After the end of the First Indochina War, the nearly century-long colonial rule of the Indochina region by the French ended with a defeat in the battle of Dien Bien Phu. In July 1954, a treaty was signed at the Geneva Conference that split Vietnam (Figure 1) in half at the 17^th North Parallel latitude line. The DRV controlled the north and the RV, with U.S. backing, controlled the south [1].

In 1959 DRV, with the objective of re-uniting the country of Vietnam, began military actions against the RV in the form of guerilla attacks. The U.S. then started to provide military assistance to “stop the spread of communism” which was called the “domino theory”. Initially, the U. S. only provided technical aid and support which included tactical herbicide weapons. However, following the August of 1964 Gulf of Tonkin incident, in which U.S. destroyers off the coast of

Vietnam were attacked, the United States officially entered the American-Vietnam War in August 1964.

At the height of the war, there were more than 500,000 U.S. military personnel serving in southern Vietnam. During the Vietnam War, the U.S. government and military (Air Force) engaged in a controversial and aggressive chemical warfare program, with the code name Operation Ranch Hand. The purpose was to destroy the North Vietnamese Army (NVA) bases forest cover, cultivated land and food crop supplies, from 1962 to 1971, in southern Vietnam. The U.S. Air Force Operation Ranch Hand sprayed 50 million liters of tactical herbicides across RV. In addition, the RV military, US Navy, CIA and US Army also sprayed millions of liters of tactical herbicides in southern Vietnam as part of the Khai Quang program. Four of the six herbicides, Agent Purple, Agent Pink, Agent Green and Agent Orange contained dioxin TCDD. Another tactical herbicide, Agent Blue contained arsenic and was used to destroy the NVA food supply including rice. Both dioxin TCDD and arsenic were extremely toxic to human health.

The U.S. began its withdrawal from RV in 1972 and the conflict between DRV and the U.S. ended following the Paris peace accords in January of 1973. The conflict between RV and DRV ended on April 30, 1975 after the surrender of the RV government.

Tactical herbicides, including Agent Blue and Agent Orange, were sprayed around suspected NVA areas (Figure 2) in southern Vietnam [1] as part of the RV Khai Quang program to improve visibility and destroy the enemy food supply [2]. The intensity of spraying was greatest in the proximity to NVA’s bases that were identified by the CIA during the Vietnam War [3]. Between 1962 and 1971, the U.S. Air Force sprayed 50 million liters of six tactical herbicides [4] across the RV. In addition, the RV military, U.S. Navy and U.S. Army sprayed Agent Blue, Agent Purple and Agent Orange on the rice paddies and mangrove forests of the RV. However, the Khai Quang program spray mission was classified or operational records were not maintained. The RV military operations, with the support of the U.S. Navy and Army, contributed to elevated dioxin TCDD and arsenic levels in the Mekong Delta landscape.

It is estimated that up to 366 kg of pure dioxin TCDD and more than 1,132,400 kg of pure arsenic were sprayed and as many as 4.8 million Vietnamese civilians were exposed [3] [4] [5]. The tolerable daily dioxin TCDD intake is defined by WHO to be between 1 and 4 pg (pictograms) per kg of body weight (one pg equals 10⁻¹⁵ kg). Numerous biological and epidemiological studies have shown robust medical linkages between herbicide exposure with dioxin TCDD or arsenic and a range of health problems. Among the most comprehensive, veterans and Agent Orange research was conducted by the National Academies of Science, Engineering and Medical. This report was updated annually and led to the Agent Orange Act of 1991 [6].

The first tactical (rainbow) herbicide delivered to Tan Son Nhut Air Base, RV, in 1962, was Agent Blue. This herbicide was in powder form and then mixed with water before spraying. This process often resulted in spills of Agent Blue

and its main ingredient cacodylic acid, both of which have short half-lives. Agent Blue and cacodylic acid were degraded to water-soluble arsenic, which has no half-life, and was released into surface water, soil and groundwater.

Records [2] indicate that 42% of the herbicide used in southern Vietnam (Figure 2) prior to 1965 was the herbicide Agent Blue with the active ingredient cacodylic acid-containing arsenic, selected by the RV government and military to destroy the rice crop. However, there is no publicly available RV military, Navy, CIA and Army records of the Agent Blue spray missions or identification of areas sprayed in the Mekong Delta, prior to 1965, and few records after that date. Stated RV and U.S. government and military goal, prior to 1965, was to eliminate the food supply of the NVA by destroying the southern Vietnamese rice crop in southern Vietnam just prior to harvest (Figure 3). Most of the rice crop was grown in the Mekong Delta and not the Central Highlands where more Operation Ranch Hand spray mission records are available. Apparently, the Agent Blue sprayed in the Mekong Delta by the RV military with the support of

US Army, CIA and US Navy was not counted as part of the U.S. Air Forces Operation Ranch Hand mission (Air Force kept and maintained their own spray mission records). The goal of the RV Khai Quang herbicide spray program, with the support of the US Army, US Navy and CIA, was to eliminate the local food supply, defoliate the jungle, including the stream banks on the canals, waterways and rivers to prevent ambushes and to expose the NVA and their base camps (Figure 2). There were at least 26 NVA mobile base camps in the Mekong Delta. Most were located in mangrove forests surrounded by rice paddies and adjacent to waterways. Agent Orange or Agent Purple was used to defoliate the forest and Agent Blue was used to destroy the rice crop. Since it took almost two weeks for leaf drops to occur after forests were sprayed with Agent Purple, Agent Orange or Agent Blue was sometimes combined with Agent Orange to speed up the defoliation process. Agent Blue applications, spraying and subsequent burning of the rice residue (to eliminate the seeds) by the US Army resulted in the Vietnamese living in the Mekong Delta losing capacity to feed themselves and the occupying NVA soldiers.

