Monograph for UKPID CAMPHOR Sarah McCrea National Poisons Information Service (London Centre) Medical Toxicology Unit Guy's & St Thomas' Hospital Trust Avonley Road London SE14 5ER UK This monograph has been produced by staff of a National Poisons Information Service Centre in the United Kingdom. The work was commissioned and funded by the UK Departments of Health, and was designed as a source of detailed information for use by poisons information centres. Peer review group: Directors of the UK National Poisons Information Service. 1. SUBSTANCE/PRODUCT NAME Camphor last updated: 17 March 1996 1.1 Origin of substance Steam distillation of communited Cinnamomum camphora trees (which should be at least 50 years old) and purification by sublimination. Also found in the plant Lippia dulcis Trev (not a major industrial source) (Compadre et al 1986). Can also be produced synthetically, modern processes start with vinyl chloride and cyclopentadiene to obtain important intermediate dehydronorbornyl chloride. The naturally occurring form is dextrorotatory and the synthetic form optically inactive (Budavari 1989, Reynolds 1993). 1.2 Name 1.2.1 Brand/trade name Balmosa Cream (camphor 4%, menthol 2%, methyl salicylate 4%, capsicum oleoresin 0.035%) (Pharmax Healthcare) Boots Vapour Rub (Boots) Earex (almond oil 33.33%, arachis oil 33.33%, camphor oil 33.33%) (Seton Healthcare) Mentholatum Vapour Rub (camphor 9%, menthol 1.35%, methyl salicylate 0.33%) (Mentholatum) Nasciodine (iodine 1.26%, menthol 0.59%, methyl salicylate 3.87%, turpentine oil 3.87%, camphor 3.87%) Nicobrevin (methyl valerate 100mg, quinine 15mg, camphor 10mg, eucalyptus oil 10mg) (Intercare Products) PR Heat Spray (camphor 0.62%, methyl salicylate 1.24%, ethyl nicotinate 1.1%) (Crookes Healthcare) Radian-B (liniment and spray: menthol 1.4%, camphor 0.6%, ammonium salicylate 1%, salicylic acid 0.54%. rub: menthol 2.54%, camphor 1.43%, methyl salicylate 0.42%, capsicin 0.042%. cream: camphor 1.43%, menthol 2.54%, methyl salicylate 0.42%, oleoresin capsicum 0.005%) (Roche Consumer Health) Tixylix inhalant (camphor 60mg, menthol 25mg, turpentine oil 50mg, eucalyptus oil 20mg) (Intercare Products) Vicks Inhaler (camphor 41.54%, menthol 41.54%, siberian pine needle oil 4.65%) %) (Procter and Gamble) Vicks Sinex (oxymetazoline 0.05%, menthol 0.025%, camphor 0.015%, eucalyptus oil 0.0075%) %) (Procter and Gamble) Vicks Vaporub (menthol 2.82%, camphor 5.46%, eucalyptus oil 1.35%, turpentine oil 4.71%) (Procter and Gamble) Non-proprietary preparations: Camphor Linctus compound (APF): Camphor spirit compound 1ml, glycerol 1.5ml, tolu syrup to 5ml. Camphor Liniment (BP 1973): Camphor 20% w/w in arachis oil (AKA Camph. Lin; Camphorated oil). Camphor Spirit (USP): Camphor 10g, alcohol to 100ml. Camphor Spirit Compound (APF): Camphor 300mg, benzoic acid 500mg, anise oil 0.3ml, alcohol (60%) to 100ml. Concentrated Camphor Water (BP) Camphor 4g, alcohol (90%) 60ml, water to 100ml. 1.2.2 Generic name Camphor 1.2.3 Synonyms 1,7,7-Trimethylbicyclo[2.2.1]heptan-2-one; 2-bornanone; 2-oxobornane; 2-camphanone; 2-keto-1,7,7-trimethyl-norcamphane; 2-keto-1,7,7-trimethylnor-camphane; 1,7,7-trimethylnorcamphor; gum camphor; Japan camphor; Formosa camphor; laurel camphor; camphor-natural, camphor-synthetic; huile de camphre (French); kampfer (German); matricaria camphor; anemone camphor. 1.2.4 Common names/street names 1.3 BNF pharmacotherapeutic group None. 1.4 Reference numbers Camphor CAS 76222 RTECS EX1225000 EINECS 2009450 Camphor-l- CAS 464482 RTECS EX1250000 EINECS 2073547 UN 2717 Camphor (1R, 4R)(+) CAS 464493 RTECS EX1260000 EINECS 2073552 1.5 Manufacturer of camphor containing products Crookes Healthcare, PO Box 57, Central Pk, Lenton Lane, Nottingham, NG7 2LJ. Tel: 0115 950 7431 Fax: 0115 968722 Intercare Products Ltd, 7 The Business Centre, Molly Millars Lane, Wokingham, Berks, RG11 2QZ. Tel: 01734 79345 Fax: 01734 772114 Mentholatum Co Ltd, 1 Redwood Ave, Peel Park Campus, East Kilbride, Glasgow, G74 5PF. Tel: 01355 848484 Fax: 01355 263387 Pharmax Ltd, Bourne Rd, Bexley, Kent, DA5 1NX. Tel: 01322 550550 Fax: 01322 558776. Procter and Gamble (Health and Beauty Care) Ltd, The Heights, Brooklands, Weybridge, Surrey, KT13 0XP. Tel: 01932 896000 Fax: 01932 896200 Roche Consumer Health, P.O Box 8, Broadwater Rd, Welwyn Garden City, Herts, AL7 3AY. Tel: 01707 366000 Fax: 01707 338297 Seton Healthcare Group Plc, Tubiton Hse, Medlock St, Oldham, Lancs, OL1 3HS. Tel: 0161 652 2222 Fax: 0161 626 9090 1.6 Supplier/importer/agent/ licence holder Not relevant 1.7 Presentation 1.7.1 Form 1.7.2 Formulation details 1.7.3 Pack sizes available 1.7.4 Packaging 1.8 Physico-chemical properties Chemical structure C10H16O Physical state Crystalline solid. Colour Colourless or white. Odour Pungent Solubility in water and organic solvents Slightly soluble in water, soluble in alcohol, ether, benzene, acetone, oil of turpentine, glacial acetic acid, chloroform, carbon disulphide, solvent naphtha and fixed and volatile oils. Also soluble in aniline, nitrobenzene, tetralin, decalin, methylhexalin, petroleum ether, higher alcohols, concentrated mineral acids, phenol, liquid ammonia and liquid sulphur dioxide. Autoignition temperature 871°F (466°C) Important chemical interactions Liquefies when triturated with chloral hydrate, menthol, resorcinol, salol, B-napthol, thymol, phenol, urethan (Budavari 1989). Camphor can diffuse through polyethylene (Polythene) (Reynolds 1989). Major products of combustion/pyrolysis Carbon monoxide may be formed Flammability Moderate Boiling point 204°C Density d=0.992 @ 25°C/4°C Relative vapour density 5.24 Flash point 150°F (65.5°C) 1.9 Uses 1.9.1 Indications Camphor acts as a counter-irritant, rubefacient and mild analgesic and is included in liniments for relief of fibrositis, neuralgia and similar conditions. By ingestion camphor has irritant and carminative properties and has been used as a mild expectorant and to relieve griping. Camphor has been used as a circulatory and respiratory stimulant (as a solution in oil given subcutaneously or intramuscularly), this use is considered hazardous. It has been used in combination with menthol and chenodeoxycholic acid to aid dispersal of bile duct stones, although this is no longer recommended (Reynolds 1989). Also used as a plasticizer for cellulose nitrate; chemical intermediate, other explosives and lacquers, insecticides, moth and mildew proofings, tooth powders, flavouring, embalming, pyrotechnics (Saks and Lewis 1987). 1.9.2 Therapeutic doses 1.9.2.1 Adults In the past, when camphor was used medicinally, the oral doses ranged from 120-300mg (Wade 1977). The parenteral dose range was from 60- 200mg (not recommended any more). 