DDT (PIM 127) (2024)

 DDT International Programme on Chemical Safety Poisons Information Monograph 127 Chemical 1. DDT 1.1 Substance Dichlorodiphenyltrichloroethane (DDT) 1.2 Group 1.3 Synonyms Alpha,alpha-bis(p-chlorophenyl)beta, beta, beta-Trichlorethane; 2,2-Bis(p-chlorophenyl)-1,1,1-Trichloroethane; Clofenotane (INN); Chlorinated diphenyloxide; Chlorophenothane (USP); p,p'-DDT; Dicophane (BP); ENT - 1506; Klorfenoton (Swedish); 1,1,1,Trichloor2,2-bis(4-chloor-fenyl)-Ethaan(Dutch); 1,1,1,Trichlor-2,2 bis(4-chlor-phenyl)aethan(German); 1,1,1,Trichloro,2,2-Di(4-chlorophenyl)ethane; 1,1-(2,2,2-trichloroethylidene)-bis (4-chlorobenzene) (CAS); 1,1,1-trichloro-2,2-bis (4-chlorophenyl) ethane (IUPAC); OMS-16; 1.4 Identification numbers 1.4.1 CAS 50-29-3 1.4.2 Other numbers UN transportation number 2761 RTECS KJ 3325000 NCI C 00464 1.5 Brand names/Trade names Anofax; Cezarex; DinozideGesarol; Guesapan; Guesarol; Gyron; Ixodex; Neocide; Neocidol; Zerdane; 1.6 Manufacturers, importers To be added by the poison control centre.  2. SUMMARY 2.1 Main risks and target organs DDT has a wide margin of safety when used judiciously, and few if any adequately documented cases of DDT poisoning in man have been fatal. It appears that the main toxicity to humans is related more to the solvent vehicle rather than the DDT itself.  DDT is a central nervous system stimulant, acting chiefly on the cerebellum and motor cortex. The liver is the only other organ significantly affected by DDT. 2.2 Summary of clinical effects The earliest symptom of poisoning by DDT is hyperaesthesia of the mouth and lower part of the face. This is followed by paraesthesia of the same area and of the tongue and then by dizziness, an objective disturbance of equilibrium, paraesthesia and tremor of the extremities, confusion, malaise, headache, fatigue, and delayed vomiting (probably centrally mediated). Convulsions only occur in severe poisoning. It is not clear whether cardiac arrhythmia might be a possible cause of death in acute poisoning. In most instances of fatalities following ingestion of DDT solutions, the signs and symptoms were predominantly or exclusively those of poisoning by the solvent vehicle. 2.3 Diagnosis Clinical diagnosis may be difficult as symptoms are not specific and are dose related. The clinical effects of DDT may be modified by the vehicle or co -ingredients. A single dose of DDT at the rate of 10 mg/kg may produce illness in some but not all subjects; smaller doses generally produce no illness.  Blood levels are not clinically useful.  There are both simple qualitative and recommended qualitative (involving thin layer chromatography) tests for biological samples (stomach contents or suspect fluids). Gas liquid chromatography can be performed on blood and urine within 72 hours. The urine can be examined for the presence of DDA when the diagnosis is uncertain.  Hyperlipoproteinaemia can be tested for if chronic exposure is suspected. 2.4 First-aid measures and management principles In the event of exposure to DDT, contaminated clothing and contact lenses should be removed to prevent further absorption. In the case of skin contact, the affected area should be washed carefully with soap and water. Wash eyes for 10 to 15 minutes with clean running water. First aid personnel should wear rubber or plastic gloves and avoid contamination.  Ingestions of small amounts of DDT do not constitute a significant risk, and may be managed by dilution with water.  The management of large quantities of ingested DDT should be primarily directed towards decontamination and supportive care, as there is no specific antidote. The use of gastric lavage for recent large ingestions and activated charcoal are indicated.  3. PHYSICO-CHEMICAL PROPERTIES 3.1 Origin of the substance A synthetic product, DDT can be manufactured by the condensation of chlorobenzene with trichloroacetaldehyde (Worthing & Walker, 1987). 3.2 Chemical Structure The chemical name for DDT is:  1,1,1-trichloro-2,2-bis(4-chlorophenyl)ethane  The empirical formula is C14H9Cl5  The relative molecular mass is 354.50 3.3 Physical properties 3.3.1 Colour White 3.3.2 State/Form Solid-crystals 3.3.3 Description At room temperature DDT is a white, tasteless, almost odourless crystalline solid (Hayes & Laws, 1991).  Solubility: Practically insoluble in water 2g/100mL ethanol 28g/100mL ether Highly soluble in apolar organic solvents  Boiling point: 185°C  Melting point: 108.5°C to 109.0°C  Flash point: 162-171 °F   Density (20°C): 1.016 kg/L  Specific gravity: 1.55  Vapour pressure (20°C) 2.53 × 10-5 Pa 3.4 Hazardous characteristics The term DDT is generally understood to refer to para para'-DDT. However, the compound's structure permits several different isomeric forms including ortho para-DDT and meta para-DDT. Technical DDT consists predominantly of para para'-DDT with smaller amounts of other compounds such as ortho para-DDT, para para'-TDE, ortho para-DDE (WHO, 1989). These other isomeric forms may add to the action of DDT as it is known that ortho para-DDT is of insecticidal value (Worthing & Walker, 1987).  DDT is resistant to destruction by light and oxidation (Budavari et al., 1989).  para para'-DDT is dehydrochlorinated, at temperatures above its melting point, to DDE which has no insecticidal properties. This reaction is catalysed by iron(III) or aluminium chlorides, UV light and in solution by alkalis (Worthing & Walker, 1987). As such, DDT should not be stored in iron containers and should not be mixed with iron and aluminium salts or with alkaline solutions.  High temperatures should also be avoided (Budavari et al., 1989).  The environmental distribution and effects of DDT arise from its unusual chemical stability and hence its persistence. DDT and some of the breakdown products of DDT, principally DDE, are highly persistent in soil, sediment and biota as they are relatively resistant to breakdown by the enzymes and higher organisms found in the soil (WHO, 1979). Thus, contamination by materials can last long after cessation of DDT use.  