prn8099 - Number 28, June 2000

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PRN tracks tobacco media ads

The National Poison Centre’s continuous lobby for the banning of indirect advertising of tobacco has been stepped up this year via the monitoring of advertisements.

Five newspapers - The New Straits Times, The Star, The Sun, Berita Harian and Utusan Malaysia - were selected for this pilot project.

 Judging criteria include size of advertisements, colour used and theme. The project is divided into three phases - January to April, May to August, and September to December.

The objective of the project is to sensitise the media, especially the newspapers, on the ill-effects of tobacco industry promotion in line with the theme of this years’ World No-Tobacco Day - “Entertainment and Tobacco Promotion - Countering Deception.”

 Berita Harian was announced “winner” of the project’s first phase, for having the least number of tobacco-related advertisements based on the set criteria.

A “Health-Friendly Media Appreciation” plaque was presented to the newspaper, courtesy of the National Poison Centre, during the launching of the National No-Tobacco Week held at Universiti Sains Malaysia on May 30, 2000.

The overall winner will be presented with “Health-Friendly Media Award” at the end of the year, while the newspaper judged to have the most tobacco-related advertisements will be presented with a “Virtual Smelly Butt” plaque for the year.N

The advertisement tracking can be seen at: http://www.prn2.usm.my/mainsite/tobacco/advertisements.html 


 Poison Centre ties with Veterinary Institute in mass production of animal vaccines

The National Poison Centre and the Veterinary Research Institute (VRI) has initiated a pilot project to mass pro duce six types of vaccines to meet the annual local demand for these vaccines. The six vaccines are:

  • Septicaemia in cattle which causes blood poisoning
  • Sheep pasteurellosis which causes pneumonia
  • Duck pasteurellosis which also causes pneumonia
  • Salmonellosis which brings about abortion
  • Chicken cholera
  • Infectious coryza which causes swollen face and cranium in chicken.

The joint-project will involve the use of a 100-litre bioreactor, the only one available in the country, at USM  to cultivate local bacterial isolates which would then be processed further to produce the vaccines. Through the use of the equipment, adequate vaccines for 20 million chickens, 10 million ducks and 850,000 heads of cattle could be produced annually so that mandatory vaccination for these animals could be initiated from the year 2001 onwards. Through such a move, the use of antibiotics in disease prevention among livestock animals could be avoided. 

According to VRI’s Deputy Director, Dr. Sharifah Syed Hassan at the launching of the project in USM recently, “The national requirement for duck pasteurellosis vaccine was four million a month but the institute could only produce 300,000 doses monthly using a traditional method.

As for the chicken cholera vaccine, the institute can produce 100,000 doses whereas the total demand is 700,000 doses monthly. In addition, VRI can only produce three million doses of the six vaccines annually which is not sufficient for local consumption. This shortage has led farmers to not only use foreign-made vaccines but also controversial antibiotics for disease prevention in livestocks.

It is well known that the residual limits of the antibiotics can cause intoxication, development of antibiotic resistance in humans and in some cases, adverse reactions in sensitive individuals such as blood dyscrasia. Also, in some cases, farmers tend not to carry out livestock vaccination due to the high cost – an oversight which ultimately causes animal diseases resulting in the loss of the animals”.

If the PRN-VRI venture proves to be successful, these local vaccines would be considered for export to the Asean market. It also serves to show a strategic partnership to tap local expertise in producing local value added biotechnological products in line with the country’s aim to move into biotechnology manufacturing.

In conclusion, the facilities available at PRN enable any interested parties to jointly involve in the pilot scale production of bio-technology product. PRN welcomes any proposal to utilise these facilities as part of its Research and Development activity. 


 

PRN Laboratory Consultancy Services

Thiabendazole

Compiled by Noor Hasani Hashim

General

CAS registry number:      148-79-8

Molecular formula:          C10H7N3S

Formula weight:                201.26

CAS chemical name:        2-(thiazol-4yl) benzimidazole

Chemical structure

Physical and chemical properties

Thiabendazole is an odourless and colourless to white to practically white powder or crystals.

