Pyrethrum

What is Pyrethrum?

Pyrethrum is a natural insecticide derived from the flowers of Dalmatian pyrethrum, specifically Chrysanthemum cinerariaefolium (also known as Tanacetum cinerariaefolium). 

Known for its potent insecticidal properties, Pyrethrum has been used historically and continues to be a tool in pest control.

Pyrethrins, the Active Chemical Constituents of Pyrethrum [3.] 

Pyrethrum consists of six insecticidal compounds known as pyrethrins, which are classified into two groups: pyrethrin I and pyrethrin II. 

The six pyrethrins are classified into two categories based on their acid component: [3.] 

• Type I: Pyrethrins containing pyrethric acid.

• Type II: Pyrethrins containing chrysanthemic acid.

Pyrethrins and Pyrethroids

Pyrethrins are plant-derived compounds, and pyrethroids are their synthetic derivatives. Pyrethroids have been chemically modified to improve stability and potency. [3., 7.] 

Mechanism of Action of Pyrethrins and Pyrethroids [3., 6.] 

These compounds act by targeting the nervous systems of insects, leading to selective neurotoxicity. They interact with sodium voltage-dependent channels, disrupting normal nerve function, which results in paralysis and death of the insect.

The mechanisms of action are slightly different between Type I and Type II pyrethrins: [7.] 

• Type I Pyrethroids (without α-cyano group): cause T-syndrome, characterized by fine tremors and increased sensitivity to external stimuli.

• Type II Pyrethroids (with α-cyano group): cause CS-syndrome, characterized by choreoathetosis, salivation, and aggressive behaviors.

Current Applications of Pyrethrum 

Pyrethrins and pyrethroids have diverse applications: [3.]

• Agriculture: used extensively for pest control.

• Household Insecticides: incorporated into various products for home use.

• Veterinary Products: formulated in collars, shampoos, and sprays to protect pets.

• Pharmaceutical Applications: used in treatments for lice, scabies, and mosquito-borne diseases like malaria.

Historical Uses of Pyrethrum

Pyrethrins have been used since the 18th century, originating from plants in the Middle East and the Balkans. 

During and after World War II, their use expanded significantly, especially for controlling mosquito populations to combat malaria and yellow fever.

The development of synthetic pyrethroids in the 1970s provided more stable and potent alternatives to natural pyrethrins.

Absorption, Metabolism and Distribution of Pyrethrum [8.] 

There is minimal information on the distribution of pyrethroids in humans.

Pyrethroids are absorbed from the gastrointestinal tract and through inhalation, with incomplete absorption but rapid metabolism. Dermal absorption is minimal. 

Pyrethroids are expected to be widely distributed in the body due to their lipophilic nature, concentrating in fatty tissues and the nervous system. 

Animal studies confirm rapid and widespread distribution, including in the liver, kidneys, and milk during lactation. In pregnant animals, pyrethroids cross the placenta minimally and do not accumulate significantly in the fetus. 

Pyrethroids are eliminated primarily through urine and bile, with little unmetabolized compound in urine.

Safety of Pyrethrum

General Safety

Pyrethrins and pyrethroids are generally considered safe for use, with low toxicity to mammals. However, they can cause neurotoxic effects, particularly at high exposures. [7.] 

Pyrethroids can have neurotoxic effects on humans, particularly at high exposures or in vulnerable populations. [7.] 

Unlike synthetic pyrethroids, there is limited human toxicokinetic data on natural pyrethrins and related compounds. [4.]

However, these substances are rapidly metabolized, producing the common urinary metabolite trans-chrysanthemumdicarboxylic acid (CDCA). [4.] Analytical methods to determine CDCA have recently become available, allowing the assessment of body burden for pyrethrins and pyrethroids in a single analytical run.

Environmental Impact

Pyrethroids are toxic to aquatic life and beneficial insects like bees. Sustainable use and careful management are necessary to minimize environmental impact and resistance development. [7.] 

Their persistence in the environment, although less than older pesticides like DDT, still raises concerns. [7.] 

Resistance Development

Overuse of pyrethroids can lead to the development of resistance in insect populations, diminishing their effectiveness and necessitating the development of new insecticidal compounds or strategies. [7.] 

