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Ruta graveolens L.

1. NAME
   1.1 Scientific name
   1.2 Family
   1.3 Common name(s) of the plant and synonyms (in each country)
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
   2.5 Poisonous parts
   2.6 Toxins
3. CHARACTERISTICS
   3.1 Description of the plant
      3.1.1 Special identification features
      3.1.2 Habitat
      3.1.3 Distribution
   3.2 Poisonous parts of the plant
   3.3 The toxin(s)
      3.3.1 Name(s)
      3.3.2 Description, chemical structure, stability
      3.3.3 Other physico-chemical characteristics
   3.4 Other chemical contents of the plant
4. USES/CIRCUMSTANCES OF POISONING
   4.1 Uses
   4.2 High risk circumstances
   4.3 High risk geographical areas
5. ROUTES OF ENTRY
   5.1 Oral
   5.2 Inhalation
   5.3 Dermal
   5.4 Eyes
   5.5 Parenteral
   5.6 Others
6. KINETICS
   6.1 Absorption by route of exposure
   6.2 Distribution by route of exposure
   6.3 Biological half-life by route of exposure
   6.4 Metabolism
   6.5 Elimination by route of exposure
7. TOXICOLOGY/TOXINOLOGY/PHARMACOLOGY
   7.1 Mode of action
   7.2 Toxicity
      7.2.1 Human data
         7.2.1.1 Adults
         7.2.1.2 Children
      7.2.2 Animal data
      7.2.3 Relevant in vitro data
   7.3 Carcinogenicity
   7.4 Teratogenicity
   7.5 Mutagenicity
   7.6 Interactions
8. TOXICOLOGICAL/TOXINOLOGICAL AND BIOMEDICAL INVESTIGATIONS
9. CLINICAL EFFECTS
   9.1 Acute poisoning:
      9.1.1 Ingestion
      9.1.2 Inhalation
      9.1.3 Skin exposure
      9.1.4 Eye contact
      9.1.5 Parenteral exposure
      9.1.6 Other
   9.2 Chronic poisoning by:
      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 muscles:
      9.4.4 Gastrointestinal
      9.4.5 Hepatic
      9.4.6 Urinary
         9.4.6.1 Renal
         9.4.6.2 Others
      9.4.7 Endocrine and reproductive systems
      9.4.8 Dermatological
      9.4.9 Eyes, ears, 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 Others
10. MANAGEMENT
   10.1 General principles
   10.2 Relevant laboratory analyses and other investigations
      10.2.1 Sample collection
      10.2.2 Biomedical analysis
      10.2.3 Toxicological/Toxinological analysis
      10.2.4 Other investigations
   10.3 Life supportive procedures and symptomatic 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 (added by the PC using monograph)
12. ADDITIONAL INFORMATION
   12.1 Availability of antidotes and antisera
   12.2 Specific preventive measures
   12.3 Other
13. REFERENCES
   13.1 Clinical and toxicological
   13.2 Botanical
14. AUTHOR(S), REVIEWER(S) DATE (INCLUDING EACH UPDATING)
    1.    NAME

      1.1   Scientific name

            Ruta graveolens L.

      1.2   Family

            Rutaceae

            The rutaceae family consists in more than 1600 different 
            species of shrubs and small trees that grow mostly in temperate 
            countries of the Old and New World. They produce a great number 
            of essences, alkaloids and glucosides.  The species of 
            toxicological importance are Ruta graveolens and Ruta 
            chalepensis. 

      1.3   Common name(s) of the plant and synonyms (in each country)

            Ruda (Latin-America, Spain)
            Arruda (Spain)
            Erruda (Spain)
            Arroda (Spain)
            Rue (USA, UK)
            Herb of grace (USA, UK)
            Country man's treacle (USA, UK)
            Herbygrass (USA, UK)
            Rue officinale (Fr.)
            Rue fetide (Fr.)
            Herbe de grace (Fr.)

    2.    SUMMARY

      2.1   Main risks and target organs

            Vomiting, diarrhoea, epigastric pain, sialorrhoea, acute 
            gastroenteritis.  

