Plant-Derived Pesticides
NICOTINE insecticide:
Source: Nicotiana tabacum and N. rustica. Nicotine and closely related insecticidal compounds like
nornicotine, anabasine, cotinine, are found in 6 genera of 5 plant families.
Colorless liquid at room temperature; oxidizes and turns brown on exposure to air. Hygroscopic;
miscible with water below 60oC; soluble in many organic solvents. The natural (S) isomer is often less
toxic than the synthetic (R) isomer.
Important before introduction of synthetic insecticides after WWII; still used. Nicotine-containing
solutions can easily be extracted from commercial tobacco1. Free base is used in fumigation; nicotine
sulfate is safer and easier to handle; the free alkaloid is liberated in alkaline conditions. Nicotine is used
as contact and stomach poison, typically in 0.05% sprays or 1-2% dusts.
Recently nicotine derivatives have been developed that have better selective toxicity. One example of
these is imidacloprid (structure shown below). The LD-50 of imidacloprid to rats is approximately 450
mg/kg, compared with 50 mg/kg for nicotine itself.
Environmentally, the neonicotinids are relatively benign, but some evidence links them to Colony
Collapse Disorder of bees.
1
Not recommended: such solutions look remarkably like tea, and are easily drunk by children.
Toxicity:
In both insects and vertebrates, nicotine simulates ACh at synapses, facilitating conduction at low doses
and blocking it at high doses. It acts at autonomic ganglia, in the central nervous system (CNS), and at
some peripheral nerves; it also induces vomiting by direct action on medulla. Symptoms are tremor,
convulsions, vomiting, stimulation of ventilation followed by depression; convulsions; altered blood
pressure (raised, then falling). Death usually results from block in neuromuscular transmission in
breathing muscles. Humans who survive onset of symptoms by 30 minutes usually survive. Readily
penetrates skin, and percutaneous exposure is most often the route for accidental poisoning. Symptoms
may be delayed 2-4 hours. Tolerance (lasting up to 3 hours) is produced by nonfatal dose of nicotine. It
is suggested that 50-60 mg (total) may be lethal to adult human, but no data were given to support this
suggestion. Lethal poisoning in small children can result from eating one cigarette butt.
Nicotine shortens gestation in rats if administered in latter part of pregnancy; it is excreted in human
milk at up to 0.5 ppm.
LD50 in rats, po: 53-188 mg/kg listed by DE Ray; 30 mg/kg by RL Metcalf. Ray lists 285 mg/kg as the
dermal rat LD50; Metcalf lists 50 mg/kg as the dermal rabbit LD50.
ADDITION NEEDED: Neonicotinoid Insecticides. I would recommend the Wikipedia article as a
starting point.
ROTENONE insecticide
Derived from derris root (the major species of economic importance are: Derris elliptica, D.
malaccensis from Malaysia, and cubé, Lonchocarpus utilis and L. urucu from South America).
Rotenone is only one of the active ingredients; 5 related compounds probably contribute significantly to
total insecticidal activity. However, rotenone itself is 5-10 times as effective as any other compound in
these roots. Rotenone is inactivated by 5-10 days exposure to sunlight, and decomposition is more rapid
in the presence of alkali.
Mechanism of toxicity: Rotenone is not a neurotoxin. It interferes with oxidation of NADH
(nicotinamide adenine dinucleotide) to NAD by cytochrome b, and so inhibits the mitochondrial
oxidation of Krebs-cycle intermediates catalyzed by NAD. Its action is the same in insects and
mammals. However, it is extremely toxic to fish, and has been used to harvest fish by native peoples, as
well as to control undesirable fish stocks in managed waters. It is active for 1-2 days on plants, and 2-6
days in water, making it an excellent pre-harvest insecticide.
LD50 of rotenone is 60-130 mg/kg if given po; it is efficiently metabolized by the liver, which limits its
oral toxicity. Given intraperitoneally (ip), its LD50 is 1-2 mg/kg. There is evidence of fetotoxicity at
doses that cause maternal toxicity, but not of malformations. Carcinogenic potential is disputed.
Rotenone delays progression of cells through the cell cycle, either because of its inhibition of
respiration, or because it is a spindle poison. As a spindle poison, it acts by inhibiting microtubule
assembly. In workers exposed to rotenone, contact dermatitis is common and potentially serious. The
only accidental human fatality in the literature was a toddler who drank an estimated 40 mg/kg of a
preparation labeled "Natural product - nontoxic".