1.9.2.2 Children 1.9.3 Contraindications Camphor and camphor containing products should be avoided in children who have a history of febrile convulsions or other predisposing factors for convulsions (Galland et al 1992). 1.9.4 Abuses Abuse of camphor for its stimulant properties has been reported (Koppel et al 1982). Vicks VapoRub and Vicks Sinex have reportedly been used, by inhalation and skin application, by nightclubbers to enhance the effects of MDMA (Rayner 1991). It has been used, historically, to procure abortion (Vasey and Karayannopoulos 1972), and the plant Lippia dulcis Trev., which contains camphor, may still be used for this purpose in South America (Compadre et al 1986). 1.10 Pharmacokinetics 1.10.1 Absorption Camphor is well absorbed after inhalation, ingestion or dermal exposure (Baselt and Cravey 1990). Peak plasma levels reached by 1 hour post-ingestion when 200mg camphor was ingested with a solvent (Tween 80), and 3 hours post-ingestion when taken without a solvent (Koeppel et al 1988). 1.10.2 Distribution Volume of distribution 2-4 L/kg (Koeppel et al 1988). Plasma protein binding has been estimated as 61% (Koppel et al 1982). 1.10.3 Metabolism Hydroxylation in the 3-, 5-, 8-, and 9-position. 5- and 8- (or 9-) hydroxycamphor further oxidised to a ketone and carbonic acid. The carbonic acid VI is conjugated with glucoronic acid (Koppel et al 1982). 1.10.4 Elimination The glucoronide is excreted in the urine, some camphor is excreted unchanged in urine and from the lungs. 1.10.5 Half-life 167 minutes (200mg camphor ingested alone); 93 minutes (200mg camphor ingested with a solvent - Tween 80) (Koppel et al 1988). 1.10.6 Special populations No data available. 1.10.7 Breast milk No data available. It seems likely that camphor will be excreted in breast milk. 1.11 Toxicokinetics 1.11.1 Absorption Peak plasma levels of camphor were reached within an hour of ingestion of an unknown quantity of 10% camphor spirit (10% camphor, 70% isopropanol, 20% water) by an adult female (Koppel et al 1988). 1.11.2 Distribution Camphor crosses the placental barrier. An infant born prematurely to a woman who had ingested 50ml of camphorated oil was healthy, but its mouth and skin smelt of camphor, as did the amniotic fluid (she gave birth within 20 hours of the ingestion) (Weiss and Catalano 1973). Camphor was found in the liver, kidneys and brain of an infant who died within 30 minutes of birth, whose mother had ingested about 12g of camphor 17 hours previously (Riggs et al 1965). 1.11.3 Metabolism Hydroxylation in the 3-, 5-, 8-, and 9-position. 5- and 8- (or 9-) hydroxycamphor further oxidised to a ketone and carbonic acid. The carbonic acid VI is conjugated with glucoronic acid (Koppel et al 1982). 1.11.4 Elimination Six metabolites of camphor were detected in the urine of two men who had ingested 6-10g of camphor (5-hydroxycamphor; 5-ketocamphor; 9-hydroxycamphor; 8-hydroxycamphor; 3-hydroxycamphor; 8 or 9-camphor carbonic acid trimethylsilylester). Camphor was also detected in its unchanged form (Koppel et al 1982). 1.11.5 Half-life No data. 1.11.6 Special populations No data. 1.11.7 Breast milk No data. 2 ADVERSE EFFECTS AND INTERACTIONS Convulsions were reported in a small child following skin exposure to camphor spirit, and recurred a year later on brief inhalation exposure (Skoglund et al 1977). Deafness has been reported in association with camphor (Davies 1985). Ulceration of the mucous membranes has been reported following the use of toothache solutions containing camphor (along with menthol, phenol, clove oil and chloroform) (Davies 1985). 3 SUMMARY 4 EPIDEMIOLOGY OF POISONING Most severe cases are associated with the ingestion of camphorated oil, either deliberately or in mistake for other medication e.g. castor oil. Camphorated oil has now been removed from the market in both the UK and the US (Reynolds, 1993) but may still be present in some households. Abuse of camphor for its stimulant properties has been reported (Koppel et al 1982). A review of 182 cases of camphor ingestion reported to two poisons centres between 1980-1983 found that the 101 cases who ingested less than 2mg/kg remained asymptomatic. 90% of the patients ingesting over 2mg/kg remained asymptomatic, 4% developed minor clinical effects (sleepy but rousable, gagging, crying - mean dose 15mg/kg), and 6% developed major clinical effects (syncope, cyanosis, hypotension, arryhthmias, mental status changes - mean dose 152mg/kg). There were no deaths in this series. The authors also reviewed the literature from 1964 -1983, and found the mean dose ingested by patients with major symptoms to be 124mg/kg, with the mean dose in fatal cases being 199mg/kg (Geller et al 1984). From 1985-1989, 32,362 human exposures to camphor were reported to the American Association of Poison Control Centres (AAPCC). Of these, life-threatening toxicity occurred in 33 children, but there were no paediatric deaths. In 5 of the cases the products contained more than 11% camphor, although products of that strength had been discontinued in 1983, at the request of the FDA. In 14 cases the products involved contained between 10-11% camphor, and in 4 cases 6-10% camphor. Major toxic symptoms were seen in 7 cases where the camphor content of the product ingested was less than 5% (Committee on Drugs 1994). Three of 23 children who had been reported to the Poison Control Centre and Pharmacovigilance Centre of Marseilles as suffering from febrile convulsions had been recently treated with medications containing camphor. The authors also reported the case of two epileptics who developed non-febrile convulsions following dermal use of VicksVaporub. They suggested that camphor and camphor containing products should be avoided in children who had a history of febrile convulsions or other predisposing factors for convulsions (Galland et al 1992). 5 MECHANISM OF ACTION/TOXICITY 5.1 Mechanism Camphor has been described as a counter-irritant, but when applied to the skin of volunteers as a 20% solution in alcohol it produced no significant sensation of irritation or pain at normal skin temperatures. It did appear to have a slight sensitising effect on the perception of temperature change during heating and cooling, and increased the sensation of burning at high temperatures (Green 1990). 5.2 Toxic dose A review of 182 cases of camphor ingestion reported to two poisons centres between 1980-1983 found that the 101 cases who ingested less than 2mg/kg remained asymptomatic. 