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CBD Oil and Benadryl

Does CBD interact with Benadryl and other antihistamines?

 

Benadryl is the brand name for a substance known as diphenhydramine HCL. Diphenhydramine belongs to a class of medications called antihistamines. 

 

Antihistamines work by blocking the activity of histamine, a substance in the body that causes allergic symptoms (1).

 

Diphenhydramine is used to alleviate symptoms, like red, itchy, irritated, and watery eyes, sneezing, and runny nose caused by allergies, hay fever, or the common cold. 

 

Diphenhydramine is also used to relieve coughs caused by minor throat or airway irritation. Moreover, diphenhydramine is used to prevent and treat motion sickness, and to treat insomnia (difficulty falling asleep or staying asleep) (2).

Can CBD Be Taken With Benadryl?

There is no known interaction between CBD (cannabidiol) and Benadryl. However, there is a potential risk when combining CBD and Benadryl, as both are metabolized (broken down) through the cytochrome P450 enzyme system.

Due to how Benadryl is metabolized, the concentrations of the drug could potentially increase when taken with CBD.

The CYP450 liver enzymes are responsible for metabolizing potentially toxic compounds, including over 60% of any over-the-counter or prescription drugs consumed.

Certain substances can affect processing times within this system, making drugs metabolize faster or slower than they would on their own.

Cannabidiol can inhibit the cytochrome P450 system’s ability to metabolize certain drugs, leading to an overall increase in processing times (3). 

Antihistamines use the cytochrome P450 enzyme system and can interact with CBD, as reiterated by authors Eileen Konieczny, RN, and Lauren Wilson, in their book, Healing with CBD (4).

According to an article written in August 2019 by Peter Grinspoon, MD, any medicine can have different effects on different people. 

 

For example, Benadryl, an antihistamine, makes some people sleepy yet can make others wide awake. Thus, it is not inconsistent for a particular medicine to cause a symptom in one person and to help alleviate it in another (5).

 

Until studies that specifically look at how CBD interacts with Benadryl are completed, talk with a doctor to make sure that there are no CBD drug interactions with other medications currently taken.

Can CBD Replace Benadryl?

There is no scientific study that recommends using CBD as a substitute for Benadryl. However, studies have shown that CBD possesses therapeutic characteristics that may help with symptoms of medical conditions for which Benadryl is indicated. 

 

These conditions include nausea, insomnia, mucus production, minor throat or airway irritation, and inflammation.

A review from the European Journal of Pharmacology established the potential of cannabis to limit or prevent nausea and vomiting from a wide range of causes (6). Results also demonstrated the crucial role of cannabinoids and their receptors in the regulation of nausea and vomiting.

A study from January 2019 looked at the role of CBD in anxiety and sleep, showing a positive correlation. The results, published in The Permanente Journal, indicated that individuals with anxiety or poor sleep experienced an improvement in both or either cases when taking CBD every day. 

CBD has been shown to interact with the endocannabinoid system to reduce mucus production, as one review in Future Medicinal Chemistry indicated (7).

 

In another 2019 study, which was published in the European Journal of Pharmacology, scientists found that CBD helped to reduce airway inflammation and fibrosis in animal subjects that were experiencing an allergic asthmatic response (8).

 

Meanwhile, CBD’s potent anti-inflammatory properties were demonstrated in a 2018 study published in the Journal of Pharmacology and Experimental Therapeutics (9). CBD may also be useful in treating different types of chronic pain (10).

Conclusion

Benadryl has been used for many common symptoms and medical conditions. However, as with most pharmaceuticals, Benadryl use comes with side effects and health risks.

In a 2015 report published in JAMA Internal Medicine, researchers offered compelling evidence of a link between long-term use of Benadryl and dementia (11).

Meanwhile, studies have shown that CBD possesses therapeutic characteristics that may help with symptoms of medical conditions that Benadryl addresses. 

 

However, no scientific study recommends using CBD or any CBD products with Benadryl. Neither is there a study that promotes CBD as a substitute for Benadryl.

While CBD is generally safe, as the 2011 review in the Current Drug Safety Journal suggests, the long-term effects are yet to be examined further (12). 

 

References

  1. MedlinePlus. (2020, Feb 18).v Diphenhydramine. Retrieved from https://medlineplus.gov/druginfo/meds/a682539.html
  2. Ibid. 
  3. Pharmotech SA. CBD Drug Interactions. Retrieved from https://pharmotech.ch/cbd-drug-interactions/
  4. Eileen Konieczny and Lauren Wilson. Healing with CBD: How Cannabidiol Can Transform Your Health without the High (California: Ulysses Press, 2018). P46-47.
  5. Grinspoon, P. (2018, Aug 24). Cannabidiol (CBD) — what we know and what we don’t. Retrieved from https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-2018082414476.
  6. Sharkey KA, Darmani NA, Parker LA. Regulation of nausea and vomiting by cannabinoids and the endocannabinoid system. Eur J Pharmacol. 2014;722:134–146. DOI:10.1016/j.ejphar.2013.09.068. 
  7. Nagarkatti P, Pandey R, Rieder SA, Hegde VL, Nagarkatti M. Cannabinoids as novel anti-inflammatory drugs. Future Med Chem. 2009;1(7):1333–1349. DOI:10.4155/fmc.09.93.
  8. Vuolo F, Abreu SC, Michels M, et al. Cannabidiol reduces airway inflammation and fibrosis in experimental allergic asthma. Eur J Pharmacol. 2019;843:251–259. DOI:10.1016/j.ejphar.2018.11.029.
  9. Petrosino S et al. Anti-inflammatory Properties of Cannabidiol, a Nonpsychotropic Cannabinoid, in Experimental Allergic Contact Dermatitis. Journal of Pharmacology and Experimental Therapeutics June 2018, 365 (3) 652-663; DOI: https://doi.org/10.1124/jpet.117.244368.
  10. Grinspoon, P. (2018, Aug 24). Cannabidiol (CBD) — what we know and what we don’t. Retrieved from https://www.health.harvard.edu/blog/cannabidiol-cbd-what-we-know-and-what-we-dont-2018082414476.
  11. Gray SL, Anderson ML, Dublin S, et al. Cumulative Use of Strong Anticholinergics and Incident Dementia: A Prospective Cohort Study. JAMA Intern Med. 2015;175(3):401–407. doi:10.1001/jamainternmed.2014.7663. 
  12. Bergamaschi MM, Queiroz RH, Zuardi AW, Crippa JA. Safety and side effects of cannabidiol, a Cannabis sativa constituent. Curr Drug Saf. 2011 Sep 1;6(4):237-49.

