(2)
Background and overview
Mirex. Animal studies demonstrate that mirex may result in a variety of toxic reactions in populations that are exposed. The organs affected are the thyroid, liver, selected developmental endpoints, and kidneys. Mirex may cause decreased hepatobiliary function and decreased glycogen storage. Glomerulosclerosis and proteinuria have been observed in the kidneys. If exposure occurs during a specific time period after birth, ocular lesions including cataracts in the eyes of the young. An increase in cystic follicles has been seen in the thyroid. There has been evidence of decreased fertility and developmental toxicity after exposure to the pesticide. Mirex results in testicular atrophy and reproductive failure. Included in the developmental effects in fetuses are cardiovascular disturbances, visceral anomalies, cataracts, increased stillbirths, and increased resorptions. In animals m,irex is a carcinogen in liver cells.
Chlordecone: Primary targets of chlordecone are the kidney, liver, reproductive system, nervous system, selected developmental endpoints, and the endocrine system. Humans exposed to chlordecone while working show toxicity in the reproductive system, the nervous system, and the liver. In high exposure cases, tremors, anxiety or irritability, blurring of vision, headache, and increased cerebrospinal fluid pressure we indicated. “Reproductive toxicity consisted of decreased sperm and sperm motility” (U.S. Department of Health and Human Services, May 2019).
Mechanism of Action:
The mechanism of action by which mirex is transferred into the systemic circulation is not yet known. It is a highly stable compound, that is also lipophilic and resistant to metabolism. It is readily absorbed by fat and can be accumulated in tissues. Mirex demonstrates a very high potential for accumulation in tissues because it is readily absorbed in tissues.
The mechanism of action by which chlordecone is absorbed into the systemic circulation is not yet known either. It is thought that it is transported in the plasms differently from other organochlorine compounds because it is mainly distributed to the liver instead of fat tissue. In vivo and In vitro studies in human, rat, and pig plasma show that chlordecone is mostly bound to albumin and HD, high-density lipoproteins.
Studies have attempted to outline the mechanism mirex and chlordecone use to inhibit hepatobiliary excretion. At high levels, the two agents depress ATPase activity. Moderate to high doses can also decrease cellular energy utilization and subsequently inhibiting biliary secretions. There are other possible explanations for the hepatotoxicity that mirex and chlordecone cause but are other body systems affected by their toxic effects.
Neurotoxicity has been demonstrated from mirex and chlordecone but there is no known mechanism of action. However, some studies show that chlordecone does not appear to act through a mechanism similar to other chlorinated hydrocarbons insecticides and demonstrates a different neurotoxicity profile. Chlordecone mainly causes tremors and hyperexcitability, with convulsions, and doesn’t act at the GABA receptor in mammals. The tremors induced by chlordecone appear to be started in the central nervous system above the level of the spinal cord.
Mechanisms underlying many of the adverse effects of chlordecone on reproductive function may be related to the estrogenic properties of chlordecone (U.S. Department of Health and Human Services, May 2019). Findings show that Chlordecone binds to estrogen receptors and causes translocation of the receptor. It has also been indicated in tumor suppression and developmental toxicity.
Mirex is absorbed from the digestive tract in animals, the majority of excretion via feces, with the fecal mirex unabsorbed. Widely distributed throughout the body with long retention time in the body. Mirex can also be excreted in human milk. Chlordecone is absorbed via oral routes and via inhalation.it is readily absorbed in the GI tract of humans and widely distributes throughout the body with higher concentrations in the liver. The agent is metabolized to chlordecone alcohol, which is excreted in the bile along with the parent substance. It is also excreted in saliva and mother milk.
Radiolabeling experiments demonstrate that mirex is not metabolized by humans, rodents, cows, or minipigs. It is believed that the suspected metabolite may have arisen as a result of bacterial action in the lower gut or feces (U.S. Department of Health and Human Services, May 2019)
Besides the biomarkers already mentioned, there is a lack of information about mirex and chlordecone biomarkers because their mechanism of action is still mostly unknown.
Signs and symptoms:
Studies assessing Mirex and Chlordecone test for diabetes, cancers, development, and reproductive endpoints. Clinical signs of Mirex include(1):
- cataracts
- cardiac dysrhythmias
- lesions of the lens
- histopathologic effects on reproductive organs and decreased fertility
- adaptive changes to the liver and decreased hepatobiliary function, histopathological lesions, and decreased glycogen storage
- Increases in glomerulosclerosis and proteinuria in kidneys
- carcinogenicity in the liver
Clinical signs and symptoms of Chlordecone include but, like Mirex, are not limited to (1):
- hepatomegaly
- evidence of increased microsomal enzyme activity
- mild inflammatory changes
- fatty degeneration
- selected kidney lesions in rats
- increased weight, depletion of epinephrine, hyperplasia, loss of adrenal lipid, and histopathologic lesions in the adrenal gland
- tremors,
- unfounded anxiety or irritability,
- blurring of vision,
- headache
- increases in cerebrospinal fluid pressure
- decreases in sperm count and motility
- increased stillbirths
- decreased postnatal viability
- delayed skeletal ossification
- selected anomalies and malformations
- subtle neurological changes
Treatments:
Although treatments and pretreatments are under assessment for symptoms of Mirex and Chlordecone toxicities, they are still being explored and certain treatments have been known to exacerbate tremors(3).
References:
https://www.atsdr.cdc.gov/toxprofiles/tp66.pdf (1)
https://www.rt.com/news/440765-french-indies-cancer-pesticide/ (2)
https://www.atsdr.cdc.gov/toxprofiles/mirex_and_chlordecone_addendum.pdf (3)