Encyclopedia of Toxicology (eBook)

Bruce Anderson, Shayne C. Gad, P.J. Bert Hakkinen, Michael Kamrin, Betty Locey, Harihara M. Mehendale, Ann de Peyster, Carey Pope, Lee Shugart (Herausgeber)

eBook Download: EPUB

2005 | 2. Auflage
2000 Seiten
Elsevier Science (Verlag)
978-0-08-054800-5 (ISBN)

The second edition of the Encyclopedia of Toxicology continues its comprehensive survey of toxicology. This new edition continues to present entries devoted to key concepts and specific chemicals. There has been an increase in entries devoted to international organizations and well-known toxic-related incidents such as Love Canal and Chernobyl. Along with the traditional scientifically based entries, new articles focus on the societal implications of toxicological knowledge including environmental crimes, chemical and biological warfare in ancient times, and a history of the U.S. environmental movement. With more than 1150 entries, this second edition has been expanded in length, breadth and depth, and provides an extensive overview of the many facets of toxicology.Also available online via ScienceDirect - featuring extensive browsing, searching, and internal cross-referencing between articles in the work, plus dynamic linking to journal articles and abstract databases, making navigation flexible and easy. For more information, pricing options and availability visit www.info.sciencedirect.com.*Second edition has been expanded to 4 volumes*Encyclopedic A-Z arrangement of chemicals and all core areas of the science of toxicology*Covers related areas such as organizations, toxic accidents, historical and social issues, and laws*New topics covered include computational toxicology, cancer potency factors, chemical accidents, non-lethal chemical weapons, drugs of abuse, and consumer products and many more!

2,4,5-T

Lynn Weber

University of Saskatchewan, Saskatoon, SK, Canada

• Chemical Abstracts Service Registry Number: CAS 93-76-5

• Synonyms: 2,4,5-Trichlorophenol

• Chemical/Pharmaceutical/Other Class: Chlorinated phenoxyacetic acids. A closely related compound is 2,4-D (2,4-dichlorophenoxyacetic acid)

• Chemical Structure:

Uses

2,4,5-T is manufactured for use as a broad-spectrum herbicide. Its use in the United States has been suspended.

Background Information

A combination of the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D) and 2,4,5-T (Agent Orange), was used by the US military during the Vietnam War for defoliation. Long-term health consequences from exposure to Agent Orange, in particular to dioxin contaminants, have been suspected.

Exposure Routes and Pathways

Exposure to 2,4,5-T is by the oral, inhalation, and dermal routes.

Toxicokinetics

2,4,5-T is absorbed dermally in humans. Radioactivity was found in all tissues examined as well as in milk and fetuses after single oral administration of 0.17–41mgkg−1 [14C]2,4,5-T to pregnant rats. 2,4,5-T is eliminated largely unchanged. No metabolites are known, although it is possible that a small amount is eliminated as a glucuronide conjugate. The volume of distribution after a single oral dose of 5mgkg−1 varies as follows: in humans, 0.079lkg−1; in rats, 0.14lkg−1; and in dogs, 0.22lkg−1. 2,4,5-T is bound extensively to the plasma protein, which could limit renal clearance of the herbicide; 2,4,5-T is also bound to renal cortex microsomal and cytosol fractions. 2,4,5-T given orally to volunteers (100–150mg) was readily absorbed and gradually eliminated from blood plasma, showing a first-order elimination rate; more than 80% of a dose was excreted in urine in intact form within 72h. Clearance of 2,4,5-T from plasma and body of dogs, mice, and humans is slower than that in rats.

Mechanism of Toxicity

The effect of 2,4,5-T was investigated in in vitro studies with sublethal concentrations of 2,4,5-T, which showed an inhibitory effect on calcium-dependent ATPase. In vivo exposure to various sublethal concentrations of 2,4,5-T during 96h caused a significant inhibition of microsomal calcium-dependent ATPase. 2,4,5-T inhibits renal anion transport. Exposure of cells to 2,4,5-T resulted in a dose-dependent inhibition of DNA synthesis. Also, 2,4,5-T was shown to combine with choline to form 2,4,5-T-acetylcholine, a false neurotransmitter that inhibited muscle contraction. Since the false neurotransmitter could be formed at muscarinic as well as nicotinic synaptic sites, this interference with cholingeric neurotransmission may at least partially explain myotonia, ventricular fibrillation, and fetal growth retardation reported after 2,4,5-T exposure. Finally, 2,4,5-T is a well-known peroxisome proliferator agent, particularly in rodent liver.

Acute and Short-Term Toxicity (or Exposure)

Animal

2,4,5-T in pure form is considered to be of relatively low toxicity.

Oral LD50s were as follows: mouse, 389mgkg−1; rat, 500mgkg−1; guinea pig, 381mgkg−1; dog, >100mgkg−1. The percutaneous LD50 in rats was >5000mgkg−1. Single oral doses of 100mgkg−1 body weight of 2,4,5-T fed to pigs caused anorexia, vomiting, diarrhea, and ataxia; at autopsy, hemorrhagic enteritis and congestion of liver and kidney were found. 2,4,5-T (containing no detectable 2,3,7,8-tetrachlorodibenzo-p-dioxin) affected chromosomes of bone marrow cells of mongolian gerbil (Meriones unguiculatus) that received five consecutive daily intraperitoneal injections by causing significant increases in chromatid gaps, chromatid breaks, and fragments after total doses of 250mgkg−1 or more but not after 150mgkg−1 or less.