            Hepatic and renal impairment.  Haemodynamic alterations and 
            shock in severe cases.  Uterine haemorrhage and abortion in 
            pregnancy.  Seizures may be observed.  Death can occur either 
            as a result of severe haemodynamic disturbances or secondary to 
            hepatorenal insufficiency. 

      2.2   Summary of clinical effects

            After ingestion of the plant or its infusion, the patient may 
            develop acute epigastric pain, vomiting and salivation.  Oedema 
            and fibrillary movements of the tongue may be observed.  
            Excitation may precede seizures.  Hypotension and bradycardia 
            may be followed by haemodynamic shock. 

            In women, hypogastric pain, uterine haemorrhage and abortion 
            may occur. 

            Death may occur ear;y after ingestion, or later secondary to 
            hepatorenal insufficiency.  In case of cutaneous contact with 
            the plant, dermatitis due to photosensitization may be 
            observed. 

      2.3   Diagnosis

            No specific toxicological analysis is usually required, except 
            for the pharmacognostic identification of the plant specimen.  
            Laboratory tests required for treatment and follow-up include 
            urinalysis, blood count, hepatic and renal functional studies, 
            and any other examination relevant to the clinical evolution.  
            A plant specimen should be collected (as complete as possible) 
            for botanical identification. In case of ingestion of an 
            infusion, the infusion should be kept for assay of the active 
            principles and their concentration. 

      2.4   First-aid measures and management principles

            In case of ingestion of the plant or infusion, perform gastric 
            lavage with an orogastric tube if the clinical condition of the 
            patient allows it, followed by administration of activated 
            charcoal.  There is no antidote.  Treatment is symptomatic, 
            based upon maintenance of vital functions and correction of 
            hepatic or renal insufficiency.  Haemodialysis may be required.  
            Consultation with other specialists (nephrologist, 
            gynaecologist) may be required. 

      2.5   Poisonous parts

            All the parts of the plant contain the active principles, 
            especially the leaves. 

      2.6   Toxins

            They are:  rutine (glycoside), furocoumarins, alkaloids 
            (quinolones), tannin and essential oils.  Furocoumarins are 
            responsible for photosensitization, hepatotoxicity and 
            nephrotoxicity; methyl-nonyl-ketone (an essential oil) has 
            effects on the uterus. 

    3.    CHARACTERISTICS

      3.1   Description of the plant  

            3.1.1 Special identification features
   
                  This is a hardy, evergreen shrub of up to one metre tall, 
                  with a characteristic greyish color and a sharp 
                  unpleasant odour.  The leaves are small, oblong, deeply 
                  divided, pinnate, glandular dotted (when looked at 
                  against the light they have translucid little points). 
                  The stems are very ramified. The flowers are small (13 
                  mm), yellow and in clusters during Spring and Summer. 
                  They have 4 petals, except for the central flower,  which 
                  has 5 petals. The fruits are round, small and 4- or 5-

                  lobulated.  The taste is slightly stinging but is masked 
                  by the strong bitter odour (Font-Quer, 1979). 


            3.1.2 Habitat
 
                  Ruta is an ornamental, aromatic, culinary and medicinal 
                  plant, cultivated in gardens.  It prefers rocky, well-
                  drained soils and it resists dry weather. 

            3.1.3 Distribution

                  It is native to Europe, specially the Mediterranean 
                  region, but widely distributed into all the temperate and 
                  tropical regions.  It is a very popular and attractive 
                  garden shrub in South America, where it is grown not only 
                  for ornamental and medicinal reasons but also because of 
                  the belief that it provides protection against evil. 

      3.2   Poisonous parts of the plant

            All parts of the plant contain the active principles, although 
            they are mostly encountered in leaves (especially before 
            blooming). 

      3.3   The toxin(s)

            3.3.1 Name(s)

            The main active principles of the plant are:

            a)    glycosides, such as rutine, a flavonoid. 

            b)    alkaloids (quinolones): coquisagenine, skimmianine and 
                  graveoline. 

            c)    furocoumarins (psoralens):  bergaptene (3-
                  methoxypsoralen) and xantotoxine (8-methoxypsoralen). 

            d)    essential oils:  methyl-nonyl-ketone, methyl-n-octyl-
                  ketone and methyl-heptyl-ketone. 

            e)    alcohols: methyl-ethyl-carbinol, pinene, limenenes.

            f)    other compounds are:  dictamine, gammafagarine, 
                  skimmianine, pteleine and kokusaginine. 
      