Melting point:             304-305oC

Boiling point:              Sublimes at 310oC

Specific gravity :        1.103 at 25oC

Solubility in water:    3.84% pH=2.2 at 0oC

Uses

Thiabendazole is a systemic benzimidazole fungicide used to control fruit and vegetable diseases such as mold, rot, blight and stain. It is also active against storage diseases and Dutch Elm disease. In livestock and human, it is applied to treat several helminth species such as roundworms, threadworms, hookworms, whipworms and pinworms. Thiabendazole is also used medicinally as a chelating agent to bind metals.

Clinical effects

Accidental or suicidal ingestion of this compound may result in anorexia, nausea,  vomiting, epigastric distress, vertigo, pruritus, skin rashes, diarrhea,  headache, fatigue, drowsiness, hyperglycemia, xanthopsia, leukopenia, bradycardia, hypotension, crystalluria and erythema multiforme.

Other symptoms include dry eyes, dry mouth, cholestatic jaundice, hypersensitivity, jaundice, parenchymal liver damage, giddiness, numbness, hyper-irritability, convulsions, collapse, psychic disturbances, tinnitus, abnormal sensation in eyes, blurring of vision, hematuria, enuresis, malodour of the urine, facial flush, chills, conjunctival injection, angiodema, anaphylaxis and lymphadenopathy.

Exposure may also cause fever, itching, body odor, hypotension and fainting.  Central nervous system depression may occur. Decrease in pulse rate and systolic blood pressure and perianal rash may also occur.N

Analytical Method Developed by PRN*

Sample : Apple, pear , potato and citrus fruit.

Specimen requirement: 0.5 - 1.0 Kg

Scope of analysis: Thiabendazole Method of Analysis.

Method of analysis: High Performance Liquid Chromatography.

Reporting limit: 0.03 ppm.

Cost per sample: RM 150.00

*For  advice on sample collection and delivery, please contact  04 – 6570009

Attention: En. Noor Hasani Hashim or En. Razak Hj.Lajis 


 PRN CONSULT

Review on

Pyrethrins and Synthetic Pyrethroids Poisoning

by Mohamed Isa Abd Majid, PhD

Besides the major insecticides which include the group of orga nophosphates and carbamates and the organochlorines, pyrethrins and synthetic pyrethroids represent another major insecticide made available for home uses. In fact, pyrethrin is the oldest and most widely used agent to kill insect.

What are pyrethrins and synthetic pyretroids?

Pyrethrum is the extract of the Chrysanthemum flower, subjected to various refinement processes. The flowers are dried and ground to produce pyrethrum, which is actually a composite of six active chemicals known as pyrethrins. Pyrethrins are esters of pyrethric and chrysanthemic acids formed by the keto alcohols pyrethrolone, cinerolone, and jasmololone. The active constituents of pyrethrum extract include pyrethrin I, pyrethrin II, cinerin I, cinerin II, jasmolin I, and jasmolin II. Pyrethrin I and pyrethrin II are two of the most potent derivatives from the extract.

Synthetic derivatives of these compounds are also widely available and are called pyrethroids. In terms of the chemical structure, these synthetic substances are similar to the pyrethrins, with subtle modification to resist photolysis and thus improve their stability in the natural environment. Some of the synthetic pyrethroids are: allethrin (Pynamin), bioallethrin (d-trans-alleth) cymethrin, permethrin, (Ambush, Pounce), resme-thrin, tetramethrin (Neo-Pynamin, Phthalthrin), decamethrin, fenothrin, fenvalerate (Pydrin) and furamethrin.

On the shelf, pyrethrum and pyrethroids may be available as dusts or liquids usually in a hydrocarbon base. Usually most insecticides containing the pyrethrins are combined with a synergist piperonyl butoxide which increases their effectiveness. Besides the approved ones, various illegally imported insecticidal chalks contain deltamethrin 37.6 mg. Among the brand names for these products include Miraculous Insecticide Chalk, Chinese Chalk, and Cockroach Wipeout Chalk.

