(14)C labeled 1,2,4-trichlorobenzene was admin orally (10 mg/kg) and iv (10 mg/kg) to ... rhesus monkeys. Glucuronides of 2,4,5-trichlorophenol and 2,3,5-trichlorophenol accounted for 14-37% of the monkey's urinary metabolites.
IDENTIFICATION AND USE: 2, 4, 5-Trichlorophenol (2, 4, 5-TCP) comes in the form of colorless needles from alcohols or in gray flakes. It was formerly used as a fungicide, bactericide, biocide; intermediate in production of herbicides, in adhesives as a preservative in polyvinyl acetate emulsions; in the automotive industry to preserve rubber gaskets; in textiles to preserve emulsions used in the rayon industry; in cooling towers; paper and pulp mill systems; hide and leather processing; on swimming pool related surfaces; sickroom equipment; and food processing plants and equipment. 2,4,5-TCP is not registered for current use in the U.S., but approved pesticide uses may change periodically and so federal, state and local authorities must be consulted for currently approved uses. HUMAN EXPOSURE AND TOXICITY: In the eye, trichlorophenols induce conjunctival irritation and sometimes corneal injury and iritis. dusts are irritating to nose and pharynx. Dermatoses, including photoallergic contact dermatitis, have been reported in man after exposure to 2,4,5-TCP, these include papulofollicular lesions, comedones, sebaceous cysts, and marked hyperkeratosis. During the clean-up following explosions during 2,4,5-TCP manufacture, chloracne was generally severe, and many cases had some signs or symptoms or lab abnormalities indicating systemic toxicity. Systemic effects of trichlorophenols presumably resemble phenol. Symptoms from upper airways and chest were more common among 7 subjects exposed to trichlorophenol than in control subjects (60% and 10%). The findings suggest an irritating effect on the lung of trichlorophenol, and it cannot be excluded that long-term exposure may produce pulmonary fibrosis. 2,4,5-TCP has not been shown to have a teratogenic effect. In a study of workers exposed to 2, 4, 5-TCP 10 years earlier, neither chromosomal aberrations nor sister chromatid exchanges were observed. Exposure to chlorophenols has been shown to cause an increased incidence of carcinomas including a significant trend observed for total gastrointestinal system cancer related to work in 2,4,5-TCP and 2-(2,4,5-trichlorophenoxy)-propionic-acid production areas. ANIMAL STUDIES: Restlessness and increased rate of respiration followed by rapidly developing motor weakness. tremors, clonic convulsions (induced by noise or touch), dyspnea, and coma continue until death. D-amino acid oxidase and heart muscle flavoproteins were inhibited by 2,4,5-TCP in vitro. In rat and rabbit hyperpyrexia from injections of trichlorophenols has been reported. In a 98-day feeding study in rats, 0.3 g and 1 g/kg body weight/day doses of 2,4,5-trichlorophenol retarded weight gain and caused diuresis, mild centrilobular changes in the liver, moderate degenerative changes in the convoluted tubules of the kidneys and early proliferative changes in the kidney interstitial tissue. Slight proliferation of bile ducts and early portal cirrhosis were also observed. The severity of effects was dose related. No significant effects were observed with doses of 100 mg/kg body weight/day (0.1% in diet) or less. 2,4,5-TCP given by gavage to pregnant mice in single doses of 800-900 mg/kg or multiple doses of 250-300 mg/kg caused no significant fetal effects and the results obtained in Hydra attenuata and whole embryo culture assays suggest that chlorinated phenols are not potent teratogens. Hydra attenuata and whole embryo culture studies demonstrated a linear relationship between toxicity and the degree of chlorine substitution with pentachlorophenol > 2,3,4,5-tetrachlorophenol > 2,3,5-TCP > 3,5-dichlorophenol > 4-chlorophenol > phenol. The developmental hazard index A/D ratios from the Hydra attenuata assay were approximately 1 for all of the chemicals tested. Findings from the whole embryo culture assay indicated similar results based on growth, gross morphology, and DNA and protein content of embryos. The results obtained in the Hydra attenuata and whole embryo culture assays suggest that the chlorinated phenols are not potent teratogens. 