    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  871F (466C)

    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            204C
    Density                  d=0.992 @ 25C/4C
    Relative vapour density  5.24
    Flash point              150F (65.5C)

    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
    0.3g/ml (9h pi)               1.5g (symptomatic)                  Bavoux et al 1985
    >2g/ml                        NK (symptomatic)                    Bavoux et al 1985
    0.45g/ml (17h post exposure)  160mg/kg/24h (dermal/symptomatic)   Bavoux et al 1985
    ND                             112mg/18h (symptomatic)             Bavoux et al 1985
    5.5g/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 >2g/ml, 32g 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 0.452g/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 0.30g/ml 9 hours post ingestion, 12g of camphor was
    recovered from the urine during the first 16 hours, and 220g of the
    glucuronide metabolite; in the following 24 hours urinary excretion
    increased to 165g of camphor and 1540g 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 1.7g/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.
    DICP 10: 631-634

    Baselt RC and Cravey RH. 1990
    Disposition of toxic drugs and chemicals and drugs 3rd ed.
    Year Book Medical Publishers Inc

    Bavoux F, Bodiou C, Castot A et al. 1985
    Le camphre en pediatrie.
    Therapie 40: 25-30

    Benz RW. 1919
    Camphorated oil poisoning with no mortality - report of twenty cases.
    JAMA 72(17): 1217-1218

    Budavari S (editor). 1989
    The Merck Index. 11th Edition.
    Merck and Co Inc, Rahway, USA.

    Committee on Drugs. 1994
    Camphor revisited: focus on toxicity.
    Pediatrics 94(1): 127-128

    Compadre CM, Robbins EF and Kinghorn AD. 1986
    The intensely sweet herb,  Lippia dulcis Trev.: historical uses,
    field enquiries, and constituents.
    J Ethnopharmacol 15(1): 89-106

    Davies DM (editor). 1991
    Textbook of adverse drug reactions. 4th Edition.
    Oxford Medical Publications, Oxford.

    Galland MC et al. 1992
    Convulsions febriles: faut-il contre-indiquer certains medicaments?
    Therapie 47(5): 409-414

    Geller RJ, Spyker DA, Garrettson LK and Rogol AD. 1984
    Camphor toxicity: development of a triage strategy.
    Vet Hum Toxicol 26 (Suppl 2): 8-10

    Gibson DE, Moore GP and Pfaff JA. 1989
    Camphor ingestion.
    Am J Emerg Med 7: 41-43

    Ginn HE, Anderson KE, Mercier RK, Stevens TW and Matter BJ. 1968
    Camphor intoxication treated by lipid dialysis.
    JAMA 203(3): 164-165

    Grant WM and Schuman JS. 1993
    Toxicology of the Eye. 4th Edition.
    Charles C Thomas, Springfield, Illinois.

    Green BG. 1990
    Sensory characteristics of camphor.
    J Invest Dermatol 94: 662-666

    Jimenez JF et al. 1983
    Chronic camphor ingestion mimicking Reye's syndrome.
    Gastroenterology 84: 374-398

    Kopelman et al. 1979
    Camphor intoxication treated by resin hemoperfusion.
    JAMA 241: 727-728

    Koppel C, Martens F, Schirop Th and Ibe K. 1988
    Hemoperfusion in acute camphor poisoning.
    Intensive Care Med 14: 431-433

    Koppel C, Tenczer J, Schirop T and Ibe K. 1982
    Camphor poisoning - abuse of camphor as a stimulant.
    Arch Toxicol 51: 101-106

    McCollam A, Block R, Lipscomb JW and Pompei P. 1989
    Chronic camphor ingestion: a case report of granulomatous hepatitis
    (abstract).
    Vet Hum Toxicol 31(4): 337

    Mascie-Taylor BH, Widdop B and Davison AM. 1981
    Camphor intoxication treated by charcoal haemoperfusion.
    Postgraduate Med J 57: 725-726

    Mercier C et al. 1984
    A propos des dangers des pansements camphres chez l'enfant.
    Archives Francaises de Pediatrie 1984, 41(1): 74

    Phelan WJ. 1976
    Camphor poisoning: over-the-counter dangers.
    Pediatrics 57(3): 428-431

    Rayner J. 1991
    Rubbing shoulders is all the rave.
    Independent on Sunday (London) 8th December

    Reid FM. 1979
    Accidental camphor ingestion (letter).
    JACEP 8: 339-340

    Reynolds JEF ( Editor). 1989
    Martindale The Extra Pharmacopeia. 29th edition.
    The Pharmaceutical Press, London.

    Reynolds JEF ( Editor). 1993
    Martindale The Extra Pharmacopeia. 30th edition.
    The Pharmaceutical Press, London.

    Riggs J, Hamilton R, Hormel S et al. 1965
    Camphorated oil intoxication in pregnancy.
    Obstet Gynecol 25: 255-258

    RTECS 1996
    Camphor
    Micromedex Inc, Vol. 28

    Sax NI. 1984
    Dangerous properties of industrial materials. 6th edition.
    Van Nostrand Reinhold Co, New York.

    Sax NI and Lewis RJ. 1987
    Hawley's Condensed Chemical Dictionary. 11th edition.
    Van Nostrand Reinhold Co, New York.

    Skoglund RR, Ware LL, Schanberger JE. 1977
    Prolonged seizures due to contact and inhalation exposure to camphor.
    Clin Pediatr 16: 901

    Smith A and Margolis G. 1954
    Camphor poisoning.
    Am J Pathol 30: 857-868

    Soen G, Frydman M, Fulga V and Savir H. 1992
    Corneal erosions and encephalopathy following exposure to Rhino-Caps.
    J Pediatr Ophthalmol Strabismus 29: 191

    TERIS. 1993
    CAMPHOR
    Micromedex Inc, Vol. 87

    Trestrail JH and Spartz ME. 1977
    Camphorated oil and castor oil confusion and its toxic results.
    Clin Toxicol 11(2): 151-158

    Vasey RH and Karayannopoulos SJ. 1972
    Camphorated oil (letter).
    Br Med J i: 112

    Wade A (ed). 1977
    Martindale The Extra Pharmacopeia. 27th edition.
    The Pharmaceutical Press, London.

