List of interstellar and circumstellar molecules

From Wikipedia, the free encyclopedia

This is a list of molecules that have been detected in the interstellar medium and circumstellar envelopes, grouped by the number of component atoms. The chemical formula is listed for each detected compound, along with any ionized form that has also been observed.

Detection

The molecules listed below were detected by spectroscopy. Their spectral features are generated by transitions of component electrons between different energy levels, or by rotational or vibrational spectra. Detection usually occurs in radio, microwave, or infrared portions of the spectrum.^[1]
Interstellar molecules are formed by chemical reactions within very sparse interstellar or circumstellar clouds of dust and gas. Usually this occurs when a molecule becomes ionized, often as the result of an interaction with a cosmic ray. This positively charged molecule then draws in a nearby reactant by electrostatic attraction of the neutral molecule's electrons. Molecules can also be generated by reactions between neutral atoms and molecules, although this process is generally slower.^[2] The dust plays a critical role of shielding the molecules from the ionizing effect of ultraviolet radiation emitted by stars.^[3]

History

The first carbon-containing molecule detected in the interstellar medium was the methylidyne radical (CH) in 1937.^[4] From the early 1970s it was becoming evident that interstellar dust consisted of a large component of more complex organic molecules, probably polymers. Chandra Wickramasinghe proposed the existence of polymeric composition based on the molecule formaldehyde (H₂CO).^[5] Fred Hoyle and Chandra Wickramasinghe later proposed the identification of bicyclic aromatic compounds from an analysis of the ultraviolet extinction absorption at 2175A.,^[6] thus demonstrating the existence of polycyclic aromatic hydrocarbon molecules in space.

In 2004, scientists reported^[7] detecting the spectral signatures of anthracene and pyrene in the ultraviolet light emitted by the Red Rectangle nebula (no other such complex molecules had ever been found before in outer space). This discovery was considered a confirmation of a hypothesis that as nebulae of the same type as the Red Rectangle approach the ends of their lives, convection currents cause carbon and hydrogen in the nebulae's core to get caught in stellar winds, and radiate outward.^[8] As they cool, the atoms supposedly bond to each other in various ways and eventually form particles of a million or more atoms. The scientists inferred^[7] that since they discovered polycyclic aromatic hydrocarbons (PAHs) — which may have been vital in the formation of early life on Earth — in a nebula, by necessity they must originate in nebulae.^[8]

In 2010, fullerenes (or "buckyballs") were detected in nebulae.^[9] Fullerenes have been implicated in the origin of life; according to astronomer Letizia Stanghellini, "It's possible that buckyballs from outer space provided seeds for life on Earth."^[10]

In October 2011, scientists found using spectroscopy that cosmic dust contains complex organic matter ("amorphous organic solids with a mixed aromatic-aliphatic structure") that could be created naturally, and rapidly, by stars.^[11][12][13] The compounds are so complex that their chemical structures resemble the makeup of coal and petroleum; such chemical complexity was previously thought to arise only from living organisms.^[11] These observations suggest that organic compounds introduced on Earth by interstellar dust particles could serve as basic ingredients for life due to their surface-catalytic activities.^[14][15] One of the scientists suggested that these compounds may have been related to the development of life on Earth and said that, "If this is the case, life on Earth may have had an easier time getting started as these organics can serve as basic ingredients for life."^[11]

In August 2012, astronomers at Copenhagen University reported the detection of a specific sugar molecule, glycolaldehyde, in a distant star system. The molecule was found around the protostellarbinary IRAS 16293-2422, which is located 400 light years from Earth.^[16][17] Glycolaldehyde is needed to form ribonucleic acid, or RNA, which is similar in function to DNA. This finding suggests that complex organic molecules may form in stellar systems prior to the formation of planets, eventually arriving on young planets early in their formation.^[18]

In September 2012, NASA scientists reported that PAHs, subjected to interstellar medium (ISM) conditions, are transformed, through hydrogenation, oxygenation, and hydroxylation, to more complex organics — "a step along the path toward amino acids and nucleotides, the raw materials of proteins and DNA, respectively".^[19][20] Further, as a result of these transformations, the PAHs lose their spectroscopic signature which could be one of the reasons "for the lack of PAH detection in interstellar ice grains, particularly the outer regions of cold, dense clouds or the upper molecular layers of protoplanetary disks."^[19][20]

In June 2013, PAHs were detected in the upper atmosphere of Titan, the largest moon of the planet Saturn.^[21]

In 2013, Dwayne Heard at the University of Leeds suggested^[22] that quantum mechanical tunneling could explain a reaction his group observed taking place, at a significantly higher than expected rate, between cold (around 63 Kelvin) hydroxyl and methanol molecules, apparently bypassing intramolecular energy barriers which would have to be overcome by thermal energy or ionization events for the same rate to exist at warmer temperatures. The proposed tunneling mechanism may help explain the common observation of fairly complex molecules (up to tens of atoms) in interstellar space.

