Chronic toxicity organophosphates

A biological problem of concern to industrial and environmental toxicologists is the question of chronic toxicity as a consequence of continual exposure to low concentrations of organophosphates (B16, V3, V4). If it is necessary to compare exposed and nonexposed populations in order to assess relative organophosphate uptake, the determination of population averages of cholinesterase activities appears to be all that is needed. 

There are literally thousands of chemicals and/or formulations in the major categories (i.e., insecticides, herbicides, fungicides, roden-ticides, fumigants, nematocides) of pesticides. Therefore, no attempt was made to provide a review of representatives of all the major classes of pesticides. In the section which follows, selected pesticides from three chemical classes, the organophosphates, the halogenated hydrocarbons, and the pyrethroids, will be discussed in regard to the differences and similarities between acute and chronic toxicity. The criteria for selection of the examples are mainly related to the availability of current information in the literature. 

Chronic toxicity of organophosphates may be discussed under four different areas carcinogenicity, delayed neurotoxicity, experimental myopathy, and, in humans, psychiatric disorders. In 1983, the IARC (International Agency for Research on Cancer) evaluated the carcinogenic potential of, among other pesticides, five organophosphate insecticides/acaricides (malathion, methyl parathion, parathion,... 

Garg, U. K. Pal, A. K. Jha, G. J. Jadhao, S. B. Haemato-biochemical and immuno-pathophysio-logical effects of chronic toxicity with synthetic pyrethroid, organophosphate and chlorinated pesticides in broiler chicks. Int. Immunopharmacol. 2004, 4, 1709-1722. 

Polyalphaolefin Hydraulic Fluids. Because no chronic-duration human or animal inhalation, oral, or dermal exposure studies using polyalphaolefin hydraulic fluids were located, chronic-duration inhalation or oral MRLs could not be derived. Systemic toxicity studies in which animals were exposed via inhalation, oral, and dermal routes would be useful in identifying the end points of toxicity for humans living at or near hazardous waste sites and exposed for chronic durations. Further carcinogenicity studies on individual organophosphate ester components of hydraulic fluids maybe useful. 

Malathion is an organophosphate cholinesterase inhibitor. Up to 8% of the topically applied dose may be absorbed. Malathion is used as a treatment for head lice, body lice and scabies. It effectively kills both the eggs and the adult lice. Malathion is an insecticide of relatively low human toxicity. However if malathion is used in an indoor environment, as it breaks down into malaoxon, it can be seriously and chronically poisonous. The safety of malathion in pregnancy and in lactating women and in children has not been established. 

Farm workers are especially susceptible to organophosphate insecticide poisoning. Unsafe spraying conditions can lead to accumulated toxicity and chronic symptoms. Since there are many enzymes in the body which are in the serine esterase family along with Achase and can complex... 

Ray, D.E., Richards, P.G. (2001). The potential for toxic effects of chronic, low-dose exposure to organophosphates. Toxicol. Lett. 120 343-51. 

Effects As described in Chapter 7, these agents produce increased muscarinic and nicotinic stimulation. The effects include pinpoint pupils, sweating, salivation, bronchoconstric-tion, vomiting and diarrhea, CNS stimulation followed by depression, and muscle fascicula-tions, weakness, and paralysis. The most common cause of death is respiratory failure. Chronic exposure to some organophosphates (not carbamates) has resulted in a delayed neurotoxicity with axonal degeneration. The toxic mechanism appears to involve phosphorylation of a neuropathy target esterase (NTE). 

Extremely toxic carbamate exhibits acute, delayed and chronic effects similar to organophosphates cholinesterase inhibitor found to be more toxic to rats by dermal than oral route (Merck 1996) toxic symptoms include trembling, pinpoint pupils, lacrimation, excessive salivation, sweating, slurring of speech, jerky movements, nausea, vomiting, loss of bladder control, slight blueness of skin, lips, and nail beds, as well as convulsion, and coma (Gossehn et al. 

Althongh strnctural feature in the molecule varies from most other organophosphorus pesticides, the toxic actions are similar to parathion and other phosphate esters. Extremely toxic by all routes of exposure cholinesterase inhibitor can present a serious inhalation hazard, if spilled, due to relatively high vapor pressure exhibits acute, delayed, and chronic effects symptoms of cholinergic effects similar to those of other organophosphates death can result from respiratory arrest ingestion of 0.3-2 g could be fatal to adult human. 

---