Symptoms and treatment of acute poisoning of Barbiturates and Heavy metals
Barbituartes are derivatives of barbituric acid which are used as sedatives and hypnotics. They have a depressant action of CNS. Large doses directly depress the medullary respiratory centre.
Signs and symptoms:
a. Drowsiness and short period of confusion, excitement delirium and hallucination is common.
b. Ataxia, vertigo, slurred speech, headache, parasthesis and visual disturbances can occur.
c. A stupor progressing to deep coma with inhibition or loss of reflexes and gradual loss of response to painful stimuli occur.
d. Mild but progressive CV collapse, evidenced by cyanosis, hypotension and weak rapid pulse occur.
e. Pupils are first constricted, but later dilate because of hypoxia.
f. Body temperative is usually reduced.
g. Blisters on skin, often on area of eythema, strongly suggest barbiturate poisoning.
h. Chronic barbiturate use results in development of tolerance and abrupt withdrawal results in anorexia, tremor, insomnia, cramps, seizures, delirium and orthostatic hypotension.
Treatment:
a. Gastric lavage with warm water mixed with potassium permanganate and suspension of activated charcoal or tannic aid. If patient presents within 60 minutes of ingestion, lavage may be considered. Insert an orogastric tube and follow with fluid, usually normal saline. Aspirate back the fluid in an attempt to remove any toxicant. If patient is neurologically impaired, airway protection with a cuffed endotracheal tube is indicated prior to gastric lavage. Lavage performed more than 60 minutes after ingestion has not proven to be beneficial and runs risk of inducing bleeding, perforation, or scarring due to additional trauma to already traumatized tissues. It is always necessary first to control seizures before attempting gastric lavage or any other method of GI decontamination. There is further evidence that lavage may propel material into small bowel, thus increasing absorption.
Gastric lavage should not be routinely used in management of poisons. Lavage is indicated only when a patient has ingested a potentially life-threatening amount of poison and procedure can be done within 60 minutes of ingestion. Even then, clinical benefit has not been confirmed in controlled studies.
b. Forced alkaline diuresis is useful in poisoning by barbiturates-Forced diuresis may cause volume overload and electrolyte abnormalities and is not recommended. Renal elimination of a few toxins can be enhanced by alteration of urinary pH. For example, urinary alkalinization is useful in cases of salicylate overdose. Acidification may increase the urine concentration of drugs such as phencyclidine and amphetamines but is not advised because it may worsen renal complications from rhabdomyolysis, which often accompanies the intoxication.
c. Hemodialyis and hemoperfusion Hemodialysis is more efficient than peritoneal dialysis. It assists in correction of fluid and electrolyte imbalance and may also enhance removal of toxic metabolites For instance; it has long been proposed that treatment of overdoses of barbiturates (pKa values between 7.2 and 7.5) may be effectively treated with sodium bicarbonate.
d. Scandinavian method is used for antishock measures, maintainence of patient airway and adequate respiratory support.
e. Bowels should be evacuated by enema,
f. Antibiotics to minimize the risk of pneumonia.
Heavy metal poisoning is the major cause for morbidity and mortality. Lead, mercury, arsenic and lead are the main metals which case poisoning.
Lead:
Signs and symptoms are
Acute Lead Poisoning:-
a. Local actions in mouth produce marked astringency, thirst, and metallic taste.
b. Nausea, abdominal pain, and vomiting ensue. The vomitus may be milky from the presence of lead chloride. Stools may be black from lead sulfide, and there may be diarrhea or constipation.
c. Acute CNS symptoms include paresthesias, pain, and muscle weakness.
d. An acute hemolytic crisis sometimes causes severe anemia and hemoglobinuria.
e. The kidneys are damaged, and oliguria and urinary changes are evident. Death may occur in 1 or 2 days.
Chronic Lead Poisoning.
a. Signs and symptoms of plumbism can be divided into six categories: GI, neuromuscular, CNS, hematological, renal, and other. The neuromuscular and CNS syndromes result from intense exposure, whereas, GI syndrome reflects a very slowly and insidiously developing intoxication. The CNS syndrome is more common among children, whereas GI syndrome is prevalent in adults.