A particularly large and rich region for detecting interstellar molecules is Sagittarius B2 (Sgr B2). This giant molecular cloud lies near the center of the Milky Way galaxy and is a frequent target for new searches. About half of the molecules listed below were first found near Sgr B2, and nearly every other molecule has since been detected in this feature.^[23] A rich source of investigation for circumstellar molecules is the relatively nearby star CW Leonis (IRC +10216), where about 50 compounds have been identified.^[24]

Molecules

The following tables list molecules that have been detected in the interstellar medium, grouped by the number of component atoms. If there is no entry in the Molecule column, only the ionized form has been detected. For molecules where no designation was given in the scientific literature, that field is left empty. Mass is given in Atomic mass units. The total number of unique species, including distinct ionization states, is listed in parentheses in each section header.

Most of the molecules detected so far are organic. Only one inorganic species has been observed in molecules which contain at least five atoms, SiH₄.^[25] Larger molecules have so far all had at least one carbon atom, with no N-N or O-O bonds.^[25]

Carbon monoxide is frequently used to trace the distribution of mass in molecular clouds.^[26]

Diatomic (43)

Molecule	Designation	Mass	Ions
AlCl	Aluminium monochloride[27][28]	62.5	—
AlF	Aluminium monofluoride[27][29]	46	—
AlO	Aluminium monoxide[30]	43	—
—	Argon hydride[31][32]	41	ArH+
C2	Diatomic carbon[33][34]	24	—
—	Fluoromethylidynium	31	CF+[35]
CH	Methylidyne radical[36]	13	CH+[37]
CN	Cyanogen radical[27][36][38][39]	26	CN+,[40] CN-[41]
CO	Carbon monoxide[27][42][43]	28	CO+[44]
CP	Carbon monophosphide[39]	43	—
CS	Carbon monosulfide[27]	44	—
FeO	Iron(II) oxide[45]	82	—
H2	Molecular hydrogen[46]	2	—
HCl	Hydrogen chloride[47]	36.5	HCl+[48]
HF	Hydrogen fluoride[49]	20	—
HO	Hydroxyl radical[27]	17	OH+[50]
KCl	Potassium chloride[27][28]	75.5	—
NH	Nitrogen monohydride[51][52]	15	—
N2	Molecular nitrogen[53][54]	28	—
NO	Nitric oxide[55]	30	NO+[40]
NS	Nitrogen sulfide[27]	46	—
NaCl	Sodium chloride[27][28]	58.5	—
—	Magnesium monohydride cation	25.3	MgH+[40]
NaI	Sodium iodide[56]	150	—
O2	Molecular oxygen[57]	32	—
PN	Phosphorus nitride[58]	45	—
PO	Phosphorus monoxide[59]	47	—
SH	Sulfur monohydride[60]	33	SH+[61]
SO	Sulfur monoxide[27]	48	SO+[37]
SiC	Carborundum[27][62]	40	—
SiN	Silicon mononitride[27]	42	—
SiO	Silicon monoxide[27]	44	—
SiS	Silicon monosulfide[27]	60	—
TiO	Titanium oxide[63]	63.9	—

The H₃⁺ cation is one of the most abundant ions in the universe. It was first detected in 1993.^[2][64]

Triatomic (41)

Molecule	Designation	Mass	Ions
AlNC	Aluminium isocyanide[27]	53	—
AlOH	Aluminium hydroxide[65]	44	—
C3	Tricarbon[34]	36	—
C2H	Ethynyl radical[27][38]	25	—
C2O	Dicarbon monoxide[66]	40	—
C2S	Thioxoethenylidene[67]	56	—
C2P	—[68]	55	—
CO2	Carbon dioxide[69]	44	—
FeCN	Iron cyanide[70]	82	—
—	Protonated molecular hydrogen	3	H3+[2][64]
H2C	Methylene radical[33]	14	—
—	Chloronium	37.5	H2Cl+[71]
H2O	Water[72]	18	H2O+[73]
HO2	Hydroperoxyl[74]	33	—
H2S	Hydrogen sulfide[27]	34	—
HCN	Hydrogen cyanide[27][38][75]	27	—
HNC	Hydrogen isocyanide[76]	27	—
HCO	Formyl radical[77]	29	HCO+[37][77][78]
HCP	Phosphaethyne[79]	44	—
—	Thioformyl	45	HCS+[37][78]
HNC	Hydrogen isocyanide[80]	27	—
—	Diazenylium	29	HN2+[78]
HNO	Nitroxyl[81]	31	—
—	Isoformyl	29	HOC+[38]
KCN	Potassium cyanide[27]	65	—
MgCN	Magnesium cyanide[27]	50	—
MgNC	Magnesium isocyanide[27]	50	—
NH2	Amino radical[82]	16	—
—	—	29	N2H+[37][83]
N2O	Nitrous oxide[84]	44	—
NaCN	Sodium cyanide[27]	49	—
NaOH	Sodium hydroxide[85]	40	—
OCS	Carbonyl sulfide[86]	60	—
O3	Ozone[87]	48	—
SO2	Sulfur dioxide[27][88]	64	—
c-SiC2	c-Silicon dicarbide[27][62]	52	—
SiCN	Silicon carbonitride[89]	54	—
SiNC	[90]	54	—
TiO2	Titanium dioxide[63]	79.9	—