What are the toxic signs and symptoms of both compounds?

In poisoning  cases involving ingestion,  two main effects are usually seen depending on the forms of pyrethrin. The Class I compounds which include allethrin, cismethrin, permethrin and resmethrin produce hyper-reactivity. In animal studies using rats, this is manifested as aggressive behaviour in reaction to sudden stimulus with uncontrolled bouts of general tremors. The final stages of poisoning consist of convulsive twitching, prostration and death. Class II compounds which include cypermethrin, deltamethrin and fenvalerate produce excessive salivation and irregular jerking of the limbs, progressing to rolling convulsions (choreoathetosis) and ocassionally to both tonic and clonic convulsion.

The mammalian toxicity of natural pyrethrins is generally low. Very young children are perhaps more susceptible to poisoning because they may not hydrolyze the pyrethrum esters efficiently. Pyrethrins can cause severe allergic dermatitis and systemic allergic reactions. Following inhalation, a stuffy, runny nose and scratchy throat are common. Hypersensitivity reactions including wheezing, sneezing, shortness of breath and bronchospasm may be noted. Eye exposures may result in mild to severe corneal damage.

As to the mechansim of toxicity, one of the chief virtues of the pyrethrins and pyrethroids is that they cause a much lower toxic effect in mammals than in insects. In insects, these compounds are powerful paralytic poisons causing “quick knockdown” and death when sufficient dosage has been given. The low toxicity in mammals is due primarily to rapid metabolic breakdown through ester cleavage. Despite low systemic toxicity, natural pyrethrum contains impurities, such as pyrethrosin, which are allergenic, affecting the skin and the upper respiratory tract. However, refined pyrethrins and synthetic pyrethroids are said to have little or no allergenic effect. In certain formulations,  piperonyl butoxide is added to the pesticide formula. This compound is a moderately active hepatic enzyme inducer in mammals.

How are these compounds being used in Malaysia?

In Malaysia, the pyrethrin- and pyrethroid-containing products are available for two main uses viz. agriculture and household purposes. For the field applications, the synthetic pyrethroids being used are cypermethrin, d-phenothrin, deltamethrin, cyfluthrin, esfenvalerate, fenvalerate, lambda-cyhalothrin, permethrin, prallethrin and tetramethrin. Some of these products are formulated in combination with an organophosphate, chlorpyrifos. In contrast, the synthetic pyrethroids are being formulated as household insecticides. Examples include: alphacy-permethrin, bioallethrin, bioresmethrin, permethrin, cyfluthrin, cyhalothrin, tetramethrin, cyphenothrin, d-allethrin, d-phenothrin, flumethrin and d-trans allethrin. Although the same chemicals were approved for usage in the household, the amount being supplied to the home users are considerably lower.

What is the physiochemical characteristic of selected pyrethrins?

The characteristics of some selected pyrethroids are as follows:

Cypermethrin

The acute toxicity of cypermethrin for mammals is of a moderate order. The oral LD50  for rat ranged from 200-4000 mg/kg body weight. Short term and long term toxicity studies on rats, mice and dogs have shown effects on growth, the liver and the kidneys, the nervous system and the blood. Cypermethrin was found to be not carcinogenic in mice and rats fed with diets containing the compound over a 2-year period.

Cypermethrin was not teratogenic in either rats at 70 mg/kg body weight or rabbits at 30 mg/kg body weight. No effects on reproductive performance were seen in a 3 generation reproduction study on rats administered 10 mg/kg of cypermethrin/kg diet.

From human occupational studies, it seems that the skin sensation seen in workers handling cypermethrin generally lasts only a few hours and does not persist for more than one day after exposure. Other neurological signs have not been observed. These skin sensations may be considered as an early warning that exposure has occurred and that work practice should be reviewed. Cypermethrin may cause eye irritation and may be a sensitizer for certain persons.

