Methoxychlor toxicity

Tegeris AS, Earl FL, Smalley HE Jr, Curtis JM Methoxychlor toxicity. Arch Environ Health 13 776-787, 1966... 

Methoxychlor is degraded in vivo by 0-dealkylation and excreted as mono-and bis-phenols. It is much less environmentally persistent also much less toxic to rats (oral LD q> 6000 mg/Kg compared with LD q 118 mg/Kg for DDT Metcalf, ref. 16). However, methoxychlor toxicity in fish approaches that of DDT, and in cold water fish, e.g., Atlantic salmon, it can accumulate to excessive levels. Although much less toxic in mammals than DDT it is similar in its estrogenic action. Methylchlor is less toxic to fish than methoxychlor, but also rather ineffectual as an insecticide. Comparison of the persistence characteristics of the methyl and methoxy analogs of DDT shows the microsomal side chain oxidation of the alkyl group to be more efficient than microsomal 0-dealkylation. 

From the toxicological point of view, the different metabolic profiles of methoxychlor observed in different animal species may need to be considered to understand the metabolism-induced methoxychlor toxicity in individual animal species. In the case of mouse and quail, only trace amounts of bis-OH-MXC, which is believed to be the most active metabolite causing methoxychlor induced estrogenic responses 4, 8-10)j were detected, therefore, the toxic activity of the main metabolite, mono-OH-MXC and its O-glucuronide, also need to be considered. As for enantiotopic metabolites, it would be also important to understand if there is a difference in toxicological activity between (ft)- and (5)-isomers. If marked toxicological difference is observed between these two isomers, the toxicity induced by stereoselective metabolism may need to be further considered. 

The commonly used organic insect toxicants do not interfere in the analysis of Compound 118 by this new procedure. Hexane solutions of chlordan, DDT, methoxychlor, hexachlorocyclohexane (BHC), and toxaphene treated according to the procedure for determining Compound 118 gave a pale yellow color similar to that of the blank. 

For some important insect pests there are still no satisfactory chemical controls. Such problems should be given due consideration in the development program. Many of these problems appeared to be solved with the discovery of DDT, benzene hexachlo-ride (hexachlorocyclohexane), and some of the more recent insecticides. Further studies of the toxicity of some of these products to warm-blooded animals have raised the important question of the advisability of continuing their use where food and feed products are concerned. Considerable attention is being centered on finding safer analogs, such as TDE and methoxychlor, and new and better insecticides. 

Toxic organic compounds commonly found in groundwater are presented in Table 18.4. Other toxic organic compounds (representing 1% of cases) include PCBs (polychlorinated biphenyls), 2,4-D, 2,4,5-TP (silvex), toxaphene, methoxychlor, lindane, and endrin, of which 2,4-D and silvex are commonly used for killing aquatic and land weeds. Inorganic toxic substances commonly found in... 

A waste is toxic under 40 CFR Part 261 if the extract from a sample of the waste exceeds specified limits for any one of eight elements and five pesticides (arsenic, barium, cadmium, chromium, lead, mercury, selenium, silver, endrin, methoxychlor, toxaphene, 2,4-D and 2,4,5-TP Silvex using extraction procedure (EP) toxicity test methods. Note that this narrow definition of toxicity relates to whether a waste is defined as hazardous for regulatory purposes in the context of this chapter, toxicity has a broader meaning because most deep-well-injected wastes have properties that can be toxic to living organisms. 

Chlordane interacts with other chemicals to produce additive or more-than-additive toxicity. For example, chlordane increased hepatotoxic effects of carbon tetrachloride in the rat (USEPA 1980 WHO 1984), and in combination with dimethylnitrosamine acts more than additively in producing liver neoplasms in mice (Williams and Numoto 1984). Chlordane in combination with either endrin, methoxychlor, or aldrin is additive or more-than-additive in toxicity to mice (Klaassen et al. 1986). Protein deficiency doubles the acute toxicity of chlordane to rats (WHO 1984). In contrast, chlordane exerts a protective effect against several organophosphorus and carbamate insecticides (WHO 1984), protects mouse embryos against influenza virus infection, and mouse newborns against oxazolone delayed hypersensitivity response (Barnett et al. 1985). More research seems warranted on interactions of chlordane with other agricultural chemicals. 

Andersen RL, DeFoe DL. 1980. Toxicity and bioaccumulation of endrin and methoxychlor in aquatic invertebrates and fish. Environmental Pollution 22 11 -121. 

Agency for Toxic Substances and Disease Registry (ATSDR) Toxicological Profile for Methoxychlor. pp 1-244. US Department of Health and Human Services, Public Health Service, 2002... 

Shimizu N, Aoyama H, Hojo H, et al Prenatal developmental toxicity studies of 1,1,1-trichloro-2,2-bis(4-methoxyphenyl)ethane (methoxychlor) in rats and rabbits. Congenital Anomalies 41(4) 329-337, 2001... 

Many chlorinated hydrocarbon alternatives to DD T have been developed. One of the earliest substitutes was methoxychlor, shown in Figure 15.18. This compound has a much lower toxicity in most animals and, unlike DDT, is not readily stored in animal fat. Look carefully at the structures of methoxychlor and DDT, and you ll see that they are identical except that methoxychlor has two ether groups where DDT has two chlorine atoms. Because the structures are nearly identical, they have nearly the same level of toxicity in insects. In higher... 

R and R in the aryl moieties (e.g., methoxychlor, methylchlor) and to moving R and/or R1 to the ortho position. Animal toxicity studies led to the early (1950) observation of the hormonal action of DDT and its analogs and the later attribution of greater estrogenic activity to the o,p -isomer of DDT (ref. 84a). 

