Pythroid Poisons - Not Safe at Any Level

Subject:   PYRETHROID DOCUMENTED RESEARCH-----
Date:      Wed, 02 Aug 2000 07:41:05 -0400
From:        Stephen Tvedten <steve@getipm.com>
Organization:     Get Set Inc. (www.getipm.com)

To: Paul Helliker <phelliker@cdpr.ca.gov>
Director, State of California, Department of Pesticide Regulation

Dear Mr. Helliker: I thought you might like to read some research on your "registered" Pyrethroid POISONS.

1: J Steroid Biochem 1990 Mar;35(3-4):409-14 - The binding properties of pyrethroids to human skin fibroblast androgen receptors and to sex hormone binding globulin. - Eil C, Nisula BC

Department of Medicine, Roger Williams General Hospital, Brown University, Providence, RI 02908.

The pyrethroids are a class of natural and synthetic pesticides which were associated with an epidemic of gynecomastia in Haitian men in 1981. In the present study we tested several pyrethroids for their ability to interact with androgen binding sites in dispersed, intact human genital skin fibroblasts and in human plasma to sex hormone binding globulin (SHBG). All the pyrethroids tested inhibited fibroblast binding of [3H]methyltrienolone (R1881) at 22 degrees C with the following rank order of potency:pyrethrins greater than bioallethrin greater than fenvalerate greater than fenothrin greater than fluvalinate greater than permethrin greater than resmethrin. 50% displacement of [3H]R1881 binding to fibroblast androgen receptors was achieved by 1.5-44 x 10(-5) M concentrations of the competitors, respectively. Previous studies with cimetidine, a known inhibitor of androgen receptor binding, showed 50% competition at a concentration of 1.4 x 10(-4) M in this system. Scatchard analysis of binding experiments performed with increasing concentrations of [3H]R1881 in the presence of the pyrethroids indicated that the binding inhibition was competitive. On the other hand, of the pyrethroids examined only the pyrethrins (50% inhibition) and bioallethrin (43% inhibition) were able to displace [3H]testosterone from SHBG when tested at a concentration of 10(-4) M. These data indicate that a novel class of non-steroidal compounds, the pyrethroids, can interact competitively with human androgen receptors and SHBG. These findings provide a mechanism by which chronic exposure of humans or animals to pesticides containing these compounds may result in disturbances in endocrine effects relating to androgen action. PMID: 2325407, UI: 90219830

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The signs of intoxication by pyrethroids develop rapidly and there exist different poisoning syndromes for the two types of compounds. Typical signs of intoxication by Type 1 pyrethroids include hyperexcitability and convulsions in insects and a whole body tremor in mammals. In insects, the Type 2 pyrethroids cause predominantly ataxia and incoordination, while in mammals they produce choreoathetosis (sinuous writhing) and salivation. In insects, the effects of pyrethroids (especially Type 1) can develop within 1-2 minutes after treatment and can result in knockdown, which is a loss of normal posture and locomotion. Human dermal exposure to either type of pyrethroid can cause paresthesia, a tingling or burning sensation of the skin, but this effect is more intense for Type 2 compounds

These ion fluxes occur due to the opening and closing of specific ion channel proteins embedded within the nerve membrane. The action potential is propagated down the axon until it reaches the nerve terminal, where it stimulates the release of chemical transmitters. Type 1 compounds induce multiple spike discharges in peripheral sensory and motor nerves, as well as interneurons within the central nervous system (CNS). In contrast, Type 2 pyrethroids depolarize the axon membrane potential, which reduces the amplitude of the action potential and eventually leads to a loss of electrical excitability. All these effects occur because pyrethroids prolong the current flowing through sodium channels by slowing or preventing the shutting of the channels. The somewhat different actions observed for Type 1 and Type 2 compounds are due to differences in the degree of physiological effect: the duration of modified sodium currents by Type 1 compounds lasts tens or hundreds of milliseconds, while those of Type 2 compounds last for minutes or longer. These effects on the sodium current also cause a profound increase in the release of neurotransmitters from nerve terminals. The insect neuromuscular synapse is an especially important target for the pyrethroids, as well as other insecticides .

Bloomquist, J. R. Neuroreceptor mechanisms in pyrethroid mode of action and resistance. Rev. Pestic. Tox. 2: 185-226 (1993). Bloomquist, J. R. Ion channels as targets for insecticides. Ann. Rev. Entomol. 41: 163-90 (1996).