Allethrin

Based on its chemical structure, allethrin is an ester of chrysanthemic acid with allethrolone. The compound can exist as stereoisomers or in mixtures of d-allethrin, bioallethrin, esbiothrin and S-bioallethrin. These compounds are used in major household insecticides such as aerosols, sprays, smoke coils, electric mats and emulsifiable concentrates with or without synergists and other insecticides.

Human exposure to allethrins is thought to occur mainly through the inhalation of mists from aerosol sprays and from other household applications such as the electric mat and mosquito coil. Air levels arising from the conventional household application in the form of an aerosol are not expected to exceed 0.5 mg/cc.

Although the allethrins have been used for many years, insufficient data still exist for its toxicity effects on humans. The results of short-term studies on experimental animals suggest that allethrins are weakly to moderately toxic ranging from 210 to 4290 mg/kg body weight.

Also on the basis of inhalational studies on mice and rats from exposure to mosquito mats and coils at a range of dose levels (10x, 20x, 25x normal use concentration), the short term toxicities of S-bioallethrin and d-allethrin appear to be low.

Allethrins have shown mild primary eye and skin irritation in rabbits but no skin sensitization. Allethrins at near lethal doses are likely to cause hyperactivity, tremors, and convulsions . The allethrins were found to be not mutagenic in a varity of test systems including gene mutations, DNA damage, DNA repairs and chromosomal effects.

Deltamethrin

Deltamethrin is mostly used on cotton (45% of the consumption)  and on crops such as coffee, maize, wheat, soya beans, fruit, vegetables and hops. It is also used in public health programmes and to protect stored crops, primarily cereal grains. It is used in animal facilities and against cattle infestation.

Deltamethrin can induce skin sensations in exposed workers. Vertigo and numbness, itching, tingling and burning of the skin have been frequently reported. Most of these symptoms were transient and disappeared within 5 to 7 days. No long term adverse effects have been reported. There has been non-fatal cases of deltamethrin poisoning after the ingestion of several grams of the product.

Permethrin

Permethrin is mostly used in agriculture and may be used to protect stored grain. It has been used in aerial application for forest protection and vector control, to control noxious insects in the household  and on cattle, to control body lice and in mosquito nets.

Permethrin can induce skin sensations  and paresthesia in exposed workers. It develops after a latent period of 30 minutes, peak by 8 hours and disappear within 24 hours. Numbness, itching, tingling and burning are symptoms frequently reported.

Fenvalerate

Fenvalerate is used  primarily in agriculture and also in homes and gardens for insect control and on cattle alone or in combination with other insecticides. The general population may be exposed to fenvalerate mainly through residues in food. Residue levels in crops that have been grown with agricultural practices are generally low.

In exposed workers, fenvalerate can cause skin sensations and paresthesia that develop after a latent period of 30 minutes, peak by 8 hours, and disappear within 24 hours. Numbness, itching, tingling and burning are symptoms frequently reported.

Cyhalothrin and lamba-cyhalotrin

Cyhalothrin is highly active against a wide variety of species of Lepidoptera, Hemiptera, Diptera and  Coleoptera. It has also some miticidal activity. Lamda cyhalothrin have the same spectrum of insecticidal activity as cyhalothrin but is more active. The compound is a stomach and contact insecticide. It shows adulticidal, ovicidal and larvicidal activity. Apart from agricultural uses, cyhalothrin also has public and animal health applications in which it effectively controls a broad spectrum of insects including cockroaches, flies, mosquitoes and ticks. It is active as a residual spray on inert surfaces.

What is the management of such poisoning cases?

In manufacturing, formulation, laboratory work and field usage, symptoms of subjective facial sensation have been reported. This effect generally lasts only a few hours but occasionally persists for up to 72 hours after exposure.

The facial sensation is believed to be brought about by repetitive firing of sensory nerve terminals in the skin; they may be considered as an early warning signal indicating that overexposure of the bare skin has occurred.