Some of the rural Vietnamese in southern Vietnam supported the NVA soldiers while others did not. However, the NVA soldiers had weapons and could take the rice, if not freely provided by local farmers. As a result, many of the rural Vietnamese in southern Vietnam, during the 1960s, were without a stable food supply and forced to move to the slums of Saigon and/or other urban areas. Nearly 2 million Vietnamese, living in both the Mekong Delta and Central Highlands were re-located into slums of Saigon as part of a RV government Strategic Hamlet project (easier to defend the rural Vietnamese population if concentrated in urban areas or hamlets). All of the southern Vietnam rural providences lost population during the Vietnam War (1960-1975) because of both population shifts (hamlet strategy) and civilians being killed during the war.

The US Army, Blue Water Navy and Brown Water Navy continued to spray the Mekong Delta stream banks (Figure 4) and rice paddies and mangrove forests after the U.S. government officially entered the Vietnam War in 1965. Despite the official declaration of war, Mekong Delta Agent Blue spray records were classified or not maintained. Agent Blue (arsenic), along with Agent Orange (with 2,4,5-T with unknown amounts of dioxin TCDD), were also used in combination by US Air Force as part of Operation Ranch Hand, after 1965, to defoliate the mangrove forests used by the NVA as base camps in the Mekong Delta. This deforestation exposed the stream banks and shoreline to soil erosion and destroyed the livelihoods of the local woodcutters.

The total amount of Agent Blue shipped to Vietnam was much more than the Operation Ranch Hand C-123s (Figure 5) and helicopters sprayed, according to the official Operation Ranch Hand records for the American-Vietnam War (from 1962 to 1971). This does not include the RV government’s Khai Quang Program. The Agent Blue, in powder form, was mixed with water and sprayed by the RV military, with the support of US military, on NVA base camps and adjacent lands in the Central Highlands and Mekong Delta (Figure 2). The RV military, US Navy and US Army spray records were classified or not maintained.

The purpose of the RV Khai Quang program spraying was to eliminate the local food supply (primarily rice) in southern Vietnam so the rural Vietnamese could not feed themselves or the NVA soldiers. Agent Blue was applied by RV

soldiers, with the support of the US military, on the perimeter of the NVA base camps and adjacent lands and selectively on more populated areas of the Central Highlands and the Mekong Delta. The spray equipment used included hand and backpack sprayers (Army), sprayers on Brown Water Navy boats, from Army military vehicles (Figure 6) and from military based helicopters including those on Blue Water Navy ships. While it was easy for the U.S. Government to explain and justify the Operation Ranch Hand defoliation objective to the media and the public, it was not so easy to explain and justify why the U.S. and RV governments and militaries were eliminating the local Vietnamese food supply and starving of the rural Vietnamese living in southern Vietnam. The elimination of the local food supply by the US military was done at the request of the RV government and military to force the rural Vietnamese into hamlets, which would be easier for the RV military to defend and to prevent the feeding of the NVA.

In southern Vietnam, Agent Blue was used as a contact herbicide for grassy plant control and rice destruction. More than 4.6 million liters of Agent Blue (664,393 kg of As) and known as Phytar 560-G and manufactured at the Ansul Chemical Plant on the Menominee River (Figure 7) in Wisconsin and Michigan, was sprayed as part of the DOD and USDA herbicide program code named Operation Ranch Hand. This was in addition to the RV Khai Quang program which also sprayed Agent Blue. In total, over 7.8 million liters of Agent Blue with 1,132,400 kg of arsenic (As) were sprayed on southern Vietnam (Figure 8).

The fact that RV and U.S. militaries were eliminating the food supply of the Vietnamese living in southern Vietnam to make it easier for the RV soldiers to defend the civilians from enemy attacks, became the official reason. However, the RV and U.S. military attempts to destroy the local Vietnamese food supply

was not considered by the media and the public to be a noble mission. Perhaps that destruction of the local food supply was part of the reason the RV military, US Army, CIA and US Navy the Khai Quang program spray records were classified or not maintained. Most of the U.S. media focus, after 1965, was on Agent Orange and the U.S. attempts to defoliate the jungle and expose the enemy (NVA).

