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The effects of single acute oral doses of 1, 2.1, and 3.5 mg/kg oxamyl (a carbamate insecticide) on selected biochemical parameters in male Sprague-Dawley rats were investigated. The animals exhibited significantly decreased weight gain when compared to control animals. The compound inhibited brain and blood acetylcholinesterase significantly in the first few hours of exposure. Liver glucose-6-phosphatase was inhibited substantially after 7 and 4 days at the levels of 2.1 and 3.5 mg/kg, respectively. Maximum inhibition of liver succinic acid dehydrogenase was noted after 1 day at the level of 1 mg/kg and after 6 hr at the level of 2.1 and 3.5 mg/kg. Significant changes in serum total lipids and glucose were observed when oxamyl was given at 2.1 and 3.5 mg/kg, but serum protein was not affected at any dose level. However, the absence of statistically significant effects between Days 7 and 14 in most of the investigated parameters is indicative of an overall moderate degree of toxicity of oxamyl following acute oral administration of the selected doses.

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In 1986, the voters of California passed a law regarding the concept of extrapolating animal toxicity data to humans. The California Safe Drinking Water and Toxic Enforcement Act of 1986, known as Proposition 65, does five things: 1. It creates a list of chemicals (including a number of agricultural chemicals) known to cause cancer or reproductive toxicity; 2. It limits discharges of listed chemicals to drinking water sources; 3. It requires prior warning before exposure to listed chemicals by anyone in the course of doing business; 4. It creates a list of chemicals requiring testing for carcinogenicity or reproductive toxicity; and 5. It requires the Governor to consult with qualified experts (a 12-member "Scientific Advisory Panel" was appointed) as necessary to carry out his duties. This paper discusses the details and implications of this proposition. Areas of responsibility have been assigned. The definition of significant risk is being addressed.

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Since the 1920s ethylene dibromide's (EDB's) primary use has been as a scavenger of lead compounds in gasoline. Gasoline evaporation contributed to EDB emissions into the environment. In 1973, the United States Environmental Protection Agency (EPA) issued regulations to reduce the use of leaded gasoline and this has resulted in lower EDB usage and emissions. In addition, EDB has been used extensively as a fumigant since 1948. Its volatility and versatility, based on chemical and biocidal properties, led to its use as a soil sterilant, as a spot fumigant of grain milling machinery, and as a control agent in grain, fruit and vegetable infestations. In 1977 the EPA began a review of EDB's pesticidal uses which eventually led to its cancellation for most agricultural applications. Disposal of EDB and contamination of water supplies remain major environmental concerns. EDB can be absorbed via the dermal, oral and inhalation routes. It appears to be metabolized in vivo by an oxidative pathway (cytochrome P-450) and a conjugation pathway (glutathione S-transferase). The metabolites play an important role in exerting its toxicity. Few human poisonings have been reported from either acute or chronic exposure. However, EDB is irritating to the skin and eyes. Limited information indicates that EDB can damage the liver and kidneys following extensive or prolonged exposure. The genotoxicity of EDB has been clearly demonstrated. It binds to DNA in vivo and in vitro, and a DNA adduct has been identified. EDB has been shown to be mutagenic in numerous bacterial assays, in fungi, in plants, in insects, and in mammalian cell culture. Some evidence indicates that EDB can cause sister chromatid exchange and chromosomal aberrations. EDB is a reproductive toxin, but it does not appear to be teratogenic. It has been shown to affect spermatogenesis in rats, bulls and rams and to affect fertility in fowl. Human studies indicate that EDB exposure may harm sperm and decrease fertility. The toxic effect of greatest concern that may result from EDB exposure is cancer. In rats and mice, EDB produced tumors at the application site and at distant sites. When given orally, EDB has produced tumors in the forestomach, lung, and the circulatory system. When administered by inhalation, EDB produced tumors in the nasal cavity, lung, and the circulatory system. Dermal application of EDB produced skin and lung tumors. Analyses of risks from EDB exposure have focused on potential carcinogenic effects. Initial risk estimates, based on animal studies, indicated that citrus workers had essentially a 100% chance of contracting cancer.(ABSTRACT TRUNCATED AT 400 WORDS)

