Aldrin is an

organochlorine insecticide Insecticides are substances used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. Insecticides are used in agriculture, medicine, industry and by consumers. Insecticides are claimed to b ...

that was widely used until the 1990s, when it was banned in most countries. Aldrin is a member of the so-called "classic organochlorines" (COC) group of pesticides. COCs enjoyed a very sharp rise in popularity during and after

The Second World War World War II or the Second World War, often abbreviated as WWII or WW2, was a world war that lasted from 1939 to 1945. It involved the vast majority of the world's countries—including all of the great powers—forming two opposing ...

. Other noteworthy examples of COCs include

DDT Dichlorodiphenyltrichloroethane, commonly known as DDT, is a colorless, tasteless, and almost odorless crystalline chemical compound, an organochloride. Originally developed as an insecticide, it became infamous for its environmental impacts. ...

. After research showed that organochlorines can be highly toxic to the ecosystem through bioaccumulation, most were banned from use. It is a colourless solid. Before the ban, it was heavily used as a pesticide to treat seed and soil. Aldrin and related "cyclodiene" pesticides (a term for pesticides derived from

Hexachlorocyclopentadiene Hexachlorocyclopentadiene (HCCPD), also known as C-56, Graphlox, and HRS 1655, is an organochlorine compound with the formula C5Cl6. It is a precursor to pesticides, flame retardants, and dyes. It is a colourless liquid, although commercial sample ...

) became notorious as

persistent organic pollutant Persistent organic pollutants (POPs), sometimes known as "forever chemicals", are organic compounds that are resistant to environmental degradation through chemical, biological, and photolytic processes. They are toxic chemicals that adversel ...

s.Robert L. Metcalf "Insect Control" in Ullmann’s Encyclopedia of Industrial Chemistry" Wiley-VCH, Weinheim, 2002.

Structure & Reactivity

The structure formula of aldrin is C₁₂H₈Cl₆. The molecule has a

molecular weight A molecule is a group of two or more atoms held together by attractive forces known as chemical bonds; depending on context, the term may or may not include ions which satisfy this criterion. In quantum physics, organic chemistry, and bioch ...

of 364.896 g/mol. The

melting point The melting point (or, rarely, liquefaction point) of a substance is the temperature at which it changes state from solid to liquid. At the melting point the solid and liquid phase exist in equilibrium. The melting point of a substance depen ...

of aldrin is a temperature of 105 °C and the

octanol-water partition coefficient The ''n''-octanol-water partition coefficient, ''K''ow is a partition coefficient for the two-phase system consisting of ''n''-octanol and water. ''K''ow is also frequently referred to by the symbol P, especially in the English literature. It is a ...

is 6.5 (logP). Pure aldrin takes form as a white crystalline powder. Though it is not soluble in water (0.003%% solubility), aldrin dissolves very well in organic solvents, such as ketones and paraffins. Aldrin decays very slowly once released into the environment. Though it is rapidly converted to dieldrin by plants and bacteria, dieldrin maintains the same toxic effects and slow decay of aldrin. Aldrin is easily transported through the air by dust particles. Aldrin does not react with mild acids or bases and is stable in an environment with a pH between 4 and 8. It is highly flammable when exposed to temperatures above 200 °C In the presence of

oxidizing agent An oxidizing agent (also known as an oxidant, oxidizer, electron recipient, or electron acceptor) is a substance in a redox chemical reaction that gains or " accepts"/"receives" an electron from a (called the , , or ). In other words, an oxi ...

s aldrin reacts with concentrated acids and phenols.