To the credit of the US Air Force, they did keep excellent spray mission records, as part of Operation Ranch Hand; however, the total Agent Blue applied did not include the Khai Quang program Agent Blue applied and sprayed by the RV military, US Blue and Brown Water Navy, CIA and US Army. Without these spray mission records, it is hard, after 50 years, to locate the areas where Agent Blue was used to destroy the rice crop, especially in the Mekong Delta. Therefore, it is difficult (nearly impossible) to overlay the known arsenic spikes in the Mekong Delta groundwater with the spray and application mission records [3] [4] [5] of the RV military, US Navy, CIA and US Army as part of Khai Quang program.

Arsenic has no half-life and is water-soluble. Once it leaches into the groundwater it can be pumped back to the surface by hundreds of thousands of tube wells (Figure 9), constructed after 1975 to supply the freshwater needs of the rice paddies, and shrimp ponds and to meet the household and drinking water needs of the Vietnamese living on Mekong Delta or Central Highlands. Most of the anthropic arsenic remains in the southern Vietnam environment to this day. The primary loss of anthropic arsenic from the southern Vietnam landscape would have occurred when Agent Blue spray drifted into or was sprayed directly

on the rivers or adjacent stream banks. Surface runoff waters, with water-soluble cacodylic acid and arsenic components, flowed into the Mekong Delta Rivers, the South China Sea or Gulf of Thailand (Figure 10). However, most of the Agent Blue was utilized to destroy the rice crops and arsenic, with no half-life, has remained in the rice paddy root zone soils and/or leached into the groundwater only to be returned to the soil surface by tube wells, for urban and agricultural use.

The Menominee River flows into Lake Michigan via Green Bay (Figure 11). The Ansul Chemical Company at Marinette, Wisconsin manufactured almost all of the Agent Blue, an As containing herbicide, used during the Vietnam War in the 1960s and 1970s [7]. Agent Blue was shipped via Green Bay, the Great Lakes and the St. Lawrence Seaway to the Atlantic Ocean (Figure 12). Approximately 98% of the Agent Blue used during the Vietnam War from 1962 to 1971 was manufactured at Ansul Chemical plants on the Menominee River in Michigan and Wisconsin [7]. The As contaminated surface water and sediments near Ansul manufacturing plant flowed into the Menominee River (Figure 13). The groundwater and the river bottom sediments were heavily contaminated with As, which had been released by Ansul Company from 1957 to 1977, as waste products from the manufacture of Agent Blue for the Vietnam War effort. Ocean going-ships carrying the herbicide then passed through the Panama Canal [8] and the Pacific Ocean on the way to the South China Sea (Figure 14).

In 2009, the Ansul Company operated under two consent orders for environmental mitigation; one from the Wisconsin Department of Natural Resources and another from the USEPA. In September of 2009, Ansul Company agreed to spend an estimated $28 million on:

1) Removal of 56,600 m³ of arsenic-contaminated sediments from the Menominee River;

2) Construction of an impermeable barrier to bedrock for about 160,000 m² of sediment;

3) Cap or remove 17,000 m² of surface soils contaminated with arsenic levels above 16 - 32 ppm;

4) To pump and treat contaminated groundwater;

5) The total remediation costs were: 1976-1984, $11 million to pump and treat contaminated groundwater at the southern property border and to install a groundwater interceptor trench [7] in 1998-1999, $12.4 million to remove arsenic-contaminated sediment from the 8^th Street section of the Menominee River and

6) An impermeable barrier system was installed to bedrock near the 8^th Street slip and adjacent salt vault.

In 2012-2013, approximately $25 million was spent to dredge and then cap As contaminated river sediments due to an EPA order for the removal of 190,000 m³ of sediment from the main channel. The project cleanup began in July of 2012 after Ansul (Tyco) Company hired Stevenson Environmental Services of New York as the general contractor.

Cacodylic acid is manufactured by reducing disodium methyl arsenate with sulfur dioxide and methylating the sodium salt to the resultant arsenomethane. The solubility in water of both the acid and sodium salt is extremely high. The chemical is non-volatile and stable in sunlight; physical and chemical properties contribute to its effects and fate in plants and soil [7].

Cacodylic acid (Figure 15) is a contact herbicide because it lacks mobility and only kills tissues into which the compound enters causing the chemical symptoms to appear within two days. It is less effective if rain falls within a few hours of the treatment and before the chemical induces its full effects on the plants. Sub-lethal doses induce defoliation and malformed inflorescence and fewer seeds due to incomplete destruction of the rice plants. Cacodylic acid appears to undergo little breakdown within plant tissues.

In the soil, cacodylic acid undergoes microbial degradation. The breakdown is slow under aerobic conditions but much more rapid in flooded, anaerobic soils. The ultimate environmental fate is a change to inorganic arsenate or arsenite, which are mostly bound as relatively insoluble compounds in soil. Soils naturally contain As in this form, with the average content being 5 ppm. In Southeast Asia, sodium arsenite has been applied as a pesticide in rubber plantations at high rates for over 20 years without causing any crop injury [9].