90% of the patients ingesting over 2mg/kg remained asymptomatic, 4% developed minor symptoms (mean dose 15mg/kg), and 6% developed major symptoms (mean dose 152mg/kg). There were no deaths in this series. The authors also reviewed the literature from 1964-1983, and found the mean dose ingested by patients with major symptoms to be 124mg/kg, with the mean dose in fatal cases being 199mg/kg. They suggested, based on their analysis of these figures, that patients ingesting less than 10mg/kg of camphor and displaying no symptoms required no treatment (Geller et al 1984). Adults have survived ingestions of up to 42g, but usually doses in excess of 2g produce dangerous effects. Fatal doses in children have ranged from 0.7-1.0g (Committee on Drugs 1994). 6 FEATURES OF POISONING 6.1 Acute 6.1.1 Ingestion Most common route of exposure. Nausea, vomiting, convulsions, coma and respiratory depression may occur. 6.1.2 Inhalation Convulsions were reported in a small child following skin exposure to camphor spirit, and recurred a year later on brief inhalation exposure (Skoglund et al 1977). A 3 month old infant became pale, collapsed, stopped breathing and had convulsions immediately after a single inhalation of Vicks Inhaler (40% camphor [sic]) (Bavoux et al 1985). 6.1.3 Dermal Camphor applied to the skin of volunteers as a 20% solution in alcohol produced no significant sensation of irritation or pain at normal skin temperatures (Green 1990). Table 1 Blood levels Dose Author 1.95mg/100ml 7h pi undetectable 21h pi 0.7g (convulsions) Phelan 1976 0.0015mg/100ml 0.5-1g (asymptomatic) Phelan 1976 300 + 400ng/ml (nk time) 6-10g (symptomatic) Koppel et al 1982 ND 3g/kg (24.5) over 6 months Jimenez et al 1983 ND 9g/24h (dermal/symptomatic) Mercier et al 1984 0.3µg/ml (9h pi) 1.5g (symptomatic) Bavoux et al 1985 >2µg/ml NK (symptomatic) Bavoux et al 1985 0.45µg/ml (17h post exposure) 160mg/kg/24h (dermal/symptomatic) Bavoux et al 1985 ND 112mg/18h (symptomatic) Bavoux et al 1985 5.5µg/ml (1h pi) NK Koppel et al 1988 ND 1g (approx) (symptomatic) Gibson et al 1989 ND 1g (19months/death) Smith and Margolis 1954 Present, not measured 12g (symptomatic and baby died) Riggs et al 1965 ND 12g (symptomatic) Ginn et al 1968 ND 30g (symptomatic) Vasey and Karayannopoulos 1972 ND 10g (symptomatic) Weiss and Catalano 1973 ND 0.5g (asymptomatic) Aronow and Spigiel 1976 ND 6g (symptomatic) Aronow and Spigiel 1976 ND 23g (symptomatic) Aronow and Spigiel 1976 ND 12g (symptomatic) Trestrail and Spartz 1977 ND 6-12g (asymptomatic) Trestrail and Spartz 1977 ND 12g (symptomatic) Trestrail and Spartz 1977 ND 6g (symptomatic) Reid 1979 ND 6g (symptomatic) Reid 1979 3.1mg/l (3h pi) 5g (symptomatic) Mascie-Taylor et al 1981 Table showing relationship between blood levels and reported ingested dose of camphor in humans. Note: ND=Not Done; pi=post ingestion; NK=Not Known Convulsions were reported in a small child following skin exposure to camphor spirit, and recurred a year later on brief inhalation exposure (Skoglund et al 1977). A 30 month old child with burns to 45% of body surface area developed vomiting, drowsiness, coma and convulsions after the application of camphor containing dressings (total dose 9g). The symptoms gradually disappeared after the removal of the dressings (Mercier et al 1984). Convulsions were reported in 4 children who had had burns dressed with camphor-containing gauze (9.6% camphor) for periods of time ranging from 4 hours to 3 weeks, the extent of the burns ranged from 5-50% (all second degree) (Bavoux et al 1985). 6.1.4 Ocular No data. 6.1.5 Other routes Application of Vicks Vaporub (5% camphor) to the nostrils, lips and chin of a 6 month old infant over a 3 day period resulted in 4 apnoeic episodes (2 following generalised convulsions) from 48 hours into the exposure (Bavoux et al 1985). 6.2 Chronic toxicity 6.2.1 Ingestion An illness initially resembling Reye's syndrome with coma and hepatomegaly, resulting in death was described in a 6 month old child who had been chronically administered a home-made remedy containing camphor 29.2 mg/ml in 33.3% alcohol (Jimenez et al 1983). Weakness, fever, anorexia, intense pruritis and weight loss developed in a woman who regularly ingested an ointment containing camphor. On examination, hepatomegaly was found, with granulomas, necrosis and eosinophils apparent on biopsy (McClollam et al 1989). 6.2.2 Inhalation Corneal erosions have been reported in association with the use of inhalant capsules containing camphor (Soen et al 1992). 6.2.3 Dermal No data. 6.2.4 Ocular No data. 6.2.5 Other routes No data. 6.3 Systematic description of clinical effects 6.3.1 Cardiovascular Peripheral circulatory shock has been seen (in association with severe vomiting and dehydration) (Vasey and Karayannopoulos 1972). Tachycardia and hypotension may occur (Koppel et al 1988). An adult female who ingested 12g had a period of asystole (with apnoea) for 30-45 seconds following a convulsion (Riggs et al 1965). 6.3.2 Respiration Respiratory depression (Benz 1919), apnoea (Smith and Margolis 1954) and collapsed lung secondary to aspiration of stomach contents (Kopelman et al 1979) may occur. Respiratory arrest been reported (Aronow and Spigiel 1976). Apnoea has been described in young children following exposure, often in conjunction with convulsions, and in one case from a single inhalation in a 3 month old (Bavoux et al 1985). An adult female who ingested 12g had a period of apnoea (with asystole) for 30-45 seconds following a convulsion (Riggs et al 1965). 6.3.3 Neurological Convulsions (tonic-clonic and grand-mal) are relatively common following exposure to camphor (Benz 1919, Antman et al 1978, Kopelman et al 1979, Koppel et al 1988, Gibson et al 1989). Convulsions, with, on postmortem examination, neuronal death in the hippocampus, cerebral cortex and ischaemic necrosis in the medulla have been reported (Smith and Margolis 1954). Convulsions were reported in a small child following skin exposure to camphor spirit, and recurred a year later on brief inhalation exposure (Skoglund et al 1977). Hyperexciteable emotional state (Antman et al 1978), irritability, confusion, (Phelan 1976, Ginn et al 1968), somatic hallucinations, restlessness (Aronow and Spigiel 1976), anxiety and agitation (Koppel et al 1982) and coma (Kopelman et al 1979) have also been reported. Coma with, on postmortem examination, cerebral oedema, neuronal degeneration and frank necrosis in the hippocampus and frontal cortex was seen in a 6 month old with chronic oral exposure to camphor (Jimenez et al 1983). 