                  The active principles of clinical importance are the  
                  psoralens, responsible for hepatoxicity and 
                  photosensitization and methyl-nonyl-ketone, which 
                  accounts for effects on the uterus. 

            3.3.2 Description, chemical structure, stability

                  Methyl-nonyl-ketone = C11 H22 O


            3.3.3 Other physico-chemical characteristics

                  


      3.4   Other chemical contents of the plant

            Tannin, resins and ascorbic acid have also been found in the 
            plant. 

            The composition of ruta essence is 90% methyl-heptyl-ketone and 
            methyl-nonyl-ketone, but other components are:  l-a-pineol, 
            cineol and l-limonene (approximately 1% and methyl-n-
            nonylcarbinol. 

            The dried herb contains a small amount of volatile oil (about 
            0.1%). 

    4.    USES/CIRCUMSTANCES OF POISONING

      4.1   Uses

            Culinary use:  as an aperitif in alcoholic beverages (very 
            bitter taste) and as an additive to salads, meats and cheeses 
            in some European countries. 

            Medicinal use: Rue oil and infusions of rue were formerly used 
            as antispasmodics and emmenagogues. Rue oil is a powerful local 
            irritant (Martindale, 1982). It is recommended in herbal 
            treatment of insomnia, headaches, nervousness, abdominal 
            cramps, and renal troubles. It is a well-known emmenagogue. The 
            plant may be part of sedative and hypnotic herbal preparations 
            (rue oil is a commonly-used homoeopathic medicine as 
            rubefacient, for certain dermatoses as eczemas and psoriasis), 
            and as an antiviral agent (Vigneau, 1985) when combined with 
            other herbs. 

            Applied or rubbed on the skin it has a rubefacient effect (for 
            rheumatic pains). 
      
            The most frequent, intentional use of the plant has been for 
            induction of abortion. 
      
      4.2   High risk circumstances

            Although some cases of poisoning are due to errors in the 
            preparation of medicinal infusions, most clinical cases are due 
            to intentional ingestion to induce abortion.  The traditional 
            medicinal infusion is made with a full spoon of leaves per 250 
            ml of boiling water and not more that 2 cups are generally used 
            per day.  In case of intentional abortion the preparation is 
            highly concentrated and usually mixed with other herbs. 

            Dermatitis may be observed in persons that manipulate the plant 
            and are exposed to the sun (occupational photodermatitis). 


      4.3   High risk geographical areas

            In Mediterranean and South American countries the plant is 
            widely spread and well-known; severe cases of poisoning are 
            reported in countries where voluntary abortion is illegal. 


    5.    ROUTES OF ENTRY

      5.1   Oral

            This is the main route of entry, usually by drinking an 
            infusion prepared from the leaves. 

      5.2   Inhalation  

            No data available.

      5.3   Dermal

            Contact with the plant may cause irritation or 
            photosensitization. 

      5.4   Eyes  

            No data available.

      5.5   Parenteral

            No data available.

      5.6   Others  

            No data available.

    6.    KINETICS

      6.1   Absorption by route of exposure

            No data available.

      6.2   Distribution by route of exposure

            No data available.

      6.3   Biological half-life by route of exposure

            No data available.

      6.4   Metabolism

            No data available.

      6.5   Elimination by route of exposure

            No data available.

    7.    TOXICOLOGY/TOXINOLOGY/PHARMACOLOGY

      7.1   Mode of action    

            Methyl-nonyl-ketone induces uterine contractions and pelvic 
            congestion, leading to uterine haemorrhage and possibly 
            abortion in pregnancy (Jouglard, 1977). 