Treatment of Lead Poisoning:
a. Initial treatment of acute phase of lead intoxication involves supportive measures. Prevention of further exposure is important.
b. Seizures are treated with diazepam or phenytoin, fluid and electrolyte balances must be maintained, and cerebral edema is treated with mannitol and dexamethasone or controlled hyperventilation.
c. Chelation therapy is indicated in symptomatic patients: Four chelators are employed: edetate calcium disodium (CaNa2EDTA), dimercaprol (BAL), D- penicillamine, and succimer, CaNa2, EDTA and dimercaprol are used in combination for lead encephalopathy.
d. CaNa2EDTA is initiated at dose of 30 to 50 mg/kg per day in two divided doses either by deep intramuscular injection or slow intravenous infusion for up to 5 consecutive days.
e. Dimercaprol is given intramuscularly at a dose of 4 mg/kg every 4 hours for 48 hours, then every 6 hours for 48 hours, and finally, every 6 to 12 hours for an additional 7 days.
f. D-Penicillamine is effective orally and may be included in the regimen at a dosage of 250 mg given four times daily for 5 days.
g. Succimer is the first orally active lead chelator available for children, with a safety and efficacy profile that surpasses that of D-penicillamine
Mercury
Signs and symptoms
Short-term exposure to vapor of elemental mercury may produce symptoms:
a. Weakness, chills, metallic taste, nausea, vomiting, diarrhea, dyspnea, cough, and a feeling of tightness in the chest.
b. Pulmonary toxicity may progress to an interstitial pneumonitis with severe compromise of respiratory function
Chronic exposure to mercury vapor
a. The syndrome, termed the asthenic vegetative syndrome, consists of neurasthenic symptoms in addition to three or more of the following findings: goiter, increased uptake of radioiodine by the thyroid, tachycardia, labile pulse, gingivitis, dermographia, and increased mercury in the urine.
b. With continued exposure to mercury vapor, tremor becomes noticeable, and psychological changes consist of depression, irritability, excessive shyness, insomnia, reduced self-confidence, emotional instability, forgetfulness, confusion, impatience, and vasomotor disturbance.
Treatment of Mercury Poisoning-
a. Measurement of concentration of mercury in blood should be performed as soon as possible after poisoning with any form of metal.
b. Elemental Mercury Vapor: Therapeutic measures include immediate termination of exposure and close monitoring of pulmonary status. Short-term respiratory support may be necessary.
c. Inorganic Mercury: Prompt attention to fluid and electrolyte balance and hematological status is of critical importance in moderate-to-severe oral exposures.
d. Emesis can be induced if patient is awake and alert, although emesis should not be induced where there is corrosive injury. If ingestion of mercury is more than 30 to 60 minutes before treatment, emesis may have little efficacy.
e. Activated charcoal is recommended by some, although it lacks proven efficacy. Administration of charcoal may make endoscopy difficult or impossible.
f. Chelation Therapy with dimercaprol (for high-level exposures or symptomatic patients) or penicillamine (for low-level exposures or asymptomatic patients) is used to treat poisoning with either inorganic or elemental mercury. The duration of chelation therapy will vary, and progress can be monitored by following concentrations of mercury in urine and blood. The orally effective chelator succimer appears to be an effective chelator for mercury.
Arsenic
Signs and symptoms
Acute Arsenic Poisoning-
a. GI discomfort is experienced within an hour after intake.
b. Burning lips, constriction of the throat, and difficulty in swallowing may be the first symptoms, followed by excruciating gastric pain, projectile vomiting, and severe diarrhea.
c. Oliguria with proteinuria and hematuria usually is present; eventually, anuria may occur.
d. The patient often complains of marked skeletal muscle cramps and severe thirst.
e. As the loss of fluid proceeds, symptoms of shock appear. Hypoxic convulsions may occur terminally; coma and death ensue.
Chronic Arsenic Poisoning-
a. Muscle weakness and aching, skin pigmentation (especially the neck, eyelids, nipples, and axillae), hyperkeratosis, and edema. GI involvement is less prominent in long-term exposures.
b. Garlic odor of the breath and perspiration, excessive salivation and sweating, stomatitis, generalized itching, sore throat, coryza, lacrimation, numbness, burning or tingling of the extremities, dermatitis, viriligo, and alopecia.
c. Poisoning may begin insidiously with symptoms of weakness, languor, anorexia, occasional nausea and vomiting, and diarrhea or constipation. Subsequent symptoms may simulate acute coryza.
d. Dermatitis and keratosis of the palms and soles are common features.
e. The bone marrow is seriously damaged by arsenic.