DDT and its metabolites are highly toxic to fish and, besides their lethal effects, they affect development, behaviour and biochemical processes. DDT and its metabolites, should be regarded as hazardous to fish productivity and distribution and, hence, to human food supplies. Accumulated DDT and its metabolites are further transferred from aquatic organisms to consumers, including birds, mammals, and, ultimately, humans (WHO, 1979).  When exposed to simulated atmospheric conditions DDT decomposes to carbon dioxide and hydrochloric acid (WHO, 1979).  Fires involving DDT may produce irritating or poisonous gases. Fire fighters should wear self contained breathing apparatus and chemical protective clothing. For small fires, use dry chemical, CO2, halon, water spray or standard foam extinguishment. For larger fires, water spray, fog or standard foam is recommended. For spills, take up with sand or other non-combustible absorbent material and place into containers for later disposal (DOT, 1987).  4. USES 4.1 Uses 4.1.1 Uses Pesticide For Use Against Invertebrate Animals Insecticide 4.1.2 Description DDT is a potent non-systemic stomach and contact insecticide. It is persistent on solid surfaces, in soil, sediment and biota (Worthing & Walker, 1987).  DDT has had a wide usage, particularly in agriculture and vector control, and as such has been formulated in almost every conceivable form. These include solutions in xylene and petroleum distillates, emulsifiable concentrates, water- wettable powders, granules, aerosols, smoke candles, and charges for vaporisers (Hayes & Laws, 1991).  For its use as a topical medication it has also been formulated as lotions, dusting powders and shampoos (Reynolds, 1989).  The use of DDT is restricted or banned in some countries except when it is needed for the protection of health. 4.2 High risk circ*mstances of poisoning Accidental poisoning of children by DDT present in the home or garage (mostly a problem when in non aqueous solution, and the vehicle is often more of a problem than the DDT).  Accidental exposure among adult farm workers and secondary exposure to their children.  Suicide attempts.  Exposure of the general population may occur through the consumption of foodstuffs treated incorrectly with DDT or harvested prematurely before residues have declined to acceptable levels, from contact with treated areas or from domestic use.  Use and contact with DDT formulated with oils, fats and lipid solvents. 4.3 Occupationally Exposed Population Factory workers involved in synthesising DDT.  Workers involved in formulating and dispensing DDT.  Agricultural spray workers.  Crop harvesters during disease vector control periods.  Public health workers involved in vector control.  5. ROUTES OF EXPOSURE 5.1 Oral Ingestion occurs through accidental or deliberate ingestion and ingestion via contaminated foodstuffs. 5.2 Inhalation DDT is relatively non volatile and, although inhalation of spray drift may occur during occupational use, respiratory exposure is a less significant route. 5.3 Dermal DDT is poorly absorbed via the dermal route and as such is a less important route of entry. Dermal absorption increases when DDT is formulated in oily solutions. 5.4 Eye Exposure to vapours, dust and aerosols. 5.5 Parenteral Accidental or intentional. 5.6 Others No data available  6. KINETICS 6.1 Absorption by route of exposure In inhalation, most DDT dust is of such large particle size that any that is inhaled is deposited in the upper respiratory tract and eventually is swallowed (Hayes & Laws, 1991).  Absorption of DDT from the gastrointestinal tract is slow. Studies based on toxicity indicate that DDT dissolved in animal or vegetable fats is absorbed from the gastrointestinal tract about 1.5- to times more effectively than is undissolved DDT. Convulsions occur only after 2 hours when DDT is administered orally at a rate of 2 or more times the oral LD50 value (Hayes & Laws, 1991).  Intravenous injection at the rate of 50 mg/kg produces convulsions in rats in 20 minutes (Hayes & Laws, 1991).  Dermal absorption of DDT is very limited (Hayes & Laws, 1991). 6.2 Distribution by route of exposure DDT is stored in all tissues. Storage of the compound in blood, liver, kidney, heart and the central nervous system (CNS) has been reported. Higher concentrations of DDT are usually found in adipose tissue than in other tissues (Hayes & Laws, 1991).  In the general population DDT and some of its metabolic derivatives can be stored in the tissues and excreted in urine and milk (Hayes & Laws, 1991).  DDT and one of its major metabolic products, DDE, have high fat: water partition coefficients and, therefore, tend to accumulate in adipose tissue. Studies in both humans and laboratory animals indicate that there is a log-log relationship between the daily intake and the residues of both DDT and DDT-derived material in adipose tissue. At a constant rate of intake, however, the concentration of insecticide in adipose tissue reaches an equilibrium and remains relatively constant (Klaassen et al., 1986). 6.3 Biological half-life by route of exposure In a study of volunteer adult males who ingested between 3.5 and 35 mg DDT/person/day, the storage of DDT was proportional to dosage. DDT was slowly lost from storage in fat after dosing was stopped. The concentration remaining following 25.5 months of recovery was from 32 to 35% of the maximum stored for those who had received 35 mg DDT/person/day but was 66% for those who received only 3.5 mg DDT/person/day. This indicated that a slower loss occurred at lower storage levels (Hayes & Laws, 1991). 6.4 Metabolism DDT is converted to a slight extent to the much less toxic DDE by dehydrochlorination; DDE apparently does not undergo further biotransformation, but it is stored for an indefinite period of time in adipose tissues. Most of the para, para-DDE present in human fat represents preformed dietary DDE rather than endogenously produced DDE. The major detoxification pathway of DDT is via dechlorination to DDD, an active insecticide which readily degrades to DDA, a water soluble, rapidly excreted detoxification product (Baselt, 1982). 