    Weiss J and Catalano P. 1973
    Camphorated oil intoxication during pregnancy.
    Pediatrics 52: 713-714
    

See Also:
        CAMPHOR (PIM 095)

Camphor
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 Brand names, Trade names
1.6 Manufacturers, 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 Properties of the substance
3.3.2 Properties of the locally available formulation
3.4 Other characteristics
3.4.1 Shelf-life of the substance
3.4.2 Shelf-life of the locally available formulation
3.4.3 Storage conditions
3.4.4 Bioavailability
3.4.5 Specific properties and composition
4. USES
4.1 Indications
4.2 Therapeutic dosage
4.2.1 Adults
4.2.2 Children
4.3 Contraindications
5. ROUTES OF ENTRY
5.1 Oral
5.2 Inhalation
5.3 Dermal
5.4 Eye
5.5 Parenteral
5.6 Other
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 by route of exposure
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
7.1.1 Toxicodynamics
7.1.2 Pharmacodynamics
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
7.3 Carcinogenicity
7.4 Teratogenicity
7.5 Mutagenicity
7.6 Interactions
7.7 Main adverse effects
8. TOXICOLOGICAL ANALYSES 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
8.6 References
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 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, ear, nose, throat: local effects
9.4.10 Haematological
9.4.11 Immunological
9.4.12 Metabolic
9.4.12.1 Acid-base disturbances
9.4.12.2 Fluid and electrolyte disturbances
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 Relevant laboratory analyses
10.2.1 Sample collection
10.2.2 Biomedical analysis
10.2.3 Toxicological analysis
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic/specific treatment
10.4 Decontamination
10.5 Elimination
10.6 Antidote treatment
10.6.1 Adults
10.6.2 Children
10.7 Management discussion
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
11.2 Internally extracted data on cases
11.3 Internal cases
12. Additional information
12.1 Availability of antidotes
12.2 Specific preventive measures
12.3 Other
13. REFERENCES
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE ADDRESS(ES)


PHARMACEUTICALS
1. NAME
1.1 Substance
Camphor
1.2 Group
Rubefacient/counter-irritant
1.3 Synonyms
1,7,7-trimethyl bicyclo (2,2,1)-heptan-2-one
2-bornanone
2-camphanone
2-keto-1,7, 7-trimethylnorcamphane
2-oxo-bornane
alcanfor
camfora
camphor-natural
camphor-synthetic
formasa-camphor
Gum camphor
Japan camphor
l,7,7-trimethy1norcamphor
laurel camphor
matricaria camphor
root bark oil
spirit of camphor
tramfer
1.4 Identification numbers
1.4.1 CAS number
76-22-2
1.4.2 Other numbers
U.N. Number: 2717
1.5 Brand names, Trade names
Camphora synthetic tablets, camphora (see Section 4).
1.6 Manufacturers, Importers
NMD (Norwegian Medicinal Depot).
2. SUMMARY
2.1 Main risks and target organs
Central nervous system (CNS) and kidney: convulsions followed
by depression, and renal damage may occur after intake of
relatively small amounts of camphor may occur. The main risks
are apnoea, asystole, and severe post-convulsive coma. Toxic
effects appear after the ingestion of approximately 2 g
(lethal dose LD adults: 4 g; children: 1 g of pure camphor).
2.2 Summary of clinical effects
Clinical effects are: gastric irritation, colic, nausea,
vomiting, and diarrhoea; anxiety, excitement, delirium, and
epileptiform convulsions; apnoea and asystole. CNS depression
follows the excitatory phase, and may result in coma or,
rarely, death. Anuria may occur. The breath has the
characteristic odour of camphor.
2.3 Diagnosis
Poisoning by camphor is associated with an initial excitatory
phase, with vomiting, diarrhoea and excitement, followed by NS
depression and death. A characteristic odour of camphor is
present on the breath.

The symptoms may appear 5 to 90 min after ingestion depending

on the product ingested (solid or liquid). Oral and
epigastric burning sensations, nausea, and vomiting usually
occur early. The onset of convulsions may be sudden and
without warning, or may be preceded by confusion and
irritability, neuromuscular hyperactivity, and jerky movements
of the extremities.

Convulsions may be followed by coma, apnoea, and death.
Camphor is irritating to the eyes, skin and mucous membranes.

Blood and urine samples should be taken for routine analysis
and follow-up.

No specific laboratory analyses are indicated: camphor levels
are not clinically useful.

Camphor is recognized by its characteristic odour on the
patient's breath.
2.4 First aid measures and management principles
Camphor induces convulsive states which may be life-
threatening and must be considered before attempting emesis or
gastric lavage.

If camphor has been ingested recently, and the condition of
the patient allows, perform gastric lavage with warm water (38°
C to 40 °C). If only small amounts have been ingested,
administer cathartics. Administration of vaseline oil
(laxative mineral oil) is controversial.

If camphor has been inhaled, remove patient from exposure,
administer fresh air or oxygen, and establish respiration.

If there has been external contact with camphor, wash skin
thoroughly with soap and water. Irrigate eyes with large
amounts of water.

Send patient immediately to hospital.

In case of severe poisoning:

Establish respiration if depressed - artificial respiration
may be necessary.

Treat convulsions (e.g., with diazepam).

With the airway protected (endotracheal intubation), gastric
lavage may be performed, followed by activated charcoal, and
then a saline cathartic.

Resin and charcoal haemoperfusion may be used in severe cases.
3. PHYSICO-CHEMICAL PROPERTIES
3.1 Origin of the substance
Camphor may be natural or synthetic. It occurs naturally in
the wood of the camphor tree (cinnamonum camphora), and is
xtracted by steam distillation and crystallization. Natural
camphor is dextrorotatory. Synthetic camphor may be made from

pinene which is converted into camphene by treatment with
acetic acid and nitrobenzene. Synthetic camphor is optically
inactive.
3.2 Chemical structure
C10H16O

Molecular Weight = 152.2
CH3

= O

H3C-C-CH3
3.3 Physical properties
3.3.1 Properties of the substance
Normal state at room temperature: solid,
translucent
crystals.

Colour: white crystals.

Odour: penetrating, aromatic.