Plants absorb cacodylic acid from the soil more readily than inorganic As but the evidence suggests that crops do not suffer an injury on land which has previously been treated. Excessive rates on soils unusually rich in phosphates can cause injury to sensitive plants such as rice and peanuts due to the phosphate ion blocking the adsorption of arsenate to the soil particles causing the As to remain in the soil solution. The toxicity rating of cacodylic acid for humans is coded as three (3), or medium toxicity. Toxicological data for commercial herbicides, Ansar 160 (16.8% As) and 560 (15% As), both are similar to Agent Blue [10]. Cacodylic acid is a non-selective herbicide that kills a wide variety of herbaceous plants [11]. Acute and chronic toxicity studies in a variety of animals indicate a low to medium toxicity rating [9]. Sodium cacodylate is regarded as a Special Health Hazard by the New Jersey Department of Health and EPA. The Agency for Toxic Substances and Disease Registry states, “Arsenic cannot be destroyed once added to the environment”.

During the Vietnam War Operation Ranch Hand, the project for aerial spraying of Agent Blue (Figure 16), contributed to the As contamination crisis in southern Vietnam [9]. In addition, the RV military (assisted by the US military unofficially), US Army and US Navy applied Agent Blue from 1962 to 1965 the program was extended until 1971 to the rice paddies in the Central Highland and the Mekong Delta. However, no official RV, Navy or Army spray records are publicly available. According to the US Department of the Army [12] [13] the primary goals, after 1965, were to clear out foliage and food crops [12] to achieve enhanced security, improve military intelligence, reduce cover for the enemy resistance [14], increase availability of the troops being used for combat and reduce US military personnel casualties.

The original intent of the RV and US military before the Vietnam War (1962- 1965) was to kill rice (Figure 3) and other food crops as part of a Navy and Army strategy to destroy the food supply of the Vietnamese living in southern Vietnam and the NVA [14]. Agent Blue, (CH₃)₂ As OOH) was a mixture of two As compounds, cacodylic acid and sodium cacodylate and was the most effective of all the tactical (rainbow) herbicides for killing rice [9]. The one major tactical

herbicide used for all 10 years of the war was Agent Blue. Two-thirds of Agent Blue was shipped to the 20^th Ordinance Storage Depot in Saigon and the other one-third was shipped to the 551st Ordinance Storage Depot in Da Nang. Agent Blue was primarily used on crops including cereals and grains [12] [13]. Agent Blue was aerially sprayed, by rotary (helicopters) and fixed wing (C-123) aircraft (Air Force), and since it was a desiccant, it dried plants and was used in the preparation of areas for crop burning [15]. During the 10 years, land affected, primarily rice paddies, by Agent Blue totaled 400,000 ha in southern Vietnam. The primary sprayed area was near Saigon and Da Nang with over 51,000 ha of forest defoliated by spraying at least 4 times and 27 thousand hectares of mangroves mostly along the South China Sea and the Gulf of Thailand were completely destroyed [16] [17] [18].

During the Vietnam War, Agent Blue was sprayed for the primary purpose of destroying rice and other food crops (Figure 2). As part of the RV and US government and military strategy to destroy the food supply, of both the communist insurgents and the southern Vietnamese living in rural areas, as part of the President Diem government’s “Strategic Hamlet” program [7]. Agent Blue, a mixture of two As compounds, cacodylic acid (CH₃ As O₂H) and sodium cacodylate (C₂H₆ AsNaO₂), was the most effective of all the tactical (rainbow) herbicides in killing rice. Arsenic has been a known poison since the Middle Ages. During the Vietnam War, the US government, DOD and USDA ignored warnings of thousands of scientists of its hazards and sprayed Agent Blue on rice paddies, mangroves [9], bamboo groves (Figure 17) and US military base perimeter fences. This resulted in exposure to As by Vietnamese civilians, DRV communist insurgents in the Mekong Delta and the U.S. military personnel who were stationed (boots on the ground) in southern Vietnam.

Spraying and dumping of Agent Blue by RV military with the assistance of the US Navy and Army to desiccate rice plants before maturity added massive quantities of water-soluble As to the soil root zone and the surface water and groundwater of the rice paddies [7]. Southeast Asia is a region where natural occurring As in soils and sediments tends to be higher because of the occurrence of As containing geologic formations in the region [1]. The RV Khai Quang program spraying significantly added to the As load (3.2 million liters of Agent Blue (468,008 kg of As) in southern Vietnam including the Mekong Delta environment. In addition, the U.S. used an estimated 4.6 million liters (664,392 kg As) of Agent Blue herbicide, as part of Operation Ranch Hand, as a chemical (herbicide) weapon for “crop destruction and defoliation”. For the last 50 years, As has been ingested by the Vietnamese living in southern Vietnam including the Mekong Delta via food and drinking water.

Water-soluble As leached into the soil root zone and into the groundwater

from the frequent application of Agent Blue by the RV military with the assistance of the US Army and Navy (in addition to Operation Ranch Hand (US Air Force)) and/or was transported by the surface runoff water directly into the waterways and rivers. After the Vietnam War was over, vast amounts of natural and residual manufactured arsenic-laced groundwater were pumped from private wells (Figure 18) to the surface to irrigate the rice paddies, fill shrimp ponds (Figure 19) and meet the drinking water needs of the 20 million people living in the Mekong Delta [7]. The water-soluble As continues to cause health effects in both animals and humans. In addition, during the 1962 to 1971 period, animals and humans, absorbed As primarily through skin contact with Agent Blue in their environment [18] [19].