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1. An h.p.l.c. method has been developed to quantify the GSH conjugate of 1,3-dichloropropene (DCP). 2. The GSH conjugate of DCP (GSCP) was detected in the blood of rats exposed to DCP by inhalation, and elimination of GSCP from rat blood fitted a one-compartment model. 3. Exposure of rats to 78, 155, or 404 ppm DCP gave an elimination t 1/2 of 17 h, independent of exposure concentration.

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Rats were exposed to 1,3-dichloropropene (DCP), a commonly used agricultural nematicide, by inhalation to assess the relationship between DCP concentration and the urinary excretion of the mercapturic acid of cis-DCP (3C-NAC). The nose-only exposure system that was used for simultaneously exposing up to four rodents is described. This apparatus provided for generation and monitoring of relative humidity and test vapor concentration. Animals were exposed for 1 hr to concentrations of up to 789 ppm DCP. Urine was collected for 24 hr after exposure. The quantity of 3C-NAC contained in the urine collections exhibited an exposure concentration-dependent increase from 0 to 284 ppm DCP. However, the amount of 3C-NAC was no greater for animals exposed to 398 or 789 ppm DCP than for animals exposed to 284 ppm DCP.

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Rats were exposed by inhalation to 1,3-dichloropropene (DCP) to assess the relationship between DCP exposure concentration and tissue levels of reduced glutathione (GSH). Animals were exposed for 1 h in a dynamic, nose-only system. GSH content, indicative of DCP metabolism, was measured in heart, kidney, liver, lung, nasal mucosa, and testes. A decrease in nasal GSH content was first seen at 5 ppm DCP and followed an exposure concentration-dependent curve. Exposure to concentrations above 305 ppm DCP reduced the level of liver GSH in an exposure concentration-dependent manner. Although depressed, lung GSH content remained relatively constant at approximately 75% of control following concentrations of up to 955 ppm DCP. Significant decreases in GSH content were observed in heart, liver, and testes only at 1716 ppm. Additional measurements were taken to investigate DCP distribution and potential indicators of acute toxicity. DCP was not present in the blood of animals 2 h after exposure to 955 ppm DCP or less. Serum lactate dehydrogenase activity was affected only at the highest exposure concentration, 1716 ppm DCP. Lung weight, measured at 2 and 6 h after exposure, did not differ from control for any of the exposure levels. This information demonstrated the importance of nasal tissue GSH in the metabolism of at least low levels of DCP. It also suggests the complexities involved with in vivo defence against inhaled DCP.

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An inhalation system was designed and constructed for acute nose exposure of mice to methyl bromide. Animals were exposed for 1 h to concentrations ranging from 0.87 to 5.93 mg/l. Mice exposed to concentrations up to 1.72 mg/l did not exhibit any indication of developing a toxic response. Animals exposed to concentrations to 2.20 and 2.70 mg/l exhibited significantly decreased lung and liver weights when compared to controls. Animals exposed to concentrations above 3.50 mg/l exhibited kidney lesions. At concentrations of 3.82 mg/l and above, animals exhibited abnormal clinical signs, weight loss, and mortality. In addition, at 4.70 mg/l, a liver lesion was observed. At concentrations above 5.77 mg/l, pathological changes were observed in the color and a decreased motor coordination was evident. Methyl bromide exposures of up to 3.82 mg/l did not affect the ability of mice to recall a single-task passive-avoidance test. The 1-h LC50 of methyl bromide in mice via inhalation was determined to be 4.68 mg/l (approximately 1200 ppm). The dose-response curve was quite steep and the LC10 to LC90 range of mortality was contained within a doubling of concentration.