3-Chlorophenol, 4-chlorophenol, 2,3,6-, 2,4,5-, 2,4,6-TCP, 4-chloro-2-methylphenol, and 4-chloro-3-methylphenol produced mutagenic activity at least in one tester strain (TA97, TA98, TA100, or TA104) in the Ames test. The induction of forward mutation to 6-thioguanine resistance in V79 Chinese hamster cells by six different chlorophenols was examined. Each of the chlorophenols tested reduced the plating efficiency in a dose dependent manner including 2,4,5-TCP at doses of 6.25 to 50 ug/mL. This cytotoxic effect can be attributed to the ability of pentachlorophenol and other chlorophenols to inhibit oxidative phosphorylation. ECOTOXICITY STUDIES: Chlorinated phenols represent a major component of hazardous oily and wood-preserving wastes that are widely distributed in chemical dumpsites throughout the United States. The acute toxicity of some chlorinated phenols, catechols, and cresols, incl 2,4,5-trichlorophenol, to trout was determined. The lowest lethal concn of the cmpd studied was 0.20 ppm caused by pentachlorophenols, tetrachlorophenols, and trichlorophenols. The residue of chlorophenol in larval tissue was measured and the correlation to the concentration on larval mortality was highly significant in the growth test. In the emergence test, however, mortality was low (3-13%) at all concentrations. 2, 4, 5-TCP did not affect larval growth at the concentrations used. The concentration of 2, 4, 5-TCP in the whole larvae after the 10-day exposure was proportional to sediment concentration.
2,4,5-Trichlorophenol 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.
Evaluation: There is limited evidence in humans for the carcinogenicity of combined exposures to polychlorophenols or to their sodium salts. ... There is inadequate evidence in experimental animals for the carcinogenicity of 2,4,5-trichlorophenol. ... Overall evaluation: Combined exposures to polychlorophenols or to their sodium salts are possibly carcinogenic to humans (Group 2B). /Polychlorophenols/
Acute exposure to cholinesterase inhibitors can cause a cholinergic crisis characterized by severe nausea/vomiting, salivation, sweating, bradycardia, hypotension, collapse, and convulsions. Increasing muscle weakness is a possibility and may result in death if respiratory muscles are involved. Accumulation of ACh at motor nerves causes overstimulation of nicotinic expression at the neuromuscular junction. When this occurs symptoms such as muscle weakness, fatigue, muscle cramps, fasciculation, and paralysis can be seen. When there is an accumulation of ACh at autonomic ganglia this causes overstimulation of nicotinic expression in the sympathetic system. Symptoms associated with this are hypertension, and hypoglycemia. Overstimulation of nicotinic acetylcholine receptors in the central nervous system, due to accumulation of ACh, results in anxiety, headache, convulsions, ataxia, depression of respiration and circulation, tremor, general weakness, and potentially coma. When there is expression of muscarinic overstimulation due to excess acetylcholine at muscarinic acetylcholine receptors symptoms of visual disturbances, tightness in chest, wheezing due to bronchoconstriction, increased bronchial secretions, increased salivation, lacrimation, sweating, peristalsis, and urination can occur. Certain reproductive effects in fertility, growth, and development for males and females have been linked specifically to organophosphate pesticide exposure. Most of the research on reproductive effects has been conducted on farmers working with pesticides and insecticdes in rural areas. In females menstrual cycle disturbances, longer pregnancies, spontaneous abortions, stillbirths, and some developmental effects in offspring have been linked to organophosphate pesticide exposure. Prenatal exposure has been linked to impaired fetal growth and development. Neurotoxic effects have also been linked to poisoning with OP pesticides causing four neurotoxic effects in humans: cholinergic syndrome, intermediate syndrome, organophosphate-induced delayed polyneuropathy (OPIDP), and chronic organophosphate-induced neuropsychiatric disorder (COPIND). These syndromes result after acute and chronic exposure to OP pesticides.