Treatment of Arsenic Poisoning:
a. After short-term exposure to arsenic, routine measures are taken to stabilize patient and prevent further absorption of poison.
b. Attention is directed to intravascular volume status because effects of arsenic on GI tract can result in fatal hypovolemic shock.
c. Hypotension requires fluid replacement and may necessitate pharmacological support with pressor agents such as dopamine.
d. Chelation Therapy is begun with dimercaprol until abdominal symptoms subside and charcoal is passed in feces. Oral treatment with penicillamine then may be substituted for dimercaprol. If symptoms recur after cessation of chelation therapy, a second course of penicillamine may be instituted. Succimer, is efficacious in the treatment of arsenic poisoning.
e. Dialysis may become necessary with severe arsenic-induced nephropathy; successful removal of arsenic by dialysis has been reported.
Symptoms and treatment of acute poisoning of Snake bite
Snake venom is toxic saliva secreted by modified parotid salivary gland of a venoumous snake; venom may be neurotxic, haemotoxic, or myotoxic.
Symptoms of venomous snake bite:
a. Local features: indistinct fang marks, burning pain, swelling and discolouration blister formation, which may extend to entire bittn limb and even involve the trunk.
b. Systemic features: vomiting, headache, loss of consciousness, paralysis, drowsiness, hemoptysis, bleeding gums, respiratory arrest and renal failure.
First aid:
1. Assurance to the patient.
2. Apply firm pressure over the bitten area to delay absorption of venom
3. Clean the wound with soap and water.
4. Immobilize the bitten part.
5. Local incision and suction should not be done as, it may cause bleeding and nerve injury.
Treatment:
1. Antivenom therapy to neutralize venom
2. If antisnake venom is not available, antivenese is given intravenously.
3. Neaostigmine is given if there are signs of neuroparalysis,
4. Inject tetanus antitoxin or a booster dose of tetanus toxoid
5. Paracetamol is given for pain.
6. Surgical deridement of the blebs, blood vesicles, and superficial necrosis may be necessary.
Toxicology can be defined as that branch of science that deals with poisons. By convention, toxicology also includes the study of harmful effects caused by physical phenomena, such as radiation of various kinds and noise.
Preclinical toxicity studies
After synthesizing a prospective compound. It is tested on animals to expose the whole pharmacolocial profile. Experiments are generally performed on a rodent and then on large animal.
All drugs are toxic at some dose. Seeking to correctly define the limiting toxicities of drugs and therapeutic index comparing benefits and risks of a new drug might be argued as essential part of new drug development process. Most drug candidates fail to reach market, but art of drug discovery and development is effective assessment and management of risk and not total risk avoidance.
Candidate drugs that survive the initial screening and profiling procedures must be carefully evaluated for potential risks before and during clinical testing. Although no chemical can be certified as completely "safe" (free of risk), the objective is to estimate the risk associated with exposure to drug candidate and to consider this in context of therapeutic needs and duration. Preclinical toxicity testing includes:-
Type of Test Approach
Acute toxicity Acute dose that is lethal in approximately 50% of animals and the maximum tolerated dose. Usually two species, two routes, single dose.
Subacute toxicity Three doses, two species. 4 weeks to 3 months may be necessary prior to clinical trial. The longer the duration of expected clinical use, the longer the subacute test.
Chronic toxicity Rodent and non-rodent species. 6 months or longer. Required when drug is intended to be used in humans for prolonged periods. Usually run concurrently with clinical trial.
Effect on reproductive performance Effects on animal mating behavior, reproduction, parturition, progeny, birth defects, postnatal development.
Carcinogenic potential Two years, two species. Required when drug is intended to be used in humans for prolonged periods.
Mutagenic potential Effects on genetic stability and mutations in bacteria (Ames test) or mammalian cells in culture; dominant lethal test and clastogenicity in mice.
Investigative toxicology Determine sequence and mechanisms of toxic action. Discover the genes, proteins, pathways involved. Develop new methods for assessing toxicity.
The goals of preclinical toxicity studies include identifying potential human toxicities; designing tests to further define toxic mechanisms; and predicting specific and most relevant toxicities to be monitored in clinical trials. These include the"no-effect" dose—the maximum dose at which a specified toxic effect is not seen; minimum lethal dose—the smallest dose that is observed to kill any experimental animal; and, median lethal dose (LD50)—the dose that kills approximately 50% of animals.
Presently, LD50 is estimated from smallest number of animals. These doses are used to calculate the initial dose to be tried in humans, usually taken as one hundredth to one tenth of the no-effect dose in animals.
Limitations of preclinical testing include the following:
1. Toxicity testing is time-consuming and expensive-2 to 6 years may be required to collect and analyze data on toxicity and estimates of therapeutic index before the drug can be considered ready for testing in humans.