Arsenic toxicity and health effects are complex and the impact of Agent Blue on human health was not well known for many years. Post-Vietnam War, arsenic-based industrial wood preservatives and herbicides with cacodylic acid were used throughout the U.S. in wood products, golf course management, and cotton fields (Figure 20) and for desiccating agricultural crops to hasten ripening

prior to harvesting. Today, none of these herbicides are commercially available with the exception of the weed killer monosodium meta-arsenate (MSMA) for use on U.S. cotton and for control of certain golf course vegetation. The frequent use of manufactured arsenic products in industry and agriculture has resulted in human exposure by way of inhalation, contaminated drinking water, and food. Epidemiological evidence and animal studies show excessive risks of lung and skin cancers as well as delayed health effects at relatively high exposure rates [20] [21].

Agent Blue, the As based herbicide (one of the military’s six tactical herbicides) was (Figure 21) field-tested in the United States, Puerto Rico, Canada and Thailand prior to its use in southern Vietnam. Later, Agent Blue was used at full strength during the Vietnam War. The Cancer Assessment Group of EPA currently puts As in the top category of cancer-causing chemicals. Arsenic, even at low doses has been found to be responsible for lung, bladder, and liver cancer and the arsenic is able to cross the placenta to create cancers in the fetus as well as both birth defects and childhood cancers have been linked to arsenic [21]. The effects of arsenic were delayed and can take decades to appear in humans [22]. Arsenic can cause damage to human DNA, which can adversely affect future offspring. Arsenical herbicides containing cacodylic acid as active ingredients are still being used today as weed killers and crop desiccants in some parts of the world. Less toxic formations of arsenical herbicides sold over the counter today can cause headaches, vomiting, dizziness, profuse and watery diarrhea, followed by dehydration, electrolyte imbalance, and gradual fall in blood pressure, convulsions, stupor, general paralysis, and possible death in 3 to 14 days in instances of acute poisoning [22] [23].

Cognetta et al. [24] found the most common manifestation of, As exposure in susceptible individuals is bilateral palmoplantar hyperkeratosis. Arsenic is one of the known causes of acquired palmoplantar keratoderma (PPK). Cognetta et al. [24] reported a unique case of palmoplantar hyperkeratotic lesions and numerous

squamous cell carcinoma in situ (SCCIS) which developed in a Vietnam veteran approximately 15 years after exposure to As during the Vietnam War. “It is possible that exposure to Agent Blue contributed to the development of these lesions. Though a causal link between Agent Blue and skin cancer cannot be established, increased awareness of this potential exposure may prompt further study to improve our understanding of Agent Blue and its role in cutaneous oncology. ”

During the last 50 years, the Vietnamese people living in the Mekong Delta have continued to ingest and bio-accumulate As (manufactured and natural) via their drinking water and food supply. Arsenic can bio-accumulate in animals and humans as it is transported by blood to different organs in the body [25]. However, not all of the ingested As remains in the human body. The major proportion can be excreted as organic forms of As. The portion that is not excreted, is the part that bio-accumulates.

The routes of entry of cacodylic acid into the human body are ingestion, inhalation, absorption through the skin and eye contact irritant. Cacodylic acid is more readily absorbed into the bloodstream when inhaled as an aerosol [26]. It is metabolized by the liver and bio-accumulates in and is excreted by skin, nails and hair [27]. Unlike inorganic arsenicals, dmethyl arsenic (DMAA) and monomethyl arsonic acid (MMAA) are metabolites of inorganic arsenic formed intra-cellular by most living organisms exposed to natural sources and do not bind strongly to molecules in humans. Hence, the acute toxicity seems to be less than that of the inorganic arsenicals [28]. However, recent studies of the trivalent organic arsenicals that are metabolic products of inorganic arsenic suggest they could possibly be more toxic than the parent compound [29] [30]. This includes inhibition of oxidative stress, as well as immune, endocrine, and epigenetic effects [31]. Analytical determination of arsenic poisoning can be made by examining arsenic levels in urine, hair and toenails. Kapaj and Pederson [20] found communities and individuals relying on groundwater sources for drinking water should consider a program to document arsenic levels [20].

Since arsenic poisoning of humans can occur by the gradual accumulation of small doses until the lethal levels are reached, the use of Agent Blue (during the Vietnam War) and other organic arsenicals pose a long-term danger [11]. Neurological symptoms are usually more frequent than gastro-intestinal effects over prolonged exposure to organic arsenicals [26]. Cacodylic acid may cause parathesis and/or weakness in the hands and feet [13]. Repeated skin contact may cause hyperpigmentation and keratosis. Malnourished people are more susceptible to arsenic-related skin lesions [20] [24].