Formaldehyde is an organic molecule that is widely distributed in the interstellar medium.^[91]

Four atoms (26)

Molecule	Designation	Mass	Ions
CH3	Methyl radical[92]	15	—
l-C3H	Propynylidyne[27][93]	37	l-C3H+[94]
c-C3H	Cyclopropynylidyne[95]	37	—
C3N	Cyanoethynyl[33]	50	C3N−[68]
C3O	Tricarbon monoxide[93]	52	—
C3S	Tricarbon sulfide[27][67]	68	—
—	Hydronium	19	H3O+[96]
C2H2	Acetylene[97]	26	—
H2CN	methylene amidogen[98]	28	H2CN+[37]
H2CO	Formaldehyde[99]	30	—
H2CS	Thioformaldehyde[100]	46	—
HCCN	—[101]	39	—
—	Protonated hydrogen cyanide	28	HCNH+[78]
—	Protonated carbon dioxide	45	HOCO+[102]
HCNO	Fulminic acid[103]	43	—
HOCN	Cyanic acid[104]	43	—
HOOH	Hydrogen peroxide[105]	34	—
HNCO	Isocyanic acid[88]	43	—
HNCS	Isothiocyanic acid[106]	59	—
NH3	Ammonia[27][107]	17	—
HSCN	Thiocyanic acid[108]	59	—
SiC3	Silicon tricarbide[27]	64	—
HMgNC	Hydromagnesium isocyanide[109]	51.3	—

Methane, the primary component of natural gas, has also been detected on comets and in the atmosphere of several planets in the Solar System.^[110]

Five atoms (19)

Molecule	Designation	Mass	Ions
C5	Linear C5[34]	60	—
—	Ammonium Ion[111][112]	18	NH4+
CH4	Methane[51][97]	16	—
CH3O	Methoxy radical[113]	31	—
c-C3H2	Cyclopropenylidene[38][114][115]	38	—
l-H2C3	Propadienylidene[115]	38	—
H2CCN	Cyanomethyl[citation needed]	40	—
H2C2O	Ketene[88]	42	—
H2CNH	Methylenimine[116]	29	—
HNCNH	Carbodiimide[117]	42	—
—	Protonated formaldehyde	31	H2COH+[118]
C4H	Butadiynyl[27]	49	C4H–[119]
HC3N	Cyanoacetylene[27][38][78][115][120]	51	—
HCC-NC	Isocyanoacetylene[121]	51	—
HCOOH	Formic acid[115]	46	—
NH2CN	Cyanamide[122]	42	—
HC(O)CN	Cyanoformaldehyde[123]	55	—
SiC4	Silicon-carbide cluster[62]	92	—
SiH4	Silane[124]	32	—

In the ISM, formamide (above) can combine with methylene to form acetamide.^[125]

Six atoms (15)

Molecule	Designation	Mass	Ions
c-H2C3O	Cyclopropenone[125]	54	—
E-HNCHCN	E-Cyanomethanimine[126]	54	—
C2H4	Ethylene[97]	28	—
CH3CN	Acetonitrile[88][127]	40	—
CH3NC	Methyl isocyanide[127]	40	—
CH3OH	Methanol[88]	32	—
CH3SH	Methanethiol[106]	48	—
l-H2C4	Diacetylene[27][128]	50	—
—	Protonated cyanoacetylene	52	HC3NH+[78]
HCONH2	Formamide[125]	44	—
C5H	Pentynylidyne[27][67]	61	—
C5N	Cyanobutadiynyl radical[129]	74	—
HC2CHO	Propynal[130]	54	—
HC4N	—[27]	63	—
CH2CNH	Ketenimine[114]	40	—

Acetaldehyde (above) and its isomers vinyl alcohol and ethylene oxide have all been detected in interstellar space.^[131]

Seven atoms (9)

Molecule	Designation	Mass	Ions
c-C2H4O	Ethylene oxide[132]	44	—
CH3C2H	Methylacetylene[38]	40	—
H3CNH2	Methylamine[133]	31	—
CH2CHCN	Acrylonitrile[88][127]	53	—
H2CHCOH	Vinyl alcohol[131]	44	—
C6H	Hexatriynyl radical[27][67]	73	C6H–[115][134]
HC4CN	Cyanodiacetylene[88][120][127]	75	—
CH3CHO	Acetaldehyde[27][132]	44	—

The radio signature of acetic acid, a compound found in vinegar, was confirmed in 1997.^[135]