6.3.4 Gastrointestinal Increased salivation has been reported (Smith and Margolis 1954). Abdominal pain, nausea, vomiting (Benz 1919, Kopelman et al 1979) and coffee-ground vomiting (Smith and Margolis 1954) may occur. Epigastric pain has been reported (Riggs et al 1965). 6.3.5 Hepatic Liver function test changes suggestive of acute parenchymal liver necrosis have been reported (Trestrail and Spartz 1977). Hepatomegaly with abnormal LFTs and prolonged prothrombin time was seen in a 6 month old child following chronic oral dosing of camphor. On postmortem the liver was swollen, discoloured and friable, with fatty deposits within hepatocytes (Jimenez et al 1983). Hepatomegaly was found, with granulomas, necrosis and eosinophils apparent on biopsy, in a woman who regularly ingested an ointment containing camphor (McClollam et al 1989). Central zonal congestion of the liver was observed on postmortem examination in 19 month old child who had ingested 5ml camphorated oil (Smith and Margolis 1954). 6.3.6 Urinary Changes in renal function, resolving spontaneously may occur (Trestrail and Spartz 1977). Albuminuria has been reported (Smith and Margolis 1954). 6.3.7 Endocrine and reproductive system No data. 6.3.8 Dermatological Camphor applied to the skin of volunteers as a 20% solution in alcohol produced no significant sensation of irritation or pain at normal skin temperatures (Green 1990). 6.3.9 Eye, ears, nose and throat Camphor administered in doses of 60mg-4g was reported to cause flickering, darkening or veiling of vision along with noises in the ears (Grant and Schuman 1993). Corneal erosions have been reported in association with the use of inhalant capsules containing camphor (Soen et al 1992). 6.3.10 Haematological A rise in white blood cell count has been reported in acute poisoning (Koppel et al 1982, Smith and Margolis 1954). 6.3.11 Immunological No Data 6.3.12 Metabolic 6.3.12.1 Acid-base disturbances No Data 6.3.12.2 Fluid and electrolyte disturbances Severe dehydration due to vomiting has been reported (Vasey and Karayannopoulos 1972). 6.3.12.3 Other No Data 6.3.13 Allergic reactions No Data 6.3.14 Other clinical effects The breath, vomitus and urine may smell of camphor following ingestion. The breath, skin and amniotic fluid of a baby born to a woman who ingested 50 ml of camphorated oil smelt of camphor (Weiss and Catalano 1973). 6.4 At risk groups 6.4.1 Elderly No Data 6.4.2 Pregnancy An infant born 36 hours after its mother had ingested 12g of camphorated oil failed to initiate respiration and was declared dead 30 minutes post delivery. Camphor was found in its bloodstream, liver, kidneys and brain (Riggs et al 1965). The breath, skin and amniotic fluid of a baby born to a woman who ingested 50 ml of camphorated oil smelt of camphor (although the child was healthy) (Weiss and Catalano 1973). 6.4.3 Children No data. 6.4.4 Enzyme deficiencies No data. 6.4.5 Enzyme induced No data. 6.4.6 Others No data. 7 MANAGEMENT 7.1 Decontamination As camphor is rapidly adsorbed, gastric decontamination is likely to only be of benefit within 2 hours of ingestion. Ipecac and other emetics are not recommended due to the risk of convulsions. If more than 10mg/kg has been ingested, gastric lavage should be performed (or stomach contents aspirated via a nasogastric tube if a liquid preparation has been ingested). Activated charcoal, 1g/kg body weight (max 50g), should be administered (charcoal in haemoperfusion columns has been shown to adsorb camphor). 7.2 Supportive care Camphor may cause severe vomiting and it is important to ensure adequate hydration. Diazepam should be used to control convulsions. The airway should be protected to prevent aspiration of stomach contents during convulsions. 7.3 Monitoring The liver function, renal function and hydration status of the patient should be monitored. 7.4 Antidotes None. 7.5 Elimination techniques Charcoal haemoperfusion, amberlite haemoperfusion and lipid dialysis have all been shown to remove camphor from the serum (Mascie-Taylor et al 1981, Koppel et al 1988, Kopelman et al 1979, Ginn et al 1968, Antman et al 1978). 7.6 Investigations A smell of camphor is usually apparent on the breath of poisoned patients. It can be measured in serum and urine (eg Riggs et al 1965, Phelan 1976). 7.7 Management controversies None. 8 CASE DATA Convulsions A 3 year old girl with a history of confusion, irritability, projectile vomiting and, 2 hours later, a generalised convulsion was brought to hospital. The convulsion was controlled by 25mg secobarbitone given IM, oxygen was administered because of respiratory depression following the barbiturate, she was then given 0.2g of caffeine sodium benzoate and transferred to a paediatric hospital. On admission there she was drowsy and had an odour of camphor on her breath. It then transpired that she had been found with an open jar of Vicks Vaporub 2 hours before the convulsion, and may have ingested about a tablespoonful of it (approx. 0.7g of camphor). She was asymptomatic by 21 hours after admission, and required no further anticonvulsants or respiratory support. No abnormalities in liver or renal function tests were found, and she was discharged home 24 hours after admission on phenobarbitone 5mg/kg/day. Blood levels of camphor measured 7 hours post-ingestion were 1.95mg/100ml, and undetectable by 21 hours post-ingestion. EEG at about 18 hours post-ingestion showed diffuse neuronal disturbance with excessive slow activity in the bianterior and bicentral areas and no specific paroxysmal discharges. This pattern was still apparent on the EEG 15 days after discharge, but it had returned to normal on review after 3 months. A 15 month old crawled through a spill of spirits of camphor (10% camphor). Over the next 48 hours he became progressively ataxic and had some brief, generalised motor seizures. The convulsions recurred over a 2 day period, despite anticonvulsant therapy. He recovered slowly over the next 15 days, and appeared to be completely well, with no further convulsions. However, a year later he suffered a brief convulsion when exposed to camphor from a vaporiser (camphor content of preparation being used 4.81%) (Skoglund et al 1977). Hallucinations Two 22 year old men ingested 6-10g of camphor as a substitute for hashish, and were admitted to hospital two hours later in a state of anxiety with agitation. They were both having hallucinatory feelings, one described a floating sensation, the other the feeling that his legs no longer belonged to him. The only physical findings were a slight tachycardia and leukocytosis. The patients were given 2 litres of tea, and given 10mg diazepam. They were both discharged well 24 hours post admission. Their blood