Freely soluble in ketone, alcohols, aromatic and chlorinated hydrocarbons but sparingly soluble in
petroleum solvents and mineral oils (Windholz et al., 1983)
暴露限值：
NIOSH REL: TWA 3 mg/m3, IDLH 200 mg/m3; OSHA PEL: TWA 3
mg/m3; ACGIH TLV: TWA 3 mg/m3.
物理描述：
Colorless to white solid or straw-colored liquid (above 80°F) with a slightly pungent odor.
颜色/状态：
Pure compound is a solid; technical compound is moderately volatile
O,O-Dimethyl-2,2-dichlorovinyl phosphate (dichlorvos) is a metabolite of naled as are other hydrolytic products such as methyl phosphates (mono- and di-), O-methyl 2,2-dichlorovinyl phosphate (desmethyl dichlorvos), and inorganic phosphate.
Three metabolites were identified in an in vitro study using the rat liver homogenates, dichlorvos, dichloroacetaldehyde, and bromodichloroacetaldehyde.
Metabolism of naled to dimethyl phosphate was demonstrated indirectly in individuals who were outdoors during aerial spraying with a naled and temephos mixture for mosquito control. Urinary dimethyl phosphate concentrations increased from a maximum of 0.06 ppm to a maximum of 0.50 ppm within 3 hours after spraying.
Trace residues of organophosphorus (OP) pesticides are associated with fruits and vegetables that have been sprayed with those OP pesticides to guard against insect pests. Human dietary exposure to these OP pesticides is commonly estimated by measuring the amount of OP metabolites in urine, assuming a stoichiometric relationship between a metabolite and its parent insecticide. Dialkylphosphates (DAPs) are the OP metabolites that are most often used as markers in such biomonitoring studies. However, abiotic hydrolysis, photolysis, and plant metabolism can convert OP chemicals (OP residues) to DAP residues on or in the fruits and vegetables. To evaluate the extent of these conversions, OPs and DAPs were measured in 153 produce samples. These samples from 2 lots were known to contain OP insecticide residues based on routine monitoring by California producers and shippers. A total of 12 OPs were quantified, including mevinphos, naled, acephate, methamidophos, oxidemeton-methyl, azinphos-methyl, dimethoate, malathion, methidathion, phosmet, chlorpyrifos, and diazinon. All OP insecticide residues were below their respective residue tolerances in 2002-2004. A total of 91 of 153 samples (60%) contained more DAP residues than parent OPs. The mean mole fractions [DAPs/(DAPs + OPs)] for the first and second lots of produce were 0.62 and 0.50, respectively, and the corresponding geometric means were 0.55 and 0.34. The corresponding mean mole ratios (DAPs/OP) were 7.1 and 3.4, with geometric means of 2.1 and 0.9. Any preformed DAPs ingested in the diet that are excreted in urine may inflate the estimated absorbed OP insecticide doses in occupational and environmental studies. In subsequent prospective studies, time-dependent production of dimethylphosphate (DMP) and dimethylthiophosphate (DMTP) in strawberries and leaves following malathion sprays occurred concomitant with the disappearance of the parent insecticide and its oxon. DAPs are more persistent in plants and produce at routinely measured levels than their parent OP insecticides.
Metabolism of organophosphates occurs principally by oxidation, by hydrolysis via esterases and by reaction with glutathione. Demethylation and glucuronidation may also occur. Oxidation of organophosphorus pesticides may result in moderately toxic products. In general, phosphorothioates are not directly toxic but require oxidative metabolism to the proximal toxin. The glutathione transferase reactions produce products that are, in most cases, of low toxicity. Paraoxonase (PON1) is a key enzyme in the metabolism of organophosphates. PON1 can inactivate some organophosphates through hydrolysis. PON1 hydrolyzes the active metabolites in several organophosphates insecticides as well as, nerve agents such as soman, sarin, and VX. The presence of PON1 polymorphisms causes there to be different enzyme levels and catalytic efficiency of this esterase, which in turn suggests that different individuals may be more susceptible to the toxic effect of organophosphate exposure.
IDENTIFICATION AND USE: Naled is a white solid. It is insecticide and acaricide, which is used in cooling tower, paper and pulp mill systems, hide and leather processing and disinfection. It is also used on swimming pool surfaces, household sickroom equipment, food processing plants and equipment, food contact surfaces, hospital rooms, and bathrooms. Naled is also veterinary medication. HUMAN EXPOSURE AND TOXICITY: Acute symptoms following poisoning by naled include abdominal cramps, emesis, nausea, hypersecretion, cough, and perspiration that disappeared after 2 days, while anxiety, depression, vertigo, and spontaneous horizontal nystagmus persisted for 4 months. Potential symptoms of overexposure are miosis, lacrimation; headache; chest tightness, wheezing and laryngeal spasm; salivation; cyanosis; anorexia, nausea, vomiting, abdominal cramps and diarrhea; weakness, twitching and paralysis; giddiness, ataxia and convulsions; low blood pressure; cardiac irregularities; irritation of skin and eyes. Dermal exposures to naled caused residual papular dermatitis on the arm, glazing on the skin of the cheek, mild irritation of the neck skin, and a maculopapular eruption of the abdomen that caused a contact sensitization type dermatitis. Dermatitis was also caused by picking flowers sprayed with naled. In another case, contact dermatitis was reported in an aerial applicator exposed to naled. ANIMAL STUDIES: Naled (5 mg/kg) was administered to rats via i.m. injection. Within 15 minutes, cholinergic signs appeared, and plasma and brain cholinesterases were inhibited by 79% and 80%, respectively. Naled caused severe eye and dermal irritation in rabbits and was weakly positive in a skin sensitization test in guinea pigs. In rats given a single oral dose of 25, 100, or 400 mg/kg naled, the 400-mg/kg dose produced mortality and transient decreases in body weight gain. Rats of both sexes given 100 or 400 mg/kg and females given 25 mg/kg showed marked cholinergic effects. No treatment-related neurological effects were observed 7 or 14 days after treatment at any dose level. In a lifetime study, male and female rats were administered doses of 0, 0.2, 2, or 10 mg/kg/day naled via gavage for 2 years. There was a dose-related reduction in plasma, brain, and to a lesser degree, red blood cell (RBC) cholinesterase activity among rats treated with 2 or 10 mg/kg/day. Slight tremors were noted on isolated occasions after dosing four females given 10 mg/kg/day. The incidence of neoplastic lesions in the treated animals was similar to that of controls. Pregnant rabbits were given doses of 0, 0.2, 2, or 8 mg/kg/day naled by gavage on gestational days 7 through 19. Does were sacrificed on day 29 of gestation. No maternal or developmental toxicity was related to treatment. Naled exhibited no potential to induce mutations in an in vivo mouse spot test that used mice given 3, 20, or 150 mg/kg/day naled by gavage on gestation days 8 to 12. Naled was positive for gene mutation in the S. typhimurium reverse mutation assay but did not induce DNA damage in a rec-type repair test with Proteus mirabilis strains PG713 (rec-, hcr-) and PG273 (wild-type). ECOTOXICITY STUDIES: Naled is highly toxic to bees.
