| 2500 BC | Multi-site activity | Sulfur | Reported use by Sumerians as insecticide or insect repellent |
| 470 BC-77 AD | Multi-site activity | Plant resins, dusts, possibly arsenic | Pliny Natural History – describes Amurca- olive oil solid/liquid residue used for treatment of blight or root worms; bird control using buried ashes; Sandarach – arsenic- used to control grape blight, based upon work of Greek writer Democritus (470 BC) – interpretation of “Sandarach” as arsenic uncertain |
| 900 | Multi-site activity | Arsenic sulfides | Reported use as insecticide by Chinese |
| 1494 | NAChR | Nicotine | Tobacco brought to Europe from America’s |
| 1669 | Multi-site activity | Arsenic | Mixture with honey as an ant bait |
| 1690 | NAChR | Nicotine | Nicotine wash aplied to pear trees in France to control pear lacebug |
| 1691 | NAChR | Nicotine | use of nicotine as treatment for head lice |
| 1804 | NAChR | Nicotine | Use for insect pests in early years of Australian settlement – |
| 1824 | GABA-gated chloride channel antagonists | Hexachlorocyclohexane | Synthesis of HCH |
| 1825 | NAChR | Nicotine | Nicotine “smoke”fumigations |
| 1942 | Sodium channel | Pyrethrum | Discovery of nerve action potential associated with pyrethrum – Otto Lowenstein |
| 1848 | Scientifc background | Physiology | du Bois-Reymond described the action potential in 1848 (du Bois-Reymond, E. (1849–1884) Untersuchungen über thierische Elektricität, Reimer) |
| 1854 | ChE | Tetraethylpyrophosphate | Synthesis by De Clermont and Moschnin |
| 1867 | Multi-site activity | Copper, arsenic | Used to control Colorado potato beetle outbreak |
| 1868 | Scientifc background | Physiology | Bernstein accurate description of action potential |
| 1874 | Sodium channel | DDT | Initial syntheis – Austrian chemist Othmar Zeidler. |
| 1876 | Sodium channel | Pyrethrum | Produced by Stockton factory – extract of chrysanthemums; widely available in pharmacies and other retail stores |
| 1902 | Sodium channel | Physiology | Julius Bernstein was the first to expound a membrane theory that involved altered ion permeability to explain electrical propagation. |
| 1919 | Multi-site activity | Arsenic | Western pears embargoed by the Boston Health Department for arsenic residues |
| 1923 | Multi-site activity | Arsenic | Debate on elimination of $0.02/lb tariff on Ca Arsenate for cotton – 50,000 lbs need in US Southern states to combat cotton boll weevil |
| 1924 | Sodium channel | Pyrethrin | first discovery of pyrethrin structure 1924 – H. Staudinger and L. Ruzicka, He/v. Chim. Acta, 1924, |
| 1925 | Multi-site activity | Arsenic | Importation of apples from US banned from Britain because of reported consumer illnesses |
| 1926 | Multi-site activity | Arsenic | California Department of Agriculture begins testing fresh fruits, vegetables |
| 1929 | Multi-site activity | Arsenic | 10 persons ill from Arsenic residue in flour used to bake Christmas fruit cakes |
| 1932 | Multi-site activity | Methyl Bromide | First use of methyl bromide in France |
| | ChE | Difluorophosphate esters | Short term respiratory distress in researchers doing chemical synthesis |
| 1936 | Multi-site activity | Pentachlorophenol | introduced as a wood preservative |
| | ChE | Tabun, other experimental compounds | Gerhard Schrader noted visual disturbance while synthesizing phosphorous esters containing sulfur and fluoride at IG Farber; subsequent development of Sarin (1938), Soman (1944), Cyclosarin (1949) |
| 1938 | ChE | TEPP | First organophosphate insecticide introduced |
| 1939 | Sodium channel | DDT | Swiss chemist Paul Hermann Müller discovers insecticidal action. |
| | Multi-site activity | Sulphur | NY Times article – use for controlling garden spider mites |
| 1941 | ChE | di-isopropyl fluorophosphate | Studied as Potential organophosphate nerve agent for use In WWII University of Chicago “Tox Lab” |
| 1942 | Auxin | 2,4-D | Synthesis of first herbicide mimicking natural plant auxins |
| 1942 | Sodium channel | Pyrethrin | Nature 1942 Otto Lowenstein recorded disappearance of action potential in ventral nerve cord of oriental cockroach at pyrethrin concentrations below 1.6% and a linear response below 0.33% |
| 1943 | Home & garden pesticides | Nicotine, para-dichlorobenzene, hydrocyanic acid, asphyxiant oils | New York Times discussion of war on pests |
| 1945 | Sodium channel | Chlordane | Initial synthesis |
| 1945 | Sodium channel | DDT | Government tests – how & where it can be used against pests; cleared for civilian use August 31 |
| 1946 | Sodium channel | DDT | 1946 Journal of Wildlife Management – dedicated to DDT and wildlife Cottam and Higgins reported mortality in fish and birds, warning against using it in, on or near bodies of water |
| 1947 | Sodium channel | DDT | NYT display ad – ensure a restful summer US army aerosol DDT bombs |
| | ChE | Carbaryl, other carbamates | Research on natural compound physostigmine lead to Ciba-Geigy development of multiple synthetic compounds |
| 1949 | Regulatory | Produce residues | Federal testing program announced |
| 1950 | Multi-site activity | US Inorganic pesticide use estimates | Calcium arsenate (38,842 lb), copper sulfate (124,573 lb), lead arsenate (27,490 lb), and sulfur (538,592 lb) |
| 1955 | Sodium channel | DDT | Hayes AJPH summary of DDT toxicology, residue persistence |
| 1957 | GABA-gated chloride channel antagonists | Dieldrin | documented by Hayes, malaria control programs using dieldrin10-20% of suffered seizures or other evidence of poisoning |
| 1958 | ChE | Parathion | Quinby JAMA report – residue poisoning in orchard workers |
| 1959 | GABA-gated chloride channel antagonists | Endrin | Poisoning in malaria workers, documented by Hayes, attributed to excessive dermal exposure during a long spray season. |
| 1960 | | Silica aerogel | Initial use of dehydrating agents, minimal toxicity noted |
| | Synergist | Piperonyl butoxide, MGK | Introduction of synergist compounds that block insect metabolism- most commonly used with pyrethrin and pyrethroid compounds |
| | Multi-site activity | Thiocyanates | Used as contact insecticides |
| 1962 | Sodium channel | DDT | Fish & Wildlife biologist Rachel Carson writes Silent Spring |
| 1965 | Sodium channel, ChE | DDT, carbaryl & other compounds | Allentown, PA – Hawk Mountain – litigation over use of organochlorines, complaints regarding carbaryl used for gypsy moth control program |
| 1967 | ChE | Azodrin | Organophosphate used to eradicate cotton bollworm, associated with poisoning of doves, quail, pheasants, songbirds, rabbits, hunting dogs San Joaquin Valley |
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