6.5 Elimination and excretion DDT is slowly eliminated from the body. Elimination has been estimated at a rate of approximately 1% of stored DDT per day (Klaassen et al., 1986). Urinary DDA presents about 47% of ingested precursor material during low exposure, but DDA excretion becomes quantitatively less important as DDT intake increases. Urinary DDA concentrations correlate reasonably well with DDT storage levels in body fat. DDA was undetectable in the urine of members of the general population and ranged from 0.01 to 2.67 mg/L in workers with low to high exposure to DDT. By contrast, urine concentrations of DDT, DDE and DDD in healthy unexposed persons averaged 0.007, 0.016 and 0.003 mg/L respectively, and 0.011, 0.021 and 0.006 mg/L respectively in occupationally exposed workers (Baselt, 1982). DDT is also excreted in human milk and transferred through the placenta (Hayes & Laws, 1991).  7. TOXICOLOGY 7.1 Mode of action DDT is a central nervous system stimulant acting chiefly on the cerebellum and motor cortex. Its action produces hyperexcitability, tremor and muscular weakness. Convulsions and myocardial sensitivity may occur (Dreisbach & Robertson, 1987). 7.2 Toxicity 7.2.1 Human data 7.2.1.1 Adults DDT has a wide margin of safety when used judiciously, and few if any adequately documented cases of DDT poisoning in man have been fatal (Gosselin et al., 1984). It appears that the main toxicity to humans is related more to the solvent vehicle rather than the DDT itself.  10 mg/kg is the single oral dose of DDT necessary to produce illness in some but not all subjects even though no vomiting may occur (Hayes & Laws, 1991).  Convulsions have occurred in cases when the dosage level was 16 mg/kg or greater and no effective treatment was undertaken (Hseih, 1954).  Amounts at least as high as 285 mg/kg have been ingested without fatalities. However, the amount retained is unknown as these doses lead promptly to vomiting (Hayes & Laws, 1991).  Considerable individual variation is recognized with DDT toxicity. Woodward et al. (1944) described the generally accepted acute mean lethal dose (LD50) in rats as 250 mg/kg and Gosselin et al. (1984) suggest that this is a reasonable estimate for man. Baselt (1982) states that in general, DDT is relatively safe with an estimated lethal dose of 30 g in an adult.  Fats and oils enhance the toxicity of DDT by promoting absorption. In many instances of alleged poisoning with DDT the principal symptoms have been due to the commercial vehicle that the DDT is formulated with. This vehicle has often been kerosene (Reingold & Lasky, 1947). 7.2.1.2 Children From studies in the young of animal species it has been suggested (Hayes & Laws, 1991) that the young are at no greater risk than an adult. 7.2.2 Relevant animal data Animal Formulation Oral Dermal IV LD50 LD50 LD50 mg/kg mg/kg mg/kg  Rat Water 500 1000 - suspension to 2500 or powder  Oil solution 113 250 to 47 to 450 3000  Mouse Water 300 to 375 - suspension 1600 or powder  Oil solution 100 to 250 to - 800 500  (Hayes & Laws, 1991) 7.2.3 Relevant in vitro data No data available. 7.2.4 Workplace standards STEL ACGIH 3 milligram per cubic metre (Parmeggiani, 1983)  TLV-TWA 1 milligram per cubic metre (ACGIH, 1989)  OSHA PEL-TWA 1 milligram per cubic metre (skin designation) (OSHA, 1989)  Odour threshold not pertinent as is odourless (CHRIS, 1985) 7.2.5 Acceptable daily intake (ADI) 0.02 mg/kg body weight (provisional tolerable daily intake, WHO 1995) [sum of p,p'DDT, o,p'DDT, p,p'DDE and p,p'TFE(DDD)]  Other Guideline Levels: WHO guideline value for drinking water: 1 microgram/L (total isomers) (WHO, 1984) 7.3 Carcinogenicity DDT has been evaluated by the International Agency for Research on Cancer (IARC, 1987,1991). It was concluded that the human evidence from several epidemiological studies was not adequate to indicate that DDT was carcinogenic.  Many experiments have been conducted in rodents. Liver tumours were introduced in most of the mouse and in two of the rat experiments (IARC, 1991).  Some risk of lymphoma, leukemia, pancreatic cancer, and breast cancer was found in humans exposed to DDT. Animal studies showed a significant association between DDT administration and lymphoma, respiratory cancer, liver cancer, and estrogenic effects on mammary tissue. On the basis of epidemiological principles, human studies were deficient in adequate sample sizes and were not exempt from such confounding factors as multiple chemical exposure, lifestyle factors, genetic, and other environmental influences (Jaga and Brosius, 1999). 7.4 Teratogenicity The effects of DDT on reproduction parameters have been summarised by IARC (1991). One human study has suggested that there may be a weak relationship between DDT levels in cord blood and low birth weight. Studies in rodents and rabbits have not demonstrated any teratogenic potential, but exposure of rodents to DDT impaired reproductive function (e.g., spermatogenesis, neonatal survival) in some studies. 7.5 Mutagenicity IARC (1991) reported one study in which chromosomal aberrations were observed in the peripheral lymphocytes of workers with increased plasma DDT levels. This finding is not supported by studies on bone-marrow cells of rodents. In most studies, DDT did not induce genetoxic effects in cultured rodent or human cell systems and was not mutagenic to fungi or bacteria. 7.6 Interactions DDT is known to interfere with the metabolism and function of steroid hormones. One such mechanism is by the induction of hepatic microsomal enzymes which results in an increased conversion of oestrogens, androgens, and glucocorticoids to more polar metabolites. Increased urinary excretion of the more polar metabolites is usually compensated for by increased steroid biosynthesis (Gosselin et al., 1984).  