Ruta graveolens L.
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