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Aldrin

Topic: Chemistry

 From HandWiki - Reading time: 11 min
Aldrin
Aldrin
Aldrin-from-xtal-3D-balls.png
Names
Preferred IUPAC name
(1R,4S,4aS,5S,8R,8aR)-1,2,3,4,10,10-Hexachloro-1,4,4a,5,8,8a-hexahydro-1,4:5,8-dimethanonaphthalene
Other names
HHDN[1]
octalene[1]
Identifiers
3D model (JSmol)
ChEBI
ChEMBL
ChemSpider
EC Number
  • 206-215-8
KEGG
RTECS number
  • IO2100000
UNII
UN number 2762, 2761
Properties
C12H8Cl6
Molar mass 364.90 g·mol−1
Appearance Colorless solid
Density 1.60 g/mL[1]
Melting point 104 °C (219 °F; 377 K)
slightly soluble (0.003%)[1]
Vapor pressure 7.5 × 10−5 mmHg @ 20 °C
Pharmacology
Legal status
  • AU: S6 (Poison)
Hazards
Main hazards potential occupational carcinogen[1]
GHS pictograms GHS06: ToxicGHS08: Health hazardGHS09: Environmental hazard
GHS Signal word Danger
H300, H301, H310, H311, H351, H372, H410
P201, P202, P260, P262, P264, P270, P273, P280, P281, P301+310, P302+350, P302+352, P308+313, P310, P312, P314, P321, P322, P330, P361, P363, P391, P405, P501
NFPA 704 (fire diamond)
Flammability code 0: Will not burn. E.g. waterHealth code 4: Very short exposure could cause death or major residual injury. E.g. VX gasReactivity code 0: Normally stable, even under fire exposure conditions, and is not reactive with water. E.g. liquid nitrogenSpecial hazards (white): no codeNFPA 704 four-colored diamond
0
4
0
Flash point 66 °C (151 °F; 339 K)
Lethal dose or concentration (LD, LC):
50 mg/kg (rabbit, oral)
33 mg/kg (guinea pig, oral)
39 mg/kg (rat, oral)
44 mg/kg (mouse, oral)[2]
5.8 mg/m3 (rat, 4 hr)[2]
NIOSH (US health exposure limits):
PEL (Permissible)
 TWA 0.25 mg/m3 [skin][1]
REL (Recommended)
 Ca TWA 0.25 mg/m3 [skin][1]
IDLH (Immediate danger)
 25 mg/m3[1]
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☑Y verify (what is ☑Y☒N ?)
Infobox references
Tracking categories (test):

Aldrin is an organochlorine insecticide 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. Other noteworthy examples of COCs include dieldrin and DDT.[3] After research showed that organochlorines can be highly toxic to the ecosystem through bioaccumulation, 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) became notorious as persistent organic pollutants.[4]

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 ketones and paraffins.[5] 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.[6] 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[7] In the presence of oxidizing agents aldrin reacts with concentrated acids and phenols.

Synthesis

Aldrin is not formed in nature. It is named after the German chemist Kurt Alder, one of the coinventors of this kind of reaction. Aldrin is synthesized by combining hexachlorocyclopentadiene with norbornadiene in a Diels-Alder reaction to give the adduct.[8] In 1967, the composition of technical-grade aldrin was reported to consist of 90.5% of hexachlorohexahydrodimethanonaphthalene (HHDN).[6]

Synthesis of aldrin via a Diels-Alder reaction

Similarly, an isomer of aldrin, known as isodrin, is produced by reaction of hexachloronobornadiene with cyclopentadiene.[9] Isodrin is also produced as a byproduct of aldrin synthesis, with technical-grade aldrin containing about 3,5% isodrin.[6]

An estimated 270 million kilograms of aldrin and related cyclodiene pesticides were produced between 1946 and 1976.[10] The estimated production volume of aldrin in the US peaked in the mid-1960s at about 18 million pounds a year and then declined.[11]

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.[6]

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. Studies have shown that aldrin stimulates the central nervous system (CNS), which may cause hyperexcitation and seizures.[12] This phenomenon exerts its effect through two different mechanisms.