Individuals on chronic drug therapy with phenobarbitol and/or phenytoin have increased hepatic microsomal enzymes activity. Watson et al. (1972) suggest that this increased activity accelerates the metabolism of some DDT to DDA by the slow series of dehydrohalogenation reactions.  Fat and oils increase the absorption of DDT from the intestine.  8. TOXICOLOGICAL ANALYSES AND BIOMEDICAL INVESTIGATIONS 8.1 Material sampling plan 8.1.1 Sampling and specimen collection 8.1.1.1 Toxicological analyses Sample should be drawn into a vial or tube filter with a teflon or foil lined screw cap. Polyethylene or rubber caps must be used. Sample size: 7 to 10 mL. Use whole blood without added anticoagulant (EPA, 1982). 8.1.1.2 Biomedical analyses 8.1.1.3 Arterial blood gas analysis 8.1.1.4 Haematological analyses 8.1.1.5 Other (unspecified) analyses 8.1.2 Storage of laboratory samples and specimens 8.1.2.1 Toxicological analyses If an analysis cannot be run immediately, place in refrigerator at 2 to 5°C for periods of up to 24 hours before analysis. If time interval to analysis exceeds 24 hours, sample (serum) should be stored in a deep-freeze at -15 to -25°C. Stored in this manner, analysis may be delayed up to a month. (EPA, 1982). 8.1.2.2 Biomedical analyses 8.1.2.3 Arterial blood gas analysis 8.1.2.4 Haematological analyses 8.1.2.5 Other (unspecified) analyses 8.1.3 Transport of laboratory samples and specimens 8.1.3.1 Toxicological analyses 8.1.3.2 Biomedical analyses 8.1.3.3 Arterial blood gas analysis 8.1.3.4 Haematological analyses 8.1.3.5 Other (unspecified) analyses 8.2 Toxicological Analyses and Their Interpretation 8.2.1 Tests on toxic ingredient(s) of material 8.2.1.1 Simple Qualitative Test(s) 8.2.1.2 Advanced Qualitative Confirmation Test(s) 8.2.1.3 Simple Quantitative Method(s) 8.2.1.4 Advanced Quantitative Method(s) 8.2.2 Tests for biological specimens 8.2.2.1 Simple Qualitative Test(s) Nitric-sulphuric acid colour test:  The reagent: Mix 1 mL nitric acid with 30 mL sulphuric acid  Method: Dissolve the sample in 1 mL Ethanol, and add a pellet of potassium hydroxide. Evaporate to dryness at 100°C in a waterbath. To the residue, add 0.5 mL water and 1 mL carbon tetrachloride. Shake, allow to separate, decant the lower carbon tetrachloride layer and shake it with 1 mL reagent.  Indications:  A RED colour in the acid layer suggests the presence of DDT or its metabolite DDE. The red colour changes to ORANGE then to GREEN. A RED colour is also given by DDD but the colour does not change (Moffat, 1986). 8.2.2.2 Advanced Qualitative Confirmation Test(s) Thin Layer chromatography: Recommended qualitative for biological sample (stomach contents or suspect fluids).  Sampling: 10 to 20 mL stomach content  Chemical and reagents: *Petroleum ether (40 to 60°C boiling fraction) *Aqueous sodium hydroxide (20 g/L) *Sodium sulphate (anhydrous) *Organochlorine standards (DDT, HCH, Lindane, HCB, heptachlor, aldrin, endrine) (all in 1 g/L) in methanol, Silica gel.  Equipment: TLC plates (20 × 20 cm), pipettes, spray bottle.  Method:  10 mL of sample is extracted twice with 5 mL portions of petroleum ether. Extracts are combined and washed with 5 mL portions of purified water and sodium hydroxide solution. The extract is dried over sodium sulphate and evaporated to dryness under stream of compressed air.  The extract is reconstituted in 100 mg methanol and 20 mg is spotted on TLC plate. Standard mixture is spotted on a second column. The chromatogram is developed using petroleum ether (saturated tank) and allowed to dry. The plate is sprayed with silver nitrate solution and after drying in ambient temperature, is exposed to UV light (254 nm, 15 min).  Organochlorine compounds give a BROWN-GREY reaction and identification is made by comparison with the standard chromatogram. 8.2.2.3 Simple Quantitative Method(s) 8.2.2.3 Advanced Quantitative Method(s) Recommended quantitative test for biological sample (blood).  Principle of test: A 2 mL aliquot of serum is extracted with 6 mL of hexane in a round bottom tube. The extraction is conducted for 2 hours on a slow speed rotating mixer. If emulsion forms, centrifugation may be used to effect separation. A 5 mL aliquot of the hexane layer is quantitatively transferred to an evaporative concentrator tube to which a micro-snider column is affixed. The extract is concentrated in a water bath, and the final volume is adjusted to correspond to the expected concentration of the pesticide residue. A suitable aliquot is analysed by electron capture gas chromatography.  Sampling:  7 to 10 mL blood drawn, is transferred to a vial or tube fitted with a teflon or foil lined screw. Whole blood sample is placed in the refrigerator for about 30 minutes for setting and centrifuged for 10 minutes for the separation of at least 3 mL of clear serum 2 mL of serum is used for extraction.  Chemicals and reagents: Hexane, distilled in glass, pesticide grade.  Equipment: 1. A rotatory mixer, designed to accommodate the 16 mm culture tubes and which may be operated at a rotary speed of 50 rpm. 2. Gas chromatograph, fitted with electron capture detector. 3. Tubes, culture, 16 125 mm, fitted with screw caps with teflon-faced rubber liners. 4. Micro-snider column. 5. Concentrator tube. 6. Syringe, 100 mL, Hamilton. 7. Vortex mixer. 8. Pipette, Mohr type, 1 mL grad in 0.01 mL increments. 9. Pipettes, transfer, 2,5 and 6 mL. 10. Beads solid, glass, 3 mm. 11. Water bath capable of holding temperature of 95 to 100°C. 12. Centrifuge, capable of speed of 2000 rpm.  Specimen preparation: No special preparation required.  Procedure: Mix blood serum sample thoroughly and, with a volumetric pipette, transfer 2 mL to a 15 mL round bottom culture tube. In case of the presence of any flocculent or sedimentary material, centrifuge in 5 min 2000 rpm before pipetting, in order to avoid poor reproducibility of replicated analyses of the same sample.  