2. Large numbers of animals may be needed to obtain valid preclinical data. Cell and tissue culture in vitro methods are increasingly used, but their predictive value is still severely limited.
3. Extrapolations of therapeutic index and toxicity data from animals to humans are reasonably predictive for many but not for all toxicities.
4. For statistical reasons, rare adverse effects are unlikely to be detected.
Management of poisoning
Immediate measures should be taken to assess and correct the life threatening problems produced on poisoning. In comatose patients attention must be paid to stabilize respiration circulation and to crrect CNS depression.
General Principles in the Management of Acute Poisoning are:-
a. Skin Decontamination
b. Airway Protection
c. Gastrointestinal Decontamination-
1. Gastric Lavage
2. Catharsis
3. Activated Charcoal Adsorption
4. Syrup of Ipecac
d. Antidote Administration
e. Methods of Enhancing Elimination of Toxins
a. Skin Decontamination-Shower patient with soap and water to remove chemicals from skin and hair. If there are any indications of weakness, ataxia, or other neurologic impairment, clothing should be removed and a complete bath given while victim is recumbent. The possibility of pesticide sequestered under fingernails or in skin folds should not be overlooked. Flush contaminating chemicals from eyes with copious amounts of clean water for 10-15 minutes. If eye irritation is present after decontamination, ophthalmologic consultation is appropriate. Persons attending the victim should avoid direct contact with heavily contaminated clothing and vomitus.
b. Airway Protection - Ensure that a clear airway exists. Suction any oral secretions using a large bore suction device if necessary. Intubate the trachea if patient has respiratory depression or if patient appears obtunded or otherwise neurologically impaired. Administer oxygen as necessary to maintain adequate tissue oxygenation.
c. Gastrointestinal Decontamination-
1. Gastric Lavage- If patient presents within 60 minutes of ingestion, lavage may be considered. Insert an orogastric tube and follow with fluid, usually normal saline. Aspirate back the fluid in an attempt to remove any toxicant. If patient is neurologically impaired, airway protection with a cuffed endotracheal tube is indicated prior to gastric lavage. Lavage performed more than 60 minutes after ingestion has not proven to be beneficial and runs risk of inducing bleeding, perforation, or scarring due to additional trauma to already traumatized tissues. It is always necessary first to control seizures before attempting gastric lavage or any other method of GI decontamination. There is further evidence that lavage may propel material into small bowel, thus increasing absorption.
Note on Specific Pesticides: Lavage is contraindicated in hydrocarbon ingestion, a common vehicle in many pesticide formulations.
Gastric lavage should not be routinely used in management of poisons. Lavage is indicated only when a patient has ingested a potentially life-threatening amount of poison and procedure can be done within 60 minutes of ingestion. Even then, clinical benefit has not been confirmed in controlled studies.
2. Catharsis: - Sorbitol and magnesium citrate are commonly used cathartic agents. Sorbitol is often included in charcoal formulations. It will increase gut motility to improve excretion of charcoal-poison complex. The dosage is 1-2 g/kg as a one-time dose. Repeat doses of cathartics may result in fluid and electrolyte imbalances, particularly in children, and therefore not recommended.
3. Activated Charcoal Adsorption: -Activated charcoal is an effective absorbent for many poisonings other than pesticides. Studies suggest that it will reduce amount of poison absorbed if given within 60 minutes. There are insufficient data to support or exclude its use if time from ingestion is prolonged, although some poisons that are less soluble may be adsorbed beyond 60 minutes. There is some evidence that paraquat is well adsorbed by activated charcoal.
4. Syrup of Ipecac- Ipecac is used as an emetic. In pediatric study, administration of ipecac resulted in vomiting within 30 minutes in children. However, in review of clinical effectiveness of ipecac, it is no longer recommended for use.
Seizures-Lorazepam is increasingly being recognized as drug of choice for status epilepticus. One must be prepared to assist ventilation with lorazepam and any other medication used to control seizures. For seizure management, most patients respond well to usual management consisting of benzodiazepines, or phenytoin and phenobarbital.