Synthesis

Aldrin is not formed in nature. It is synthesized by combining

hexachlorocyclopentadiene Hexachlorocyclopentadiene (HCCPD), also known as C-56, Graphlox, and HRS 1655, is an organochlorine compound with the formula C5Cl6. It is a precursor to pesticides, flame retardants, and dyes. It is a colourless liquid, although commercial sample ...

with

norbornadiene Norbornadiene is an organic compound and a bicyclic hydrocarbon. Norbornadiene is of interest as a metal-binding ligand, whose complexes are useful for homogeneous catalysis. It has been intensively studied owing to its high reactivity and distin ...

in a Diels-Alder reaction to give the adduct. In 1967, the composition of technical-grade aldrin was reported to consist of 90.5% of hexachlorohexahydrodimethanonaphthalene (HHDN). Similarly, an isomer of aldrin, known as isodrin, is produced by reaction of hexachloronobornadiene with cyclopentadiene. Isodrin is also produced as a byproduct of aldrin synthesis, with technical-grade aldrin containing about 3,5% isodrin. Aldrin is named after the German chemist

Kurt Alder Kurt Alder (; 10 July 1902 – 20 June 1958) was a German chemist and Nobel laureate. Biography Alder was born in the industrial area of Königshütte, Silesia (modern day Chorzów, Upper Silesia, Poland), where he received his early schoo ...

, one of the coinventors of this kind of reaction. An estimated 270 million kilograms of aldrin and related cyclodiene pesticides were produced between 1946 and 1976.

Available forms

There are multiple available forms of aldrin. One of these is the isomer isodrin, which cannot be found in nature, but needs to be synthesized like aldrin. When aldrin enters the human body or the environment it is rapidly converted to dieldrin. Degradation by ultraviolet radiation or microbes can convert dieldrin to photodieldrin and aldrin to photoaldrin.

Mechanism of action

Even though many toxic effects of aldrin have been discovered, the exact mechanisms underlying the toxicity are yet to be determined. The only toxic aldrin induced process that is largely understood is that of neurotoxicity.

Neurotoxicity

One of the effects that intoxication with aldrin gives rise to is

neurotoxicity Neurotoxicity is a form of toxicity in which a biological, chemical, or physical agent produces an adverse effect on the structure or function of the central and/or peripheral nervous system. It occurs when exposure to a substance – specificall ...

. Studies have shown that aldrin stimulates the central nervous system (CNS), which may cause hyperexcitation and

seizures An epileptic seizure, informally known as a seizure, is a period of symptoms due to abnormally excessive or synchronous neuronal activity in the brain. Outward effects vary from uncontrolled shaking movements involving much of the body with l ...

. This phenomenon exerts its effect through two different mechanisms. One of the mechanisms uses the ability of aldrin to inhibit brain

calcium ATPase Ca2+ ATPase is a form of P-ATPase that transfers calcium after a muscle has contracted. The two kinds of calcium ATPase are: *Plasma membrane Ca2+ ATPase (PMCA) *Sarcoplasmic reticulum Ca2+ ATPase (SERCA) Plasma membrane Ca2+ ATPase (PMCA) P ...

s. These ion pumps relieve the nerve terminal from calcium by actively pumping it out. However, when aldrin inhibits these pumps, the intracellular calcium levels rise. This results in an enhanced neurotransmitter release. The second mechanism makes use of aldrin's ability to block gamma-aminobutyric acid (GABA) activity. GABA is a major inhibitory neurotransmitter in the central nervous system. Aldrin induces neurotoxic effects by blocking the GABA_A receptor-chloride channel complex. By blocking this receptor, chloride is unable to move into the synapse, which prevents hyperpolarization of neuronal synapses. Therefore, the synapses are more likely to generate action potentials.

Metabolism

The metabolism of oral aldrin exposure has not been studied in humans. However, animal studies are able to provide an extensive overview of the metabolism of aldrin. This data can be related to humans. Biotransformation of aldrin starts with

epoxidation In organic chemistry, an epoxide is a cyclic ether () with a three-atom ring. This ring approximates an equilateral triangle, which makes it strained, and hence highly reactive, more so than other ethers. They are produced on a large scale ...

of aldrin by

mixed-function oxidase Mixed-function oxidase is the name of a family of oxidase enzymes that catalyze a reaction in which each of the two atoms of oxygen in O2 is used for a different function in the reaction. Oxidase is a general name for enzymes that catalyze oxidati ...