The initial RV military and US Army, Air Force and Navy Vietnam War objective, prior to 1965, was to spray Agent Blue, the As based rice killer, on the rice paddies of the Mekong Delta and the Central Highlands to eliminate the NVA food supply. The goal, which extended until 1972, included denying food sources to the southern Vietnamese people, who were forced to move to the slums of Saigon (Strategic Hamlets) so they would not be able to feed the enemy (RVA) or themselves and could be protected in hamlets by the RV government and military.

During the last 60 years, there has been little research work on Agent Blue and its active ingredient cacodylic acid (As) even though As is lethal when significant quantities are ingested by humans over time (Figure 22). One of the reasons that the Agent Blue contribution to the high levels of As in the Mekong Deltas groundwater can not been determined is the inability of scientists, including chemists, to separate naturally occurring As from manufactured As because the end products of As reactions in the environment are the same. Attempts were made to determine if there is a significant chemical signature difference. After 50 years no known method can separate manufactured As from naturally occurring As. We do know that arsenic can exist with oxidation states of −3 (in air), 0 (in nature and is rare), +3 (in water) and +5 (in water) charges. It appears that both natural and manufactured As are water-soluble and are in the arsenite (+3) and arsenate (+5) states. In addition, there is also organic (not harmful) and inorganic (toxic) forms of As and it is known that it may be possible for chickens to convert organic As to inorganic As.

The purpose of using the herbicide Agent Blue was to desiccate and destroy narrow-leaf plants and trees (bamboo (Figure 17), grass, rice (Figure 23), and bananas (Figure 24). “Operation Ranch Hand”, was military code name for spraying of herbicides by US Air Force in southern Vietnam from 1962 through

1971 [26]. In this case, the widespread use of Agent Blue by the RV with the support of the US Navy and Army prior to 1965 (and later extended to 1971) was an attempt to take away the enemy’s food supply by depriving them of food resources.

Agent Blue, in 208-liter barrels with a blue stripe (hence the name-Agent Blue), was sent to southern Vietnam between 1962 and 1971. The RV and US governments and militaries used an estimated 7.8 million liters of Agent Blue herbicide (1,132,400 kg of As) during US Air Forces Operation Ranch Hand and RV Khai Quang program and applied as a chemical weapon for “crop destruction and defoliation”. Agent Blue was sprayed primarily on the mangroves, rice paddies, and the surrounding forest of the Central Highlands and Mekong Delta in southern Vietnam (Figure 25). Agent Blue was also used in Laos and Cambodia, along the Ho Chi Minh trail, to kill food crops including upland rice in an attempt to deprive the North Vietnamese communist and insurgent troops of a food source. The Agent Blue was applied at the average rate of 2.831 kg As/ha to the rice paddy and forest areas. Many areas were sprayed only once while other areas received four or more applications. The forest and mangrove areas were usually sprayed at a different rate than the rice paddies (Figure 26). Unable to control the insurgent’s access to their food supplies or eliminate their grassroots village support, the RV military with US military (Army and Navy) support response was simple: “If you cannot control it, kill it” [14] [32].

Agent Blue was primarily used to defoliate narrow grass vegetation or to kill food crops by desiccation. The rice plant is highly dependent on water to survive. Spraying Agent Blue on paddies can destroy approximately 60% of an entire rice paddy and leave it unsuitable for immediate re-planting do to soil sterilization. The dried rice paddy vegetation and seeds were destroyed by burning (Figure 3). Rice-killing RV military operations with assistance of the US Army and Navy also included use of specially designed rubber or plastic fuel bladders that were probably dropped from helicopters into rice paddies, which burst on

impact to release the toxic Agent Blue herbicide into the paddy waters [3]. This usually resulted in 100% of the rice crop (spraying was only 60% effective) being destroyed [3]. Bladders of Agent Blue were also dropped into the water irrigation canals, which ruptured on contact and contaminated the water in the rivers, canals and rice paddies. Arsenic-laden Agent Blue added As to the root zone, rice, water and soil. Subsequently, more recent industrial development, especially where contaminated soil has been disturbed has resulted in an increase in bio-availability of arsenicals. After the Vietnam War was over in 1975, the Vietnamese people would harvest and eat the As tainted rice (Figure 27), fish (Figure 28) and shrimp (Figure 19) for the next 48 years.

According to Institute of Medicine [2], over 7.8 million liters of Agent Blue herbicide (1,132,400 kg of As) was applied by the RV military with the support of the US military (Khai Quang program). This total included the US Air Force (Operation Ranch Hand) sprayed Agent Blue as a military and environmental chemical weapon for crop destruction and defoliation between 1962 and 1971 and the environmental effects of Agent Blue were understated. Spray drift affected many hectares of land adjacent to the targeted NVA bases and adjacent rice paddies. Crops were sprayed and burnt which concentrated the arsenic poison and contaminated the air with dust and smoke particulates. The Vietnamese living in southern Vietnam and US and RV military personnel had to breathe [14] As particulates. The As laced ash and dust can also be spread by wind and

water transport to adjacent land and to rivers and bodies of water [32]. Shallow groundwater has become the primary source for irrigation and drinking water in southern Vietnam and during the last two decades, thousands of government-subsidized shallow tube-wells were installed. Groundwater As concentrations have measured as high as 3050 ug/L. The As from Agent Blue is one of the potential sources of anthropic As hotspots. Today, Vietnamese rice is still tainted with trace amounts of inorganic As from anthropic and natural groundwater sources [33].

