Aldrin is an

organochlorine insecticide Insecticides are pesticides used to kill insects. They include ovicides and larvicides used against insect eggs and larvae, respectively. The major use of insecticides is in agriculture, but they are also used in home and garden settings, in ...

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

World War II World War II or the Second World War (1 September 1939 – 2 September 1945) was a World war, global conflict between two coalitions: the Allies of World War II, Allies and the Axis powers. World War II by country, Nearly all of the wo ...

. Other noteworthy examples of COCs include

dieldrin Dieldrin is an organochlorine compound originally produced in 1948 by J. Hyman & Co, Denver, as an insecticide. Dieldrin is closely related to aldrin, which reacts further to form dieldrin. Aldrin is not toxic to insects; it is oxidized in the i ...

and DDT. After research showed that organochlorines can be highly toxic to the ecosystem through

bioaccumulation Bioaccumulation is the gradual accumulation of substances, such as pesticides or other chemicals, in an organism. Bioaccumulation occurs when an organism absorbs a substance faster than it can be lost or eliminated by catabolism and excretion. T ...

, most were banned from use. 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) are organic compounds that are resistant to degradation through chemical, biological, and photolytic processes. They are toxic and adversely affect human health and the environment around the world. Because ...

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

Structure and Reactivity

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

ketone In organic chemistry, a ketone is an organic compound with the structure , where R and R' can be a variety of carbon-containing substituents. Ketones contain a carbonyl group (a carbon-oxygen double bond C=O). The simplest ketone is acetone ( ...

s and paraffins. Aldrin decays very slowly once released into the environment. Though it is rapidly converted to

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 ''electron donor''). In ot ...

s aldrin reacts with concentrated acids and phenols.

Synthesis

Aldrin is not formed in nature. It 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. Aldrin 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 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 In chemistry, isomers are molecules or polyatomic ions with identical molecular formula – that is, the same number of atoms of each element (chemistry), element – but distinct arrangements of atoms in space. ''Isomerism'' refers to the exi ...

of aldrin, known as isodrin, is produced by reaction of hexachloronobornadiene with

cyclopentadiene Cyclopentadiene is an organic compound with the chemical formula, formula C5H6. It is often abbreviated CpH because the cyclopentadienyl anion is abbreviated Cp−. This colorless liquid has a strong and unpleasant odor. At room temperature, ...

. Isodrin is also produced as a byproduct of aldrin synthesis, with technical-grade aldrin containing about 3.5% isodrin. An estimated 270 million kilograms of aldrin and related cyclodiene pesticides were produced between 1946 and 1976. The estimated production volume of aldrin in the US peaked in the mid-1960s at about a year and then declined.

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

. 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 – specifical ...

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

seizures A seizure is a sudden, brief disruption of brain activity caused by abnormal, excessive, or synchronous neuronal firing. Depending on the regions of the brain involved, seizures can lead to changes in movement, sensation, behavior, awareness, o ...

. This phenomenon exerts its effect through two different mechanisms. One of the mechanisms uses the ability of aldrin to inhibit brain calcium ATPases. 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 A neurotransmitter is a signaling molecule secreted by a neuron to affect another cell across a Chemical synapse, synapse. The cell receiving the signal, or target cell, may be another neuron, but could also be a gland or muscle cell. Neurotra ...

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, where the ether forms a three-atom ring: two atoms of carbon and one atom of oxygen. This triangular structure has substantial ring strain, making epoxides highly reactive, more so than other ...

of aldrin by mixed-function oxidases ( 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 Arachidonic acid (AA, sometimes ARA) is a polyunsaturated omega−6 fatty acid 20:4(ω−6), or 20:4(5,8,11,14). It is a precursor in the formation of leukotrienes, prostaglandins, and thromboxanes. Together with omega−3 fatty acids an ...

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 epoxide ring by epoxide 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 pha ...

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 compli ...

s after exposure to 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 and humans, then feed on skin, often ...

, at a rate of . 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 insecticides that were used at the time, such as DDT,

sulfur Sulfur ( American spelling and the preferred IUPAC name) or sulphur ( Commonwealth spelling) is a chemical element; it has symbol S and atomic number 16. It is abundant, multivalent and nonmetallic. Under normal conditions, sulfur atoms ...

or lindane.

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 the increase in concentration of a substance, e.g a pesticide, in the tissue (biology), tissues of organisms at successively higher levels in a food chain. This inc ...

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

anemia Anemia (also spelt anaemia in British English) is a blood disorder in which the blood has a reduced ability to carry oxygen. This can be due to a lower than normal number of red blood cells, a reduction in the amount of hemoglobin availabl ...

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

convulsion A convulsion is a medical condition where the body muscles contract and relax rapidly and repeatedly, resulting in uncontrolled shaking. Because epileptic seizures typically include convulsions, the term ''convulsion'' is often used as a synony ...

s. Besides that other symptoms were also reported like headaches, nausea and vomiting, anorexia, muscle twitching and myoclonic jerking and EEG 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), referred to as erythrocytes (, with -''cyte'' translated as 'cell' in modern usage) in academia and medical publishing, also known as red cells, erythroid cells, and rarely haematids, are the most common type of blood cel ...

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

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 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 Stockholm Convention on Persistent Organic Pollutants is an international environmental treaty, signed on 22 May 2001 in Stockholm and effective from 17 May 2004, that aims to eliminate or restrict the production and use of persistent organi ...

. 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 of 0.006–0.01 for

trout Trout (: trout) is a generic common name for numerous species of carnivorous freshwater ray-finned fishes belonging to the genera '' Oncorhynchus'', ''Salmo'' and ''Salvelinus'', all of which are members of the subfamily Salmoninae in the ...

and

bluegill The bluegill (''Lepomis macrochirus''), sometimes referred to as "bream", "brim", "sunny", or, in Texas, "copper nose", is a species of North American freshwater fish, native to and commonly found in streams, rivers, lakes, ponds and wetlands ea ...

. 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 regulatory agency of the United States Department of Labor that originally had federal visitorial powers to inspect and examine workplaces. The United States Congress established ...

and the

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

; 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 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 Octobe ...

(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 2A 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