s ( CYP-450), which forms dieldrin. This conversion happens mainly in the liver. Tissues with low CYP-450 expression use the prostaglandin endoperoxide synthase (PES) instead. This oxidative pathway bisdioxygenises the arachidonic acid to prostaglandin G₂ (PGG₂). Subsequently, PGG₂ is reduced to prostaglandin H₂ (PGH₂) by hydroperoxidase. Dieldrin can then be directly oxidized by cytochrome oxidases, which forms 9-hydroxydieldrin. An alternative for oxidation involves the opening of the epoxied ring by epoxied hydrases, which forms the product 6,7-trans-dihydroxydihydroaldrin. Both products can be conjugated to form 6,7-trans-dihydroxydihydroaldrin glucuronide and 9-hydroxydieldrin glucuronide, respectively. 6,7-trans-dihydroxydihydroaldrin can also be oxidized to form aldrin dicarboxylic acid.

Efficacy and side effects

Considering the

toxicokinetics Toxicokinetics (often abbreviated as 'TK') is the description of both what rate a chemical will enter the body and what occurs to excrete and metabolize the compound once it is in the body. Relation to Pharmacokinetics It is an application of ph ...

of aldrin in the environment, the efficacy of the compound has been determined. In addition, the

adverse effect An adverse effect is an undesired harmful effect resulting from a medication or other intervention, such as surgery. An adverse effect may be termed a " side effect", when judged to be secondary to a main or therapeutic effect. The term compl ...

s after exposure to the aldrin are demonstrated, indicating the risk regarding the compound.

Efficacy

The ability of aldrin, in its use for the control of termites, is examined in order to determine the maximum response when applied. In 1953 US researchers tested aldrin and dieldrin on terrains with rats known to carry

chiggers ''Trombicula'', known as chiggers, red bugs, scrub-itch mites, or berry bugs, are small arachnids (eight-legged arthropods) in the Trombiculidae family. In their larval stage, they attach to various animals, including humans, and feed on skin, ...

, at a rate of 2.25 pound per acre. The Aldrin and Dieldrin treatment demonstrated a decrease of 75 times less chiggers on rats for Dieldrin treated terrains and 25 times less chiggers on the rats when treated with Aldrin. The Aldrin treatment indicate a high productivity, especially in comparison to other insecticide that were used, like

, Sulfur or BHC.

Adverse effects

Exposure of Aldrin to the environment leads to the localization of the chemical compound in the air, soil, and water. Aldrin gets changed quickly to dieldrin and that compound degrades slowly, which accounts for aldrin concentrations in the environment around the primary exposure and in the plants. These concentrations can also be found in animals, which eat contaminated plants or animals that reside in the contaminated water. This

biomagnification Biomagnification, also known as bioamplification or biological magnification, is any concentration of a toxin, such as pesticides, in the tissues of tolerant organisms at successively higher levels in a food chain. This increase can occur as a ...

can lead to a high concentrations in their fat. There are some reported cases of workers who developed

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

after multiple dieldrin exposures. However the main adverse effect of Aldrin and Dieldrin is in relationship to the central nervous system. The accumulated levels of Dieldrin in the body were believed to lead to convulsions. Besides that other symptoms were also reported like headaches, nausea and vomiting, anorexia, muscle twitching and myoclonic jerking and

EEG Electroencephalography (EEG) is a method to record an electrogram of the spontaneous electrical activity of the brain. The biosignals detected by EEG have been shown to represent the postsynaptic potentials of pyramidal neurons in the neocortex ...

distortions. In all these cases removal of the source of exposure to aldrin/dieldrin led to a rapid recovery.

Toxicity

The toxicity of aldrin and dieldrin is determined by the results of several animal studies. Reports of a significant increase in workers death in relation to aldrin has not been found, although death by anemia is reported in some cases after multiple exposure to Aldrin. Immunological tests linked an antigenic response to

erythrocytes Red blood cells (RBCs), also referred to as red cells, red blood corpuscles (in humans or other animals not having nucleus in red blood cells), haematids, erythroid cells or erythrocytes (from Greek ''erythros'' for "red" and ''kytos'' for "holl ...

coated with dieldrin in those cases. Direct dose-response relations being a cause for death are yet to be examined. The

NOAEL The no-observed-adverse-effect level (NOAEL) denotes the level of exposure of an organism, found by experiment or observation, at which there is no biologically or statistically significant increase in the frequency or severity of any adverse effec ...