There are dangers associated with the vapour, its dispersion,
and possible ignition. There is a moderate risk of fire if
camphor is exposed to heat or flame, but spontaneous
combustion does not occur.

Boiling point: 204 °C

Melting point: 176 to 180 °C

Sublimes appreciably at room temperature and normal
atmospheric pressure

Flash point: 65°C

Autoignition temperature: 466°C

Relative density: 0.99 (specific gravity)

Relative vapor density: 5.2

Vapour pressure: 20 PA at 20°C

Solubility in water: 0.125 g/100 m1 (25 °C)

Soluble in ethanol, ethylether, turpentine, and
essential oils

Explosive limits: 0.6 to 3.5 vol% in air

Relative molecular mass: 152.2.
3.3.2 Properties of the locally available formulation
No data available.
3.4 Other characteristics
3.4.1 Shelf-life of the substance

Five years.
3.4.2 Shelf-life of the locally available formulation
No data available.
3.4.3 Storage conditions
Store in airtight containers at a temperature not above
25°C.
3.4.4 Bioavailability
No data available.
3.4.5 Specific properties and composition
Strong aromatic odour.
4. USES
4.1 Indications
Camphor is used:

as a rubefacient
as a plasticizer for cellulose esters and ethers
in the manufacture of plastics (especially celluloid)
in lacquers and varnishes
in explosives and pyrotechnics
as a moth repellent
in the manufacture of cymene
as a preservative in pharmaceuticals and cosmetics.

When camphor is applied on the skin, it is analgesic. It is also
used in liniments as a counter-irritant in fibrositis, neuralgia,
and similar conditions.

In dermatology, when it is applied as lotion (0.1 to 3%), it is
an anti-pruritic and surface anaesthetic (when applied gently,
it creates a feeling of coolness).

In dentistry, it is prepared with parachlorophenol 35% (and 65%
camphor) and used as an antibacterial for infected root canals.

Taken internally, it is an irritant and carminative. It has been
used as a mild expectorant and to relieve griping (abdominal
discomfort) (this use is now discouraged because of toxicity).

Camphor was formerly administered as a solution in oil by
subcutaneous or intramuscular injection to act as a circulatory
and respiratory stimulant, but there is no evidence of its value
for this purpose (Reynolds, 1982).

According to the Dutch Information Medicamentorum (1986), camphor
is used:

For pruritus: lotion with 1 to 70 mg/g

For muscular pains: oil with 40 to 250 mg/g or alcohol solution
with 100 mg/ml

For colds: chest liniment, with 20 to 100 mg/g; nose ointment,
with 20 to 50 mg/g: nose drops/spray, with 0.15 mg/ml.

4.2 Therapeutic dosage

4.2.1 Adults
The dosage varies according to its uses (see section
4.1).
4.2.2 Children
The dosage varies according to different uses (see
section 4.1).
4.3 Contraindications
Internal use is discouraged because of its toxicity.

It is dangerous to place camphor into infants' nostrils, since
it can cause instant collapse (Reynolds, 1982).

As with all rubefacients, it should not be applied to abraded,
irritated skin.
5. ROUTES OF ENTRY
5.1 Oral
Ingestion of camphor, camphorated oils, spirits, or other
preparations is the main route of poisoning.
5.2 Inhalation
Camphor fumes may be inhaled.
5.3 Dermal
Camphor liniments, spirits, or oil can be applied in excessive
amounts.
5.4 Eye
Splash or fumes may cause irritation.
5.5 Parenteral
Subcutaneous or intramuscular injections.
5.6 Other
No data available.
6. KINETICS
6.1 Absorption by route of exposure
Camphor is readily and rapidly absorbed from the skin, and
gastrointestinal and respiratory tracts. Camphor in oil
solutions is absorbed slowly from subcutaneous or
intramuscular depots.
6.2 Distribution by route of exposure
After oral ingestion, peak blood levels are reached in 5 to 90
min. The high lipid solubility of camphor suggests that it
accumulates in adipose and other tissues. Camphor crosses the
placenta (Kresel, 1982), and has a large volume of
distribution.
6.3 Biological half-life by route of exposure
No data available.
6.4 Metabolism
Camphor is rapidly oxidized to campherols (2-hydroxycamphor
and 3-hydroxycamphor), and then conjugated in the liver to the
glucuronide form (Kresel, 1982). Camphor-related metabolites
are relatively fat-soluble and may accumulate in fatty tissue.
6.5 Elimination by route of exposure
Campherol conjugated to glucuronic acid is eliminated mainly
in the urine as an inactive compound (Kresel, 1982). Trace
amounts are eliminated by the lungs.
7. PHARMACOLOGY AND TOXICOLOGY
7.1 Mode of action
7.1.1 Toxicodynamics
Camphor is a CNS stimulant whose effects range from mild

excitation to grand-mal convulsions or status
epilepticus. These effects result from excitation of
the cerebrum and lower structures of the CNS.

Gastric irritation, together with cortical and medullary
stimulation, frequently causes vomiting and diarrhoea.

It is not clear whether camphor toxicity is due to the
parent compound, a metabolite (secondary alcohols,
including borneol and isomers of hydroxy-camphor), or
both (Kresel, 1982).
7.1.2 Pharmacodynamics
Camphor is used exclusively because of its local
effects. When rubbed on the skin, it acts as a
rubefacient and causes localized vasodilatation
(mediated by way of an axon reflex), which gives
feelings of comfort and warmth.

As an anti-pruritic gent, when applied gently on the
skin, it may create a feeling of coolness, and a mild,
local anaesthetic effect, which may be followed by
numbness.