In ingestion of a substantial amount of  the pesticide, the treatment required can be summarised as follows: Prevention of absorption may be accomplished by gastric lavage followed by activated charcoal/cathartic. Treatment is primarily supportive and includes monitoring for the development of seizures, respiratory distress, and hypersensitivity reactions. For ocular and dermal exposures, the contact area should be irrigated with large amounts of water.

Generally, emesis is not recommended due to potential rapid onset of seizures and coma. Spontaneous vomiting is common. In addition, a dose of activated charcoal as an aqueous slurry is administered to patients who are awake and able to protect their airway.

Activated charcoal is most effective when administered within one hour of ingestion. In patients who are at risk for abrupt onset of seizures or mental status depression, activated charcoal should be administered under careful observation to prevent aspiration in the event of spontaneous emesis.

Gastric lavage also needs to be performed with a large-bore orogastric tube (ADULT: external diameter 12 to 13.3 mm; CHILD: diameter 7.8 to 9.3 mm) after a potentially life threatening ingestion if it can be performed soon after ingestion (generally within 60 minutes). For the lavage fluid, use small aliquots of liquid of 150 to 200 milliliters warm tap water (preferably 38 degrees Celsius) or saline per wash. For children under 5 years of age gastric fluid of 10 milliliters/kilogram body weight may be given to the subjects. Continue until lavage return is clear. The volume of lavage return should approximate amount of fluid given to avoid fluid-electrolyte imbalance. Water should be avoided in young children because of the risk of electrolyte imbalance and water intoxication. Warm fluids avoid the risk of hypothermia in very young children and the elderly.

In cases of seizures developing in a poisoned victim, the treatment of seizures may include the use of diazepam, phenytoin, or phenobarbital.

For inhalation exposures, the victim should be brought to an open environment. Supplemental oxygen may be given. In ocular and dermal exposures, the area of contact should be irrigated with copious amounts of water.

For dermal exposure, decontamination involves washing the exposed area extremely thoroughly with soap and water. A physician may need to examine the area if irritation or pain persists after washing. Oil of vitamin E preparations appear effective as long as they contain vegetable oils such as corn oil sesame oil, safflower oil or wheat germ oil. Apply oil of vitamin E at the start of the day and every 4 hours throughout the working day or after washing. Apply a light coating to exposed skin.

If the victim develops mild hypersensitivity reactions, the treatment to be given may include the use of antihistamines with or without epinephrine. However, if severe anaphylaxis further develops, aggressive measures to be instituted include oxygen supplementation, aggressive airway management, epinephrine, ECG monitoring, and IV fluids.

Respiratory tract irritation, if severe, can progress to pulmonary edema which may be delayed in onset up to 24 to 72 hours after exposure in some cases. For non-pharmacologic treatment, maintain adequate ventilation and oxygenation with frequent monitoring of arterial blood gases. Early administration of corticosteroids was believed to be of benefit, although definitive evidence is lacking. The recommended drug is prednisone 2 to 4 milligrams/kilogram/day. Alternatively equivalent dose of intravenous methylprednisolone may be given for 1 or 2 weeks after the onset of ARDS.


Commonly available household products containing pyrethrins and synthetic pyrethroids

Insecticide Aerosol Spray

Bioallethrin

Permethrin

Bioresmethrin with piperonyl butoxide

Cyphenothrin

Cypermethrin

Tetramethrin or d-tetramethrin

d-allethrin

d-phenothrin

s-bioallethrin

Vape Mat

d-allethrin

d-trans allethrin

Prallethrin

Mosquito Coil

d-allethrin

d-trans allethrin

Others

Deltamethrin

Flumethrin

Lamda-cyhalothrin

Reference: Approved Pesticides Register, 1992-1994, Pesticide Board of Malaysia) 


Poisoning cases reported to National Poison Centre involving pyrethrins and synthetic pyrethroids  

(1995 to June 2000)

Year                     No of Cases

1995                       6

1996                     23

1997                       7

1998                     11

1999                     14

2000                       9

 


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