Parrish, P.R., Dyar, E.E., Lindberg, M.A., Shanika, C.M., Enos, J.M. (1977) Chronic toxicity of methoxychlor, malathion and carbofuran to sheepshead minnows (Cyprinodon variegatus). NTIS PB-272101. 

Toxicity Methoxychlor is practically nontoxic via the oral route, with different acute oral LD50 values of 5,000 to 6,000 mg/kg in rats, 1,850 mg/kg in mice, and 2,000 mg/kg in hamsters. The lowest oral dose that can cause lethal effects in humans is estimated to be approximately 6,400 mg/kg, and the lowest dose through the skin that produces toxic effects in humans is 2,400 mg/kg based on behavioral symptoms. It reportedly is slightly to practically nontoxic dermally, with an acute dermal LD50 in rabbits of greater than 2,000 mg/kg. 

Methoxychlor, a chemical closely related to DDT, has been used as an insecticide. The half-life for methoxychlor in water is rather short (46 days) and it is not considered to be persistent. Methoxychlor has been classified in the EPA s Group D (not classifiable). At high doses, methoxychlor has been shown to exhibit chronic toxic effects and has been detected in drinking water. 

The discovery of DDT led to the synthesis of several effective DDT analogs, such as tetrachlorodiphenylethane (TDE), methoxychlor, dicofol, and chlorobenzilate (Figure 4.1). TDE is also called DDD (dichlorodiphenyldichloroethane). These analogs are less toxic than DDT to mammals. Their oral LD50 values in rats are methoxychlor, 600 mg/kg TDE, 3400 mg/kg dicofol, 570-595 mg/kg and chlorobenzilate, 2784-3880 mg/kg. The last two compounds have very little insecticidal activity but are good acaricides. 

Toxicity. Methoxychlor is the least toxic of the chlorinated hydrocarbon insecticides. The maximum permissible atmospheric concentration is 10 mg/m and the maximum permissible concentration in food is 14 pg/g. 

Methoxychlor is slightly toxic to bird species. Met-hoxychlor is highly toxic to fish and aquatic invertebrates. Methoxychlor accumulates in aquatic organisms because these organisms metabolize methoxychlor very slowly. The compound is relatively nontoxic to bees. 

A large number of ubiquitous environmental pollutants are very toxic to the hypothalamic-pituitary-thyroid (HPT) axis when administered at high (greater than environmental) levels. To study low level effects on the HPT axis, laboratory animals were administered a mixture of 16 organochlorine pesticides and other chlorinated hydrocarbons and heavy metals, all at levels similar to those found environmentally, so as to simulate environmental exposure. The chemicals included DDT (6.91), HCB (5.73), TCDD (6.80), PCBs (6.29), methoxychlor (5.08), endosulfan (3.83), heptachlor (6.10), hexachlorocyclohexane (3.80), dieldrin (5.40), aldrin (6.50), mirex (7.18), several chlorinated benzenes (2.84-3.44), cadmium (-1.65), and lead (1.35). Effects were measured by monitoring thyroid activity. The study found that this mixture of environmental pollutants was toxic and can alter HPT physiology in sexually mature malesJ50 ... 

In general, the mono-chloro series is more toxic than the di-chloro series. Five of the mono-chloro analogs are 8-10 times more potent than pyrethrins and 6-7 times more toxic than methoxychlor to the house fly. 

Table I lists the EPA contaminants and the criteria that EPA has established to constitute a hazardous toxic waste. Table 2 shows the concentrations of the inorganic contaminants in the extract from the phosphogypsum samples. All of the organic compounds listed by EPA as hazardous toxic waste.s were tested by the standard EPA procedure none were detected. These included endrin, lindane, methoxychlor, toxaphene, 2,4-D silvex, and 2,4,5-TP silvex. All of the metals listed in Table I were found to be present in the extract at concentrations lower than allowed by EPA (as shown in Table 2). Therefore, by EPA definition phosphogypsum is not a hazardous toxic waste material. This confirms earlier research conclusions 71 that the leaching of trace elements from phosphogypsum is not significant in introducing hazardous toxic waste materials into the environment.

Pyrethroid insecticides (deltamethrin, NRDC 157, cismethrin), DDT analogs ( p,j> -DDT, (>,j> -DDT, methoxychlor, EDO), and a DDT-pyrethroid hybrid compound (GH401) enhanced veratridine-dependent sodium uptake by mouse brain synaptosomes The effectiveness of these compounds in the sodium uptake assay was in good agreement with their acute mammalian toxicities. , -DDT also enhanced veratridine-dependent sodium uptake by fish brain synaptosomes These findings demonstrate the utility of ion flux assays to study interactions of insecticides with sodium channels in the central nervous system and to explore species differences in insecticide target site sensitivity ... 

Equally troublesome is what one publication did with this statement (11). The New Farm report on this particular part of the Cornell study said, "The water in more than 200,000 rural homes contains detectable amounts of methoxychlor...While considered low in toxicity to humans, methoxychlor disrupted nervous... 

Methoxychlor. Its chemical structure and properties are similar to those of DDT, but it biodegrades more easily. Aquatic organisms metabolize it and transform it into other less toxic substances and therefore it does not lead to significant bioaccumulation phenomena. 

Methoxychlor [72-43-5], a compound similar to DDT in chemical structure soon replaced DDT after the latter s ban. It is less toxic than DDT and degrades faster in the enviromnent than DDT or its metabolite. Methoxychlor is being used to control biting flies, honseflies and mosquito larvae. Other applications include its use against elm bark-beetle that causes Dutch elm disease and in veterinary medicines to kill parasites that live on the exterior of their host. 

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