When ingested in small amounts, it creates feelings of
warmth and comfort in the stomach, but given in large
doses it acts as an irritant (Goodman et al 1985).
7.2 Toxicity
7.2.1 Human data
7.2.1.1 Adults
The probable oral lethal dose is 50 to 500
mg/kg. A dose of 2 g generally causes toxic
effects in adults. The potential lethal oral
dose in adults is 4 g pure camphor.
7.2.1.2 Children
The lethal dose for children is estimated to be
0.5 to 1.0 g (Siegel & Wason, 1986); for infants,
the oral LDLo is 70 mg/kg.
7.2.2 Relevant animal data



Species Route Effect Dose mg/kg


Rat Intraperitoneal LDLo 900


Mouse Intraperitoneal LD50 3000


Mouse Subcutaneous LDLo 2200


Dog Oral LDLo 800

Cat Intraperitoneal LDLo 400


Rabbit Oral LDLo 2000


Frog Subcutaneous LDLo 240


Guinea-pig Oral LDLo 1800

7.2.3 Relevant in vitro data
Not relevant.
7.3 Carcinogenicity
Carcinogenicity tests have been negative.
7.4 Teratogenicity
No data available.
7.5 Mutagenicity
Not mutagenic with the Ames test.
7.6 Interactions
Oils, alcohols, and fats promote gastrointestinal absorption.
Although vaseline oil has been used for gastric
decontamination, its use is controversial.
7.7 Main adverse effects
There have been reports of instant collapse in infants after
camphor has been applied to their nostrils (Reynolds, 1982).
8. TOXICOLOGICAL ANALYSES 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
General: Serum camphor levels are not
clinically useful.

A level of 15 mg/l within 20 minutes of
ingestion caused no symptoms.

A level of 19.5 microgram/l 7 h after ingestion
caused convulsions (Phelan,1976).
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
8.6 References
9. CLINICAL EFFECTS
9.1 Acute poisoning
9.1.1 Ingestion
The symptoms that occur within 5 to 90 min after
ingestion are: oral and epigastric burning sensations,
nausea, vomiting and feeling of warmth.

Mydriasis and impairment of vision have been reported.

Other symptoms are: headache, confusion, vertigo,
excitement, restlessness, delirium, and hallucinations;
increased muscular excitability, tremors, and jerky
movements; epileptiform convulsions followed by
depression; convulsions sometimes occur early in cases
of poisoning and may be severe; coma; CNS depression may
at times be the primary clinical response.

Death results from respiratory failure or from status
epilepticus.
9.1.2 Inhalation
Inhalation of concentrations above 2 ppm irritates the
nose and throat (mucous membranes). Respiratory
depression and apnoea may occur. Very large exposures
will cause the same clinical features as ingestion.
9.1.3 Skin exposure
Camphor may be a skin irritant. Acute poisoning may
occur after skin absorption. (Symptoms may be the same
as those that occur after ingestion, see section 9.1.1).
9.1.4 Eye contact
Camphor may be somewhat irritating to the eyes, but no
serious injuries have been reported.
9.1.5 Parenteral exposure

Camphor was formerly used parenterally as a circulatory
and respiratory stimulant; therefore, there is a
theoretical possibility of overdose or
poisoning by the parenteral route (clinical features as
in section 9.1.1).
9.1.6 Other
No data available.
9.2 Chronic poisoning
9.2.1 Ingestion
Symptoms include viral illness, rapid neurological
deterioration, liver injury, prolonged prothrombin time,
and low blood glucose were observed in a 6-month-old
male child who received a total dose of 3 g/kg over a 5
month period (Jimenez et al 1983).
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
If the patient survives for 24 h, recovery is likely. Death
results from respiratory failure during a convulsion or from
status epilepticus, and may also result from exhaustion and
circulatory collapse. Death may occur during an early
convulsion or as late as 20 h after ingestion.
9.4 Systematic description of clinical effects
9.4.1 Cardiovascular
Peripheral circulatory collapse and shock have been
reported (Vasey & Karayannopoulus, 1972).
9.4.2 Respiratory
Respiratory depression and apnoea may occur. Death
usually results from post-convulsive respiratory
depression.

The odour of camphor may be detected on the breath.
9.4.3 Neurological
9.4.3.1 CNS
Seizures are characteristic of camphor toxicity
and may occur suddenly, even without previous
symptoms. Confusion, hallucinations, tremors,
agitation, and irritability can also be
observed. Convulsions may be followed by CNS
depression and coma.
9.4.3.2 Peripheral nervous system
There is neuromuscular hyperactivity.
9.4.3.3 Autonomic nervous system
No data available.
9.4.3.4 Skeletal and smooth muscle
Increased muscular activity and tremor
(Ellenhorn & Barceloux, 1988).
9.4.4 Gastrointestinal

Oral and epigastric burning sensations, nausea, and
vomiting usually occur shortly after ingestion.

Symptoms may be delayed for several hours if food is
present in the stomach (Ellenhorn & Barceloux, 1988).
9.4.5 Hepatic
Mild and transient hepatic derangement may occur with
elevation of serum concentrations of SGOT, ALAT, SGPT,
and lactic dehydrogenase.
9.4.6 Urinary
9.4.6.1 Renal
Urinary retention, albuminuria, and anuria have
been described (Smith & Margolis, 1954).
9.4.6.2 Other
No data available.
9.4.7 Endocrine and reproductive systems
No data available.
9.4.8 Dermatological
Camphor may be a skin irritant when applied in excessive
amounts or too vigorously.
9.4.9 Eye, ear, nose, throat: local effects
Eyes: Camphor is an eye irritant. Keratitis is
normally transient.

Ear: No data available (but camphor is probably
irritating).

Nose: Camphor irritates the nose at concentrations
above 2 ppm or when applied directly on mucous
membranes.

Throat: Camphor may irritate mucous membranes and cause
burning pain in the mouth or throat.
9.4.10 Haematological
No data available.
9.4.11 Immunological
No data available.
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: Camphor crosses the placenta and has been
implicated in fetal and neonatal death. It has been
used to induce abortions. Camphor poisoning during
pregnancy was reported in four cases and, in each case,
camphorated oil was mistaken for castor oil (Weiss &
Capalano, 1973). The topical use of camphorated oil in
pregnancy was not associated with teratogenic effects.


Breast feeding: no data available .
9.5 Other
No data available.
9.6 Summary
10. MANAGEMENT
10.1 General principles
If 10 mg/kg has been ingested and no symptoms appear within
4 h there is no need for hospital admission (Blodgett
Regional Poison Centre, 1987).

If 30 mg/kg have been ingested, the patient must be admitted
to hospital for gastric lavage if indicated (see section
10.4) (Geller et al 1984).

Establish respiration

Treat convulsions

Initiate gastric lavage only after airway has been
protected.