(±)-Naled is a cholinesterase or acetylcholinesterase (AChE) inhibitor. A cholinesterase inhibitor (or 'anticholinesterase') suppresses the action of acetylcholinesterase. Because of its essential function, chemicals that interfere with the action of acetylcholinesterase are potent neurotoxins, causing excessive salivation and eye-watering in low doses, followed by muscle spasms and ultimately death. Nerve gases and many substances used in insecticides have been shown to act by binding a serine in the active site of acetylcholine esterase, inhibiting the enzyme completely. Acetylcholine esterase breaks down the neurotransmitter acetylcholine, which is released at nerve and muscle junctions, in order to allow the muscle or organ to relax. The result of acetylcholine esterase inhibition is that acetylcholine builds up and continues to act so that any nerve impulses are continually transmitted and muscle contractions do not stop. Among the most common acetylcholinesterase inhibitors are phosphorus-based compounds, which are designed to bind to the active site of the enzyme. The structural requirements are a phosphorus atom bearing two lipophilic groups, a leaving group (such as a halide or thiocyanate), and a terminal oxygen.
来源:Toxin and Toxin Target Database (T3DB)
毒理性
致癌性证据
癌症分类：人类非致癌性证据E组
Cancer Classification: Group E Evidence of Non-carcinogenicity for Humans
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌性证据
A4；不可归类为人类致癌物。
A4; Not classifiable as a human carcinogen.
来源:Hazardous Substances Data Bank (HSDB)
毒理性
致癌物分类
对人类不具有致癌性（未被国际癌症研究机构IARC列名）。
No indication of carcinogenicity to humans (not listed by IARC).
/MILK/ Residues were non-detectable ( < 0.01 ppm) in milk from Holstein cows subject to body and premise sprays for 14 days with the 7.2 lb/gal EC formulation.
A study of dimethylphosphate excretion in rats after either intraperitoneal or oral naled exposure indicated that the excretion rate was essentially independent of dose.
In October 2004, the Florida Department of Health (FLDOH) and the Centers for Disease Control and Prevention (CDC) assessed human exposure to ultra-low volume (ULV) aerial application of naled. Teams administered activity questionnaires regarding pesticide exposure and obtained baseline urine samples to quantify prespray naled metabolite levels. Following the spray event, participants were asked to collect postspray urine specimens within 12 hr of the spray event and at 8-hr intervals for up to 40 hr. Upon completion, a postspray activity questionnaire was administered to study participants. Two hundred five (87%) participants completed the study. The urine analysis showed that although 67% of prespray urine samples had detectable levels of a naled metabolite, the majority of postspray samples were below the limit of detection (< LOD). Only at the "postspray 6" time period, which corresponds to a time greater than 5 half-lives (> 40 hr) following exposure, the number of samples with detectable levels exceeded 50%. There was a significant decrease in naled metabolites from prespray to postspray (= .02), perhaps associated with a significant reduction (< or = 0.05) in some participants that may have resulted in pesticide exposure by means other than the mosquito control operations. These data suggest that aerial spraying of naled does not result in increased levels of naled in humans, provided the naled is used according to label instructions.
... Urinary levels of radioactivity were higher when animals inhaled the compound than when it was administered by the other routes. Levels deposited in the lung were very low.
[EN] BICYCLYL-SUBSTITUTED ISOTHIAZOLINE COMPOUNDS<br/>[FR] COMPOSÉS ISOTHIAZOLINE SUBSTITUÉS PAR UN BICYCLYLE
申请人：BASF SE
公开号：WO2014206910A1
公开（公告）日：2014-12-31
The present invention relates to bicyclyl-substituted isothiazoline compounds of formula (I) wherein the variables are as defined in the claims and description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.
The present invention relates to azoline compounds of formula (I) wherein A, B1, B2, B3, G1, G2, X1, R1, R3a, R3b, Rg1 and Rg2 are as defined in the claims and the description. The compounds are useful for combating or controlling invertebrate pests, in particular arthropod pests and nematodes. The invention also relates to a method for controlling invertebrate pests by using these compounds and to plant propagation material and to an agricultural and a veterinary composition comprising said compounds.