Add 6 mL hexane from a volumetric pipette. Tightly stopper the culture tube. Place on rotator for 2 hours of 50 rpm speed. In the case of emulsion formation centrifuge at 2000 rpm 4 to 5 minutes. Transfer 5 mL of the hexane extract to a 10 mL grad. concentrator tube, add one 3 mm glass bead and attach a modified micro - Snider column. Evaporate the extract in a steam or hot bath at 100°C. (When working with blood from high exposure donors, the 5 mL aliquot may require dilution rather than concentration) allow the tube to cool 3 to 5 minutes, remove the micro - Snider column an rinse down the sides of the tube and the column joint with hexane. Stopper the concentrator tube and hold on the Vortex mixer, set for high speed for 30 seconds for volumes of 6 mL or less. For larger volumes mix for 1 minute. Proceed with electron capture GLC.  p.p.b = \f(a b x, c y) × 0.6  Where:  a = nanograms of pesticide in standard peak b = height of sample peak c = height of standard peak x = total volume of final extract in microlitres y = microliters of extract injected  e.g.: nanograms in standard peak = 0.3 height of sample peak = 80 mm height of standard peak = 90 mm total volume of final extract = 1000 microlitre volume of final extract injected = 5 microlitre p.p.b = \f(0.3 × 80 × 1000,90 × 5) × 0.6 = 32 ppb Quality Control:  Composition of standard mixture:  a HCH 20 pg/mL HCB 20 pg/mL pp DDT 80 pg/mL  b HCH 40 pg/mL Heptachlor 20 pg/mL pp DDE 60 pg/mL  g HCH 20 pg/mL op DDT 50 pg/mL pp DDD 50 pg/mL  Specificity: It is group specific  Detection Limit: b-HCH, lindane, heptachlor, heptachlor epoxide, o,p-DDE, dieldrin:-1 ppb endrin, op-DDT,pp-DDD,pp-DDT:-2 ppb 8.2.2.5 Other Dedicated Method(s) 8.2.3 Interpretation of toxicological analyses 8.3 Biomedical investigations and their interpretation 8.3.1 Biochemical analysis 8.3.1.1 Blood, plasma or serum Blood levels are not clinically useful.  Biochemical tests to detect liver and kidney dysfunction should be performed although the results are expected to be negative (Gosselin et al., 1984).  Determination of blood sugar and sugar tolerance levels are desirable (Gosselin et al., 1984). 8.3.1.2 Urine "Basic analyses"  "Dedicated analyses"  "Optional analyses" 8.3.1.3 Other fluids 8.3.2 Arterial blood gas analyses 8.3.3 Haematological analyses "Basic analyses"  "Dedicated analyses"  "Optional analyses" 8.3.4 Interpretation of biomedical investigations 8.4 Other biomedical (diagnostic) investigations and their interpretation 8.5 Overall interpretation of all toxicological analyses and toxicological investigations Relevant laboratory analyses and other investigations: Laboratory analysis may indicate prolonged exposure to DDT but has little relation to acute exposure management as decontamination needs to be undertaken before laboratory results are available.  Sample collection: Analysis of blood and urine is required within 72 hours to detect high DDT levels.  Biomedical analysis: Blood levels are not clinically useful. Biochemical tests to detect liver and kidney dysfunction should be performed although the results are expected to be negative (Gosselin et al., 1984).  Determination of blood sugar tolerance levels are desirable (Gosselin et al., 1984).  Toxicological analysis: Gas liquid chromatography can be performed on blood and urine within 72 hours.  The urine can be examined for the presence of DDA when the diagnosis is uncertain (Gosselin et al., 1984).  Other investigations: Hyperlipoproteinaemia can be tested for if chronic exposure is suspected (Gosselin et al., 1984). 8.6 References  9. CLINICAL EFFECTS 9.1 Acute poisoning  9.1.1 Ingestion Onset of signs and symptoms depends on the dose. Onset may be as soon as 30 minutes after ingestion of a large dose or as late as 6 hours after smaller but still toxic doses.  Large doses are followed promptly by vomiting due to local gastric irritation. Delayed emesis and/or diarrhoea may occur.  Onset of signs and symptoms are characterised by paraesthesia of the tongue, lips and face. In more severe poisonings paraesthesia may also involve the extremities. The patient suffers from a sense of apprehension, dizziness, an objective disturbance of equilibrium, and ataxia. Confusion may develop, malaise, headache, fatigue and sore throat may also be present. Tremor is a characteristic manifestation, usually involving first the neck and head and particularly the eyelids. Convulsions both clonic and tonic may develop and alternate with periods of coma and paresis. In the absence of convulsions, the vital signs are essentially normal, but in severe poisoning the pulse may be irregular and abnormally slow. Because DDT sensitises the heart to endogenous adrenaline, ventricular fibrillation and sudden death may occur at any time during the acute phase of poisoning. Complicating pulmonary signs suggesting a pulmonary oedema are probably due to concomitant solvent intoxication. Death, if it occurs, is usually due to respiratory failure from medullary paralysis (Gosselin et al., 1984; Dreisbach & Robertson, 1987; Hayes & Laws, 1991). 9.1.2 Inhalation Inhalation of fine DDT aerosol or dust into the lung produces moderate irritation of nose, throat and eyes with no other detectable ill effects (Hayes & Laws, 1991). 9.1.3 Skin exposure Dermal exposure to DDT is usually associated with no illness and usually no irritation. Formulations of DDT involving solvents have been shown to cause a slight transient dermatitis. These effects have usually been shown to be related to the solvent (Hayes & Laws, 1991). 9.1.4 Eye contact Contact with the eyes may cause ocular irritation. Further effects may be due to the solvent present. 9.1.5 Parenteral exposure Intravenous administration in animals has resulted in ventricular fibrillation and death. This could be extrapolated to mean something similar in humans. 9.1.6 Other No data available. 9.2 Chronic poisoning 9.2.1 Ingestion No data available. 9.2.2 Inhalation No data available. 9.2.3 Skin exposure No data available. 9.2.4 Eye contact No data available. 9.2.5 Parenteral exposure No data available. 9.2.6 Other No data available. 