One of the mechanisms uses the ability of aldrin to inhibit brain calcium ATPases.[13] 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.[14] GABA is a major inhibitory neurotransmitter in the central nervous system. Aldrin induces neurotoxic effects by blocking the GABAA 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 of aldrin by mixed-function oxidases (CYP-450),[15] which forms dieldrin. This conversion happens mainly in the liver. Tissues with low CYP-450 expression use the prostaglandin endoperoxide synthase (PES) instead.[16] 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.[17] 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.[18][19]

Efficacy and side effects

Considering the toxicokinetics of aldrin in the environment, the efficacy of the compound has been determined. In addition, the adverse effects 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, at a rate of 2.25 pounds per acre (2.52 kg/ha). 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 DDT, sulfur or BHC.[20]

Adverse effects

Exposure of aldrin to the environment leads to the localization of the chemical compound in the air, soil, and water.[6] 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.[21] These concentrations can also be found in animals, which eat contaminated plants or animals that reside in the contaminated water. This biomagnification can lead to a high concentrations in their fat.

There are some reported cases of workers who developed anemia after multiple dieldrin exposures. However the main adverse effect of aldrin and dieldrin is in relationship to the central nervous system.[6] The accumulated levels of dieldrin in the body were believed to lead to convulsions.[22] 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.[23]

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 coated with dieldrin in those cases.[24] Direct dose-response relations being a cause for death are yet to be examined.

The NOAEL that was derived from rat studies:[6]

  • 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.[25]

Effects on animals

Most of the animal studies done with aldrin and dieldrin used rats.  High doses of aldrin and dieldrin demonstrated neurotoxicity, but in multiple rat studies also showed a unique sensitivity of the mouse liver to dieldrin induced hepatocarcinogenicity.[26] 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.[27]

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.[28]

Safety and environmental aspects

Aldrin has rat -1">50 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 and bluegill.[4]

In the US, aldrin is considered a potential occupational carcinogen by the Occupational Safety and Health Administration and the National Institute for Occupational Safety and Health; these agencies have set an occupational exposure limit for dermal exposures at 0.25 mg/m3 over an eight-hour time-weighted average.[29] 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.[30]

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 (42 U.S.C. 11002), and is subject to strict reporting requirements by facilities which produce, store, or use it in significant quantities.[31]