Symptoms of Excessive Pyrethrum Exposure

Despite their lower toxicity, pyrethroids can have neurotoxic effects on humans, particularly at high exposures or in vulnerable populations. 

Exposure can cause reversible symptoms such as paraesthesia, skin and mucosal irritations, headache, dizziness, nausea, and neurological effects like tremors or seizures. [4., 7.] 

Health Implications of Pyrethrum Exposure

Increased Risk of All-Cause and Cardiovascular Mortality

Environmental exposure to pyrethroid insecticides is significantly associated with increased risks of all-cause and cardiovascular mortality in the US adult population. 

Higher urinary levels of 3-phenoxybenzoic acid (3-PBA), a pyrethroid metabolite, were associated with increased risks of all-cause and cardiovascular mortality over 14 years. [1.] 

During the follow-up from one human study, 246 deaths occurred, including 41 from cardiovascular disease and 52 from cancer. Higher 3-PBA levels were associated with increased risks of all-cause mortality (HR, 1.56) and cardiovascular mortality (HR, 3.00), but not cancer mortality. [1.] 

Animal studies have indicated that pyrethroid exposure can cause oxidative stress, inflammation, and DNA damage. For example, rats exposed to permethrin showed increased DNA damage, altered heart cell membrane fluidity, and higher levels of cholesterol and inflammatory cytokines in plasma. [1.] 

Laboratory Testing for Pyrethrum

Test Information, Sample Collection and Preparation

Various metabolites of pyrethrum exposure have been assessed in urine, including 3-phenoxybenzoic acid (3-PBA), a metabolite of synthetic pyrethroids, and trans-chrysanthemumdicarboxylic acid (CDCA), a metabolite of natural pyrethrins. 

Some laboratory companies also offer blood testing to assess IgE responses to pyrethrum, which can also signify current or past exposure.

Urine samples may be collected in a clinical setting or from the comfort of home. Blood tests require a venipuncture. 

It is important to consult with the ordering provider prior to sample collection, as special preparation may be required. 

Interpretation of Pyrethrum Test Results

Optimal Levels of Pyrethrum Metabolites

Because pyrethrum holds some concern for its health effects, optimal levels of pyrethrum are undetectable, or very low. 

One study using trans-chrysanthemumdicarboxylic acid (CDCA) in urine as a biomarker for pyrethrum exposure noted a background level of 0.15 μg/l (95th percentile) of CDCA in urine. [4.] 

IgE responses against Pyrethrum are expected to be very low, or absent. 

Clinical Significance of Increased Pyrethrum Test Results

A finding of elevated pyrethrum metabolites in urine, or of an IgE response against pyrethrum, indicate excessive recent exposure. 

Related Biomarkers to Test Alongside Pyrethrum

Biomarkers for Oxidative Stress and DNA Damage

Exposure to pyrethrins, including Pyrethrum, can lead to oxidative stress and subsequent DNA damage. Biomarkers of these processes are critical for a comprehensive exposure assessment. 

One such biomarker is 8-oxo-2'-deoxyguanosine (8-OHdG), a product of oxidative damage to DNA. Elevated levels of 8-OHdG in urine or blood indicate increased oxidative stress and potential genotoxic effects. [2.] 

Malondialdehyde (MDA) is another biomarker of oxidative stress, formed as a result of lipid peroxidation. [5.] High MDA levels reflect cell membrane damage and provide insights into the extent of oxidative injury caused by pyrethrin exposure.

Biomarkers of Inflammation and Immune Response

Chronic exposure to pyrethrins can trigger inflammation and alter immune responses.  [1., 8.] 

Biomarkers such as C-reactive protein (CRP) are measured to assess systemic inflammation. Elevated CRP levels in blood indicate an inflammatory response, which is often linked to increased pyrethrin exposure and associated health risks. 

Interleukins, particularly IL-6 and IL-8, are cytokines that play a pivotal role in inflammation and immune regulation. 

Measuring the concentrations of these interleukins may help identify immune system activation and inflammatory processes resulting from pyrethrin exposure, providing additional insights into the biological effects of Pyrethrum and other pyrethrins.

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