SABADILLA insecticide
Derived from dried ripe seeds of Schoenocaulon officinale, a member of the lily family. Seeds contain
about 0.3% alkaloids, of which cevadine (or veratrine) is the most important. Central and South
American Indians used sabadilla against wound-inhabiting vermin (e.g., screw-worm). It is not much
used in the U.S. because of poor selectivity.
Oral rat LD50 of ground seeds is 4000 mg/kg; of the pure alkaloid (veratrine) in the blackbird, 18 mg/kg.
It is readily absorbed through the skin. It acts on sodium channels, but differently from pyrethroids sabadilla slows activation of the sodium current as well as its inactivation (in contrast to pyrethroids,
which only affect ion activation). Moreover, the nature of the block is different. There is a direct effect
on muscle, not mediated by nerve transmission; a rapid fall in blood pressure is a major symptom. It is
thought that the veratridine and cevadine portions of the molecule account for much of the toxicity of
sabadilla.
AVERMECTINS nematicide, insecticide
Complex macrocyclic disaccharides derived from Streptomyces avermitilis. Soluble in polar organic
solvents (e.g., butanol). Used subcutaneously or topically in veterinary practice against parasitic
nematodes, insects, arachnids. Acts on insects by potentiation of GABA2ergic neural and
neuromuscular transmission: result is CNS depression and consequent ataxia; also respiratory
depression, which is major cause of death in poisoned mammals. Ivermectin - the commercial
avermectin - is not metabolized well by mammals; 90% is excreted intact.
Metal-Containing Pesticides
The toxicity of metals must be separated into several categories, depending on the role of the metallic
element in organisms. Metals may be essnetial to life, not essential but not ordinarily a concern (usually
because organisms are not naturally exposed to hazardous levels), or actively and always toxic.
Metals known to be essential to normal growth, development: Chromium, copper, zinc, phosphorus, tin,
arsenic, selenium
Metals not (yet?) shown to be essential to normal growth, development: barium, bismuth, antimony,
boron, gold, silver.
Metals toxic to all/most forms of life: arsenic, lead, beryllium, cadmium, mercury, thallium
2
GABA = gamma-aminobutyric acid
In general, although organometals differ in uptake by, and distribution within, the organism, the toxicity
of the compound is characteristic of the metal (with the exception of the dithiocarbamate fungicides,
which have similar effects regardless of their metallic constituent.)
Barium carbonate -- BaCO3. Rodenticide (20-25% active ingredient in baits); neurotoxicant. Human
poisoning: pastry made with barium carbonate instead of flour.
Sodium dichromate -- Na2Cr2O7.2H2O. Cotton defoliant; wood preservative; essential element.
Bronchiogenic cancer due to chromium?
Copper sulfate -- CuSO4 (blue vitriol). Fungicide; algicide. Bordeaux mixture is CuSO4 and Ca(OH)2 is
a fungicide and seed treatment.3 Fatty degeneration of kidneys, liver; acutely, renal failure.
Pneumoconiosis following long-term occupational exposure to Bordeaux mixture. Granulomas
of liver, lungs, kidneys.
Zinc chloride -- ZnCl2. Wood preservative; essential element; LD50: po, 19140-2200 mg/kg; ip, 31
mg/kg in mouse. Zinc compounds tend to be emetic.
Zinc phosphide -- Zn3P2. Rodenticide. Toxicity is due to formation of phosphine (PH3) by stomach
acid. Phosphine causes pulmonary and sometimes cerebral edema.
Cadmium chloride -- CdCl2. Fungicide for turf. Acute exposure leads to salivation, diarrhea, vomiting.
Chronic administration leads to poor growth, anemia. No poisoning with the fungicide has been
reported, but prolonged cadmium exposure causes kidney damage. Inhalation exposure can
cause emphysema. In Japan, environmental (dietary) exposure caused bone breakage (itai-itai);
epidemiology suggests that calcium (and perhaps vitamin D) deficiency predisposes to itai-itai.
Cadmium is also suspected to cause high blood pressure, possible due to kidney damage.
Cadmium accumulates in the kidney.
MERCURY: as an element, the vapors are the primary source of intoxication. Symptoms include
dyspnea, fatigue, gingivitis and loss of teeth; tremors; "psychic disturbances" - irritability,
irascibility, difficulty in getting along with people. Depression, despondency, lethargy,
weakness, and eventually coma and death follow.
Inorganic mercury formulations: mercuric chloride, HgCl2, fungicide. LD50, 37 mg/kg, po, rat.
(However, even for inorganic mercury, it is the chronic toxicity that is of most concern).
Organic mercury formulations were used primarily as seed dressings, as fungicides in turf, and as wood
preservatives. Most countries have banned them because of their tendency to cause secondary
poisoning, as described below.