d. Antidote Administration: Administration of specific antidotes may reduce the toxicity of poisons by any of following mechanisms:-
1. Forming inert complexes: Ex:Chelating agents fro heavy metals,
2. Accelerated detoxification: Ex: Thiosulfate accelerates conversion cyanide to non-toxic thiocyanate
3. Reducing toxic conversion: Ex: Ethanol inhibits metabolism of methanol to toxic metabolites by competing for same enzyme alcohol dehydrogenase,
4. Receptor site competition. Ex: Nalaxone antagonizes the effect of opiates at opioid receptor sites
5. Receptor site blockade Ex: Atropine blocks the effects of anticholinesterase agents such as organophosphorous at muscarinic receptor sites
6. Toxic effect bypass Ex: usage of 100% oxygen in cyanide poisoning.
Example of antidotes for emergency treatment of poisonings:-
Antidote Poison(s)
Acetylcysteine (Acetabate, Mucomyst) Acetaminophen
Atropine Anticholinesterases: organophosphates, carbamates
Bicarbonate, sodium Membrane-depressant cardiotoxic drugs (tricyclic antidepressants, quinidine, etc)
Calcium Fluoride; calcium channel blockers
Deferoxamine Iron salts
Digoxin antibodies Digoxin and related cardiac glycosides
Esmolol Theophylline, caffeine, metaproterenol
Ethanol Methanol, ethylene glycol
Flumazenil Benzodiazepines
e. Methods of Enhancing Elimination of Toxins
DIALYSIS PROCEDURES
a. Peritoneal Dialysis-This is a relatively simple and available technique but is inefficient in removing most drugs.
b. Hemodialysis-it is more efficient than peritoneal dialysis. It assists in correction of fluid and electrolyte imbalance and may also enhance removal of toxic metabolites (eg, formate in methanol poisoning, oxalate and glycolate in ethylene glycol poisoning). Hemodialysis is useful in overdose cases in which the precipitating drug can be removed and fluid and electrolyte imbalances are present and can be corrected (eg, salicylate intoxication).
c. FORCED DIURESIS AND URINARY PH MANIPULATION- Forced diuresis may cause volume overload and electrolyte abnormalities and is not recommended. Renal elimination of a few toxins can be enhanced by alteration of urinary pH. For example, urinary alkalinization is useful in cases of salicylate overdose. Acidification may increase the urine concentration of drugs such as phencyclidine and amphetamines but is not advised because it may worsen renal complications from rhabdomyolysis, which often accompanies the intoxication.
Benzodiazepine poisoning
Benzodiazepines are mainly used as antianxiety and muscle relaxant agents. The commonly used drugs are diazepam, nitrazepam, alprazolam etc.
Signs and symptoms:
Symptoms appear in 1 to 3 hours:
a. Acute poisoning may produce mild drowsiness, ataxia, weakness and moderate to severe vertigo slurred speech, nystagmus, lethargy and coma.
b. Chronic poisoning cause withdrawal symptoms such as headache, anxiety, insomnia, muscles spams, tremors, anorexia, vomiting, convulsions, and respiratory depression.
Treatment
a. Acute poisoning is treated with
i. Gastric lavage,
ii. Activated charcoal,
iii. Flumazenil is used as antidote to reverse come induced by benzodiapzines.
b. Chronic poisoning is treated
i. By using phenobarbitone as substitute for withdrawal symptoms
ii. A long acting drug such as chlordiazepoxide, or diazepam are useful to prevent complications.
Neuroleptic poisoning
These are also called as antipsychotics, or major tranquilizers. These include phenothiazines, thioxanthenes, butyrophenones, indoles and dibenzoxazepines.
Signs and symptoms: Myocardial depression, miosis, agranulocytosis, hypothermia or hyperthermia, decreased sweating and salivation, decreased intestinal motility and secretions, hemolytic anaemia, tachycardia, hypotension, sedation, seizures, cholestatic jaundice, urticaria, dermatitis, gynaecomastia, photosensitivity and pigmentation.
Treatment:
1. Emesis
2. Gastric lavage,
3. Activated charcoal
4. Catharsis
5. Symptomatic treatment.
Acute toxicity
Acute toxicity can be defined as toxicity elicited immediately following short-term exposure to a chemical. Incidences of acute toxicity in environment are associated with accident (i.e., derailment of a train resulting in leakage of a chemical into a river) or imprudent use of chemical (i.e., aerial drift of a pesticide to non-target areas).
Mechanisms of Acute Toxicity are:
i. Narcosis- in toxicology is defined as toxicity resulting from chemicals associating with and disrupting lipid bilayer of membranes.
ii. Acetylcholinesterase Inhibition-Acetylcholine is neurotransmitter that functions in conveying nerve impulses across synaptic clefts within central and autonomic nervous systems and at junctures of nerves and muscles. Following transmission of an impulse across synapse by release of acetylcholine, acetylcholinesterase is released into synaptic cleft. This enzyme hydrolyzes acetylcholine to choline and acetate and transmission of nerve impulse is terminated. The inhibition of acetylcholineasterase results in prolonged, uncoordinated nerve or muscle stimulation.
iii. Ion Channel Modulators-Ion transport is central to nerve impulse transmission both along axon and at the synapse and many neurotoxicants elicit effects by interfering with normal transport of these ions.
iv. Inhibitors of Cellular Respiration Many chemicals can interfere with cellular respiration by binding to cytochromes that constitute electron transport chain and inhibiting flow of electrons along this protein complex.