Do not induce vomiting

Administer activated charcoal and then a cathartic

Resin or charcoal haemoperfusion may be indicated in very
severe cases.
10.2 Relevant laboratory analyses
10.2.1 Sample collection
Blood and urine for biomedical analysis

Sample of the product for identification.
10.2.2 Biomedical analysis
Routine blood and urine analysis

In particular:

Hepatic transaminases and LDH

Albuminuria

EEG (Phelan, 1976).
10.2.3 Toxicological analysis
Tests for qualitative and quantitative determination
of camphor levels in serum/blood are generally not
available. They can be performed by gas
chromatography (Phelan, 1976).
10.2.4 Other investigations
10.3 Life supportive procedures and symptomatic/specific
treatment
Support respiratory and cardiovascular functions

Treat seizures with:

Diazepam IV


Adults: 5 to 10 mg initially, which may be repeated every
10 to 15 min to a maximum of 30 mg.

Children: 0.25 to 0.4 mg/kg up to a maximum of 5 mg in
children aged 30 days to 5 years, and a maximum of 10 mg in
children over 5 years old.

If seizures cannot be controlled or if they recur,
administer phenytoin or phenobarbital.

Phenytoin

Adults: 150 to 250 mg of phenytoin-sodium by slow
intravenous injection at a steady rate of not more than 50
mg/min. An additional 100 to 200 mg may be given 30 min
later if necessary (Reynolds, 1982).

Children: 5 mg/kg in one dose or divided into two doses
(Reynolds, 1982).

Phenytoin administered intravenously can prevent a relapse
into a convulsive state. It should be administered very
slowly in order to avoid cardiac arrhythmias.

Phenobarbital

Adults: initially 200 mg intramuscularly that can be
repeated after 6 h if necessary (Reynolds, 1982).

Children: initially 3 to 5 mg/kg intramuscularly (Reynolds,
1982).

Doubts have been expressed as to the efficacy of
henobarbitone by intramuscular injection in an emergency
because of the slowness of absorption.

Control renal function.
10.4 Decontamination
Ingestion

Camphor is a convulsant: do not induce vomiting. Gastric
lavage is contraindicated unless it is performed immediately
after ingestion or after the airway has been protected
(endotracheal intubation), and when the camphor ingested is
in solid form (Bozza-Marrubini et al 1987).

If the amount of ingested camphor is small, give a saline
cathartic.

Activated charcoal should be administered in the usual doses
of 30 to 100 g in adults and 15 to 30 g in children.

Saline carthartics are indicated a few minutes after
activated charcoal has been given, and should be stopped
when a charcoal stool appears.


Dose of sodium sulfate: 20 to 30 g in adults and 250 mg/kg
in children

Dose of sorbitol: 30 to 50 g orally in adults.

Eye contact

Keep eyelids apart using your finger and flush eyes with
large amounts of water for at least 15 min. Keratitis is
normally transient, but if it persists, an opthalmic
examination should be performed.

Skin contact

Wash exposed area very thoroughly with soap and water.
10.5 Elimination
Both lipid haemodialysis and resin haemoperfusion have been
helpful in lowering blood camphor concentrations (Kopelman
et al, 1979).

Aqueous haemodialysis is ineffective in removing camphor.
In one patient lipid dialysis with soyabean oil removed
camphor effectively, but it is not routinely recommended
(Ginn et al, 1968).

Amberlite resin haemoperfusion was used in 1 patient;
camphor was cleared from the blood and the patient had a
good recovery (Kopelman et al, 1979).

Charcoal haemoperfusion has proven effective (Mascie-Taylor
et al, 1981)
10.6 Antidote treatment
10.6.1 Adults
There is no specific antidote.
10.6.2 Children
There is no specific antidote.
10.7 Management discussion
11. ILLUSTRATIVE CASES
11.1 Case reports from literature
Camphor has occasionally been used in attempts to induce
abortion (Briggs et al 1965): it was detected in maternal
blood 15 min after ingestion, but not after 8 h. At
delivery 36 h later, however, it was present in the amniotic
fluid, the umbilical cord, and in the fetal blood. This
distribution might reflect immature hepatic glucuronic
conjugation in the fetus - a major detoxication process for
camphor in adults. The infant appeared viable at birth, but
failed to initiate respiration. Post-mortem examination
revealed severe atelectasis and CNS-necrosis (Gosselin et al,
1984).

A patient who ingested approximately 60 g of camphorated oil
(i.e., 12 g pure camphor) was successfully treated by lipid
haemodialysis (Ginn et al, 1968).

A 3 year-old girl swallowed 1 tablespoon of camphor-
containing salve and developed violent vomiting, convulsions,
and respiratory depression (Anon, 1975).

A 2-year-old girl swallowed 2 teaspoons of a camphor
preparation and had violent vomiting but no convulsions
(Anon, 1975).

A 19-month-old infant died after ingesting 1 g of a camphor
product; autopsy showed haemorrhage and brain cell
degeneration (Anon, 1975).

A man attempted suicide with 150 ml of camphorated oil, i.e.,
30 g pure camphor (the potential lethal dose in an adult is
4 g pure camphor). He had peripheral circulatory shock and
severe dehydration because of vomiting. Severe and
prolonged grand-mal attacks occurred. The patient was fit
and well 36 h after intensive treatment. This is one of the
largest camphor overdoses of camphor associated with
survival (Vasey & Karayannopoulus, 1972; Reynolds, 1982).

A 12-year-old boy given approximately 30 g camphorated oil
(20% camphor) developed coma and convulsions. After
treatment with diazepam, his condition improved, and he was
discharged from hospital on the 3rd day (Aronow & Spigiel,
1976).

A 33-year-old woman ingested 115 g camphorated oil (20%
camphor); she had several convulsions in hospital, but was
discharged after 4 days in the intensive care unit (Aronow &
Spigiel, 1976).

A 37-year-old man ingested 18 g pure camphor and developed
grand-mal seizures. He was treated by haemoperfusion; an
amberlite system was more effective than lipid dialysis in
extracting camphor from the blood (Kopelman et al, 1979).

A 19-year-old girl ingested 60 g camphorated oil (20%
camphor) and had grand-mal seizures; she was discharged from
hospital after 13 days of treatment (Kopelman et al, 1979).

A 15-year-old boy ingested 60 g camphorated oil (20%
camphor) and had grand-mal seizures; he was discharged from
hospital after 2 days of treatment (Kopelman et al, 1979).

A 61-year-old man ingested 60 g camphorated oil (20%
camphor) and developed status epilepticus and coma; after
treatment in hospital he fully recovered (Antman et al,
1978).