levels taken at an unspecified time were 300 and 400ng/ml (Koppel et al 1982). Fatal liver damage in a child A 6 month old male with a 2-day history of cough, nasal discharge and fever was prescribed ampicillin for presumed pneumonia. By the next day the child was lethargic but rouseable, with diffuse rales and wheezing in both lungs. Chest X-ray showed hyperinflation with diffuse interstitial infiltrates, and bronchiolitis was diagnosed. Within 6 hours the child became unrousable and the liver was palpable 3cm below the costal margin, and the child was transferred to a paediatric hospital with presumed Reye's syndrome. On admission there, the child was comatose, with abnormal lung sounds, hepatomegaly and hyperactive reflexes, but normal white blood cell count and haematocrit. AST, ALT, urea and bilirubin levels were elevated, and prothrombin time increased (20.5 seconds). Supportive therapy for Reye's syndrome was commenced, with administration of hypertonic dextrose, IV mannitol as indicated by the intra-cranial pressure, and imposed respiratory alkalosis. 6 hours post-admission an EEG showed diffuse slowing with no seizure activity, and liver biopsy showed changes not characteristic of Reye's syndrome. On further questioning the family admitted to the use of a home-made remedy containing camphor in whiskey (33.3% alcohol, 29.2mg/ml camphor). This mixture had been administered to the child on a daily basis, in dropperful quantities, from the age of about a month, the total quantity administered was about 28 fl oz (828ml), of which 4 fl oz (118.4ml) had been given in the 3 days before hospitalisation (total dose of camphor approx. 24.5g or 3g/kg). The child's liver function improved, but his neurological status deteriorated, and by the fifth day in hospital deep tendon, corneal and ocular-vestibulo-cephalic reflexes were all absent, and repeat EEG showed an absence of any electrical activity. The child suffered a cardiac arrest and died later that day. On postmortem the brain was symmetrically swollen, with flattening of the gyri and narrowing of the sulci, it weighed 1250g (normal 660g). Microscopically there was diffuse oedema with patchy individual neuronal degeneration and areas of frank necrosis, mainly in the hippocampus and frontal cortex. The liver was enlarged (weight 354g compared with normal 200g), friable and discoloured yellow. Histologically there were fat deposits within the hepatocytes, irregular in size and distribution, with the majority of hepatocyte nuclei located peripherally rather than centrally. The classical changes characteristic of Reye's syndrome, such as decreased succinic dehydrogenase and cytochrome oxidase activity, were not found, neither were swollen mitochondria. There was no inflammation, bile stasis, Mallory bodies or cellular necrosis, which would be expected in alcohol-induced hepatitis (Jimenez et al 1983). Camphorated gauze Three cases of poisoning were associated with the use of camphorated gauze (9.6% camphor). A 14 month old child with 2nd degree burns to 5% of body area was treated with regular application of the gauze for 3 weeks. The child was ataxic within 3-4 days of starting treatment, and developed convulsions by the third week. The serum level of camphor at the time the gauze was removed was >2µg/ml, 32µg of camphor was recovered from the urine during the first 12 hours following exposure. A 13 year old boy with 2nd degree burns covering 35% of body surface was treated with camphor gauze dressings, for 50 hours, with the dressings changed at 24 and 48 hours. The total quantity of camphor applied was estimated to be 160mg/kg/24h. He began to have convulsions 50 hours into this treatment, the dressings were removed, and he recovered. His blood camphor level was 0.452µg/ml 17 hours after the dressings were removed, and urinary levels of metabolites were still rising by 4 days post termination of exposure. A 29 month old with 2nd degree burns to 50% of body surface area had camphor dressings applied for 4 hours until he began to have convulsions, with a respiratory arrest. He recovered. No serum or urinary camphor concentrations were measured. Poisoning from nasal and/or dermal application Two cases of poisoning were associated with nasal and/or dermal application of camphor; a 3 month old went pale, collapsed, stopped breathing and had a convulsion following one inhalation of Vicks Inhaler (40% camphor). The child was treated with phenobarbitone, on a continuing basis. A 6 month old was treated for 3 days with application of VicksVaporub to the nostrils, the lips and the chin. 48 hours into this treatment he had 4 apnoeic episodes, 2 of which followed generalised convulsions. Two cases were associated with the use of a talcum powder containing 0.3% camphor: an 8 month old with mild chicken-pox was exposed to an unknown quantity of this powder and developed convulsions with apnoea a few hours after the last exposure, but recovered. A 24 month old, again with mild chickenpox, was exposed to about 112mg worth of camphor in 18 hours (3/4 bottles of the powder). The child had convulsions after the 6-7th application of the powder, when re-exposed had another convulsion, and yet more convulsions one hour after the last application. In between the child was agitated, and the chickenpox worsened. Recovery took place over 48 hours (Bavoux et al 1985). Camphor spirit A 54 year-old, alcoholic, diabetic woman drank an unknown quantity of 10% camphor spirit (10% camphor, 70% isopropanol and 20% water) and was discovered comatose half an hour later suffering grand-mal convulsions and respiratory failure. She was given 10mg diazepam IV and intubated and ventilated, then transferred to intensive care. On arrival there she was in coma grade II, with hyporeflexia, tachycardia, and grand-mal convulsions which could be precipitated by light touch to the arms or legs. She was washed out with liquid paraffin, then haemoperfusion with amberlite XAD4 was carried out for 4 hours. Although the convulsions ceased during the haemoperfusion the patient's level of consciousness did not improve. She gradually came round over the next few days and she was extubated and transferred to an ordinary ward six days post-ingestion. One of the authors voluntarily ingested 200mg of camphor with and without a solvent in order to determine the absorption kinetics and plasma half-life. When ingested with a solvent peak plasma levels were reached by one hour post-ingestion, when ingested alone peak levels were reached by 3 hours. The elimination half life in the volunteer was 93 minutes when camphor was ingested with a solvent, and 