Eight atoms (11)

Molecule	Designation	Mass
H3CC2CN	Methylcyanoacetylene[136]	65
H2COHCHO	Glycolaldehyde[137]	60
HCOOCH3	Methyl formate[88][115][137]	60
CH3COOH	Acetic acid[135]	60
H2C6	Hexapentaenylidene[27][128]	74
CH2CHCHO	Propenal[114]	56
CH2CCHCN	Cyanoallene[114][136]	65
CH3CHNH	Ethanimine[138]	43
C7H	Heptatrienyl radical[139]	85
NH2CH2CN	Aminoacetonitrile[140]	56
(NH2)2CO	Urea[141]	60

Nine atoms (10)

Molecule	Designation	Mass	Ions
CH3C4H	Methyldiacetylene[142]	64	—
CH3OCH3	Dimethyl Ether[143]	46	—
CH3CH2CN	Propionitrile[27][88][115][127]	55	—
CH3CONH2	Acetamide[114][125]	59	—
CH3CH2OH	Ethyl Alcohol[144]	46	—
C8H	Octatetraynyl radical[145]	97	C8H–[146]
HC7N	Cyanohexatriyne or Cyanotriacetylene[27][107][147][148]	99	—
CH3CHCH2	Propylene (propene)[149]	42	—
CH3CH2SH	Ethyl mercaptan[150]	62	—

A number of polyyne-derived chemicals are among the heaviest molecules found in the interstellar medium.

Ten or more atoms (15)

Atoms	Molecule	Designation	Mass	Ions
10	(CH3)2CO	Acetone[88][151]	58	—
10	(CH2OH)2	Ethylene glycol[152][153]	62	—
10	CH3CH2CHO	Propanal[114]	58	—
10	CH3C5N	Methyl-cyano-diacetylene[114]	89	—
10	(CH3)2CHCN	Isopropyl cyanide[154][155]	69	—
11	HC8CN	Cyanotetra-acetylene[27][147]	123	—
11	C2H5OCHO	Ethyl formate[156]	74	—
11	CH3COOCH3	Methyl acetate[157]	74	—
11	CH3C6H	Methyltriacetylene[114][142]	88	—
12	C6H6	Benzene[128]	78	—
12	C3H7CN	n-Propyl cyanide[156]	69	—
13	HC10CN	Cyanodecapentayne[147]	147	—
13	HC11N	Cyanopentaacetylene[147]	159	—
60	C60	Buckminsterfullerene (C60 fullerene)[158]	720	C60+[159][160]
70	C70	C70 fullerene[158]	840	—

Deuterated molecules (17)

These molecules all contain one or more deuterium atoms, a heavier isotope of hydrogen.

Atoms	Molecule	Designation
2	HD	Hydrogen deuteride[161][162]
3	H2D+, HD2+	Trihydrogen cation[161][162]
3	HDO, D2O	Heavy water[163][164]
3	DCN	Hydrogen cyanide[165]
3	DCO	Formyl radical[165]
3	DNC	Hydrogen isocyanide[165]
3	N2D+	—[165]
4	NH2D, NHD2, ND3	Ammonia[162][166][167]
4	HDCO, D2CO	Formaldehyde[162][168]
5	NH3D+	Ammonium ion[169][170]
7	CH2DCCH, CH3CCD	Methylacetylene[171][172]

Unconfirmed (10)

Evidence for the existence of the following molecules has been reported in scientific literature, but the detections are either described as tentative by the authors, or have been challenged by other researchers. They await independent confirmation.

Atoms	Molecule	Designation
2	SiH	Silylidine[76]
4	PH3	Phosphine[173]
5	H2NCO+	-[174]
10	H2NH2CCOOH	Glycine[38][175]
12	CO(CH2OH)2	Dihydroxyacetone[176]
12	C2H5OCH3	Ethyl methyl ether[177]
18	C10H8+	Naphthalene cation[178]
24	C24	Graphene[179]
24	C14H10	Anthracene[7][180]
26	C16H10	Pyrene[7]

Neonicotinoid

From Wikipedia, the free encyclopedia

Neonicotinoids are a class of neuro-active insecticides chemically similar to nicotine. In the 1980s Shell and in the 1990s Bayer started work on their development.^[1] Neonicotinoids cause less toxicity in birds and mammals than insects, compared to the previously used organophosphate and carbamate insecticides. Some breakdown products are toxic.^[2] The neonicotinoid family includes acetamiprid, clothianidin, imidacloprid, nitenpyram, nithiazine, thiacloprid and thiamethoxam, of which imidacloprid is the most widely used insecticide in the world.^[3]

In the late 2000s some neonicotinoids came under increasing scrutiny over their environmental impacts. The use of neonicotinoids was linked in a range of studies to adverse ecological effects, including honey-bee colony collapse disorder (CCD) and loss of birds due to a reduction in insect populations. Several countries restricted or banned the use of certain neonicotinoids.^[4][5][6]

Market

Neonicotinoids are registered in more than 120 countries. With a turnover of €1.5 billion in 2008, they represented 24% of the global market for insecticides.^{[citation needed]} After the introduction of the first neonicotinoids in the 1990s, this market has grown from €155 million in 1990 to €957 million in 2008. Neonicotinoids made up 80% of all seed treatment sales in 2008.^[7]

Seven neonicotinoids from different companies are currently on the market.^[7]

Name	Company	Products	Turnover in million US$ (2009)
Imidacloprid	Bayer CropScience	Confidor, Admire, Gaucho, Advocate	1,091
Thiamethoxam	Syngenta	Actara, Platinum, Cruiser	627
Clothianidin	Sumitomo Chemical/Bayer CropScience	Poncho, Dantosu, Dantop	439
Acetamiprid	Nippon Soda	Mospilan, Assail, ChipcoTristar	276
Thiacloprid	Bayer CropScience	Calypso	112
Dinotefuran	Mitsui Chemicals	Starkle, Safari, Venom	79
Nitenpyram	Sumitomo Chemical	Capstar, Bestguard	8

Usage

In the U.S., neonicotinoids are currently used on about 95 percent of corn and canola crops; the majority of cotton, sorghum, and sugar beets; and about half of all soybeans. They are also used on the vast majority of fruit and vegetable crops, including apples, cherries, peaches, oranges, berries, leafy greens, tomatoes, and potatoes. Neonicotinoids are also applied to cereal grains, rice, nuts, and wine grapes. ^[8] Imidacloprid is effective against sucking insects, some chewing insects, soil insects and is also used to control fleas on domestic animals.^[9] It is possibly the most widely used insecticide, both within the neonicotinoids and in the worldwide market. It is also applied against soil, seed, timber and animal pests as well as foliar treatments for crops including: cereals, cotton, grain, legumes, potatoes,^[10] some fruits, rice, turf and vegetables. It is systemic with particular efficacy against sucking insects and has a long residual activity. Imidacloprid can be added to the water used to irrigate plants. Controlled release formulations of imidacloprid take 2–10 days to release 50% of imidacloprid in water.^[11]

In the field, usefulness of neonicotinoid seed treatments for pest prevention depends upon the timing of planting and pest arrival. Neonicotinoid seed treatments do not appear to produce any benefits for pest management.^[12] For soybeans, neonicotinoid seed treatments typically are not effective against the soybean aphid, because the compounds break down 35 - 42 days after planting, and soybean aphids typically are not present or at damaging population levels before this time.^[12][13][14] Neonicotinoid seed treatments can protect yield in special cases such as late-planted fields or in areas with large infestations much earlier in the growing season.^[14] Overall yield gains are not expected from neonicotinoid seed treatments for soybean insect pests in the United States, and foliar insecticides are recommended instead when insects do reach damaging levels.^[12]

History

Nicotine acts as an insecticide. ^[15] It exhibits a higher lethal dose for rats than flies.^[3] This spurred a search for insecticidal compounds that have selectively less effect on mammals. Initial investigation of nicotine-related compounds (nicotinoids) as insecticides was not successful.^[15]

The precursor to nithiazine was first synthesized by a chemist at Purdue University.^[when?] Shell researchers found in screening that this precursor showed insecticide potential and refined it to develop nithiazine.^[1] Nithiazine was later^[when?] found to be a postsynaptic acetylcholine receptor agonist,^[16] the same mode of action as nicotine. Nithiazine does not act as an acetylcholinesterase inhibitor,^[16] in contrast to the organophosphate and carbamate insecticides. While nithiazine has the desired specificity (i.e. low mammalian toxicity), it is not photostable (it breaks down in sunlight), and thus not commercially viable.

The first commercial neonicotinoid, imidacloprid, was developed by Bayer^[when?].^[1]

Most neonicotinoids are water-soluble and break down slowly in the environment, so they can be taken up by the plant and provide protection from insects as the plant grows. During the late 1990s this class of pesticides, primarily imidacloprid, became widely used. Beginning in the early 2000s, two other neonicotinoids, clothianidin and thiamethoxam entered the market. Currently,^[when?] virtually all corn planted in the Midwestern United States is treated with one of these two insecticides and various fungicides.^{[citation needed]} Most soybean seeds are treated with a neonicotinoid insecticide, usually thiamethoxam.^{[citation needed]}

Regulation

United States

The US EPA operates a 15-year registration review cycle for all pesticides.^[17] The EPA granted a conditional registration to clothianidin in 2003.^[18] The EPA issues conditional registrations when a pesticide meets the standard for registration, but there are outstanding data requirements.^[19]
Thiamethoxam is approved for use as an antimicrobial pesticide wood preservative and as a pesticide; it was first approved in 1999.^{[20]:4 & 14} Imidacloprid was registered in 1994.^[21]

As all neonicotinoids were registered after 1984, they were not subject to reregistration, but due to environmental concerns, especially concerning bees, the EPA opened dockets to evaluate them.^[22] The registration review docket for imidacloprid opened in December 2008, and the docket for nithiazine opened in March 2009. To best take advantage of new research as it becomes available, the EPA moved ahead the docket openings for the remaining neonicotinoids on the registration review schedule (acetamiprid, clothianidin, dinotefuran, thiacloprid, and thiamethoxam) to FY 2012.^[22] The EPA has said that it expects to complete the review for the neonicotinoids in 2018.^[23]

In March 2012, the Center for Food Safety, Pesticide Action Network, Beyond Pesticides and a group of beekeepers filed an Emergency Petition with the EPA asking the agency to suspend the use of clothianidin. The agency denied the petition.^[23] In March 2013, the US EPA was sued by the same group, with the Sierra Club and the Center for Environmental Health joining, which accused the agency of performing inadequate toxicity evaluations and allowing insecticide registration based on inadequate studies.^[23][24] The case, Ellis et al v. Bradbury et al, was stayed as of October 2013.^[25]

On July 12, 2013, Rep. John Conyers, on behalf of himself and Rep. Earl Blumenauer, introduced the "Save American Pollinators Act" in the House of Representatives. The Act called for suspension of the use of four neonicotinoids, including the three recently suspended by the European Union, until their review is complete, and for a joint Interior Department and EPA study of bee populations and the possible reasons for their decline.^[26] The bill was assigned to a congressional committee on July 16, 2013 and did not leave committee.^[27]

Europe

In 2008, Germany revoked the registration of clothianidin for use on seed corn after an incident that resulted in the death of millions of nearby honey bees.^[28] An investigation revealed that it was caused by a combination of factors:

• failure to use a polymer seed coating known as a "sticker";
• weather conditions that resulted in late planting when nearby canola crops were in bloom;
• a particular type of air-driven equipment used to sow the seeds which apparently blew clothianidin-laden dust off the seeds and into the air as the seeds were ejected from the machine into the ground;
• dry and windy conditions at the time of planting that blew the dust into the nearby canola fields where honey bees were foraging;^[29]

In Germany, clothianidin was also restricted for a short period from use on rapeseed; however, after evidence had shown that the problems resulting from maize seed were not transferable to rapeseed, its use was reinstated under the condition that the pesticide be fixed to the rapeseed grains by means of an additional sticker, so that abrasion dusts would not be released into the air.^[30][31]

In 2009, the German Federal Office of Consumer Protection and Food Safety decided to continue to suspend authorization for the use of clothianidin on corn. It had not yet been fully clarified to what extent and in what manner bees come into contact with the active substances in clothianidin, thiamethoxam and imidacloprid when used on corn. In addition, the question of whether liquid emitted by plants via guttation, which is taken in by bees, pose an additional risk.^[32]

Neonicotinoid seed treatment uses are banned in Italy, but foliar uses are allowed. This action was taken based on preliminary monitoring studies showing that bee losses were correlated with the application of seeds treated with these compounds; Italy based its decision on the known acute toxicity of these compounds to pollinators.^[33][34]

Sunflower and corn seed treatments of the active ingredient imidacloprid are suspended in France; other imidacloprid seed treatments, such as for sugar beets and cereals, are allowed, as are foliar uses.^[33]

In response to growing concerns about the impact of neonicotinoids on honey bees, the European Commission in 2012 asked the European Food Safety Authority (EFSA) to study the safety of three neonicotinoids. The study was published in January 2013, which stated in January 2013 that neonicotinoids pose an unacceptably high risk to bees, and that the industry-sponsored science upon which regulatory agencies' claims of safety have relied may be flawed and contain data gaps not previously considered. Their review concluded, "A high acute risk to honey bees was identified from exposure via dust drift for the seed treatment uses in maize, oilseed rape and cereals. A high acute risk was also identified from exposure via residues in nectar and/or pollen."^[35][36] EFSA reached the following conclusions:^[37][38]

• Exposure from pollen and nectar. Only uses on crops not attractive to honey bees were considered acceptable.
• Exposure from dust. A risk to honey bees was indicated or could not be excluded, with some exceptions, such as use on sugar beet and crops planted in glasshouses, and for the use of some granules.
• Exposure from guttation. The only completed assessment was for maize treated with thiamethoxam. In this case, field studies showed an acute effect on honey bees exposed to the substance through guttation fluid.

EFSA’s scientists were unable to finalize risk assessments for some uses authorized in the EU, and identified a number of data gaps. EFSA also highlighted that risk to other pollinators should be further considered. The UK Parliament asked manufacturer Bayer Cropscience to explain discrepancies in evidence that they submitted to an investigation.^[39]

In response to the study, the European Commission recommended a restriction of their use across the European Union.^[6]

On 29 April 2013, 15 of the 27 European Union member states voted to restrict the use of three neonicotinoids for two years from 1 December 2013. Eight nations voted against the ban, while four abstained. The law restricts the use of imidacloprid, clothianidin and thiamethoxam for seed treatment, soil application (granules) and foliar treatment in crops attractive to bees.^[5][6] Temporary suspensions had previously been enacted in France, Germany and Italy.^[40] In Switzerland, where neonicotinoids were never used in alpine areas, neonics were banned due to accidental poisonings of bee populations and the relatively low safety margin for other beneficial insects.^[41]

Environmentalists called the move "a significant victory for common sense and our beleaguered bee populations" and said it is "crystal clear that there is overwhelming scientific, political and public support for a ban."^[6] The United Kingdom, which voted against the bill, disagreed: "Having a healthy bee population is a top priority for us, but we did not support the proposal for a ban because our scientific evidence doesn’t support it."^[6] Bayer Cropscience, which makes two of the three banned products, remarked "Bayer remains convinced neonicotinoids are safe for bees, when used responsibly and properly ... clear scientific evidence has taken a back-seat in the decision-making process."^[40] Reaction in the scientific community was mixed. Biochemist Lin Field said the decision was based on "political lobbying" and could lead to the overlooking of other factors involved in colony collapse disorder. Zoologist Lynn Dicks of Cambridge University disagreed, saying "This is a victory for the precautionary principle, which is supposed to underlie environmental regulation."^[6] A bee expert called the ban "excellent news for pollinators", and said, "The weight of evidence from researchers clearly points to the need to have a phased ban of neonicotinoids."^[40]

Economic impact

In January 2013, the Humboldt Forum for Food and Agriculture e. V. (HFFA), a non-profit think tank, published a report on the value of neonicotinoids in the EU. At their website HFFA lists as their partners/supporters: BASE FE, the world's largest chemical company; Bayer CropScience, makers of products for crop protection and nonagricultural pest control; E.ON, an electric utility service provider; KWS Seed, a seed producer; and the food company Nestle. ^[42]

The study was supported by COPA-COGECA, the European Seed Association and the European Crop Protection Association, and financed by neonicotinoid manufacturers Bayer CropScience and Syngenta. The report looked at the short- and medium-term impacts of a complete ban of all neonicotinoids on agricultural and total value added (VA) and employment, global prices, land use and greenhouse gas (GHG) emissions. In the first year, agricultural and total VA would decline by €2.8 and €3.8 billion, respectively. The greatest losses would be in wheat, maize and rapeseed in the UK, Germany, Romania and France. 22,000 jobs would be lost, primarily in Romania and Poland, and agricultural incomes would go down by 4.7%. In the medium-term (5-year ban), losses would amount to €17 billion in VA, and 27,000 jobs. The greatest income losses would affect the UK, while most jobs losses would occur in Romania. Following a ban, the lowered production would induce more imports of agricultural commodities into the EU. Agricultural production outside the EU would expand by 3.3 million hectares, leading to additional emissions of 600 million tons of carbon dioxide equivalent.^[43]

When the report was released, a spokesperson for the Soil Association, which has been working to ban neonicotinoids in the UK, commented that since the report was funded by Bayer Crop Sciences and Syngenta, "it was probably unlikely to conclude that neonicotinoids should be banned". The spokesperson further stated: "On the one hand, the chemical companies say we risk the additional costs to farmers amounting to £630 million. On the other, the possible cost of losing pollinating insects is thought to be worth three times as much (£1.8 billion*) to UK farmers."^[44]

Mode of action

Neonicotinoids, like nicotine, bind to nicotinic acetylcholine receptors of a cell and trigger a response by that cell. In mammals, nicotinic acetylcholine receptors are located in cells of both the central and peripheral nervous systems. In insects these receptors are limited to the CNS.

While low to moderate activation of these receptors causes nervous stimulation, high levels overstimulate and block the receptors,^[3][9] causing paralysis and death. Nicotinic acetylcholine receptors are activated by the neurotransmitter acetylcholine. Acetylcholine is broken down by acetylcholinesterase to terminate signals from these receptors. However, acetylcholinesterase cannot break down neonicotinoids and the binding is irreversible.^[9] Because most neonicotinoids bind much more strongly to insect neuron receptors than to mammal neuron receptors, these insecticides are selectively more toxic to insects than mammals.^[45]

Basis of selectivity

R-nicotine (top) and desnitro-imidacloprid are both protonated in the body

Most neonicotinoids, such as imidacloprid, show low affinity for mammalian nicotinic acetylcholine receptors (nAChRs) while exhibiting high affinity for insect nAChRs.^[3][46] Mammals and insects have structural differences in nAChRs that affect how strongly particular molecules bind, both in the composition of the receptor subunits and the structures of the receptors themselves.^[45][46] The low mammalian toxicity of imidacloprid can be explained in large part by its lack of a charged nitrogen atom at physiological pH. The uncharged molecule can penetrate the insect blood–brain barrier, while the human blood–brain barrier filters it.^[3]