9.3 Course, prognosis, cause of death There have been no accidents or suicides involving respiratory or dermal exposure leading to recognised signs and symptoms of DDT poisoning.  Onset of acute poisoning may be as soon as 30 minutes after ingestion of a large dose or as late as 6 hours after smaller but still toxic doses. Recovery from mild poisoning is essentially complete in 24 hours, but recovery from severe poisoning requires several days.  The earliest symptom of poisoning by DDT is hyperaesthesia of the mouth and lower part of the face. This is followed by paraesthesia of the same area and of the tongue and then by dizziness, an objective disturbance of equilibrium, paraesthesia and tremor of the extremities, confusion, malaise, headache, fatigue, and delayed vomiting (probably centrally mediated). Convulsions only occur in severe poisoning. It is not clear whether cardiac arrhythmia might be a possible cause of death in acute poisoning. In most instances of fatalities following ingestion of DDT solutions, the signs and symptoms were predominantly or exclusively those of poisoning by the solvent vehicle (Hayes & Laws, 1991). 9.4 Systemic description of clinical effects 9.4.1 Cardiovascular Cardiac arrhythmias have been associated with death following DDT poisoning in some species of laboratory animals, but this may not be the case in acute human poisonings. Palpitations, tachycardia and irregular heart action have been noted in some cases of acute poisonings (Hayes & Laws, 1991). 9.4.2 Respiratory The effects of DDT on the respiratory system are secondary to the effects on the nervous system (Hayes & Laws, 1991). 9.4.3 Neurological 9.4.3.1 Central nervous system Dizziness, an objective disturbance of equilibrium, confusion, malaise, headache, fatigue, and delayed vomiting (probably centrally mediated) may occur following ingestion of DDT. Convulsions only occur in severe poisoning (Hayes & Laws, 1991). 9.4.3.2 Peripheral nervous system The earliest symptom of poisoning by DDT is hyperaesthesia of the mouth and lower part of the face. This is followed by paraesthesia of the same area and of the tongue, then paraesthesia of the extremities (Hayes & Laws, 1991). 9.4.3.3 Autonomic nervous system Increased salivation has been reported in persons who ingested DDT-contaminated food (Hayes & Laws, 1991). 9.4.3.4 Skeletal and smooth muscle Tremor of the extremities has been reported in persons who ingested DDT-contaminated food (Hayes & Laws, 1991). 9.4.4 Gastrointestinal Except for vomiting, which is probably centrally mediated, the gastrointestinal system has not been affected in acute poisoning (Hayes & Laws, 1991). 9.4.5 Hepatic DDT is a hepatic enzyme inducer. Involvement of the liver has been mentioned in only a small proportion of cases of accidental DDT poisoning (Hayes & Laws, 1991). 9.4.6 Urinary 9.4.6.1 Renal There is no indication of renal damage in people accidentally poisoned by DDT or in workers heavily exposed to it (Hayes & Laws, 1991). 9.4.6.2 Others 9.4.7 Endocrine and reproductive systems The effects of DDT on reproduction parameters have been summarised by IARC (1991). One human study has suggested that there may be a weak relationship between DDT levels in cord blood and low birth weight. Studies in rodents and rabbits have not demonstrated any teratogenic potential, but exposure of rodents to DDT impaired reproductive functions (e.g., spermatogenesis, neonatal survival) in some studies.  DDT is known to interfere with the metabolism and function of steroid hormones. One such mechanism is by the induction of hepatic microsomal enzymes which results in an increased conversion of oestrogens, androgens, and glucocorticoids to more polar metabolites. Increased urinary excretion of the more polar metabolites is usually compensated for by increased steroid biosynthesis (Gosselin et al., 1984). 9.4.8 Dermatologic Skin irritation results from extensive contact with organochlorine pesticides or with the white petroleum distillate vehicles. 9.4.9 Eye, ears, nose, throat: local effects Eyes-Acute  DDT has not been demonstrated to have a selective effect on the eyes. Pure DDT dissolved in purified kerosene was tested in a concentration of 0.01% on a human eye and caused no discomfort or irritation; it also proved non-irritating at 4% concentration on rabbit eyes. Rare instances have been reported of ocular irritation following contamination of the eye by powders containing DDT (Grant, 1986).  Eyes - Chronic In one instance chronic superficial punctate keratitis was associated with fatal poisoning from long exposure to DDT dust, but it was possible that constituents other than DDT were responsible, or that there was hypersensitivity (Grant, 1986).  Nose and throat-acute  Volunteers exposed to DDT dispersed into the air either by volatilising units or by continuously or by intermittently operated aerosol dispensers in some instances reported some dryness of the throat, but otherwise the results were negative (Hayes & Laws, 1991). 9.4.10 Haematological In acute poisoning a slight decrease in haemoglobin and a moderate leukocytosis without any constant deviation in the differential white count have been observed in volunteers. These findings are considered secondary to the neurological effects. 9.4.11 Immunological DDT appears to have a depressant effect on the immune system although the evidence is by no means conclusive (Hayes & Laws, 1991). 9.4.12 Metabolic 9.4.12.1 Acid base disturbances No data available 9.4.12.2 Fluid and electrolyte disturbances No data available 9.4.12.3 Others No data available 9.4.13 Allergic reactions No data available 9.4.14 Other clinical effects No data available 9.4.15 Special risks Pregnancy The effect of DDT on reproduction parameters have been summarised by IARC (1991). One human study has suggested that there may be a weak relationship between DDT levels in cord blood and low birth weight. Studies in rodents and rabbits have not demonstrated any teratogenic potential, but exposure of rodents to DDT impaired reproductive function (e.g., spermatogenesis, neonatal survival) in some studies.  