Treatment of insecticide poisoning
Treatment includes:
a. Airway protection. Ensure that clear airway exists. Intubate the patient and aspirate secretions with large-bore suction device if necessary. Administer oxygen by mechanically assisted pulmonary ventilation if depressed. Improve tissue oxygenation as much as possible before administering atropine, so as to minimize risk of ventricular fibrillation.
b. Atropine sulfate. Administer atropine sulfate intravenously, or intramuscularly, The objective is to antagonize effects of excessive concentrations of acetylcholine at end-organs having muscarinic receptors. Atropine does not reactivate cholinesterase enzyme or accelerate disposition of organophosphate. Recrudescence of poisoning may occur if tissue concentrations of organophosphate remain high when effect of atropine wears off.
Glycopyrolate is studied as an alternative to atropine and found to have similar outcomes using continuous infusion.
c. Pralidoxime. Before administration of pralidoxime, draw a blood sample (heparinized) for cholinesterase analysis. Administer pralidoxime (Protopam, 2-PAM) a cholinesterase reactivator, in cases of severe poisoning by organophosphate pesticides in which respiratory depression, muscle weakness, and/or twitching are severe.
d. Skin decontamination. In patients who have been poisoned by organophosphate contamination of skin, clothing, hair, and/or eyes, decontamination must proceed concurrently with whatever resuscitative and antidotal measures are necessary to preserve life. Flush the chemical from the eyes with copious amounts of clean water.
e. Gastrointestinal decontamination. If organophosphate has been ingested in quantity probably sufficient to cause poisoning, consideration should be given to gastrointestinal decontamination.
f. Observation. Observe patient closely for at least 72 hours
g. Furosemide may be considered if pulmonary edema persists in the lungs even after full atropinization.
h. Pulmonary ventilation.
i. Hydrocarbon aspiration
j. Cardiopulmonary monitoring.
k. Seizure control. Rarely, in severe organophosphate poisonings, convulsions occur despite therapy with atropine and pralidoxime.
Chelating agents
Chelating agents are drugs used to prevent or reverse the toxic effects of a heavy metal on an enzyme or other cellular target, or to accelerate the elimination of metal from the body.
Chelating agents are usually flexible molecules with two or more electronegative groups that form stable coordinate-covalent bonds with a cationic metal atom. In some cases, eg, succimer, the parent compound may require in vivo biotransformation to become an active complexing agent. The chelator-metal complexes formed are excreted by the body.
Ex: Edetate (ethylenediaminetetraacetate), Dimercaprol, Succimer, Ethylene diamine tetra acetic acid, Unithiol, Penicillamine, Deferoxamine, Deferasirox, Ferric hexacyanoferrate
Universal antidotes
Charcoal should not be administered concurrently with ipecac or specific antidote as it may absorb and render them ineffective. As most poisons do not dissociate from activated charcoal. If activated charcoal is not available universal antidote may be substituted. Compostion of universal antidote is activated charcoal+tannic acid+magnesium oxide.
Chronic Toxicity tests
Chronic tests are conducted over a significant part of the life span of the test animal. The duration of a chronic study is generally one year or more. Typically rat and dog are the preferred; for carcinogenicity studies, rats and mice are used.
Chronic toxicity tests are
1. Chronic feeding (including oncogenicity tests)
2. Teratogenicity
3. Reproduction (multi-generation)
Chronic toxicity tests are designed to discover any numerous toxic effects and to define safety margins to be used in regulation of chemicals.
Chronic toxicity tests may involve administration in food, in drinking water, by capsule, or by inhalation. The dose used is maximum tolerated dose (MTD) and usually two lower doses, perhaps 0.25 MTD and 0.125 MTD with lowest dose being a predicted no effect level.
Reproductive Toxicity and Teratogenicity:-The aim of developmental and reproductive testing is to examine potential for a compound to interfere with ability of an organism to reproduce. This includes testing to assess reproductive risk to mature adults as well as developing individual at various stages of life, from conception to sexual maturity.
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