            Psoralens or furocoumarins are photoactive chemicals that 
            applied to the skin and exposed to sunlight produce redness, 
            hyperpigmentation and blistering (Heskel et al, 1983).  
            Phototoxicity has also been found experimentally, in bacteria, 
            fungi and animal ovarian cells, in which mitosis is inhibited 
            and gross chromosomal changes occur. Furanoquinolones and 
            canthinones also produce phototoxic effects for which the 
            target seems to be the cell nucleus (Towers and Abramowsky, 
            1983). 

      7.2   Toxicity

            7.2.1 Human data

                  7.2.1.1  Adults
      
                        No data have been found on toxic doses of active 
                        principles, but it is known that ingestion arising 
                        from the traditional use of the infusion should not 
                        exceed 1 or 2 g/day of the plant. 

                  7.2.1.2  Children 

                        No data have been found on toxic doses for 
                        children, but in traditional medicine its use in 
                        children is contraindicated. 

            7.2.2 Animal data

                  Skimmianine was found to have significant inhibitory 
                  effect on spontaneous motor activity, exploratory 
                  behaviour, cataleptogenic activity, conditioned avoidance 
                  response and long-term isolation-induced fighting of 
                  animals, and some anti-methamphetamine effect was 
                  observed (Cheng, 1986). 

                  Extracts of Ruta graveolens demonstrated an anti-
                  implantation activity in Albino rats, inhibiting 
                  pregnancy in 50% to 60% of rats.  (Prakash et al, 1985). 

            7.2.3 Relevant in vitro data

                  No data available.

      7.3   Carcinogenicity  


            No data available.

      7.4   Teratogenicity   

            No data available.

      7.5   Mutagenicity

            Mutagenicity testing of a commercial extract form Rutae herba 
            (Tinctura Rutae), revealed a strong effect in a strain of 
            Salmonella typhimurium.  The extract contained furoquinoline 
            alkaloids dictamine, gamma-fagarine, skimmianine, pteleine and 
            kokusaginine, which may be partially responsible for the 
            mutagenic effect (Paulini et al, 1987). 

      7.6   Interactions   

            No data available.

    8.    TOXICOLOGICAL/TOXINOLOGICAL AND BIOMEDICAL INVESTIGATIONS


    9.    CLINICAL EFFECTS

      9.1   Acute poisoning:

            9.1.1 Ingestion

                  The usual route of poisoning is by ingestion of the plant 
                  or, more frequently, its concentrated infusion. There is 
                  a possibility of poisoning by the essence of Ruta. The 
                  patient may experience epigastric pain, vomiting and 
                  excessive salivation, followed by CNS excitation and 
                  seizures in severe cases.  Uterine bleeding and abortion 
                  occur in pregnant women.  The patient may have 
                  hypotension and bradycardia followed by shock.  Hepatic 
                  and renal insufficiency may develop in subsequent days. 

            9.1.2 Inhalation

                  No data available.


            9.1.3 Skin exposure

                  In case of prolonged skin contact with Ruta, an 
                  irritatant effect may be observed.  But after  exposure 
                  to sun, photodermatitis phenomena are intense due to the 
                  phototoxicity of psoralens.  Erythema, hyperpigmentation 
                  and even blistering may occur (Heskel et al, 1983, 
                  Brenner & Friedman, 1985). 

            9.1.4 Eye contact

                  No data available. 


            9.1.5 Parenteral exposure

                  No data available.

            9.1.6 Other  

                  No data available.

      9.2   Chronic poisoning by:

            9.2.1 Ingestion

                  Repetitive ingestion of Ruta, its infusion or essence may 
                  produce the same acute symptomatology but the onset may 
                  be delayed. 

            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

            In case of severe poisoning, the acute gastro-intestinal 
            symptomatology is followed by  haemodynamic alterations and 
            sometimes convulsions that may result in death during the first 
            two or three days.  If this phase is survived, hepatic 
            insufficiency may develop with jaundice and renal failure, 
            resulting in delayed death.  If the patient survives, complete 
            recovery is the rule, without sequelae. 

            The prognosis is poor in the presence of persistent 
            gastrointestinal symptoms, haemodynamic disorders, convulsions, 
            abortion, jaundice and oliguria. 

            Death occurs due to shock, seizures, and hepatic and renal 
            insufficiency. 