Cattle fed this compound at 9, 30, or 60 mg/kg body weight had 2,4,5-T3CP tissue concentrations ranging from 0.06 to 0.48 mg/kg in the liver and from 0.05 to 0.10 mg/kg in kidney. No residues were detected in samples of muscle and fat from sheep or cattle fed Silvex. Sheep exposed to 2,4,5-T in the diet at 2000 mg/kg for 28 days exhibited 2,4,5-T3CP levels of 6.1 mg/kg, 0.90 mg/kg, 0.13 mg/kg, and 0.05 mg/kg tissue, in the liver, kidney, muscle, and fat, respectively.
The 2,4,5-trichlorophenol-derived herbicides 2,4,5-T and Silvex, were fed at dose levels of 0, 300, 1000 and 2000 mg/kg diet to adult cattle and sheep for 28 days. ... No residues of 2,4,5-trichlorophenol were found in the fat of sheep receiving 2000 mg/kg diet 2,4,5-T (0.05 mg/kg detection limit); average residue levels in liver were over 6 times the average in kidney: 6.1 versus 0.90 and 4.4 versus 0.81 mg/kg in tissues taken 1 day and 7 days after treatment, respectively. ... /In/ sheep and cattle fed Silvex, levels were 0.06-0.63 mg/kg in liver and less than 0.05-0.17 mg/kg in kidney.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
三氯苯酚似乎不会显著穿透完整兔或豚鼠皮肤（经皮吸收）...。
/Trichlorophenols/ appear not to penetrate intact rabbit or guinea pig skin (percutaneous absorption) in significant amt ... .
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
尿液样本中检测到的2,4,5-三氯酚是21名工人体内六氯环己烷（γ-BHC）的主要代谢物。
2,4,5-Trichlorophenol was identified in urine samples as a major metabolite of gamma-hexachlorocyclohexane (gamma-BHC) in 21 workers.
来源:Hazardous Substances Data Bank (HSDB)
吸收、分配和排泄
氯酚从胃肠道和注射部位被吸收。/氯酚/
The chlorophenols are absorbed from the gastroenteric tract and from parenteral sites of injection. /Chlorophenols/
1.周国泰，化学危险品安全技术全书，化学工业出版社，1997 2.国家环保局有毒化学品管理办公室、北京化工研究院合编，化学品毒性法规环境数据手册，中国环境科学出版社.1992 3.Canadian Centre for Occupational Health and Safety,CHEMINFO Database.1998 4.Canadian Centre for Occupational Health and Safety, RTECS Database, 1989
Structure-Activity Study of Tripeptide Thrombin Inhibitors Using .alpha.-Alkyl Amino Acids and Other Conformationally Constrained Amino Acid Substitutions
摘要：
In our continuing effort to design novel thrombin inhibitors, a series of conformationally constrained amino acids (e.g. alpha-alkyl, N-alkyl cyclic, etc.) were utilized in a systematic structure-activity study of the P3, P2, and P1 positions of tripeptide arginal thrombin inhibitors. Early examples of this effort include: D-MePhe-Pro-Arg-H (15), Boc-D-Phg-Pro-Arg-H (18), D-1-Tiq-Pro-Arg-H (23, D-1-Tiq D-1,2,3,4-tetrahydroisoquinolin-1-ylcarbonyl), and Boc-D-Phe-Pro-Arg-H (25).(10a,20) The current work clarifies the contribution of each residue of the tripeptide arginals toward the potent and selective inhibition of thrombin relative to that of t-PA and plasmin. The alpha-methylarginal modification in the P1 residue resulted in analogs 30 (D-MePhe at P3) and 32 (D-1-Tiq at P3) which had lower potency toward thrombin while exhibiting improved selectivity. Analogs modified at the P2 site were found to be very sensitive to the conformational changes induced by variations in side chain ring size with the flexible pipecolinic acid 31 being 2 orders of magnitude less potent at thrombin inhibition than the conformationally constrained azetidine analog 20. Examination of the P3 binding region indicated that alpha-alkylphenylglycine residues resulted in a tendency to exhibit substantial improvements in selectivity over the nonalkylated residues. Combinations of optimal P3 and P2 changes led to compounds TFA-D-Phg(alpha Et)-Azt-Arg-H (16), TFA-D-Phg(alpha Me)-Azt-Arg-H (17), Ac-D-Phg(alpha Me)-Azt-Arg-H (21), TFA-D-Phg(alpha Me)-Pro-Arg-H (27), 30, and 32, which are clearly more selective for thrombin versus plasmin than the nonconformationally constrained compounds.