167 minutes when ingested alone. The plasma elimination half life measured in the patient during haemoperfusion was 128 minutes (Koppel et al 1988). Chronic ingestion of camphor containing rub A 72 year old woman presented to hospital with a history of weakness, fever, pruritis, anorexia and weight loss. On examination she was found to have hepatomegaly, on biopsy the liver displayed granulomas with necrosis and eosinophils. This pattern of symptoms and liver damage was seen again 4 months later at another hospital. The patient claimed to have ingested Vicks Vaporub regularly over a period of about 5 years, consuming about one jar a year. The patient was instructed to discontinue her use of the rub, and the liver damage and other symptoms resolved slowly (McCollam et al 1989). Eye exposure to inhalant preparation A 4 month old girl was brought to hospital with a 2 day history of fever, nasal congestion and bilateral eye irritation. An hour earlier she had been placed, lying face-up, on a pillow which had been sprinkled with a decongestant mixture (Rhino-Caps: camphor 25mg, eucalyptol 125mg, menthol 55mg, terpineol 120mg and chlorothymol 5mg), but the parents denied any direct contact of the substance to her eyes. On examination she had bilateral corneal erosions, conjunctivitis, and a burn to the temporal conjunctiva, but had no other symptoms other than nasal congestion. The eyes were irrigated with saline, and antibiotic and steroid drops applied. By 12 hours post the initial admission she was noticed by her parents to be lethargic and weak, and was re-admitted. On the second examination she was drowsy and hypotonic, with marked head lag. She was observed for 8 hours, by the end of which time she was alert. The corneal erosions healed within 2 days (Soen et al 1992). Ingestion of camphorated oil A 15 month old infant ingested 1.5g of camphor in the form of camphorated oil and had two convulsions 45 minutes post ingestion. The stomach was washed out (the first washing smelt strongly of camphor), and phenobarbitone and diazepam administered. The blood level of camphor was 0.30µg/ml 9 hours post ingestion, 12µg of camphor was recovered from the urine during the first 16 hours, and 220µg of the glucuronide metabolite; in the following 24 hours urinary excretion increased to 165µg of camphor and 1540µg of the metabolite. An unspecified number of children (aged from 4-10 years) were each given between 1-1.5 tablespoons of camphorated oil, in place of castor oil. The first child to become unwell developed symptoms 45 minutes later, and by the time a physician arrived on the scene the children were displaying "all kinds of symptoms, from...nausea to convulsions". Twenty of the children were in fact convulsing. The most severely affected child was unconscious and rigid, cold to the touch, with blue-black lips, tachycardia and slow, shallow respirations. The child had dilated pupils, the eyes were fixed staring straight ahead, the jaws were locked, with tetanic contraction of the masseters, cervical rigidity and tonic contraction of the arms, extension of the legs. This child remained unconscious for 20 hours, but had recovered by 29 hours post-ingestion. The treatments which the children received included administration of mustard water as an emetic, and immersion in hot mustard water (for the more severely ill children) followed by oral mustard water (given forcibly). Most of the children were reportedly well within 3-4 hours of treatment, and all survived (Benz 1919). A 19 month old male ingested about 5ml of camphorated oil and vomited within minutes, then remained well until 3 hours later when he developed salivating and rigidity. A local doctor then administered pethidine 50mg, caffeine and sodium benzoate, with little effect, the child was therefore transferred to hospital. On admission he was pyrexial, tachycardic, with a raised white blood cell count and albuminuria. Shortly after admission the child vomited coffee-ground material which smelt of camphor and he then went into a coma, with repeated tonic convulsions and hyperreflexia. He was given penicillin, fluid by hypodermoclysis (subcutaneous administration) and intermittent phenobarbitone, nasal oxygen and sponge baths. By 3 days post admission the right pupil was fixed and dilated, and the blood pressure had risen to 150/100 mmHg. Recurrent periods of apnoea developed, which increased in severity, and required artificial ventilation. Tracheotomy was performed, but the child died 5 days post-ingestion. On postmortem examination the lungs were oedematous, with congestion of both lower lobes, and the right side of the heart was dilated. The liver, spleen and kidneys were congested. The brain was swollen and soft, weighing 1350g (350g more than expected). There was extensive neuronal degeneration, spread throughout the cerebral cortex and basal ganglia, most severe in Sommer's section of the hippocampus, where almost all the pyramidal cells were necrotic. There was a small area of ischaemic necrosis in the medulla, but the cerebellar Purkinje cells were unchanged. There was no glial or vascular injury apparent, nor any inflammatory changes (Smith and Margolis 1954). A 20 year old pregnant woman (40 weeks) ingested 12g of camphorated oil in mistake for castor oil while being observed in hospital for mild pre-eclampsia. She was found 15 minutes later prostrate, agitated and irrational. She had dilated pupils, her eyes were undergoing slow, rhythmic divergent and convergent movements, she had fine tremors of the hands and feet and general hyperreflexia. The woman's blood pressure was 140/70 and the foetal heart rate was 140/minute. Stomach washout was performed, but the patient developed opisthotonus and had tonic-clonic movements of the extremities, within 30 minutes of the ingestion. She then suffered a period of apnoea and asystole lasting 30-45 seconds, the convulsion terminated spontaneously 2 minutes after it had started. The mothers blood pressure and the foetal heart rate remained unchanged. Sodium amytal 500mg IV and phenobarbitone 60mg IM were given and the tremors of the hands and feet and the abnormal eye movements gradually disappeared. Stomach washout was continued until the odour of camphor was no longer detectable in the return washings. The tremors, hyperreflexia and ocular movements returned about 8 hours post ingestion, but disappeared again on the administration of another 60mg of phenobarbitone. The patient remained rational and awake, but had epigastric pain relieved by antacids. Labour began spontaneously 17 hours after the ingestion. Amniocentesis was performed 19.5 hours post ingestion, and produced bright red blood, believed to be placental in origin. 