      9.4   Systematic description of clinical effects

            9.4.1 Cardiovascular

                  After acute poisoning, hypotension and bradycardia may 
                  precede haemodynamic shock.  Severe gastroenteritis may 
                  contribute to fluid loss and its cardiovascular 
                  consequences. 

            9.4.2 Respiratory

                  Coma may be complicated by respiratory impairment (e.g.
                  pneumonitis).

            9.4.3 Neurological

                  9.4.3.1     CNS

                        Convulsions may occur, preceded by excitation.

                  9.4.3.2     Peripheral nervous system 

                        No data available.
  
                  9.4.3.3     Autonomic nervous system 

                        No data available.

                  9.4.3.4     Skeletal and smooth muscles:  

                        No data available.

            9.4.4 Gastrointestinal

                  In acute poisoning, intense epigastric pain, nausea, 
                  vomiting, diarrhoea and hypersalivation are 
                  characteristic. Tongue oedema and fibrillation may be 
                  observed. 

            9.4.5 Hepatic

                  The first signs of hepatic damage occur 2 - 4 days after 
                  repeated or massive ingestion of Ruta; these include 
                  jaundice, coagulation disorders and metabolic imbalance 
                  (accompanied by renal failure). 

            9.4.6 Urinary

                  9.4.6.1     Renal

                        Acute renal failure may occur very early in severe 
                        cases and may determine the outcome. Renal failure 
                        usually results from acute tubular necrosis and 
                        requires immediate, repeated haemodialysis. 

                  9.4.6.2     Others  

                        No data available.


            9.4.7 Endocrine and reproductive systems

                  Acute severe poisoning is characterized by increased 
                  uterine contractility, with hypogastric pain, haemorrhage 
                  and abortion in case of pregnancy.  
      
                  No endocrine effects have been reported, although Ruta 
                  was traditionally indicated for reduction of 
                  spermatogenesis (Font-Quer, 1979). 

            9.4.8 Dermatological

                  Skin contact with Ruta may produce irritation but when 
                  also exposed to sun light it causes photodermatitis, with 
                  erythema and blistering. 

            9.4.9 Eyes, ears, nose, throat: local effects
      
                  Tongue irritation and oedema may be observed, possibly 
                  accompanied by fibrillary movements. 

            9.4.10 Haematological

                  Coagulation disorders are associated with hepatic 
                  insufficiency. 

                  Uterine bleeding is observed due to the effects of Ruta  
                  on the uterus. 

            9.4.11 Immunological

                  No data available.

            9.4.12 Metabolic

                  No data available.

                  9.4.12.1    Acid Base disturbances

                        May result from severe coma and hepatorenal failure 

                  9.4.12.2    Fluid and electrolyte disturbances

                        May result from severe gastroenteritis and 
                        hepatorenal failure. 

                  9.4.12.3    Others  

                        No data available.


            9.4.13 Allergic reactions

                  May occur, depending upon individual susceptibility.

            9.4.14 Other clinical effects

                  No data available.

            9.4.15 Special risks

                  Early pregnancy may be interrupted by the abortifacient 
                  effect of Ruta. 

      9.5   Others

            Unknown

    10.   MANAGEMENT

      10.1  General principles

            Decontamination by gastric lavage or emesis induction 
            (according to clinical state of the patient and the time 
            elapsed since ingestion).  Activated charcoal is recommended, 
            but cathartics are contraindicated in the presence of 
            diarrhoea. 

            Supportive care is paramount:  control seizures and correct 
            cardiovascular status and electrolyte imbalances in acute 
            poisoning. Hepatic and renal insufficiency should be managed 
            conventionally. 

            Mild cases will require decontamination and symptomatic 
            treatment of abdominal pain and gastroenteritis. 

            In case of topical irritation or phototoxicity, treatment is 
            symptomatic and may require topical corticosteroid therapy. 
      
      10.2  Relevant laboratory analyses and other investigations

            10.2.1 Sample collection

                  A sample of the plant (stem, leaves, flowers) should be 
                  collected for botanical identification. 

                  In case of ingestion of infusion or Ruta essence, the 
                  substance may be of interest for toxicological analysis. 