Nicotine, like the natural ligand acetylcholine, has a positively charged nitrogen (N) atom at physiological pH.^[3][45] This positive charge gives nicotine a strong affinity to mammalian nAChRs as it binds to the same negatively charged site as acetylcholine (which is positively charged like nicotine). Although the blood–brain barrier reduces access of ions to the central nervous system, nicotine is highly lipophilic and at physiological pH is quickly and widely distributed. This can be demonstrated by the fact that nicotine is well absorbed transdermally, one of the most difficult tissues to penetrate. Neonicotinoids, on the other hand, have a negatively charged nitro or cyano group, which interacts with a unique, positively charged amino acid residue present on insect, but not mammalian nAChRs.^[47]

However, desnitro-imidacloprid, which is formed in a mammal's body during metabolism^[45] as well as in environmental breakdown,^[48] has a charged nitrogen and shows high affinity to mammalian nAChRs.^[45] Desnitro-imidacloprid is quite toxic to mice.^[2]

Independent studies show that the photodegradation half-life time of most neonicotinoids is around 34 days when exposed to sunlight. However, it might take up to 1,386 days (3.8 years) for these compounds to degrade in the absence of sunlight and micro-organism activity. Some researchers are concerned that neonicotinoids applied agriculturally might accumulate in aquifers.^[49]

Toxicity

Decline in bee population

A dramatic rise in the number of annual beehive losses noticed around 2006 spurred interest in factors potentially affecting bee health.^[50][51] When first introduced, neonicotinoids were thought to have low-toxicity to many insects, but recent research has suggested a potential toxicity to honey bees and other beneficial insects even with low levels of contact. Neonicotinoids may impact bees’ ability to forage, learn and remember navigation routes to and from food sources.^[52] Separate from lethal and sublethal effects solely due to neonicotinoid exposure, neonicotinoids are also being explored with a combination with other factors, such as mites and pathogens, as potential causes of colony collapse disorder.^[53] Neonicotinoids may be responsible for detrimental effects on bumble bee colony growth and queen production.^[54]

Previously undetected routes of exposure for bees include particulate matter or dust, pollen and nectar^[55] Bees can fail to return to the hive without immediate lethality due to sub-nanogram toxicity,^[56] one primary symptom of colony collapse disorder.^[57] Separate research showed environmental persistence in agricultural irrigation channels and soil.^[58]

A 2012 study showed the presence of thiamethoxam and clothianidin in bees found dead in and around hives situated near agricultural fields. Other bees at the hives exhibited tremors, uncoordinated movement and convulsions, all signs of insecticide poisoning. The insecticides were also consistently found at low levels in soil up to two years after treated seed was planted and on nearby dandelion flowers and in corn pollen gathered by the bees. Insecticide-treated seeds are covered with a sticky substance to control its release into the environment, however they are then coated with talc to facilitate machine planting. This talc may be released into the environment in large amounts. The study found that the exhausted talc showed up to about 700,000 times the lethal insecticide dose for a bee. Exhausted talc containing the insecticides is concentrated enough that even small amounts on flowering plants can kill foragers or be transported to the hive in contaminated pollen. Tests also showed that the corn pollen that bees were bringing back to hives tested positive for neonicotinoids at levels roughly below 100 parts per billion, an amount not acutely toxic, but enough to kill bees if sufficient amounts are consumed.^[59]

A 2013 peer reviewed literature review concluded that neonicotinoids in the amounts that they are typically used harm bees and that safer alternatives are urgently needed.^[60] An October 2013 study by Italian researchers demonstrated that neonicotinoids disrupt the innate immune systems of bees, making them susceptible to viral infections to which the bees are normally resistant.^[61][62]

Other wildlife

In March 2013, the American Bird Conservancy published a review of 200 studies on neonicotinoids calling for a ban on neonicotinoid use as seed treatments because of their toxicity to birds, aquatic invertebrates, and other wildlife.^[63]

A 2013 Dutch study determined that water containing allowable concentrations of neonicotinoids had 50% fewer invertebrate species compared with uncontaminated water.^[64]

In the July 2014 issue of the journal Nature, a study based on an observed correlation between declines in some bird populations and the use of neonicotinoid pesticides in the Netherlands demonstrated that the level of neonicotinoids detected in environmental samples correlated strongly with the decline in populations of insect-eating birds.^[65] An editorial published in the same edition^[66] found the possible link between neonicotinoid pesticide use and a decline in bird numbers "worrying," pointing out that the persistence of the compounds (half-life of 1000 days) and the low direct toxicity to birds themselves implies that the depletion of the birds' food source (insects) is likely responsible for the decline and that the compounds are distributed widely in the environment. The editors write that while correlation is not the same as causation, "the authors of the study also rule out confounding effects from other land-use changes or pre-existing trends in bird declines".