18.5h after the start of labour vaginal bleeding and foetal bradycardia were noticed. When the child was delivered 1.5 hours later it was limp and cyanosed, with a heart rate of 80/minute and no respiratory effort. Aspiration of nose, pharynx, and stomach was performed, and positive pressure ventilation with a paediatric face mask was instituted, with no response. The heart rate gradually dropped, and the child was pronounced dead 30 minutes after delivery. The mother remained well apart from transient changes in liver function tests (elevation of bilirubin and alkaline phosphatase levels). On postmortem examination the infant was small (2250g), with marked congestion of all organs, and severe pulmonary atelectasis with many air-filled blebs on the pleural surface of the lungs. Within the central nervous system there was general congestion and neuronal necrosis. Camphor was found to be present in maternal blood samples taken just prior to the convulsion, but not 8 hours post ingestion or later. No camphor was found in the blood obtained during amniocentesis (and presumed to be placental), but it was detected in amniotic fluid taken at that time. Camphor was detectable in the amniotic fluid, cord blood, and foetal blood at 36 hours post ingestion. The liver, kidneys and brain of the infant also contained camphor (Riggs et al 1965). A 77 year old man ingested 60ml of camphorated oil (dispensed in error instead of cough mixture). Thirty minutes post-ingestion he vomited and had a grand-mal convulsion, and was brought to hospital. The vomitus smelt strongly of camphor. On admission he was post-ictal, but became progressively more agitated, disorientated and had two further convulsions despite being given IV barbiturates. His breath and urine smelt of camphor, but urinalysis, whole blood count, blood sugar, urea and electrolytes and liver function tests were all normal. Haemodialysis using soya bean oil as the dialysate was initiated within 4 hours of the ingestion. The procedure was carried out for 4.5 hours, and the patient became alert and orientated after 3 hours of dialysis. He was discharged the next day, asymptomatic. The soybean oil had removed 6.56g of camphor (on analysis by gas chromatography) (Ginn et al 1968). An adult male who had deliberately ingested 150ml of camphorated oil (B.P. 20%) was admitted to a regional Poisons Unit in peripheral circulatory shock and severely dehydrated due to vomiting. He was resuscitated and then stomach washout was performed under general anaesthetic, with a cuffed ET tube in place. Shortly after admission he developed 3 severe, prolonged grand mal convulsions, which were controlled with diazepam IV. He required intensive supportive treatment, but was discharged well 36 hours post admission (Vasey and Karayannopoulos 1972). A pregnant woman who ingested 50 ml of camphorated oil in mistake for castor oil had a total of three grand-mal convulsions, and went into labour prematurely (20 hours post-ingestion). The infant was healthy, but its breath and skin, and the amniotic fluid, smelt of camphor (Weiss and Catalano 1973). A 2 month old girl was given 2.5ml of camphorated oil by mistake, and taken immediately to hospital. There gastric washout was performed, and she was admitted for observation. No symptoms developed, and she was discharged within 24 hours. A 12 year old boy who was given 1 fl oz (29.6ml) of camphorated oil complained of the taste, was given a glass of milk and immediately vomited. He was taken straight to hospital, but appeared to lose consciousness for ten minutes on the way. On admission, about 2 hours post-ingestion, he was convulsing. He was given diazepam IV which controlled the convulsions, and remained alert for the next 48 hours with only mild, intermittent abdominal cramps. He was discharged 3 days post-ingestion(Aronow and Spigiel 1976). A 19 year old woman ingested 2 fl oz (59.2ml) of camphorated oil in mistake for castor oil was found 45 minutes later unresponsive with stiff arms and legs, hands stiffly pronated bilaterally, salivating, and with eyes rolled back. She was vomiting and had a grand mal convulsion in the first hospital she was taken to, and on admission to the second hospital was semi-conscious and agitated, requiring restraint. She was transferred to ITU and where she was managed conservatively, slowly improved and was discharged 13 days after admission. During her stay she developed liver function test changes suggestive of acute parenchymal liver necrosis, also slightly deranged renal function, both of which resolved. A 15 year old male ingested 2 fl oz (59.2ml) of camphorated oil, again in mistake for castor oil, and shortly thereafter had a convulsion and vomited. The patient was admitted to hospital within 2 hours of the ingestion, but the mistake was not realised until 10 hours post-ingestion, by which time he was complaining of blurred vision. He was managed conservatively and discharged after 2 days (Trestrail and Spartz 1977). A 56 year old female ingested 12 ml of 20% camphor oil, and developed epigastric burning, nausea and vomiting 45 minutes later, and was brought to the emergency room. On admission she had no symptoms other than a smell of camphor on the breath, but rapidly developed a hyperexcitable emotional state, neuromuscular hyperactivity, and jerky movements of the extremities. She had a transient mild elevation in serum glutamic oxaloacetic transaminase and lactic dehydrogenase and nasogastric aspirate was positive for blood. Haemodialysis with soy-bean oil dialysate was carried out for 4.5 hours. The odour of camphor cleared from her breath and became noticeable in the dialysate compartment; the patient recovered and remained well during 2.5 years of follow-up (Antman et al 1978). A 37 year old man was brought to hospital 1 hour and 40 minutes after ingesting up to 90ml of camphorated oil (18g camphor). He was complaining of abdominal pain, and had vomited twice, the first time twenty minutes post-ingestion. Although he was conscious and alert on presentation, grand mal convulsions developed within minutes of arrival, and the patient aspirated stomach contents. He was then intubated, and gastric lavage performed. His breath, vomitus and urine all smelt strongly of camphor. Recurrent convulsions occurred during his first 12 hours in hospital, and were treated with diazepam 100mg, chlorpromazine 50mg, secobarbital 300mg and phenobarbitone 300mg (IV). He was given IV fluids, and underwent bronchoscopy to reexpand the right upper lobe