                  Blood and urine samples should be collected for routine 
                  examination and to assess the possibility of 
                  toxicological screening (e.g. ingestion of other drugs). 

            10.2.2 Biomedical analysis

                  The severely poisoned patient requires a routine 
                  screening, including serum electrolytes, creatinine and 
                  glucose; complete blood count (CBC), arterial blood gases 
                  (ABG), urinalysis and chest X-ray. 

                  Kidney function should be monitored with serum 
                  creatinine, urinalysis and urine output. 

                  Liver function should be evaluated via bilirubinaemia 
                  (total/direct) and serum concentrations of alanine-
                  aminotransferase (ALT, or SGPT), aspartate 
                  aminotransferase (AST, or SGOT). 

                  The need for other analyses (EKG, EEG, blood coagulation, 
                  blood cultures) will be determined by clinical need. 

            10.2.3 Toxicological/Toxinological analysis

            10.2.4 Other investigations
            
      10.3  Life supportive procedures and symptomatic treatment

            The patient should be hospitalized for clinical observation and 
            appropriate treatment. 

            1.    Monitor vital signs and airway status in case of coma.

            2.    Seizures should be controlled with diazepam 5 - 10 mg IV.  
                  Phenytoin is a suitable alternative as a second choice 
                  (10 - 15 mg/kg as a loading dose). 

            3.    The risk of infection (especially of uterine origin) 
                  should be investigated. 

            4.    Acid-base, electrolyte and osmolar balance should be 
                  closely monitored and treated accordingly, with adequate 
                  fluid replacement. 

            5.    Haemodialysis should be considered in cases with renal 
                  failure. 

            6.    Hepatic failure should be treated conventionally, with 
                  careful adjustment of fluid and electrolyte balance 
                  (avoiding overloading), reduction of protein intake and 
                  symptomatic care. 

            7.    Late abdominal pain may be treated with analgesic-
                  spasmolytic compounds. 

            8.    If abortion occurs, gynaecological evaluation is 
                  essential to determine whether intrauterine devices are 
                  present which may induce uterine bleeding and sepsis.  
                  Evidence of infection should be sought. 

      10.4  Decontamination

                  Empty the stomach by inducing vomiting or performing 
                  gastric lavage if the patient's clinical condition allows 
                  it and if timing is appropriate (e.g. up to 24 hours 
                  after ingestion). 

                  Administer activated charcoal if the patient is not 
                  vomiting. 

      10.5  Elimination

            No specific elimination procedures are indicated.

      10.6  Antidote treatment 

            10.6.1 Adults

                  No data available.

            10.6.2 Children

                  No data available.

      10.7  Management discussion

            Although several poisonings occur every year in South American 
            countries, very few case reports have been published and 
            therefore detailed and comparative consideration of management 
            is not possible.  Treatment is basically symptomatic and 
            supportive, and outcome may depend upon the facilities for 
            dealing with severe cases of hepato-renal failure. 

            No information is available on what serum concentrations of 
            methyl ethyl ketone or other Ruta principles are toxic or 
            abortifacient. One of the main difficulties is that ingestion 
            of Ruta is usually accompanied by ingestion of other plants or 
            drugs and the use of intrauterine devices which may enhance 
            infection and sepsis.  Therefore, a severely poisoned woman 
            experiencing abortion may also have a serious septic state with 
            jaundice, coma and haemodynamic complications. 

    11.   ILLUSTRATIVE CASES

      11.1  Case reports from literature

                  Heskel et al (1983) reported a phyto-photodermatitis in a 
                  5 year-old boy, his 6 year-old sister and mother who 
                  handled Ruta  graveolens. Erythema, hyperpigmentation and 
                  blistering were due to psoralens. 

                  Other case reportsd include Gawkrodger and Savin (1983) 
                  and Brenner and Friedman (1983). 

      11.2  Internally extracted data on cases

                  Several cases of acute renal and hepatic insufficiency 
                  have been registered in the University Hospital (Hospital 
                  de Clinicas, Uruguay)  in young women who ingested a Ruta 
                  concoction as an abortifacient. They all required 
                  haemodialysis and most of them died.  Some had abortions.  
                  Autopsy studies demonstrated acute tubular necrosis with 
                  interstitial oedema and an acute hepatitis with central 
                  lobular cholestasis. 