Breast feeding Concentrations of DDT in the milk of women in various populations have been reported. Values reported from Guatemala (0.48 to 4.07 ppm total DDT, 1970-1974) and early values from the USSR (1.22 to 4.88 ppm total DDT, 1964) were much higher than those of other countries, and yet there was no indication of illness among babies fed such milk (Hayes & Laws, 1991).  Enzyme deficiencies DDT is known to interfere with the metabolism and function of steroid hormones. One such mechanism is by the induction of hepatic microsomal enzymes which results in an increased conversion of oestrogens, androgens, and glucocorticoids to more polar metabolites. Increased urinary excretion of the more polar metabolites is usually compensated for by increased steroid biosynthesis (Gosselin et al., 1984).  Individuals on chronic drug therapy with phenobarbitol and/or phenytoin have increased hepatic microsomal enzyme activity. Watson et al. (1972) suggest that this increased activity accelerates the metabolism of some DDT to DDA by the slow series of dehydrohalogenation reactions. 9.5 Others No data available 9.6 Summary  10. MANAGEMENT 10.1 General principles Management should be directed towards decontamination of the patient especially where hydrocarbon solvents are involved. Care must be taken to minimise further problems, due to aspiration of solvents that may follow spontaneous emesis or treatment. Other solvent effects should also be monitored. The patient should be observed carefully especially for central nervous system effects such as convulsions. Convulsions, hypoxaemia and resultant acidosis are the immediate life-threatening emergencies. Diazepam is the anticonvulsant of choice. Moderate to severely poisoned patients should have intravenous lines and a cardiac monitor in place as DDT also sensitises myocardial tissue.  Affected skin must also be decontaminated. Wash the area well with soap and water.  Oils and fats should not be given. Do not administer adrenaline, other adrenergic amines or stimulants, because of the enhanced myocardial sensitivity induced by DDT these may induce ventricular fibrillation. 10.2 Life supportive procedures and symptomatic treatment Make a proper assessment of airway, breathing, circulation and neurological status of the patient.  Control convulsions with appropriate drug regimen.  Monitor blood pressure and ECG.  Control cardiac dysrhythmias with proper drug regimen (proper means).  Monitor acid-base balance.  Where spontaneous emesis has occurred monitor respiratory functions and watch for signs of pulmonary aspiration. 10.3 Decontamination Oral exposure:  Emesis is contra indicated.  Perform gastric lavage for recent large ingestions.  Administer activated charcoal. If an oro- or naso-gastric tube is in place, administer after lavage through the tube.  If the patient is obtunded, convulsing or comatose, or if the poison involved may induce these conditions rapidly, insert an oro- or naso-gastric tube and lavage after endotracheal intubation.  Inhalation:  Move patient to fresh air and monitor respiratory function.  Eye exposure:  Irrigate exposed eyes with copious amount of water. Remove contact lenses.   Dermal exposure:  Remove and discard contaminated clothing. Wash skin with soap and copious amounts of water. 10.4 Enhanced Elimination Elimination techniques such as dialysis, diuresis and haemoperfusion have not been shown to be effective due to extensive tissue binding and large volume of distribution. 10.5 Antidote treatment 10.5.1 Adults No specific antidote is available. 10.5.2 Children No specific antidote is available. 10.6 Management discussion As body stores diminish, the elimination half-life of DDT for the remaining store increases dramatically. This is probably due to complex lipoprotein binding, wherein different bound forms exhibit different association characteristics. This requires further research and clarification in order to understand the mechanism sufficiently to be able to successfully mobilise DDT from adipose tissue.  11. ILLUSTRATIVE CASES 11.1 Case reports from the literature Oral (food contamination), male, adults  In three men who ate pancakes made with DDT and who ingested 5 to 6 g each, slight jaundice appeared after 4 to 5 days and lasted 3 to 4 days (Hayes & Laws, 1991).  Oral, child  A 2-year-old child drank an unknown quantity of flyspray, which 5% was DDT, but the nature of the other active ingredients or the solvent was unknown. About one hour after taking the material, the child became unconscious and had a generalised, sustained convulsion. Convulsions were present when the child was hospitalised 2 hours post-ingestion, and these were controlled by barbiturates and other sedatives. Convulsions re-occurred on Day 4, and again on Day 21, but responded to treatment. On day 12, it was noted that the patient was deaf. Hearing began to improve about Day 24 and was normal, as were other neurological findings, when the patient was seen at 2.5 months after the accident (Hayes & Laws, 1991).  12. ADDITIONAL INFORMATION 12.1 Specific preventive measures It is essential that persons intending to use DDT be provided with adequate health precautions and other safety instructions prior to usage. This information should be provided by the manufacturer in the form of either an information leaflet or on a label attached to the DDT container.  Protective clothing is important. Protective measures may include wearing a long-sleeved shirt, long trousers or overalls, and a hat of some sort. Respiratory protection should be considered. The label should give these details.  Clothing worn during spraying should be washed daily after use. Contaminated clothing should be washed separately from the general wash to avoid cross-contamination. When working with liquids, there is often a danger of a splash in the eyes. This may damage the eyes. Simple goggles or a face shield will protect against this. Eye protection is most important if wearing contact lenses, because DDT may get in behind the lenses. They must be removed before the eyes are washed.  