of his lung at about 8 hours post-ingestion (it had collapsed due to aspiration of stomach contents). The patient was still comatose and having recurrent convulsions, and it was decided to attempt to speed up the elimination of the camphor by instituting haemoperfusion against an amberlite resin, followed by lipid dialysis (connected in series, as the efficacy of amberlite haemoperfusion was unproven). Combined haemoperfusion and lipid dialysis were carried out for 45 minutes, until clotting occurred in the perfusion column and it was discontinued; lipid dialysis alone was carried out for a further 3 hours 45 minutes. The patient had started to awaken by 2.5 hours after the start of the extracorporeal elimination procedure, and was fully alert by about 32 hours post-ingestion, and discharged about 60 hours post-ingestion. The plasma camphor level measured before the start of the elimination procedure was 1.7µg/ml. Samples taken after passage through the haemoperfusion column showed no detectable camphor, while when the lipid dialysis system was operating alone it extracted about 60% of the camphor (Kopelman et al 1979). A 60-year old woman accidentally drank about 25ml of camphorated oil (about 5g or 100mg/kg camphor), and became nauseated and vomited once shortly after ingestion. She then suffered two grand mal convulsions, the second witnessed by medical personnel during her journey to hospital. On admission (about 1 hour post-ingestion) the patient was responsive only to pain. A stomach washout was performed, and the patient was intubated. She was treated with combined charcoal haemoperfusion and lipid dialysis arranged in series, starting from about 3 hours post-ingestion and continuing for 4 hours. At the end of this time the patient had recovered, however the total amount of camphor removed from the bloodstream was calculated to be only 48.7mg (less than 1% of the ingested dose). The initial plasma level of camphor in this patient was 3.1mg/L (at about 3 hours post-ingestion), and the clearance rate using the charcoal haemoperfusion column was 240ml/min. The lipid dialysis column induced haemolysis, and so was disconnected, clearance rates for it were therefore not measured (Mascie-Taylor et al 1981). NPIS (L) Cases 100 cases on file where adequate follow-up information was received, covering the period 1964-1991. Most of the cases involved children (89%), and the source of the camphor was most commonly camphorated oil (95% of cases). There were no fatalities reported. Example cases 84/2625 Male, 4 years old ingested a mouthful of camphorated oil, vomited twice and had a convulsion 15 minutes post-ingestion. He was well after overnight observation. 84/12478 A schizophrenic, 43 year old female ingested an unknown amount and suffered grand-mal convulsions and hallucinations, she was treated with diazepam and observed in ITU. 84/13439 A 4 year old male ingested about 25ml and developed rolling eyes and twitching within 1.5 hours, also vomiting and abdominal pain. He was given activated charcoal and an irritant laxative, and observed overnight. 84/3873 A 1 year old female ingested 50ml camphorated oil and developed vomiting and drowsiness, and had a minor epileptic fit. She was given activated charcoal 2 hourly and recovered by 24 hours. 9 ANALYSIS 9.1 Agent/toxin/metabolite 9.2 Sample containers to be used 9.3 Optimum storage conditions 9.4 Transport of samples 9.5 Interpretation of data 9.6 Conversion factors 9.7 Other recommendations 10 OTHER TOXICOLOGICAL DATA 10.1 Carcinogenicity No evidence of carcinogenicity has been found in human tests (ACGIH 1986). 10.2 Genotoxicity 10.3 Mutagenicity Sister chromatid exchange has been reported in mice given 80mg/kg doses of camphor intraperitoneally (RTECS 1996). 10.4 Reprotoxicity Camphor crosses the placental barrier (Weiss and Catalano 1973). It has been used, historically, to procure abortion (Vasey and Karayannopoulos 1972), and the plant Lippia dulcia Trev., which contains camphor, may still be used for this purpose in South America (Compadre et al 1986). 10.5 Teratogenicity None to minimal risk (TERIS 1993). 10.6 Relevant animal data Camphor was administered to rabbits and mice, to examine the changes (if any) occurring in their brain as a result, and to see if barbiturates had a protective effect. All rabbits administered camphorated oil via oral tube developed convulsions within 5-40 minutes of administration, with convulsions occurring later in those receiving the lower doses. The animals who died had intermittent convulsions up to the time of death, those which recovered stopped convulsing by 4 hours post-ingestion. Mice were administered camphor by intraperitoneal (IP) injection, and again, convulsions occurred. On post-mortem examination, the rabbit brains showed no significant changes, but some of the mice had necrosis of neurons in the brain stem, basal ganglia, medulla, hippocampus and cerebral cortex. The experiment was repeated in mice, the test group being given camphor and pentobarbitone IP and the controls camphor alone. The animals given camphor and pentobarbitone all became stuporose within 10 minutes, but recovered within about 1.5 hours and developed no convulsions, whereas the control group all developed convulsions, and 7/10 died. The mice who had received pentobarbitone as well as camphor showed no cerebral changes when examined after death (Smith and Margolis 1954). 10.7 Relevant in vitro data Amberlite haemoperfusion resin was found to be superior to an activated charcoal column - relative clearance of camphor by amberlite was 98% compared with 59% for the charcoal (Koppel et al 1982). Author Sarah McCrea National Poisons Information Service (London Centre) Medical Toxicology Unit Guy's & St Thomas' Hospital Trust Avonley Road London SE14 5ER UK This monograph was produced by the staff of the London Centre of the National Poisons Information Service in the United Kingdom. The work was commissioned and funded by the UK Departments of Health, and was designed as a source of detailed information for use by poisons information centres. Peer review was undertaken by the Directors of the UK National Poisons Information Service. 11 REFERENCES ACGIH 1986 Documentation of the Threshold Limit Values and biological exposure indices. 5th ed. Am Conference of Govt Ind Hyg, Inc. Cincinnati, OH. Antman E, Jacob G, Volpe B, Finkel S and Savona M. 1978 Camphor overdosage - therapeutic considerations. NY State J Med 896-897 Aronow R and Spigiel RW. 1976 Implications of camphor poisoning - therapeutic and administrative. 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