A 56-year-old woman ingested 12 ml camphorated oil (20%
camphor). She had nausea, vomiting, and convulsions. The
odour of camphor on her breath helped to diagnose her
condition. Lipid haemodialysis with soybean oil dialysate
was performed for 4 to 5 h and she recovered fully (Antman
et al, 1978).


A 6-month-old boy received a total dose of 3 g/kg camphor
over a 5-month period and developed clinical symptoms
consistent with a diagnosis of Reye's syndrome (Jimenez et
al, 1983).

A 3-year-old girl ingested 7OO mg camphor from 1 tablespoon
of Vicks VapoRub (R). This product had also been placed in
her nostrils twice daily for 5 months. Grand-mal seizures
occurred 2 h after ingestion. Coma and respiratory
depression lasted 21 h. Full recovery ensued (Phelan,
1976).
11.2 Internally extracted data on cases
11.3 Internal cases
(to be added by PC using the monograph).
12. Additional information
12.1 Availability of antidotes
12.2 Specific preventive measures
Keep pharmaceutical preparations and moth-repellents out of
the reach of children and irresponsible people.

Label camphorated oil appropriately to avoid mistaking it
for castor oil and cough syrups.

Do not place camphor ointments into infants' nostrils.

Do not use the rubefacient on abraded skin.

In the workplace, the maximum permissible atmospheric
concentration is 2 ppm.
12.3 Other
No data available.
13. REFERENCES
Abdernalden's Handbuck der Biologischen Arbveitsmetoden (1935)
Vol 4, p l289 Leipzig, Germany.

Anon (1975) Camphor may do more harm than good. J Am Med Assoc
234: No 2, p l45.

Antman E, Jacob G, Volpe B, Finkel S & Savona M (1978) Camphor
Overdosage: therapeutic considerations. NY State J Med, 6: 896-
897.

Arena JM (197O) Poisoning. Toxicology, Symptoms, Treatments.
2nd Ed, p 73. Springfield, Illinois, CC Thomas.

Aronow R (1976). Camphor Poisoning. J Am Med Assoc, 235: l26O.

Aronow R & Spigiel RW (1976) Implications of Camphor Poisoning.
Drug Intelligence and Clinical Pharmacy, lO: 63l.

Baselt RC (1982) Disposition of toxic drugs and chemicals in
man. 2nd ed, pll2. California, Biomedical Publications.

Bozza-Marrubini ML, Ghezzi R, Ucelli P (1987) Intossicasioni
acute 2nd ed. Org Editoriale Medico Farmacentica Milano.


Briggs GG, Freeman RK & Yaffe SJ (1986) Drugs in pregnancy and
lactation. 2nd ed p 56c Baltimore, Williams & Wilkins.

"Documentation of Threshold Limit Values for Substances in
Workroom Air" (1971). Cincinnati, Ohio, Amer Conf of
Governmental Industrial Hygienists, Vol;3 p 37.

Dreisbach RH & Robertson WD (1987) Handbook of Poisoning. l2th
ed p 419 Connecticut, Appleton & Lange.

Dupeyron IP, Quattrocchi F, Castaing H & Fabiani P (1976) Child
poisoning after external application of a revulsive ointment.
Eur J Toxicol, 9: 3l3-32O.

Ellenhorn MJ, Barceloux DG (1988) Medical Toxicology - Diagnosis
and Treatment of Human Poisoning, 1st ed, New York, Elsevier.

Fuhner H (1932) Beitrage zer vergleichenden Pharmakologie I. Die
giftigen und t÷dlichen Gaben einiger substanzen fnr fr÷sche und
m_use. Nauynschmiedebergs Archir fnr Experimentelle Pathalogie
und Pharmacologie, 166: 443.

Geller RJ, Spyker DA, Garrettson LK & Rogol AD (1984) Camphor
toxicity. Development of a triage system. Vet Hum Toxicol,
(Suppl 2): 8-10.

Ginn HE, Anderson KE, Mercier RK, Stevens TW, Matter BJ (1968)
Camphor Intoxication Treated by Lipid Dialysis. J Am Med Assoc
2O3: 23O-23l.

Goodman LS, Gilman AG, Rall TW & Murad F (1985) Goodman and
Gilman's The Pharmacological Basis of Therapeutics, 7th ed, New
York, Macmillan.

Gosselin RE, Hodge HC, Smith RP & Gleason MN (1984). Clinical
Toxicology of Commercial Products, 4th ed p 259 & p 84. USA,
Williams & Wilkins.

Grant WM (1986). Toxicology of the eye. 3rd ed Springfield, CC
Thomas.

Haddad LM & Winchester JF (1983). Clinical Management of
Poisoning and Drug Overdose, p 428-43l. Philadelphia, W.B
Saunders & Co.

Hawley, GG (1981). The Condensed Chemical Dictionary. 10th ed
New York, van Nostrand Reinhold Co.

Jimenez JF, Brown AL, Arnold WC (1983). Chronic camphor
ingestion mimicking Reye's syndrome. Gastroenterology 84: 394-
398.

Kelly RC, Kopelman RC, Sunshine I (1976) A simple gas
chromatographic procedure for the determination of camphor in
plasma. J Anal Toxicol 3: 76.


Kopelman R, Miller S, Kelly RC & Sunshine I (1979). Camphor
Intoxication Treated by Resin Hemoperfusion. J Am Med Assoc 24l:
727-728.

Koppel C, Tenczer J, Schirop TH & Ibe K (1981). Camphor
poisoning. Abuse of camphor as a stimulant. Arch Toxicol 51:
101-106.

Kresel JJ (1982) Camphor. Clin Toxic Rev, 4(7): l.

Mascie-Taylor BH, Widdop B, Davison AM (1982) Camphor
intoxication treated by hemoperfusion. Postgrad Med J, 57: 725-
726.

Merck Index (1983) lOth ed p 238, (1983). New Jersey, Merck & Co
Inc.

Phelan WJ (1976) Camphor poisoning: over the counter dangers.
Pediatrics, 57: 427-43l.

Plunkett (1987) Handbook of Industrial Toxicology, 3rd ed p l64.
London Edward Arnold.

Poisindex, February 1988.

Proctor NH & Hughes JP (1978) Chemical Hazard of the Workplace,
p l43. Philadelphia, Lippincott.