Greater precautions are necessary when mixing the concentrated material than when spraying. Measurements should be accurate and spillages should be cleaned up promptly. Mix the chemical carefully using a stick or paddle. Ensure there is minimal skin exposure by he use of gloves. If any concentrate is spilled on the skin, wash it off as soon as possible.  The hazards of spraying increase dramatically on a windy day, as there is an increased risk of inhaling spray drift or contaminating the skin.  Always wash hands before eating, drinking, or smoking. After spraying, shower and change clothing.  By preference, DDT should be stored in a locked shed, safely out of reach of children and animals. DDT should also be kept away from work areas and separate from other stored materials such as animal foods. Always leave DDT in its original containers, or if it must be transferred to another container ensure that this is one not normally used for food or drink. This secondary container should be well labelled and of a variety that is not likely to leak.  Empty containers must be disposed of carefully, so as to ensure that rivers, streams, and other water sources are not polluted, and that unsuspecting people or animals are not exposed to residues of concentrate. Crushing or burning, followed by burial, is generally the best method. 12.2 Other No data available  13. REFERENCES ACGIH (1981) Documentation of the Threshold limit value, 4th Ed, American Conference of Governmental Industrial Hygienists, Cincinnati, Ohio.  Baselt RC (1982) Disposition of Toxic Drugs and Chemicals in Man pp. 220-222, 2nd Edition. Biomedical Publications, Davis, California, USA.  Budavari S, O'Neil MJ, Smith A & Heckleman PE (1989) The Merck Index: An encyclopedia of chemicals, drugs and biologicals. 446pp 11th ed. Merck & CO., Inc, Rahway, N.J., USA.  Chris (1985) Chris hazardous chemical data. US Department of Transportation, US Coast Guard, Washington, DC,.  Dot (1987) US Department of Transportation 1987 Emergency Response Guide Book. Office of Hazardous Materials Transportation. Research and Special Programs Administration, Washington DC, Guide Number 55.  Dreisbach RH & Robertson WO (1987) Handbook of Poisoning: Prevention, Diagnosis & Treatment. Appleton & Lange, Connecticut, 99-100 pp.  EPA (1982) Manual of analytical methods for the analysis of pesticide residues in human and environmental samples.  EPA (1982) Management of Pesticide Poisoning.  Gosselin RE, Smith RP & Hodge HC (1984) Clinical toxicology of commercial products, Williams & Wilkins, Baltimore 134-136 pp.  Grant WM (ed) (1986) Toxicology of the eye, pp. 305-306, 3rd edition. Charles C Thomas, Springfield, Illinois, USA.  Hayes WJ (Jr) & Laws ER (Jr) (eds) (1991) Handbook of pesticide toxicology, Academic Press, Inc. 743-780 pp.  Hsieh HC (1954) DDT intoxication in a family of southern Taiwan. Arch. Ind. Hyg. Occup. Med. 10:3 44-346.  IARC (1991) IARC Monograph: Occupational Exposures in Insecticide Application and Some Pesticides. Vol. 53 179-248 pp.  IARC (1987) IARC Monographs: An updating of IARC Monographs Vol. 2 to 42 Supplement 7 440 pp.  Jaga K & Brosius D (1999) Pesticide exposure: human cancers on the horizon. Reviews on Environmental Health. 14(1):39-50  Klaassen CC, Amdur MO & Doull J (eds) (1986) Casarett & Doull's Toxicology: The basic science of poisons. 3rd ed. Macmillan Publishing Co., New York, pp. 543-549.  Moffat AC (ed) (1986) Clarke's Isolation and Identification of Drugs. 2nd Edition The Pharmaceutical Press, London, pp. 143.  OSHA (1989) Department of Labour, Occupational Safety and Health Administration: 29 CFR Part 1910; Air contaminants; final rule. Federal register 54(12):2332-2983.  Parmeggiani L. (ed) (1983) Encyclopedia of Occupational Health and Safety. 592-593 pp Vol. 1, 3rd (revised) edition. International Labour Office, Geneva.  Reingold I & Lasky II (1947) Acute fatal poisoning following ingestion of a solution of DDT. Ann. Intern. Med. 26:945-947.  Reynolds JEF (ed) (1989) Martindale: The Extra Pharmacopoeia 29th ed, Pharmaceutical Press, London, 1347-1348 pp.  Watson M, Gabica J & Benson WW (1972) Serum organochlorine pesticides in mentally retarded patients on differing drug regimens. Clin. Pharmacol. Ther 13:186-192.  WHO (1979) DDT and its derivatives. Environmental Health Criteria 9. WHO, Geneva.  WHO (1984) Guidelines for drinking water quality Vol. 2 Health Criteria and other Supporting Information 335 pp.  WHO (1989) DDT and its derivatives - environmental aspects. Environmental Health Criteria 83. WHO, Geneva 12 pp.  WHO (1995) Pesticide residues in food-1994. Report of the Joint meeting of the FAO Panel of Experts on Pesticide Residues in Food and the Environment and a WHO Expert Group on Pesticide Residues. FAO Plant Production and Protection paper, 127, 1995.   Woodward G, Nelson AA & Calvery HO (1944) Acute and sub-acute toxicity of DDT (2,2-bis(p-chlorophenyl)-1,1,1-trichloroethane) to laboratory animals. J. Pharmacol. Exp. Ther. 82:152-158.  Worthing CR & Walker SB (eds) (1987) The pesticide manual: A World Compendium 8th ed. The British Crop Protection Council 231-232 pp.  14. AUTHOR(S), REVIEWER(S), DATE (INCLUDING EACH UP-DATE), COMPLETE ADDRESSES Author:  Dr Nida Besbelli Poison Centre Refik Saydam Hygiene Institute Cemal Gürsel Cad. No. 18 Sihhiye 06100 Ankara Turkey  Prepared: February 1990  Reviewers:  Dr Wayne A. Temple National Toxicology Group University of Otago Medical School  Dr Nerida A. Smith Pharmacy School University of Otago Medical School  P.O. Box 913 Dunedin, New Zealand Telephone 64 3 4797244 Facsimile 64 3 4770509  Reviewed: August 1992  Updated and Peer Reviewed, Sao Paulo INTOX-11, October 21,1999.  Drs W. Temple, New Zealand- co-ordinator; B. Groszek, Poland; J. de Kom, Surinam; J.C. Rios Bustamante, Chile; J.C. Piola, Argentina.