that was derived from rat studies: * The minimal risk level at acute oral exposure to Aldrin is 0.002 mg/kg/day. * The minimal risk level at intermediate exposure to Dieldrin is 0.0001 mg/kg/day. * The minimal risk level at chronic exposure to Aldrin is 0.00003 mg/kg/day. * The minimal risk level at chronic exposure to Dieldrin is 0.00005 mg/kg/day. In addition to these studies, breast cancer risk studies were performed demonstrating a significant increased breast cancer risk. After comparing blood concentrations to number of lymph nodes and tumor size a 5-fold higher risk of death was determined, comparing the highest quartile range in the research to the lower quartile range. Young children are also more susceptible to the drug, causing severe generalized convulsions.

Effects on animals

Most of the animal studies done with aldrin and dieldrin used rats. High doses of aldrin and dieldrin demonstrated

, but in multiple rat studies also showed a unique sensitivity of the mouse liver to dieldrin induced hepatocarcinogenicity. Furthermore, Aldrin treated rats demonstrated an increased

post-natal The postpartum (or postnatal) period begins after childbirth and is typically considered to end within 6 weeks as the mother's body, including hormone levels and uterus size, returns to a non-pregnant state. The terms puerperium, puerperal perio ...

mortality, in which adults showed an increased susceptibility to the compounds compared to children in rats.

Environmental impact and regulation

Like related polychlorinated pesticides, aldrin is highly lipophilic. Its solubility in water is only 0.027 mg/L, which exacerbates its persistence in the environment. It was banned by the Stockholm Convention on Persistent Organic Pollutants. In the U.S., aldrin was cancelled in 1974. The substance is banned from use for plant protection by the EU.

Safety and environmental aspects

Aldrin has rat of 39 to 60 mg/kg (oral in rats). For fish however, it is extremely toxic, with an

LC50 In toxicology, the median lethal dose, LD50 (abbreviation for " lethal dose, 50%"), LC50 (lethal concentration, 50%) or LCt50 is a toxic unit that measures the lethal dose of a toxin, radiation, or pathogen. The value of LD50 for a substance is ...

of 0.006 – 0.01 for

trout Trout are species of freshwater fish belonging to the genera '' Oncorhynchus'', '' Salmo'' and '' Salvelinus'', all of the subfamily Salmoninae of the family Salmonidae. The word ''trout'' is also used as part of the name of some non-salm ...

and bluegill. In the US, aldrin is considered a potential occupational carcinogen by the

Occupational Safety and Health Administration The Occupational Safety and Health Administration'' (OSHA ) is a large regulatory agency of the United States Department of Labor that originally had federal visitorial powers to inspect and examine workplaces. Congress established the agenc ...

and the

National Institute for Occupational Safety and Health The National Institute for Occupational Safety and Health (NIOSH, ) is the United States federal agency responsible for conducting research and making recommendations for the prevention of work-related injury and illness. NIOSH is part of the C ...

; these agencies have set an occupational exposure limit for dermal exposures at 0.25 mg/m³ over an eight-hour time-weighted average. Further, an

IDLH The term immediately dangerous to life or health (IDLH) is defined by the US National Institute for Occupational Safety and Health (NIOSH) as exposure to airborne contaminants that is "likely to cause death or immediate or delayed permanent advers ...

limit has been set at 25 mg/m³, based on acute toxicity data in humans to which subjects reacted with convulsions within 20 minutes of exposure. It is classified as an extremely hazardous substance in the United States as defined in Section 302 of the U.S.

Emergency Planning and Community Right-to-Know Act The Emergency Planning and Community Right-to-Know Act of 1986 is a United States federal law passed by the 99th United States Congress located at Title 42, Chapter 116 of the U.S. Code, concerned with emergency response preparedness. On October ...

(42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.

References

{{insecticides Obsolete pesticides IARC Group 3 carcinogens Organochloride insecticides Endocrine disruptors Neurotoxins Persistent organic pollutants under the Stockholm Convention Persistent organic pollutants under the Convention on Long-Range Transboundary Air Pollution