References

  1. ↑ 1.0 1.1 1.2 1.3 1.4 1.5 1.6 1.7 NIOSH Pocket Guide to Chemical Hazards. "#0016". National Institute for Occupational Safety and Health (NIOSH). https://www.cdc.gov/niosh/npg/npgd0016.html. 
  2. ↑ 2.0 2.1 "Aldrin". Immediately Dangerous to Life and Health Concentrations (IDLH). National Institute for Occupational Safety and Health (NIOSH). https://www.cdc.gov/niosh/idlh/309002.html. 
  3. ↑ Zitko, Vladimir (2003), "Chlorinated Pesticides: Aldrin, DDT, Endrin, Dieldrin, Mirex", in Fiedler, H., Persistent Organic Pollutants, The Handbook of Environmental Chemistry, 3O, Springer Berlin Heidelberg, pp. 47–90, doi:10.1007/10751132_4, ISBN 9783540479321 
  4. ↑ 4.0 4.1 Robert L. Metcalf "Insect Control" in Ullmann’s Encyclopedia of Industrial Chemistry" Wiley-VCH, Weinheim, 2002. doi:10.1002/14356007.a14_263
  5. ↑ "International Programme on Chemical Safety, Poisons Information Monograph 573 Aldrin". http://www.inchem.org/documents/pims/chemical/pim573.htm. 
  6. ↑ 6.0 6.1 6.2 6.3 6.4 6.5 6.6 "ATSDR (2022). Toxicological profile for aldrin/dieldrin". https://www.atsdr.cdc.gov/toxprofiles/tp1.pdf. 
  7. ↑ PubChem. "Aldrin". https://pubchem.ncbi.nlm.nih.gov/compound/12310947. 
  8. ↑ Jubb, A. H. (1975). Basic Organic Chemistry, Part 5 Industrial products. London: Wiley. ISBN 0-471-85014-4. https://archive.org/details/trent_0116401244110. 
  9. ↑ Bird, C. W.; Cookson, R. C.; Crundwell, E. (1961). "946. Cyclisations and rearrangements in the isodrin?aldrin series". Journal of the Chemical Society (Resumed): 4809–4816. doi:10.1039/JR9610004809. 
  10. ↑ Mrema, Ezra J.; Rubino, Federico M.; Colosio, Claudio (2013), Simeonov, Lubomir I.; Macaev, Fliur Z.; Simeonova, Biana G., eds., "Obsolete Pesticides – A Threat to Environment, Biodiversity and Human Health" (in en), Environmental Security Assessment and Management of Obsolete Pesticides in Southeast Europe, NATO Science for Peace and Security Series C: Environmental Security (Dordrecht: Springer Netherlands): pp. 1–21, doi:10.1007/978-94-007-6461-3_1, ISBN 978-94-007-6460-6 
  11. ↑ Jorgensen, JL. (2001). "Aldrin and dieldrin: A review of research on their production environmental deposition and fate, bioaccumulation, toxicology, and epidemiology in the United States". Environmental Health Perspectives 109 (Suppl.) (Suppl 1): 113–39. doi:10.1289/ehp.01109s1113. PMID 11250811. 
  12. ↑ Gupta (May 1975). "Neurotoxicity of chronic chlorinated hydrocarbon insecticide poisoning: A clinical and electroencephalographic study in man". The Indian Journal of Medical Research 63 (4): 601–606. PMID 55381. https://www.researchgate.net/publication/23079248. 
  13. ↑ Mehrotra, B. D.; Ravichandra Reddy, S.; Desaiah, D. (1988). "Effect of subchronic dieldrin treatment on calmodulin-regulated Ca2+ pump activity in rat brain". Journal of Toxicology and Environmental Health 25 (4): 461–469. doi:10.1080/15287398809531224. ISSN 0098-4108. PMID 2974087. Bibcode: 1988JTEHA..25..461M. 
  14. ↑ Glotfelty, Dwight E. (1978-09-01). "The Atmosphere as a Sink for Applied Pesticides". Journal of the Air Pollution Control Association 28 (9): 917–921. doi:10.1080/00022470.1978.11490579. ISSN 0002-2470. 
  15. ↑ Wong, D. T.; Terriere, L. C. (March 1965). "Epoxidation of aldrin, isodrin, and heptachlor by rat liver microsomes". Biochemical Pharmacology 14 (3): 375–377. doi:10.1016/0006-2952(65)90210-8. ISSN 0006-2952. PMID 14314340. 
  16. ↑ Lang, B.; Frei, K.; Maier, P. (1986-10-15). "Prostaglandin synthase dependent aldrin epoxidation in hepatic and extrahepatic tissues of rats". Biochemical Pharmacology 35 (20): 3643–3645. doi:10.1016/0006-2952(86)90640-4. ISSN 0006-2952. PMID 3094543. 