The groundwater of the Red River alluvial floodplain soils in Hanoi is anoxic and rich in iron due to naturally occurring organic matter in sediment [34]. Arsenic problems are caused primarily by “tube wells”, which draw water from depths of between 10 and 40 m. The wells, designed to provide safe drinking water by avoiding polluted surface waters, can bring up water from arsenic-contaminated underground aquifers [19]. The Red River valley (Figure 29) was not sprayed with tactical herbicides, including Agent Blue, but still has high levels of arsenic and natural or anthropic arsenic spikes.

Industrial development in Vietnam raised bio-available arsenicals to dangerous levels [35]. The arsenic contamination levels varied from 1 - 3050 ug/L with

an average arsenic concentration of 159 ug/L in rural groundwater samples from private small-scale tube wells. In a highly affected rural area, the groundwater used for drinking water had an average concentration of 430 ug/l. Analysis of raw groundwater pumped from the lower aquifer for the Hanoi water supply yielded arsenic levels of 240 - 320 ug/L in three of eight water treatment plants and 37 - 82 ug/L in another five plants. Aeration and sand filtration applied in the treatment plants to remove iron lowered the arsenic concentration to 25 - 91 ug/L, but 50% remained above the Vietnam standard of 50 ug/L. The arsenic in the sediments may be associated with iron oxyhydroxides and released into the groundwater by reductive dissolution of iron. The oxidation of sulfide phases could also release arsenic to the groundwater, but sulfur concentrations in sediments were below 1 mg/g. The high arsenic concentrations found in the tube wells (48% above 50 ug/L and 20% above 150 ug/L) indicate that several million people consuming untreated ground water, in rural areas might be at a considerable risk of chronic arsenic poisoning [34]. According to Berg [19], “arsenic contamination levels in aquifers in Vietnam area of the same order of magnitude as in Bangladesh where tainted groundwater contributed to what a World Health Organization report called “the biggest poisoning of a population in history”.

Agent Blue contained 4.7% cacodylic acid (also known as hydroxydimethyarsinine oxide or dimethylarsenic acid – DMAA), and 26.4% sodium cacodylate as the active ingredients [36] [37]. Cacodylic acid (Figure 15) is a colorless, odorless, and hygroscopic crystalline solid. It was also commercially available in the form of soluble concentrates. Water solutions of cacodylic acid were sometimes blue in color [10]. Cacodylic acid is 54% arsenic [11]. Besides DMAA, another organic arsenical compound which forms the active ingredient of pesticides and herbicides used mainly for weed control is monomethylarsonic acid (MMAA). DMAA and MMAA are also metabolites of inorganic arsenic formed intra-cellular by most living organisms (animals, plants and bacteria) [38].

The routes of entry of cacodylic acid are by ingestion, inhalation, eye contact (irritant), and absorption through the skin [10]. Cacodylic acid is more readily absorbed into the bloodstream when inhaled [26]. It is metabolized by the liver and bioaccumulates in and is excreted in urine as well as by skin, nails and hair [27]. Unlike inorganic arsenicals, DMAA and MMAA do not bind strongly to molecules in humans. Hence, their acute toxicity seems to be less than that of the inorganic arsenicals [28]. However, recent studies indicate that trivalent organic arsenicals [e.g., MMA (III) and DMA (III)] that are metabolic products of inorganic arsenic could possibly be more toxic than the parent compound [29] [30].

The mechanism of toxicity of arsenic includes enzyme inhibition and oxidative stress, as well as immune, endocrine, and epigenetic effects [39] [40]. Analytical determinations of arsenic poisoning can be determined by examining arsenic levels in urine, hair and toenails. Communities and individuals relying on groundwater sources for drinking water need to measure arsenic levels to ensure that their supplies are safe, and communities with arsenic levels greater than 5 μg/L in drinking water should consider a program to document arsenic levels in the population [20].

The use of tactical herbicides in southern Vietnam began as an initiative of Republic of Vietnam (RV) Vietnam President Ngo Dinh Diem. Part of the RV government’s policy was to move the rural population into “strategic hamlets” that could be more easily be secured and defended than the existing villages. This also allowed the destruction of the rice crops, a potential North Vietnam Army (NVA) food source, to discourage NVA activities. President Ngo Dinh Diem insisted that Agent Blue be used to destroy the rice crop in southern Vietnam and President Kennedy finally gave the okay for testing Agent Blue use on the food crops in southern Vietnam [41], according to Lindsey Arison III in his report “The Herbicidal Warfare Program in Vietnam, 1961-1971”. In the early 1960s, the RV program, known as Khai Quang Program, was designed to make battlefield more visible by clearing foliage leaves and eliminating the food crops. This secret NVA program, from 1962 to 1965, was supported by the US military (Air Force, Army and Navy) and the CIA. These Agent Blue missions required US military handlers dressed in civilian clothing, aircraft without US military markings and if the military personnel were captured the US government would not acknowledge the crew as members of the US military [14] [15]. Most of the handlers of Agent Blue were Vietnamese and no US military warnings or safety equipment was provided. Nor were the RV military soldiers and handlers warned against drinking the water from rivers where Agent Blue was sprayed. No Vietnamese military or civilian personnel knew about the contamination or the inherent health hazards of the Agent Blue the chemical herbicide they were handling. Approximately, 3.2 million liters of Agent Blue (468,008 kg As) was sprayed or dumped by the RV military with the support of the US military during the extended Khai Quang Program (1962 to 1971) [2].