The 1st organomercury compounds, introduced in 1915, were phenylmercury salts. Alkylmercury salts
were tested as early as 1929. Unlike inorganic mercury compounds, organomercury compounds are
absorbed (slowly) through skin, and efficiently by the gastrointestinal (GI) tract and the lungs. They also
differ from inorganic Hg in that neurological damage is seen first, not GI symptoms. The nerve damage
3
Bordeaux mixture must not be used with pesticides that degrade under alkaline conditions.
is in the central nervous system (CNS); symptoms consist of tremors, loss of side vision, incoordination;
irritability progressing to dementia. If exposure is stopped, some improvement is seen over a period of
years, but severe cases do not recover completely.
Acute toxicity of alkylmercury compounds is around 30 mg/kg (rats, po); 0.5 mg/kg/day given for 150
days did not produce any overt toxicity (therefore is "no observable effect level" or NOEL).
Organic mercury is excreted to the fetus by pregnant women. It causes cerebral palsy-like symptoms,
and often begins with convulsions soon after birth. Spyker (1972) showed that prenatally exposed mice
had balance disturbances at methyl mercury doses to low to cause any physically apparent
malformations. In general, developmental mercury toxicity must be assumed to be irreversible, since
the damage is done in the actual formation of the nervous system.
Arylmercury compounds (usually phenylmercury salts) caused acrodynia or "pink disease" in children
when used as a diaper fungicide (?) or as pediatric lotion -- very painful, pink fingertips are mark of this
disease.
THALLIUM was used as a rodenticide. Its acute toxicity is 15.8±9.0 mg/kg (po, rats). It is better
known as a cumulative toxicant, and causes restlessness, ataxia, and hair loss.
ARSENIC compounds have been used as insecticides and herbicides. Paris green,
Cu(CH3COO)2.3Cu(AsO2), was introduced as an insecticide against the Colorado potato beetle in 1865.
NaAsO2 is still used as a poison bait against grasshoppers, and as a livestock bait.
PbHAsO4, with an LD50 of 800 mg/kg in rats (po), was used to control codling moths and against gypsy
moths. It is somewhat less harmful to foliage than the lead arsenate, and U.S. use was 38,000,000 kg in
1942.
On the whole, insecticidal use of arsenic-containing insecticides has declined drastically since the
introduction of the newer synthetic insecticides. Arsenicals are now commercialized primarily as
herbicides, notably cacodylic acid, (CH3)2AsO(OH). Cacodylic acid has an LD50 of 830 mg/kg (po in
rats).
In general, 1.6 mg/kg arsenic per day is considered the NOEL (no observed effect level) of arsenite for
rats; 3.2 mg/kg is the NOEL for arsenates.
There is no proven need for arsenic in humans or animals. However, arsenic has been used
therapeutically: to improve "wind" in horses, complexion in Styrian peasants, and against acne in the
U.S. until about 1960. Tolerance occurs from repeated low dose exposure in all species. Acute toxicity
is manifested by GI tract symptoms. The biochemical mechanism of acute arsenic toxicity is to increase
the permeability of capillaries, leading to rapid decreases in blood pressure, shock, and death.
The chronic toxicity of arsenic in humans is strikingly different from what is seen in animals. Only
humans exhibit skin lesions and polyneuropathy; only humans develop cancer. Arsenic induces skin
and lung cancer; it is not entirely clear whether route of exposure determines site of the cancer.
Although inhalation exposure (by people living downwind from a copper smelter) typically causes lung
cancer, skin cancer results from ingestion of arsenic, not from topical application. Since arsenic is
deposited in skin and hair, the skin cancer may simply reflect the high levels present in this tissue.
TIN
Tin is one of the least toxic metals, almost certainly because it and its salts do not easily enter the body.
Once tin enters the body - most easily as an alkyltin or phenyltin compound - it is a neurotoxin.
Organotins can have the form RSnX3, RSn2X2, RSn3X, or RSn4X, where X is a simple or complex ion
and R is an alkyl or aryl group.
Fentin acetate (triphenyltin acetate) was introduced in 1954 as a fungicide. More recently it has been
used as a molluscicide and algicide. As a molluscicide, it was added to boat paints in the 1970s and
1980s. Because it caused excessive toxicity to harbor ecosystems, it was later banned.4
The LD50 of Fentin acetate is quite dependent on solvents; it is poorly absorbed from the stomach. In
mice and rats, fentin in arachis oil had an LD50 of 491 mg/kg, whereas in methylcellulose, the LD50 to
rats of unspecified sex was 136 mg/kg.
4
This was one of the quieter pesticide bannings. Perhaps because of the specialized market, it received little
attention in the popular press