Definition
Description
Top Gene Interactions
Related Pathways
General Information
- Metabolism: Upon absorption of allethrine , biotransformation takes place through hydrolysis of the central ester bond, oxidative attacks at several sites, and conjugation reactions to produce a complex array of primary and secondary water-soluble metabolites that undergo urinary and biliary excretion. Allethrin is oxidized not only at the chrysanthemate isobutenyl moiety to the corresponding primary alcohol but also at the allyl group to 1'-hydroxyprop-2'-enyl and 2',3'-dihydroxy-propyl derivatives, or at a methyl group on the cyclopropyl moiety to a hydroxy derivative. It is widely accepted that metabolism results in the formation of compounds that have little or no demonstrable toxicity, although the formation of reactive or toxic intermediates cannot be ruled out, and it appears that cleavage of the ester bond results in substantial detoxification. Allethrin is also converted to chrysanthemum dicarboxylic acid and allethrolone. Allethrin leaves the body quickly, mainly in the urine, but also in feces and breath. (L857, A558)
- Uses/Sources: Pyrethroids are used as insecticides. (L857)
- Health Effects: As for every type I pyrethroid, allethrin effects typically include rapid onset of aggressive behavior and increased sensitivity to external stimuli, followed by fine tremor, prostration with coarse whole body tremor, elevated body temperature, coma, and death. Paresthesia can also occur after dermal exposure to allethrin. It is likely to be a human carcinogen by the oral route. (L857)
- Symptoms: Following dermal exposure to allethrin, feelings of numbness, itching, burning, stinging, tingling, or warmth may occur, that could last for a few hours. Dizziness, headache, nausea, muscle twitching, reduced energy, and changes in awareness can result from inhalation or ingestion of large amounts of allethrin. (L857)
- Treatment: Following oral exposure, the treatment is symptomatic and supportive and includes monitoring for the development of hypersensitivity reactions with respiratory distress. Provide adequate airway management when needed. Gastric decontamination is usually not required unless the pyrethrin product is combined with a hydrocarbon. Following inhalation exposure, move patient to fresh air. monitor for respiratory distress. If cough or difficulty breathing develops, evaluate for respiratory tract irritation, bronchitis, or pneumonitis. Administer oxygen and assist ventilation as required. Treat bronchospasm with inhaled beta2 agonist and oral or parenteral corticosteroids. In case of eye exposure, irrigate exposed eyes with copious amounts of room temperature water for at least 15 minutes. If irritation, pain, swelling, lacrimation, or photophobia persist, the patient should be seen in a health care facility. If the contamination occurs through dermal exposure, Remove contaminated clothing and wash exposed area thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists. Vitamin E topical application is highly effective in relieving parenthesis. (L363)
- Route of Exposure: Inhalation (L858) ; oral (L858) ; dermal (L858) ; eye contact (L858).
Toxicity
- Carcinogenicity: Not listed by IARC.
- Toxicity: LD50: 1100 mg/kg (Oral, Rat) (L859) LD50: 480 mg/kg (Oral, Mouse) (L859) LD50: >2500 mg/kg (Dermal, Rat) (L859)
Mechanism of Action
Target Name | Mechanism of Action | References |
---|---|---|
Nuclear receptor subfamily 1 group I member 2 |
21115097 |
|
Calcium-transporting ATPase type 2C member 1 Calcium-transporting ATPase type 2C member 2 Sarcoplasmic/endoplasmic reticulum calcium ATPase 1 Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 Sodium channel subunit beta-1 Sodium channel subunit beta-2 Sodium channel subunit beta-3 Sodium channel subunit beta-4 Sodium channel protein type 1 subunit alpha Sodium channel protein type 10 subunit alpha Sodium channel protein type 11 subunit alpha Sodium channel protein type 2 subunit alpha Sodium channel protein type 3 subunit alpha Sodium channel protein type 4 subunit alpha Sodium channel protein type 7 subunit alpha Sodium channel protein type 8 subunit alpha Sodium channel protein type 5 subunit alpha Sodium channel protein type 9 subunit alpha |
This pyrethroid exerts its profound effect by prolonging the open phase of the sodium channel gates when a nerve cell is excited. This pyrethroid is a axonic poison that block the closing of the sodium gates in the nerves, and, thus, prolongs the return of the membrane potential to its resting state leading to hyperactivity of the nervous system which can result in paralysis and/or death. Type I Pyrethroid esters (lacking the alpha-cyano substituents) affect sodium channels in nerve membranes, causing repetitive (sensory, motor) neuronal discharge and a prolonged negative afterpotential, the effects being quite similar to those produced by DDT (L857, A560). |
2003 15950969 1995 |
Calcium release-activated calcium channel protein 1 Calcium-activated potassium channel subunit alpha-1 |
This pyrethroid inhibits Na+/K+ ATPase and Ca2+ and Mg2+ ATPase, which are essential for the transport of calcium across membranes. This results in the accumulation of intracellular free calcium ions, which promotes release of neurotransmitters from storage vesicles, the subsequent depolarization of adjacent neurons, and the propagation of stimuli throughout the central nervous system. (T10) |
2003 |
Allethrin Interacts with Diseases
Disease | Inference Score | References/Inference Genes |
Diabetes Mellitus, Experimental | 41.0 |
|
Brain Ischemia | 37.87 |
|
Neoplasm Metastasis | 31.49 |
|
Colonic neoplasm | 28.25 |
|
Breast carcinoma | 27.65 |
|
Reperfusion Injury | 26.43 |
|
Myocardial infarction | 25.34 |
|
Asthma | 25.31 |
|
Sepsis | 25.16 |
|
Cell Transformation, Neoplastic | 24.77 |
|
Adenocarcinoma | 24.32 |
|
Neoplasm Invasiveness | 23.85 |
|
Radiation Injuries, Experimental | 23.24 |
|
Hypertension | 22.82 |
|
Alzheimer's Disease | 22.56 |
|
Alcoholic liver cirrhosis | 22.23 |
|
Pancreatic carcinoma | 22.15 |
|
Nerve Degeneration | 22.06 |
|
Squamous cell carcinoma | 21.96 |
|
Osteoporosis, Postmenopausal | 21.72 |
|