                  A 21 year-old woman was admited to the emergency room 
                  with vomiting, diarrhoea and abdominal pain, followed by 
                  convulsions. Conjunctival irritation and jaundice were 
                  noted.  The patient was pregnant and a gynaecological 
                  examination revealed an abortion in progress. It was 
                  subsequently discovered that the young woman had been 
                  drinking Ruta infusions as an abortifacient during the 
                  preceding days.  Treatment was symptomatic and intensive 
                  but the patient died the following day (Pronczuk & 
                  Laborde, 1987). 

      11.3  Internal cases (added by the PC using monograph)

    12.   ADDITIONAL INFORMATION

      12.1  Availability of antidotes and antisera

            No data available.

      12.2  Specific preventive measures

                  Use of herbal preparations of Ruta should be avoided 
                  unless there is accurate knowledge of their constituents 
                  and possible effects. 

                  Pregnant women should avoid the ingestion of infusions 
                  that may contain abortifacient (emenagogue) plants. 

                  Skin contact with Ruta should be avoided.

                  Herbs and infusions should not be administered to 
                  children. 

                  It is recommended that Rue oil be prohibited for use in 
                  foods as a flavouring agent (Martindale, 1982). 

      12.3  Other

            No data available.

    13.   REFERENCES

      13.1  Clinical and toxicological

            Brener S, Friedman J (1985).  Phytophotodermatitis induced by 
            Ruta chalepensis L.  Contact-Dermatitis  12 (4): 230-2. 

            Cheng JT (1986).  Effect  of skimmianine on animal behavior. 
            Arch Int Pharmacodyn Ther  281(1): 35-43. 

            Gawkrodger DJ, Savin JA (1983).  Phytophotodermatitis due to 
            common rue (Ruta graveolens).  Contact Dermatitis 9(3):224. 

            Heskel NS, Amon RB, Storrs FJ, White CR Jr (1983).  
            Phytophotodermatitis due to Ruta graveolens.  Contact 
            Dermatitis 9(4):278-80. 

            Jouglard J (1977).  Intoxication d'origine vegetale.  
            Encyclopedie Medico Chirurgicale 16065 A 10. 

            Paulini H, Eilert U, Schimmer O (1987).  Mutagenic compounds in 
            an extract forma rutae herba (Ruta graveolens L)  Mutagenicity 
            is partially causesd by furoquinoline alkaloids.  Mutagenesis 
            2(4):271-3 

            Prakash AO, Saxena V, Shukla S et al (1985). Anti-implantation 
            activity of some indigenous plants in rats.  Acta Eur Fertil 
            16(6) 441-8. 

            Pronczuk J, Laborde A (1987). "Plantas silvestres y de cultivo" 
            - Universidad de la Republica, Montevideo, Uruguay. 

            Reynolds JF (ed) (1982). Martindale,  The Extra Pharmacopeia 
            28th. The Pharmaceutical Press, London. 

            Towers GH, Abromowsky Z (1983).  UV-mediated genotoxicity of 
            furanoquinoline and of certain tryptophan-derived alkaloids.  J 
            Nat Prod 46(4):576-81. 

            Vigneau C (1985).  "Plantes Medicinales:  Thérapeutique 
            Toxicité"  Nº 129. Ed. Masson, France. 

      13.2  Botanical

            Font-Quer P (1979). "Plantas medicinales". Ed Labor, Barcelona. 

            Gilg E, Brandt W (1926).  "Farmacognocsia". Ed Labor, 
            Barcelona. 

    14.   AUTHOR(S), REVIEWER(S) DATE (INCLUDING EACH UPDATING)

      Author:     Dr J. Pronczuk
                  CIAT 7° piso
                  Hospital de Clínicas
                  Av. Italia s/n
                  Montevideo
                  Uruguay

                  Tel: 598-2-470300
                  Fax: 598-2-470300

      Date:       October 1989

      Peer Review: Singapore, November 1989



    See Also:
       Toxicological Abbreviations