The no-effect levels for embryotoxicity for commercial 2,4,5-T were as follows: rat, 25mgkg−1day−1; mouse, 20mgkg−1day−1; hamster, 40mgkg−1day−1; and monkey, 40mgkg−1day−1.

Human

2,4,5-T in pure form is considered to be of relatively low toxicity. Limited data are available on exact toxic doses. Intravenous injection of up to 28mgkg−1 of 2,4-D has been well tolerated, while a dose of 50mgkg−1 produced toxicity. Death has resulted following ingestion of 80mgkg−1.

Common findings after acute ingestion included miosis, coma, fever, hypotension, emesis, tachycardia, and muscle rigidity. Complications may include respiratory failure, pulmonary edema, and rhabdomyolysis. Ingestions cause burning of the mouth, esophagus, and stomach. Irritation of skin, eyes, nose, and throat may also occur. Tachycardia is common. Cardiac arrhythmias occurred in one suicide case. Pulmonary edema has been reported. Respiratory paralysis and bradypnea are common in large ingestions. Vertigo, headache, malaise, and paresthesias have been reported occasionally in occupational handlers. Higher doses may produce muscle twitching and spasms, followed by profound muscle weakness and unconsciousness. Individual idiosyncrasies may be involved in reported neuropathies. Rhabdomyolysis may occur. Myotonia (stiffness of legs) has been observed in severely poisoned persons. Vomiting and diarrhea have been reported. Elevated LDH, SGOT (AST), and SGPT (ALT) (LDH, lactate dehydrogenase; SGOT, serum glutamic oxaloacetic transaminase; AST, aspartate aminotransferase; SGPT, serum glutamic pyruvic transaminase; ALT, alamine aminotransferase) have been reported. Albuminuria, hemoglobinuria, and azotemia may occur. Acute exposure may cause irritation of the skin. Chloracne from chlorodioxin contaminants in 2,4,5-T has been reported in heavily exposed workers.

Chronic Toxicity (or Exposure)

Animal

2,4,5-T itself is not believed to be carcinogenic or teratogenic in animals; these effects, produced by technical grades of the chemical, are believed to be due to the dioxin that is present as an impurity. In 2year feeding trials no effect was observed in rats receiving 30mgkg−1 diet or in 90day trials in beagle dogs at 60mgkg−1 diet.

Human

2,4,5-T itself is not believed to be carcinogenic or teratogenic in humans; these effects, produced by technical grades of the chemical are believed due to the dioxin that is present as an impurity.

Chronic 2,4,5-T exposure may reduce metabolic rate and subsequently lead to perinatal growth retardation. There may be an association of 2,4,5-T exposure with hydantidiform mole formation. However, the effects of 2,4,5-T and dioxin (an impurity in 2,4,5-T preparations) cannot be distinguished from each other in most studies.

Classification of Carcinogenicity

Evidence in humans is limited; overall summary evaluation of carcinogenic risk to humans is group 2B: the agent is possibly carcinogenic to humans. Recent studies conducted to clarify the carcinogenic potential found that although the closely related 2,4-D is mutagenic in a yeast test, cultured mammalian cells, and in vivo treated mice, 2,4,5-T appears to exhibit little or no mutagenicity.

Clinical Management

These herbicides can be measured in plasma and urine by high-performance liquid chromatography. Chlorophenoxy compounds do not affect blood cholinesterase activities.

Emesis may be indicated in recent substantial ingestion unless the patient is or could rapidly become obtunded, comatose, or convulsing. It is most effective if initiated within 30min. For activated charcoal/cathartic, a charcoal slurry, aqueous or mixed with saline cathartic or sorbitol, should be administered. A baseline complete blood count (CBC), electrolytes, and renal and hepatic function test should be obtained. Urine should be tested for protein, RBCs, and myoglobin. Urine output should be monitored. LDH, SGOT (AST), and alkaline phosphatase should be followed to detect liver injury, and creatine phosphokinase (CPK) should be followed to detect muscle damage. Urine pH, arterial pH, and bicarbonate should be measured to detect acidosis. Respiratory depression, hypotension, and metabolic acidosis should be treated. Adequate urine flow should be maintained with intravenous fluids if victim is dehydrated. The patient should be monitored closely for cardiac arrhythmias, hyperthermia, and seizures.

If exposed via inhalation, the victim should be moved to fresh air and monitored for respiratory distress. If cough or difficulty in breathing develop, evaluation for respiratory tract irritation, bronchitis, or pneumonitis should be performed. Humidified supplemental oxygen...

Erscheint lt. Verlag	31.5.2005
Mitarbeit	Chef-Herausgeber: Philip Wexler
Sprache	englisch
Themenwelt	Schulbuch / Wörterbuch ► Lexikon / Chroniken
Themenwelt	Studium ► 2. Studienabschnitt (Klinik) ► Pharmakologie / Toxikologie
ISBN-10	0-08-054800-8 / 0080548008
ISBN-13	978-0-08-054800-5 / 9780080548005

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