1-Propanephosphonic Acid Cyclic Anhydride (T3P) as an Efficient Promoter for the Lossen Rearrangement: Application to the Synthesis of Urea and Carbamate Derivatives
The synthesis of hydroxamic acids starting from carboxylic acids employing 1-propanephosphonic acid cyclic anhydride (T3P) activation is described. Application of ultrasonication accelerates this conversion. Further, the T3P has also been employed to activate the hydroxamates, leading to isocyanates via the Lossenrearrangement. The isocyanates were trapped with suitable nucleophiles to afford the
Synthèse d'analogues structuraux de l'élédoïsine. 1<sup>re</sup>partie: Préparation des produits intermédiaires
作者：Ed. Sandrin、R. A. Boissonnas
DOI：10.1002/hlca.19630460518
日期：——
The preparation of new dipeptides and tripeptides, which are useful intermediates in the synthesis of Eledoisin analogues, is described.
描述了新的二肽和三肽的制备，它们是Eledoisin类似物合成中的有用中间体。
Hypocholesterolemic activity of 1,3-bis(substituted phenoxy)-2-propanones
作者：Claude Piantadosi、Iris H. Hall、Steven D. Wyrick、Khalid S. Ishaq
DOI：10.1021/jm00224a006
日期：1976.2
phenoxy)-2-propanones was found to be active hypocholesterolemicagents at 10 mg/kg/day. The p-chloro- and p-methyl-substituted phenoxy compounds possess the highest activity. These compounds did not possess the estrogenic and antifertility activities of the related previously reported derivatives of the bis(beta-phenylethyl) ketone series. The 1,3-bis(p-methylphenoxy)-2-propanone (7) also lowered serum triglycerides
发现一系列的1,3-双（取代的苯氧基）-2-丙烷是有效的降胆固醇药，剂量为10 mg / kg / day。对氯-和对甲基取代的苯氧基化合物具有最高的活性。这些化合物不具有以前报道过的双（β-苯乙基）酮系列相关衍生物的雌激素和抗生育活性。1,3-双（对甲基苯氧基）-2-丙酮（7）也会降低血清甘油三酸酯和甘油，这似乎是由于血清脂肪酶水平升高和肝脂肪酶活性降低所致。肝脏减少了游离脂肪酸向复杂脂质中的掺入。胆固醇在治疗的动物中排泄更快。
The reactions of unactivated aryl halides with sodium methoxide in HMPA
Sodiummethoxide reacts with dichlorobenzenes in HMPA to give the chloroanisoles as a result of a SNAr process. Excess MeONa then effects the demethylation of the ethers to give the chlorophenols via an SN2 reaction. With tri- and tetrachlorobenzenes the initially formed chloroanisoles can be dealkylated to chlorophenols or can suffer further substitution to give the chlorodimethoxybenzenes; these
由于S N Ar过程，甲醇钠与HMPA中的二氯苯反应生成氯茴香醚。然后过量的MeONa通过S N 2反应使醚脱甲基，得到氯酚。用三氯苯和四氯苯可以将最初形成的氯茴香醚脱烷基化为氯酚，或者可以进一步取代生成氯二甲氧基苯；它们与过量的MeONa反应，得到氯甲氧基苯酚。在取代基的电子效应的基础上，介绍并讨论了用二，三和四氯苯的各种异构体获得的结果。
Catalysis and inhibition of ester hydrolysis in the presence of resorcinarene hosts functionalized with dimethylamino groups
作者：Giorgio Cevasco、Sergio Thea、Daniele Vigo、Andrew Williams、Flora Zaman
DOI：10.1002/poc.1101
日期：2006.10
Complexation and catalysis of two calixresorcinarene (RES) derivatives with nucleophilic N,N-dimethylamino functions attached to their upper rims in the hydrolysis of carboxylate and sulfonate esters of 4-nitrophenol and 2,4-dinitrophenol have been investigated. Rate constants obey the complexation equation:
