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Aldrin 1. NAME 1.1 Substance 1.2 Group 1.3 Synonyms 1.4 Identification numbers 1.4.1 CAS number 1.4.2 Other numbers 1.5 Main brand names/main trade names 1.6 Main manufacturers/main importers 2. SUMMARY 2.1 Main risks and target organs 2.2 Summary of clinical effects 2.3 Diagnosis 2.4 First-aid measures and management principles 3. PHYSICO-CHEMICAL PROPERTIES 3.1 Origin of the substance 3.2 Chemical structure 3.3 Physical properties 3.3.1 Colour 3.3.2 State/from 3.3.3 Description 3.4 Hazardous characteristics 4. USES 4.1 Uses 4.1.1 Uses 4.1.2 Description 4.2 High risk circumstance of poisoning 4.3 Occupationally exposed populations 5. ROUTES OF ENTRY 5.1 Oral 5.2 Inhalation 5.3 Dermal 5.4 Eye 5.5 Parenteral 5.6 Others 6. KINETICS 6.1 Absorption by route of exposure 6.2 Distribution by route of exposure 6.3 Biological half-life by route of exposure 6.4 Metabolism 6.5 Elimination and excretion 7. TOXICOLOGY 7.1 Mode of action 7.2 Toxicity 7.2.1 Human data 7.2.1.1 Adults 7.2.1.2 Children 7.2.2 Relevant animal data 7.2.3 Relevant in vitro data 7.2.4 Workplace standards 7.2.5 Acceptable daily intake (ADI) 7.3 Carcinogenicity 7.4 Teratogenicity 7.5 Mutagenicity 7.6 Interactions 8. TOXICOLOGICAL ANALYSIS AND BIOMEDICAL INVESTIGATIONS 8.1 Material sampling plan 8.1.1 Sampling and specimen collection 8.1.1.1 Toxicological analyses 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 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) 8.2.2.2 Advanced qualitative confirmation test(s) 8.2.2.3 Simple quantitative method(s) 8.2.2.4 Advanced quantitative method(s) 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 8.3.1.2 Urine 8.3.1.3 Other fluids 8.3.2 Arterial blood gas analyses 8.3.3 Haematological 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 9. CLINICAL EFFECTS 9.1 Acute poisoning 9.1.1 Ingestion 9.1.2 Inhalation 9.1.3 Skin exposure 9.1.4 Eye contact 9.1.5 Parenteral exposure 9.1.6 Other 9.2 Chronic poisoning 9.2.1 Ingestion 9.2.2 Inhalation 9.2.3 Skin exposure 9.2.4 Eye contact 9.2.5 Parenteral exposure 9.2.6 Other 9.3 Course, prognosis, cause of death 9.4 Systematic description of clinical effects 9.4.1 Cardiovascular 9.4.2 Respiratory 9.4.3 Neurological 9.4.3.1 Central Nervous System (CNS) 9.4.3.2 Peripheral nervous system 9.4.3.3 Autonomic nervous system 9.4.3.4 Skeletal and smooth muscle 9.4.4 Gastrointestinal 9.4.5 Hepatic 9.4.6 Urinary 9.4.6.1 Renal 9.4.6.2 Other 9.4.7 Endocrine and reproductive systems 9.4.8 Dermatological 9.4.9 Eye, ears, nose, throat: local effects 9.4.10 Haematological 9.4.11 Immunological 9.4.12 Metabolic 9.4.12.1 Acid-base disturbance 9.4.12.2 Fluid and electrolyte disturbance 9.4.12.3 Others 9.4.13 Allergic reactions 9.4.14 Other clinical effects 9.4.15 Special risks 9.5 Other 9.6 Summary 10. MANAGEMENT 10.1 General principles 10.2 Life support procedures and symptomatic/specific treatment 10.3 Decontamination 10.4 Enhanced elimination 10.5 Antidote treatment 10.5.1 Adults 10.5.2 Children 10.6 Management discussion 11. ILLUSTRATIVE CASES 11.1 Case reports from literature 12. ADDITIONAL INFORMATION 12.1 Specific preventive measures 12.2 Other 13. REFERENCES 14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES) ALDRIN International Programme on Chemical Safety Poisons Information Monograph 573 Chemical 1. NAME 1.1 Substance Aldrin 1.2 Group Diene-organochlorine or chlorinated 'cyclodiene' insecticide 1.3 Synonyms Common names: Aldrin; Aldrine; HHDN; Compound 118; Octalene; OMS 194. Chemical names: Hexachloro-hexahydro-endo-exo-dimethanonaphthalene; 1,2,3,4,10,10-hexachloro-1,4,4a,5,8,8a-hexahydro-1,4:5,8dimethanonapthalene 1.4 Identification numbers 1.4.1 CAS number 309-00-2 1.4.2 Other numbers NIOSH RTECS: EPA hazardous waste: OHM/TADS: DOT/UN/NA/IMCO: HSDB (1992): NCI: 1.5 IO2100000 P004 7215090 IMO6.1NA2762 199 C00044 Main brand names/main trade names Aldrex; Altox; Drinox; Octalene; Toxadrin 1.6 Main manufacturers/main importers 1948-1974: 1954-1990: 2. J Hyman & Co., Denver, CO, USA Shell Chemical Corporation, Pernis, The Netherlands SUMMARY 2.1 Main risks and target organs The CNS seems to be the primary site with resultant seizures. Toxic exposures produce tremors, giddiness, hyperexcitability, seizures, and coma. Few case reports of fatalities exist. Poisoning occurs mainly through absorption through the skin. Epidemiological studies do not show any carcinogenic risk. 2.2 Summary of clinical effects Absorption can occur by inhalational, dermal, and gastrointestinal routes. Clinical toxicity from aldrin actually is due to its rapid metabolism in the body to dieldrin. Symptoms reflect CNS toxicity due to GABA neurotransmission inhibition: headache, tremors, giddiness, hyperexcitability, seizures and coma. Most deaths are intentional or accidental exposures to concentrated amounts. Aldrin is used in various formulations which include emulsifiable concentrates, wettable powders, granules, dusts and solutions in hydrocarbon liquids (deJong, 1991). 2.3 Diagnosis The diagnosis is based on the history of exposure (dermal, inhalational or gastrointestinal) and signs of CNS hyperexcitability including seizures. Blood levels of dieldrin (as aldrin is rapidly metabolized to dieldrin) help confirm the exposure (to aldrin or dieldrin) where available, although treatment will be determined by clinical status. Background levels of dieldrin in the general population is in the order of 1 ng/mL. 2.4 First-aid measures and management principles Skin decontamination should occur when dermal absorption is suspected, along with protection of healthcare workers. Because of the potential for seizures, do not induce vomiting. Gastric lavage can be performed after adequate airway protection, in cases where large amounts (greater than 1 mg/kg) of concentrated product has been ingested and the patient presents early. Standard supportive care is recommended in severe cases. 3. PHYSICO-CHEMICAL PROPERTIES 3.1 Origin of the substance Manufactured by the Diels-Alder condensation of hexachlorocyclopentadiene with bicyclo[2.2.1]-2,5-heptadiene. 3.2 Chemical structure C12H8Cl6 MW: 3.3 364.91 Physical properties 3.3.1 Colour Pure aldrin is a white crystalline solid. Technical grade aldrin is tan in colour. 3.3.2 State/from Crystalline solid. 3.3.3 Description Aldrin has a mild chemical odor, and is very soluble in most organic solvents (aromatics, esters, ketones, paraffins, halogenated solvents). Density: 1.7 g/L at 20°C Conversion factor: 1 ppm = 14.96 mg/m3 at 25°C, 1 atm (ATSDR, 1993) 3.4 Hazardous characteristics Melting point: 104°C (pure), 40 to 60°C (technical grade) Boiling point: 145°C Impurities of aldrin include octachlorocyclopentene (0.4%), hexachloro-butadiene (0.5%), toluene (0.6%), a complex mixture of compounds formed by polymerization during the aldrin reaction (3.7%) and carbonyl compounds (2%) (FAO/WHO, 1968). 4. USES 4.1 Uses 4.1.1 Uses 4.1.2 Description Aldrin is a very effective soil insecticide and has been used to treat seed also. It has been used to control termites, corn rootworms, seed corn beetle, seed corn maggot, wireworms, rice water weevil, grasshoppers, and Japanese beetles. It also is used, in an emulsifiable concentrate or wettable powder, to protect wooden structures from termite destruction both pre- and post-construction in building exteriors. It is also used to coat and protect rice. Additional use includes soil treatment for non-food crops (de Jong, 1991). 4.2 High risk circumstance of poisoning In countries where aldrin is used for treating crops and grain, severe acute poisoning (accidental or intentional) may occur. Higher rates of exposure may occur in homes treated with aldrin for termite control. Air concentrations of dieldrin were elevated in home interior areas (Dobbs & Williams, 1983). However, the concentration that was measured (0.3 to 75 mg/m3 ) in crawl spaces and in slab houses during application was less than most threshold limit values, time weighted average (Marlow et al., 1982). This seems to imply that workers may not be seriously exposed as long as they are wearing appropriate equipment; household members may get low level, long term exposure contributing to their overall body burden. In public buildings contamination may occur, and in one school building hard surfaces and carpets had the highest concentrations of aldrin (Calder et al., 1993). Persons living near hazardous waste sites may potentially be exposed to dieldrin (as aldrin would be expected to decompose to dieldrin) from contamination of water supplies. In one community built over contaminated soil, Acceptable Dietary Intake (ADI) limits were exceeded (Van Wijnen & Stijkel, 1988). 4.3 Occupationally exposed populations Since aldrin is no longer manufactured, production workers are currently not exposed. However, aldrin is still used in certain countries and pest control operators and field workers may have significant exposures. Hazardous waste site clean-up workers potentially may be exposed (ATSDR, 1993). 5. ROUTES OF ENTRY 5.1 Oral Aldrin is readily absorbed after ingestion. 5.2 Inhalation Aldrin vapor is absorbed by inhalation. 5.3 Dermal Aldrin is readily absorbed after dermal contact, and is variable depending on the type of solvent used. 5.4 Eye No data available. 5.5 Parenteral No data available. 5.6 Others Not applicable. 6. KINETICS 6.1 Absorption by route of exposure Skin absorption rate not available (ATSDR, 1993). Gastrointestinal absorption rate not available. Respiratory absorption occurs; expiratory aldrin concentrations are decreased compared to inspired concentrations. However, dieldrin blood concentrations remained below 1 ng/L (de Jong, 1991; Bragt et al., 1984; Beyermann & Eckrich, 1973). 6.2 Distribution by route of exposure Oral Aldrin is rapidly converted to dieldrin primarily in the liver. Consequently little aldrin is found in the blood or tissues. Dieldrin is found in a ratio of 156:1 (adipose:blood) in the body (Hunter & Robinson, 1967). Autopsy cases show dieldrin levels in brain (0.0061 mg/kg white matter, 0.0047 mg/kg grey matter), liver (0.03 mg/kg) and adipose tissue (0.13 to 0.36 mg/kg) (Adeshina & Todd, 1990; Ahmad et al., 1988; Holt et al., 1986; DeVlieger et al., 1968). 6.3 Biological half-life by route of exposure After chronic, oral human exposure, blood dieldrin concentration decreases exponentially following first order kinetics with an estimated half-life of 369 days (Hunter et al., 1969). No information is available for other routes of exposure. 6.4 Metabolism Aldrin is quickly metabolized to dieldrin, mediated by the mixed-function mono-oxygenases. Liver tissue has the largest activity but several other organs such as the lung and skin also have this enzymatic process. Dieldrin is then metabolized at a much slower rate to hydrophilic metabolites (de Jong, 1991; ATSDR, 1993). 6.5 Elimination and excretion Elimination occurs primarily through the feces via the bile. 9-Hydroxydieldrin seems to be the major metabolite excreted. Dieldrin is also excreted in breast milk (ATSDR, 1993; Richardson & Robinson, 1971). Small amounts (3 to 8%) of dieldrin metabolites are excreted in the urine after either topical or intravenous administration (Feldman & Maibach, 1974). Dieldrin metabolites may also be found in the urine after ingestion. 7. TOXICOLOGY 7.1 Mode of action Aldrin and dieldrin may have several modes of action. First, it may increase pre-synaptic neurotransmitter release. In addition, aldrin and dieldrin may inhibit GABA (gamma aminobutyric acid) mediated neuroinhibition (ATSDR, 1993; Obata et al., 1988; Gant et al., 1987; Abalis et al., 1986; Cole & Casida, 1986; Bloomquist et al., 1986; Bloomquist & Soderlund, 1985; Lawrence & Casida, 1984). 7.2 Toxicity 7.2.1 Human data 7.2.1.1 Adults An acute convulsive episode may occur without, or with minor, development of warning symptoms when the dieldrin blood concentration reaches 200 µg/L or higher. Repetitive, small dose exposures to aldrin may cause dieldrin to accumulate and cause symptoms of intoxication (de Jong, 1991). Concentrations of dieldrin in the blood correlate with toxicity. Asymptomatic people had concentrations in the blood ranging from 0.5 to 2 µg/L (IPCS, 1989a). Blood levels greater than 105 µg/L are needed to develop toxicity; this corresponds to a daily intake of 0.02 mg dieldrin/kg/day (IPCS, 1989a). Dieldrin concentrations in adipose tissue range from 0.1 to 0.3 mg dieldrin per kg body fat (IPCS, 1989a) Exposure may occur through only one route or through a combination of dermal, inhalational or gastrointestinal absorption (de Jong, 1991). Acute ingestion of 25.6 mg/kg with resulting severe toxicity has been reported with survival (Smith, 1991). 7.2.1.2 Children There have been few cases of aldrin toxicity (accidental) in children with resulting signs of CNS stimulation similar to adults. Death has occurred after acute ingestion of 8.2 mg/kg (Smith,1991). Theoretically the very young are at risk because of their smaller rates of glucoronide conjugation and subsequent excretion (Calabrese, 1978). The fetus concentrates dieldrin, and the possibility of contaminated breast milk consumption increase the risk of CNS effects in the very young (IPCS, 1989a; Polishuk et al., 1977). However, based on average breast milk dieldrin concentrations (up to 6 µ/L) and a child drinking approximately 150 mL milk/kg body weight, the estimated daily intake would be 0.15 to 0.9 µg dieldrin/kg body weight (IPCS, 1989a). Other estimates place this estimated daily intake at 0.65 to 0.70 µg/day for the first four months of breast feeding (Acker et al., 1984). Because of these small levels, the presence of dieldrin in the blood is considered clinically insignificant. 7.2.2 Relevant animal data Oral LD50 (rats) is 39 to 64 mg/kg (Gaines, 1960; Treon et al., 1952). Chronic exposure for six weeks showed an increase in rat mortality at doses of 8 mg/kg/day (NCI, 1978). Inhalation exposure to aldrin in several species resulted in death in at least some of each species at levels greater than 108 mg/m3 (Treon et al., 1957). Single dermal applications (in xylene) produce death in 50% of animals given 98 mg/kg/day (Gaines, 1960). Oral administration of aldrin to rats causes convulsions like in humans, at doses of 10 mg/kg/day (Mehrotra et al., 1989). 7.2.3 Relevant in vitro data Aldrin (1 to 1000 µmol/L) induced unscheduled DNA synthesis in SV-40 transformed human fibroblast cells (VA-4) both in the presence and absence of rat liver microsomes (Ahmed et al., 1977; Zelle & Lohman, 1977). The DNA breakage rates in an Escherichia coli plasmid after treatment with aldrin or dieldrin did not differ from those in untreated plasmid DNA, suggesting that, at least in these studies, the compounds did not interact directly with DNA (Griffin & Hill, 1978). The effects of aldrin and dieldrin (both at 100 µg/mL) on the uptake of tritiated thymidine by cultured rat thymocytes and human lymphocytes were tested under different experimental conditions. Both compounds appeared to have marginal effects on thymidine uptake, suggesting inhibition of DNA synthesis (Rocchi et al., 1980). Aldrin (100 mmol/L) and dieldrin (500 mmol/L) did not induce unscheduled DNA synthesis in primary cultures of Fischer 344 rat hepatocytes (Probst et al., 1981). Williams (1982) reported the results of the hepatocyte primary culture/DNA repair test, using freshly isolated hepatocytes of high metabolic capability to monitor the production of DNA damage by measuring DNA repair synthesis. Aldrin and dieldrin gave equivocal results concerning DNA repair, but there was no damage to DNA. Aldrin (0.3 to 3 mmol/L) induced DNA strand breaks in an alkaline elution/rat hepatocyte assay (Sina et al., 1983). Both aldrin and dieldrin inhibited gap junctional intercellular communication between 6-thioguanine-sensitive and 6-thioguanine-resistant human teratocarcinoma cells in culture (Zhong-Xiang et al., 1986). 7.2.4 Workplace standards Argentina Max. permiss. conc. TWA STEL 0.25 mg/m3 0.75 mg/m3 Australia TLV-TWA 0.25 mg/m3 Belgium TLV-TWA 0.25 mg/m3 Finland Max. permis. conc. TWA STEL 0.25 mg/m3 0.75 mg/m3 Germany Max. work-site conc.(MAK) TWA STEL (30 min) 0.25 mg/m3 2.5 mg/m3 Netherlands Max. limit TWA 0.25 mg/m3 Poland Max. permis. conc. CLV 0.01 mg/m3 Romania Max. permis. conc. TWA Ceiling value (CLV) 0.20 mg/m3 0.25 mg/m3 Switzerland MAK-TWA 0.25 mg/m3 Thailand Max. permiss. conc. 0.25 mg/m3 UK (recommended) TWA STEL (10 min) 0.25 mg/m3 0.75 mg/m3 USA OSHA PEL-TWA (skin) 0.25 mg/m3(OSHA, 1989) ACGIH TLV-TWA (skin) NIOSH REL-TWA (skin) 0.25 mg/m3(ACGIH, 1993) 0.25 mg/m3(NIOSH, 1992) USSR MAC-CLV 0.01 mg/m3 Yugoslavia MAC-TWA 0.25 mg/m3 (IPCS, 1989b) 7.2.5 Acceptable daily intake (ADI) WHO (diet) WHO (water) 7.3 0.1 µg/kg (IPCS, 1989a) 0.03 mg/L recommended (IPCS, 1989b) Carcinogenicity No increased incidence of malignant neoplasms has been found in several studies (de Jong, 1991; Ribbens, 1985; Van Raalte, 1977). In animal assays however, an increased incidence of hepatic tumors including hepatocellular adenomas was found (Davis & Fitzhugh, 1962; NCI, 1978). The data does not allow any conclusions to be made concerning an increased risk of cancer development with aldrin or dieldrin (IARC, 1974a; IARC, 1974b). 7.4 Teratogenicity No human studies were identified. In animals an increase in fetal mortality, increased incidence of cleft palate and webbed foot and a decreased postnatal survival have been reported (Ottolenghi et al., 1974; Virgo & Bellward, 1975; Treon et al., 1954). 7.5 Mutagenicity Increased sister chromatid exchanges and exchange-type chromosome aberrations were noted in floriculturists after exposure to several pesticides including aldrin (Dulout et al., 1985). 7.6 Interactions Possible additive effects with other organochlorine pesticides have been postulated (ATSDR, 1993). 8. TOXICOLOGICAL ANALYSIS AND BIOMEDICAL INVESTIGATIONS 8.1 Material sampling plan 8.1.1 Sampling and specimen collection 8.1.1.1 Toxicological analyses 8.1.1.2 Biomedical analyses 8.1.1.3 Arterial blood gas analysis 8.1.2 8.1.3 8.2 Haematological analyses 8.1.1.5 Other (unspecified) analyses Storage of laboratory samples and specimens 8.1.2.1 Toxicological analyses 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 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 Toxicological Analyses and Their Interpretation 8.2.1 8.2.2 8.2.3 8.3 8.1.1.4 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) Tests for biological specimens 8.2.2.1 Simple qualitative test(s) 8.2.2.2 Advanced qualitative confirmation test(s) 8.2.2.3 Simple quantitative method(s) 8.2.2.4 Advanced quantitative method(s) 8.2.2.5 Other dedicated method(s) Interpretation of toxicological analyses Biomedical investigations and their interpretation 8.3.1 Biochemical analysis 8.3.1.1 Blood, plasma or serum 8.3.1.2 Urine 8.3.1.3 Other fluids 8.3.2 Arterial blood gas analyses 8.3.3 Haematological 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 Sample collection Blood collection for aldrin and dieldrin levels may be done. However, aldrin may not be found as it is metabolized quickly to dieldrin. Keep containers and any remaining product for further identification. Typically collect 1 to 5 mL of serum (preferred) or whole blood in an anticoagulant free evacuated tube, which has an uncoated interior. Biomedical analysis Measurement of aldrin and dieldrin levels may be done. However, aldrin may not be found as it is metabolized quickly to dieldrin. Another problem is that few laboratories are capable of determining dieldrin levels. Remember that management is not dependent on levels and is supportive and symptomatic. 9. CLINICAL EFFECTS 9.1 Acute poisoning 9.1.1 Ingestion Case reports describe the onset of symptoms within 15 minutes after oral exposure (Garrettson & Curley, 1969; Spiotta, 1951; Black, 1974). Central nervous system hyperirritability is the most common manifestation attributable to aldrin. Symptoms may include headache, dizziness, hyperirritability, malaise, nausea and vomiting, anorexia, muscle twitching, and myclonic jerking prior to the development of seizures (Jager, 1970). Seizures may be prolonged and signs of hyperirritability may last several days (Spiotta, 1951; Black, 1974). Renal dysfunction followed an acute ingestion of aldrin. This resulted in an elevated blood urea nitrogen, gross hematuria, and albuminuria (Spiotta, 1951). 9.1.2 Inhalation This route of exposure usually occurs in workers manufacturing or spraying the insecticide. However, no acute poisoning cases were identified by this exposure route. Most of these cases probably represent multiple subacute and asymptomatic exposures with a sudden unexpected seizure episode being the first clinical effect (see chronic poisoning below). 9.1.3 Skin exposure This route of exposure is difficult to separate from inhalation, and both may be occurring simultaneously (ATSDR, 1993) Like inhalation exposures, dermal absorption primarily occurs in workers. If the exposure is severe one would expect a progression of symptoms similar to oral exposure. However, many exposures in workers involve multiple subacute contacts which remain asymptomatic until a seizure was the first observed clinical effect. 9.1.4 Eye contact No data available. 9.1.5 Parenteral exposure No data available. 9.1.6 Other No data available. 9.2 Chronic poisoning 9.2.1 Ingestion No neurological, hepatic or hematological effects are noted in humans at levels under 0.003 mg/kg/day (Hunter & Robinson, 1967). 9.2.2 Inhalation Convulsions may appear suddenly and without early signs and may be due to the accumulation of aldrin (and its metabolite dieldrin) over several days (Jager, 1970). Hemolytic anemia (dieldrin) and aplastic anemia (aldrin) has been described after prolonged exposure (Muirhead et al., 1959; Pick et al., 1965; de Jong, 1991). 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 After an acute ingestion (or possibly through dermal or inhalational methods) signs of CNS hyperirritability develop as soon as 15 minutes after exposure. Seizures soon follow and may last for several hours before being controlled with medication. Motor hyperexcitabiltiy and restlessness may persist for several days. The course may be mild or severe depending on the amount ingested and any efforts to limit absorption. The outcome may be fatal if complications from seizures develop. Survivors recover completely; irreversible effects have not been described in humans (IPCS, 1989a). 9.4 Systematic description of clinical effects 9.4.1 Cardiovascular No specific cardiovascular toxicity effect has been described. Blood pressure fluctuations and tachycardia have been described after overdose, but these occurred in the presence of (and presumably due to) CNS excitation and seizures (Spiotta, 1951; Black, 1974). 9.4.2 Respiratory No data available. 9.4.3 Neurological 9.4.3.1 Central Nervous System (CNS) Central nervous system excitation is the primary adverse effect seen in humans. Convulsions can occur suddenly after a massive ingestion or after multiple, subacute exposures. Typically a prodrome precedes development of seizures and consists of headache, dizziness, hyperirritability, malaise, nausea and vomiting, and myoclonic twitching (Patel & Rao, 1958; Jager 1970). Persistent effects consisting of motor hyperexcitability and restlessness for several days have been reported (Spiotta, 1951). 9.4.3.2 Peripheral nervous system An increased incidence of PNS diseases was noted in pesticide workers. However this increase was due to a higher incidence of cervicobrachial and lumbosacral syndromes; syndromes associated with manual labor in a plant, not insecticide exposure (de Jong, 1991). 9.4.3.3 Autonomic nervous system No data available. 9.4.3.4 Skeletal and smooth muscle No data available. 9.4.4 Gastrointestinal Nausea, vomiting and anorexia may occur. 9.4.5 Hepatic No data available with aldrin. Few case reports with dieldrin which showed transient transaminase elevation for several days, although the effects of solvents (such as toluene) could not be discounted (Garrettson & Curley, 1969; Black, 1974). 9.4.6 Urinary 9.4.6.1 Renal Only one case report mentions an elevation of blood urea nitrogen, gross hematuria and albuminuria for several days after an acute overdose although causality was not established (Spiotta, 1951). 9.4.6.2 Other None. 9.4.7 Endocrine and reproductive systems Although aldrin levels in blood and placental tissues were higher in women with premature labor or spontaneous abortion than in women with normal deliveries, other organochlorine pesticide levels were also higher and therefore assigning causality to aldrin is not possible. In addition other confounders were not addressed in that study such as smoking or alcohol consumption (Saxena et al., 1980). 9.4.8 Dermatological No evidence of dermatitis was seen in pesticide manufacturing workers (Jager, 1970). 9.4.9 Eye, ears, nose, throat: local effects No data available. 9.4.10 Haematological Normal haematological parameters were noted in pesticide manufacturing workers during at least four years of follow up (Jager, 1970). No increased relative risk in pesticide workers has been noted (de Jong, 1991). However a worker developed haemolytic anaemia after working in an area sprayed with aldrin, although it was not shown to be directly responsible because other chemicals were in use also (Pick et al., 1965). 9.4.11 Immunological Although no data was found on aldrin, dieldrin was associated with the development of immunohaemolytic anaemia after eating contaminated food (Hamilton et al., 1978). 9.4.12 Metabolic 9.4.12.1 Acid-base disturbance May be observed in seizure states. 9.4.12.2 Fluid and electrolyte disturbance 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 There was no increased incidence of malignant neoplasm in pesticide workers (de Jong, 1991). 9.4.15 Special risks Theoretically the very young are at risk because of their smaller rates of glucuronide conjugation and subsequent excretion (Calabrese, 1978). The fetus concentrates dieldrin, and the possibility of contaminated breast milk consumption increase the risk of CNS effects in the very young (IPCS, 1989a; Polishuk et al., 1977). However, based on average breast milk dieldrin concentrations (up to 6 µg/L) and a child drinking approximately 150 mL milk/kg body weight, the estimated daily intake would be 0.15 to 0.9 µg dieldrin/kg body weight (IPCS, 1989a). Other estimates place this estimated daily intake at 0.65 to 0.70 µg/day for the first four months of breast feeding (Acker et al., 1984). Because of these small levels, the presence of dieldrin in the blood is considered clinically insignificant. 9.5 Other No data available. 9.6 Summary 10. MANAGEMENT 10.1 General principles Clinical observation after appropriate decontamination, and symptomatic treatment is usually sufficient. 10.2 Life support procedures and symptomatic/specific treatment Make a proper assessment of airway, breathing, circulation and neurological status of the patient. Maintain a clear airway. Aspirate secretions from airway. Administer oxygen. Perform endotracheal intubation and support ventilation using appropriate mechanical device when necessary. Control convulsions with benzodiazepines or phenobarbital. Open and maintain at least one intravenous route. Perform cardio-respiratory resuscitation when necessary. Monitor vital signs. Correct hypotension as required. Monitor blood pressure and ECG. Monitor fluid and electrolyte balance. Monitor acid-base balance.(de Jong, 1991; Ellenhorn & Barceloux, 1988). 10.3 Decontamination Remove and discard contaminated clothing. Irrigate exposed eyes with copious amounts of water (or saline). Wash skin with copious amounts of water. Emesis is contraindicated. If the patient is obtunded, convulsing or comatose, or since aldrin may induce these conditions rapidly, insert an oro- or a naso-gastric tube and lavage after endotracheal intubation. Administer activated charcoal. If an oro- or naso-gastric tube is in place, administer after lavage through the tube. Administer a cathartic unless already given with activated charcoal. 10.4 Enhanced elimination No data is available as to whether haemodialysis or haemoperfusion are effective. However the large molecular weight and lipophylic nature of aldrin would seem to indicate that haemodialysis would not be effective. Forced diuresis, alkalinization, acidifiction are not effective. 10.5 Antidote treatment 10.5.1 Adults There is no antidote. 10.5.2 Children There is no antidote. 10.6 Management discussion Additional data is needed to identify differences in toxicity from different routes of exposure. Also information on less subtle forms of CNS effects is lacking (ATSDR, 1993). The metabolism of aldrin may include some element of enterohepatic recirculation, although this has not been demonstrated. 11. ILLUSTRATIVE CASES 11.1 Case reports from literature No cases of poisoning with aldrin were identified. The following two cases reflect poisoning with dieldrin which would be expected to be similar to aldrin poisoning. Two siblings aged 2 and 4 years apparently ingested dieldrin (5% solution) and within 15 minutes were noticed to be salivating heavily when generalized convulsions started. By the time a physician arrived the younger child was dead, and the four year old male was treated with mechanical respirator, anticonvulsants (phenobarbital, paraladehyde and phenytoin) and general supportive care. He recovered completely and was discharged (Garettson and Curley, 1969). A 21-year-old male ingested 9 g (120 mg/kg) of dieldrin in a 15% solution with toluene. Within 20 minutes he was frothing at the mouth, cyanotic and semi-conscious. En route to the hospital he lost consciousness and had a grand mal seizure. He was treated with an endotracheal tube, gastric lavage, catharsis (with mannitol), anticonvulsants (diazepam, phenobarbital, phenytoin and muscular paralysis), beta blockers for tachycardia and hypertension and general supportive treatment (Black, 1974). 12. ADDITIONAL INFORMATION 12.1 Specific preventive measures The substance is not produced in most countries to our knowledge, and is banned in many countries.Caution in using this product with appropriate protective gear to prevent absorption (dermal, inhalational, or gastrointestinal) is imperative. Workers should be educated as to the proper handling and use (IPCS, 1989a). Use in the treatment of termite control for buildings as long as it is used appropriately appears safe for the occupants. 12.2 Other Infants and toddlers appear to have higher dietary intake of aldrin (and dieldrin) compared to adults. However, the rates of intake have been decreasing over time as use of aldrin and dieldrin have decreased (Gartell et al., 1986a, 1986b). 13. REFERENCES Abalis IM, Eldefrawi ME, Eldefrawi AT (1986). Effects of insecticides on GABA-induced chloride influx into rat brain microsacs. J Toxicol Environ Health, 18: 13-23. ACGIH (1993). Threshold limit values and biological exposure indices for 1993-1994. American Conference of Governmental Industrial Hygenists, Cincinnati, Ohio. Acker L, Barke E, Hapke HJ, et al. (1984). [Residues and impurities in breast milk.] Milchwissenschaft, 39(9): 541-544 (in German). Adeshina F & Todd EL (1990). Organochlorine compounds in human adipose tissue from north Texas. J Toxicol Environ Health, 29: 147-156. 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Benitez, M.D. Toxicology Treatment University of Pittsburgh Medical Center Room NE 583, MUH 200 Lothrop Street Pittsburgh, PA 15213 U.S.A. Tel: Fax: 412-257-2142 412-648-6855 Date: September 1995 Peer review: Berlin, Germany, October 1995 Finalized: IPCS, September 1996 Editor: Mrs J. Duménil International Programme on Chemical Safety Date: June 1999 See Also: Toxicological Abbreviations Aldrin (ICSC) Aldrin (FAO Meeting Report PL/1965/10/1) Aldrin (FAO/PL:CP/15) Aldrin (FAO/PL:1967/M/11/1) Aldrin (IARC Summary & Evaluation, Supplement7, 1987) Aldrin (IARC Summary & Evaluation, Volume 5, 1974)