpa A, García-Alanís C, López-Arellano ME, et al. In vitro nematicidal effect of Chenopodium ambrosioides and Castela tortuosa n-hexane extracts against Haemonchus contortus (Nematoda) and their anthelmintic effect in gerbils.J Helminthol · 2019 · 93(4):434-439doi:10.1017/S0022149X18000433 · PMID 29729678

    A modern veterinary test of the plant against a parasitic nematode. Strong killing of larvae in the dish, but only partial reduction of worm burden in infected gerbils even when given by injection into the abdomen, which is the usual gap between dish and animal.

73. 73
    Chu SS, Feng Hu J, Liu ZL. Composition of essential oil of Chinese Chenopodium ambrosioides and insecticidal activity against maize weevil, Sitophilus zeamais.Pest Manag Sci · 2011 · 67(6):714-8doi:10.1002/ps.2112 · PMID 21360645

    Bioassay-guided fractionation naming (Z)-ascaridole as the active insecticidal constituent, several times more potent than the crude oil by both fumigation and contact.

74. 74
    Bekele T, Lachisa L, Tsegaye A, Bacha K, Ketema T. Efficacy of Albendazole and Mebendazole Against Soil Transmitted Infections among Pre-School and School Age Children: A Systematic Review and Meta-Analysis.J Epidemiol Glob Health · 2024 · 14(3):884-904doi:10.1007/s44197-024-00231-7 · PMID 38696109

    Sixty-six studies pooled. Gives current egg reduction rates and cure rates for the two standard drugs against roundworm, whipworm and hookworm in children, the figures against which any revival of an older agent would be judged.

75. 75
    Lotz CN, Mrimi EC, Schneeberger PHH, Ali SM, Hattendorf J, Keiser J. Performance of real-time polymerase chain reaction and Kato-Katz for diagnosing soil-transmitted helminth infections and evaluating treatment efficacy of emodepside in randomized controlled trials.PLoS Negl Trop Dis · 2025 · 19(2):e0012872doi:10.1371/journal.pntd.0012872 · PMID 39965016

    Randomized controlled trial data on emodepside at six single doses from 5 to 30 milligrams against 400 milligrams of albendazole, read two ways. Emodepside gave higher cure rates than albendazole against Trichuris trichiura and Ascaris lumbricoides; efficacy measured by polymerase chain reaction was lower than by Kato-Katz for every drug and dose, so the diagnostic method sets the apparent result.

76. 76
    Moser W, Schindler C, Keiser J. Efficacy of recommended drugs against soil transmitted helminths: systematic review and network meta-analysis.BMJ · 2017 · 358:j4307doi:10.1136/bmj.j4307 · PMID 28947636

    The benchmark the old oil would have to beat today. All four recommended drugs clear roundworm well; only albendazole works well against hookworm; all are poor against whipworm; and albendazole's effect on whipworm fell measurably between 1995 and 2015.

77. 77
    Clarke NE, Doi SAR, Wangdi K, et al. Efficacy of Anthelminthic Drugs and Drug Combinations Against Soil-transmitted Helminths: A Systematic Review and Network Meta-analysis.Clin Infect Dis · 2019 · 68(1):96-105doi:10.1093/cid/ciy423 · PMID 29788074

    Twenty-one regimens compared across 114 studies. The gap left by the benzimidazoles against whipworm is being filled by drug combinations, not by returning to older single agents.

78. 78
    Zhang Y, Jian S, Li Z, et al. Single-Atom-Modulated Reactive Oxygen Species Generation and Network Crosslinking in Porphyrin-Based Metallacages for Selective Photocatalysis.Angew Chem Int Ed Engl · 2025 · 65(6):e25287doi:10.1002/anie.202525287 · PMID 41450311

    Shows the fork in the road cleanly: changing only the metal atom at the center of a porphyrin switches the oxidation of alpha-terpinene between p-cymene, by way of superoxide, and ascaridole, by way of singlet oxygen.