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Mice were exposed via inhalation to high concentrations of either dichloromethane (168 mg/l) or carbon tetrachloride (134.3 mg/l). The mice were tested for learning ability using a passive-avoidance conditioning task. Exposed animals were found to have a significantly decreased ability to learn when compared with controls. The 3-wk-old mice were more affected than the 5-wk-old and the 8-wk-old mice. The exposed animals were indistinguishable from controls in terms of motor activity, weight gain, and absence of analgesia.

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The dermal toxicity of five commonly used organophosphate insecticides was investigated with a mouse intermittent self-exposure model. Blood cholinesterases were monitored on d -3 and -1 before exposure and for 4--6 d during exposure to foliar residues. Responses were much greater in unmuzzled than in muzzled animals due to oral contamination. After two 10-h exposures, muzzled mice showed log-linear cholinesterase responses across a wide range of foliar pesticide concentrations. Foliar pesticide levels that caused 50% depression in plasma or red blood cell cholinesterase were determined with log-probit dose-response analysis. The greatest cholinesterase responses for both emulsifiable concentrate and encapsulated formulations were found with diazinon, followed by parathion and methyl parathion. Azinphos-methyl and mevinphos produced no significant responses in muzzled mice at maximal foliar concentrations. Symptomatology, food consumption, and body weight provided less sensitive indicators of response than cholinesterases. No consistent relation existed between the mouse intermittent self-exposure toxicities and mouse dermal LD50 values. Use of data from acutely exposed animals to predict the hazard of intermittent foliar exposure appears inadvisable.

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Percutaneous penetration of [14C]parathion in mouse skin of nose, hind foot, scrotum, and tail was measured by recovery of excreted radioactivity relative to an intravenous dose. Oral ingestion was prevented by use of face muzzles and polyethylene rings at application sites. Penetration per unit area was in the following order (iv = 1.0): nose (0.8), scrotum (0.4), foot (0.3), and tail (0.3). Because of their greater surface area, tail and foot regions would contribute most to absorption in uniform ventral exposure. Daily recovery curves indicate apparent first-order kinetics of elimination.

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Dermal LD50 values for five organophosphate insecticides were determined in mice by application of solutions to hind feet. Values were simultaneously generated for the ED50 (milligrams per kilogram) for both cholinesterase and acetylcholinesterase. Lethality was greatest with mevinphos, followed by parathion, methyl parathion, diazinon, and azinphosmethyl. LD50 values were higher than reported values for mice treated on shaved back skin. Cholinesterase ED50 values roughly agreed with LD50 values for mevinphos, parathion, methyl parathion, and azinphos-methyl, but diazinon appeared much more inhibitory of blood than neuronal cholinesterase. Red blood cell and plasma cholinesterase activities were equally sensitive for all but mevinphos and diazinon.

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Toxaphene was separated into 13 fractions and the toxicity of each fraction was determined. The acute toxicities (LD50) to houseflies (topical in acetone) ranged from 21 to greater than 246 mg/kg (toxaphene LD50 = 33 mg/kg) and the relative toxicities ranged from 0.6 to greater than 7.5. A similar pattern was found in mice when the toxicities of several fractions were determined. The acute toxicities (LD50, ip injection in dimethyl sulfoxide) in mice ranged from 20 to 67 mg/kg (toxaphene LD50 = 33 mg/kg) for the fractions tested. The most toxic fraction was further separated into six subfractions and their toxicities (housefly LD50) were found to range from 10 to 74 mg/kg. The most toxic subfraction appeared to be an almost pure compound and was purified for further identification. It was found to be identical to a previously reported highly toxic C10H10Cl8 mixture of predominantly two components. The components were reported to be 2,2,5-endo,6-exo, 8,8,9,10-octachlorobornane and 2,2,5-endo,6-exo,8,9,9,10-octachlorobornane. This highly toxic mixture has now been isolated independently by three research teams using different separation schemes.

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