Reynolds EF (ed) (1982). Martindale, The Extra Pharmacopoeia,
28th ed, p 35l. London, Pharmaceutical Press.

Sampson WL & Fernandez L (1939). Experimental convulsions in the
rat. J Pharmacol Exp Ther, 65: 275-280.

Sax NI (1977). Dangerous Properties of Industrial Materials. 6th
ed, p 625. New York, van Nostrand Reinhold.

Siegel E & Wason S (1986). Camphor toxicity. Pediatric Clinics
of North America, 33: 375-379.

Sittig M (1985). Handbook of Toxic and Hazardous Chemicals and
Carcinogens. 2nd ed New Jersey, Noyes.

Skoglund RR, Ware LL Jr, Schanberger JE (1977). Prolonged
seizures due to contact and inhalation exposure to camphor. A
case report. Clin Pediatr, l6: 9Ol-9O2.

Smith EG, Margolis G (1954). Camphor poisoning: anatomical and
pharmacological study. Report of a fatal case. Experimental
investigation of protective action of barbiturates. Am J Pathol,
3O: 857-868.

Thienes CH & Haley TJ (1972). Clinical Toxicology, 5th ed p l6.
Philadelphoa, Lea & Febiger.


Trestrail JH & Spartz EM (1977). Camphorated and castor oil
confusion and its toxic results. Clin Toxicol, ll: l5l-l58.

Vasey RH & Karayannopoulus SJ (1972). Camphorated oil. Brit Med,
1l2.

Weiss J, Capalano P (1973). Camphorated oil intoxication during
pregnancy. Pediatrics, 52: 7l3-74O.
14. AUTHOR(S), REVIEWER(S), DATE(S) (INCLUDING UPDATES), COMPLETE
ADDRESS(ES)
Author: Elsa Wickstrom
National Poison Center
P.O. Box 8189 DEP
0034 Oslo
Norway

Tel: 47-2-456063
Fax: 47-2-454374

Date: 29 February 1988.

Peer review: Hamilton, Canada, May 1989

 


See Also:
Camphor (UK PID)

 

INTOX Home Page

ACUTE DYSTONIA

DEFINITION

Dystonia is a brief or sustained muscle spasm, often with slow
abnormal movements. Although any muscle group may be involved, it
most commonly affects facial muscles (eyes, jaw, tongue).

TOXIC CAUSES

Numerous pharmaceutical agents are associated with acute dystonic
reactions. Important examples include:

Benzamides: metoclopramide
sulpiride
Butyrophenones: haloperidol
Chloroquine and hydroxychloroquine
Cocaine
Levodopa
Lithium
Phenothiazines, especially piperazine compounds:
trifluoperazine
perphenazine
fluphenazine
prochlorperazine
thiethylperazine

Serotonin syndrome and neuroleptic malignant syndrome are specific
toxic syndromes, associated with increased muscle tone, that
require specific management.

NON-TOXIC CAUSES

Degenerative: Spinocerebellar degeneration

Focal dystonias: Blepharospasm
Writer's cramp

Infective: Encephalitis
Tetanus

Metabolic: Thyrotoxicosis
Wilson's disease

Structural: Arterio-venous malformation
Cerebrovascular accident
Tumour

CLINICAL FEATURES

Onset of dystonia may occur up to 20 hours following the
administration of the causative agent.

Various types of dystonia, involving particular muscle groups have
been described:

Laryngeal dystonia - spasm of pharyngeal and laryngeal muscles
resulting in stridor.

Oculogyric crisis - spasm of extra-ocular muscles, forcing the
eyes into upward or lateral gaze.

Opisthotonus - spasm of all paravertebral muscles, forcing the
trunk and neck into hyperextension.

Retrocollis - spasm of paravertebral neck muscles, forcing the
neck into hyperextension.

Torticollis - spasm of lateral neck muscles, twisting the neck
to one side.

DIFFERENTIAL DIAGNOSIS

Catatonic states
Dyskinesias
Seizures (tonic phase)

RELEVANT INVESTIGATIONS

Usually, no specific investigations are required to evaluate acute
toxic dystonias. Where indicated, the following may be useful:

CPK
EEG or CT scan of head (to exclude seizures or central organic
lesions)
Toxicology screens
Urinalysis

TREATMENT

Dystonias may increase in severity after initial presentation and
therefore all patients should be treated. Initial treatment is
usually provided with a parenteral formulation, followed by oral
medication for 2 to 3 days to prevent recurrence. Milder forms can
be treated with oral medication alone.

Suggested agents include:

Benztropine 1 to 2 mg by intramuscular or intravenous injection
(0.02 mg/kg in children). This dose may be repeated in 10 minutes
if the response is incomplete and anticholinergic side effects have
not occurred. Follow with 1 mg (0.02 mg/kg in children) orally
every 12 hours for 2 days. Benztropine is not the agent of choice
in children less than 3 years of age.

Diphenhydramine 1 mg/kg intravenously or intramuscularly to a
maximum of 30 mg. This dose may be repeated in 30 minutes if the
response is incomplete and anticholinergic side effects have not
occurred. Follow with 25 mg (0.5 mg/kg in children) orally, every
6 hours for 2 days.

Diazepam 0.1 mg/kg by slow intravenous injection. This dose may
by repeated in 30 minutes if the response is incomplete and
excessive sedation has not occurred.

Procyclidine 5 to 10 mg (0.5 to 2 mg in children under 2 years
of age, 2 to 5 mg in children over 2 years of age) intramuscularly
or intravenously. This dose may be repeated after 20 minutes if
the response is incomplete. Follow with 2.5 mg orally every 8
hours for 2 days.

CLINICAL COURSE AND MONITORING

Patients should be observed until symptom free. Prior to
discharge, they should be instructed that recurrent dystonia can
occur for up to 48 hours. In this event, they should return for
medical evaluation. The clinical course may be prolonged in the
case of dystonic reactions following injection of depot
preparations.

LONG-TERM COMPLICATIONS

Unusual.

AUTHOR(S)/PEER REVIEW

Author: Robert Dowsett
Consultant Toxicologist
Departments of Clinical Pharmacology and Emergency
Medicine
Westmead Hospital
Westmead, NSW 2145
Australia

Peer Review: London, March 1998: P. Dargan, T. Della Puppa, L.
Murray, A. Nantel, M. Nicholls.