  17. ↑ Iatropoulos, M. J. (December 1975). "Absorption, transport and organotropism of dichlorobiphenyl (DCB), dieldrin, and hexachlorobenzene (HCB) in rats". Environmental Research 10 (3): 384–389. doi:10.1016/0013-9351(75)90033-X. ISSN 0013-9351. PMID 1213019. Bibcode: 1975ER.....10..384I. 
  18. ↑ Baldwin, M. K.; Robinson, J.; Parke, D. V. (June 1972). "A comparison of the metabolism of HEOD (dieldrin) in the CF1 mouse with that in the CFE rat". Food and Cosmetics Toxicology 10 (3): 333–351. doi:10.1016/S0015-6264(72)80252-9. ISSN 0015-6264. PMID 5045677. 
  19. ↑ Hutson, D. H. (December 1976). "Comparative metabolism of dieldrin in the rat (CFE) and in two strains of mouse (CF1 and LACG)". Food and Cosmetics Toxicology 14 (6): 577–591. doi:10.1016/S0015-6264(76)80012-0. ISSN 0015-6264. PMID 1017774. 
  20. ↑ Traub, Robert; Newson, Harold D.; Walton, Bryce C.; Audy, J. R. (1954-06-01). "Efficacy of Dieldrin and Aldrin in Area Control of the Chigger Vectors of Scrub Typhus". Journal of Economic Entomology 47 (3): 429–435. doi:10.1093/jee/47.3.429. ISSN 1938-291X. 
  21. ↑ Castro, Teresita F.; Yoshida, Tomio. (November 1971). "Degradation of organochlorine insecticides in flooded soils in the Philippines". Journal of Agricultural and Food Chemistry 19 (6): 1168–1170. doi:10.1021/jf60178a041. ISSN 0021-8561. PMID 5132645. 
  22. ↑ Versteeg, J. P. J.; Jager, K. W. (1973-04-01). "Long-term occupational exposure to the insecticides aldrin dieldrin, endrin, and telodrin". Occupational and Environmental Medicine 30 (2): 201–202. doi:10.1136/oem.30.2.201. ISSN 1351-0711. PMID 4703092. 
  23. ↑ Avar, P.; Czegledi-Janko, G. (1970-07-01). "Occupational exposure to aldrin: clinical and laboratory findings". Occupational and Environmental Medicine 27 (3): 279–282. doi:10.1136/oem.27.3.279. ISSN 1351-0711. PMID 4194425. 
  24. ↑ Krzystyniak, Krzystof; Hugo, Patrice; Flipo, Denis; Fournier, Michel (September 1985). "Increased susceptibility to mouse hepatitis virus 3 of peritoneal macrophages exposed to dieldrin". Toxicology and Applied Pharmacology 80 (3): 397–408. doi:10.1016/0041-008x(85)90384-9. ISSN 0041-008X. PMID 2994259. 
  25. ↑ Høyer, Annette Pernille; Jørgensen, Torben; Brock, John W.; Grandjean, Philippe (March 2000). "Organochlorine exposure and breast cancer survival". Journal of Clinical Epidemiology 53 (3): 323–330. doi:10.1016/s0895-4356(99)00165-1. ISSN 0895-4356. PMID 10760644. 
  26. ↑ Black, A. M. S. (November 1974). "Self Poisoning with Dieldrin: A Case Report and Pharmacokinetic Discussion". Anaesthesia and Intensive Care 2 (4): 369–374. doi:10.1177/0310057x7400200413. ISSN 0310-057X. PMID 4614682. 
  27. ↑ Virgo, Bruce B.; Bellward, Gail D. (October 1975). "Effect of Dietary Dieldrin on the Liver and Drug Metabolism in the Female Swiss-Vancouver Mouse". Canadian Journal of Physiology and Pharmacology 53 (5): 903–911. doi:10.1139/y75-124. ISSN 0008-4212. PMID 1201496. 
  28. ↑ Chemicals Regulation Directorate. "Banned and Non-Authorised Pesticides in the United Kingdom". http://www.pesticides.gov.uk/approvals.asp?id=55. 
  29. ↑ Centers for Disease Control and Prevention (4 April 2011). "Aldrin". NIOSH Pocket Guide to Chemical Hazards. https://www.cdc.gov/niosh/npg/npgd0016.html. 
  30. ↑ Centers for Disease Control and Prevention (May 1994). "Aldrin". Documentation for Immediately Dangerous To Life or Health Concentrations (IDLHs). https://www.cdc.gov/niosh/idlh/309002.html. 
  31. ↑ 40 C.F.R.: Appendix A to Part 355—The List of Extremely Hazardous Substances and Their Threshold Planning Quantities (July 1, 2008 ed.). Government Printing Office. http://edocket.access.gpo.gov/cfr_2008/julqtr/pdf/40cfr355AppA.pdf. Retrieved October 29, 2011. 



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