____________________________________________________________________________ 1: J Toxicol Clin Toxicol 2000;38(2):95-101

Pyrethroid insecticides: poisoning syndromes, synergies, and therapy. Ray DE, Forshaw PJ

Medical Research Council Toxicology Unit, Centre for Mechanisms in Human Toxicology, Leicester, United Kingdom. der2@le.ac.uk

BACKGROUND: Pyrethroid insecticides are widely used, but there have been relatively few reports of systemic poisoning. These reports have, however, shown that pharmacotherapy is difficult and that the duration of poisoning can be unexpectedly long. Pyrethroids are ion channel toxins prolonging neuronal excitation, but are not directly cytotoxic. Two basic poisoning syndromes are seen. Type I pyrethroids produce reflex hyperexcitability and fine tremor. Type II pyrethroids produce salivation, hyperexcitability, choreoathetosis, and seizures. Both produce potent sympathetic activation. Local effects are also seen: skin contamination producing paresthesia and ingestion producing gastrointestinal irritation. The slow absorption of pyrethroids across the skin usually prevents systemic poisoning, although a significant reservoir of pyrethroid may remain bound to the epidermis. Carboxyesterase inhibitors can enhance pyrethroid toxicity in high-dose experimental studies. Hence, the unauthorized pyrethroid/organophosphate mixtures marketed in some developing countries may precipitate human poisoning. Pyrethroid paresthesia can be treated by decontamination of the skin, but systemic poisoning is difficult to control with anticonvulsants. Pentobarbitone, however, is surprisingly effective as therapy against systemic type II pyrethroid poisoning in rats, probably due to its dual action as a chloride channel agonist and a membrane stabilizer. Publication Types:

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1: Comp Biochem Physiol C 1986;84(2):373-9 - Synaptic effects of the synthetic pyrethroid resmethrin in rat brain in vitro. - Doherty JD, Lauter CJ, Salem N Jr

Resmethrin (30 microM) induced release of transmitters was not affected by manipulation of the Na+ current with either choline or tetrodotoxin agents which readily reversed the effects of veratridine, deltamethrin and cypermethrin. Resmethrin (I50: 2.2 microM) inhibited the ATP dependent uptake of Ca2+ but deltamethrin and cypermethrin were much less effective. Resmethrin also displaced Ca2+ from crude synaptosomal membranes. The release promoting effects of resmethrin in rat brain in vitro are better explained by its effects on Ca2+ rather than through a specific effect on the Na+ channel. In contrast, the effects of deltamethrin and cypermethrin promote transmitter release by a Na+ dependent process.

PMID: 2427274, UI: 86299535 ___________________________________________________________________

1: Chung Hua Yu Fang I Hsueh Tsa Chih 1989 Mar;23(2):80-2 -[Effect of pyrethroids on rat brain synaptosomal ATPase activities]. [Article in Chinese] - Tang CY

In vitro Effect of several pyrethroids on rat brain synaptosomal ATPase activities was investigated. No significant changes in Na+, K+-ATPase and oligomycin-insensitive Mg2+-ATPase activities were observed under present experimental conditions, but all pyrethroids tested caused significant inhibition of oligomycin-sensitive Mg2+-ATPase activity with certain concentration dependence. The results suggest a possibility that pyrethroids may alter the cellular energy metabolism of the nervous system.

Well Mr. Helliker, As a pest control operator, I have watched all of your "registered" cyclodiene POISONS, all of your chlorinated hydrocarbon POISONS, all of your carbamate POISONS and now basically all of your "registered" organophosphate POISONS become more and more restricted until they all were banned and/or voluntarily withdrawn. All that really remains of all of your (used to be "registered") POISONS are your "registered" Pyrethroid POISONS - and most pests are already resistant to them. We however, obviously are not. I would like to point out that DDT was your first "registered" pyrethroid POISON. I find it very strange that you STILL want to demand that only your "registered" POISONS can be used to "control" pest problems in California. I have virtually eliminated all (even resistant) pest problems inside and outside in over 350 schools and I have never once used any of your "registered" volatile POISONS. Why (in your opinion) are these safe and far more effective unregistered alternatives STILL "illegal" in California?

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