79. 79
    Main MU, Taylor D, Amicosante L, et al. Host Cavities Enhance the Photocatalytic Conversion of α-Terpinene to Ascaridole Under Visible-Light Irradiation.Chemistry · 2025 · 31(55):e02113doi:10.1002/chem.202502113 · PMID 40891547

    Dye-functionalized cage molecules that bind alpha-terpinene and deliver singlet oxygen to it, raising the rate of conversion to ascaridole up to twenty-eight-fold. One of several 2025 papers that use Schenck's reaction as the benchmark for a new photocatalyst.

80. 80
    Behm K, Fazekas E, Paterson MJ, Vilela F, McIntosh RD. Discrete Ti-O-Ti Complexes: Visible-Light-Activated, Homogeneous Alternative to TiO2 Photosensitisers.Chemistry · 2020 · 26(43):9486-9494doi:10.1002/chem.202001678 · PMID 32428304

    Another photosensitizer series benchmarked on the same reaction, and useful here because it contrasts the wanted product, ascaridole, with the unwanted one, p-cymene, formed when the chemistry goes by a different route.

81. 81
    Pereira LPLA, Ribeiro ECG, Brito MCA, et al. Molluscicidal and cercaricidal activities of the essential oil of Dysphania ambrosioides (L.) Mosyakin & Clemants: Implications for the control of schistosomiasis.Acta Trop · 2022 · 230:106393doi:10.1016/j.actatropica.2022.106393 · PMID 35278368

    The oil killed the snail host and the free-swimming stage of the blood fluke, but it was also lethal to zebrafish at a lower concentration than it killed the snails, which the authors state as a limit on its field use.

82. 82
    Heredia Severino A, Fernandez-Lopez J, Borras-Rocher F, Viuda-Martos M. Essential Oils and Extracts from Epazote (Dysphania ambrosioides): A Phytochemical Treasure with Multiple Applications.Plants (Basel) · 2025 · 14(13):1903doi:10.3390/plants14131903 · PMID 40647909

    A 2025 narrative review of the source plant, screened with an artificial-intelligence clustering tool that cut 814 Scopus records by 86.73 percent. Reports antiparasitic, antimicrobial, antioxidant and anticancer properties and concludes that the mechanisms are not understood and that safety and efficacy have not been evaluated in clinical trials. The PubMed record strips the species name from the title.

83. 83
    Manzo RM, Iglesias AE, Guajardo JJ, et al. Bioactivity of Essential Oils from Patagonian Wild Plants: Acaricidal and Insecticidal Effects on Varroa destructor and Apis mellifera.Plants (Basel) · 2025 · 14(16):2484doi:10.3390/plants14162484 · PMID 40872107

    Read in full from PubMed Central. Three Patagonian oils against the honeybee mite and against honeybees. The paico oil, from Dysphania ambrosioides, was 34.87 percent ascaridole; it repelled the mite and reduced the survival of adult bees and larvae. Selectivity indexes between mite and bee at 24 hours were 25, 3.1 and above 100, the last for the alpha-pinene-rich Senecio oil, which was the authors' preferred candidate. Both the PubMed record and the PubMed Central full text strip the italicized species names, so individual oils cannot be matched to every figure with certainty from the text as retrieved; the two lower indexes belong to the ascaridole and esquelenone oils.

84. 84
    el-Mofty MM, Khudoley VV, Sakr SA, Ganem NF. Induction of neoplasms in Egyptian toads Bufo regularis by oil of chenopodium.Oncology · 1992 · 49(3):253-5doi:10.1159/000227050 · PMID 1495755

    The only carcinogenicity experiment on the oil: hepatocellular carcinoma in 23 percent of treated toads, with metastases in the kidneys of six and an average latent period of 3.6 plus or minus 0.4 months. An amphibian model with a small number of animals and no mammalian replication; it supports caution, not a conclusion about people.