President Kennedy’s Joint Chiefs of Staff stated, in early 1960s, that “Care must be taken to assure that the U.S. government does not become an international target for charges of employing biological or chemical weapons”. International repercussions against the United States could become significant [22]. After considerable internal debate, President Kennedy gave the approval needed to use Agent Blue on food crops including rice.

On 9 January 1962 the first shipment of sodium salt of cacodylic acid and code-named “Blue” were received at Tan Son Nhut Air Base, RV. These first shipments of Blue were in powder form and had to be mixed with water before spraying. Later shipments of Agent Blue barrels had a blue colored band painted around the centers of the 208-liter drums and designed as an identification aid for support personnel. Agent Blue was the first tactical (rainbow) herbicide used in Operation Ranch Hand, the tactical aerial spraying program in southern Vietnam of the U.S. Air Force [42] [43].

The first recorded use of Agent Blue by the US Air Force was in November of 1962. During the next nine years 4.6 million liters (664,392 kg of As) were sprayed during Operation Ranch Hand missions [3] [4]. This was in addition to the 3.2 million liters of Agent Blue (468,008 kg As) previously sprayed or dumped by the RV military, with the support of the US military, during the Khai Quang Program [2]. The Institute of Medicine [2] estimated a total of 7.8 million liters (1,132,400 kg As) of Agent Blue was applied to southern Vietnam from 1961 to 1971. This total includes both the Agent Blue used in US Air Force Operation Ranch Hand and the Agent Blue used in the RV Khai Quang program which was assisted by the US Air Force, Army and Navy. New studies of US military flight logs suggest an even greater use of Agent Blue; however, the Agent Blue application total of 7.8 million liters (1,132,400 kg As) applied to southern Vietnam, from 1961 to 1971, is the best available documented As total available at this time [2].

Agent Blue was first delivered and used in southern Vietnam in early 1962. There are records that 42% [2] of all tactical herbicides used before 1965 was the arsenic-based Agent Blue herbicide. The RV government and military with the support of the US Army, US Navy and CIA did not document their spraying locations like the US Air Force did and make them available to the media and public. The Mekong Delta region had a complex water network of wetlands, forest vegetated stream banks, small streams and natural river distributaries of the Mekong River as well as intricate human engineering canals, dykes, and ditches used to produce paddy rice.

These drainage systems crossed the entire Mekong Delta Region. These drainage waterways were used as a navigation network and were accessible by non-motorized and motorized boats and floating platoons that were used by locals and militaries. To access and destroy the NVA base camps in the Mekong Delta and destroy rice food supply would have required the skills of water and land-based military forces including the US Army and Navy. Because there are no RV military, US Army and US Navy records of Agent Blue spraying in much of the Delta region, it is now impossible to distinguish natural from anthropogenic arsenic spikes in the Delta groundwater. However, one could surmise that arsenic based Agent Blue herbicide was one of the vegetation management tools available to the RV military, US Army and US Navy and that its use throughout the delta increased the concentration of arsenic in the Mekong Delta groundwater.

During the Vietnam War (1962-1971), herbicides were sprayed by RV and US military forces at an order of magnitude greater than amounts used for domestic weed control [12] [14]. The herbicides were stored and shipped in 208-litre barrels, and named after the colored band painted on each barrel [33]. They were mostly sprayed by RV military, with the support of the US military, over the forests of southern Vietnam to kill crops in order to deprive the NVA troops of food, and to remove the vegetation cover used for concealment (Figure 4), making ambushes more difficult [32]. RV and US Army soldiers used mortars and grenades in an attempted to destroy rice paddies and rice stocks, but rice grains were very durable and not easily destroyed [15]. Soon, the “rice-killing operations” became more sophisticated. Rubber or plastic bladders were dropped directly into rice paddies, bursting on impact and releasing toxic herbicides including Agent Blue, and barrels of herbicides were also dropped into the water irrigating rice paddies, polluting rivers and poisoning the soil and people for many years [7]. Agent Blue was used as a contact herbicide in southern Vietnam for rapid defoliation, grassy plant control and rice destruction. Agent Blue was the agent of choice for the destruction of rice crops by the RV military with the support of the US Army and Navy.

More than 4.6 million liters of Agent Blue (also known as Phytar 560-G), were dispensed in the DOD herbicide program, according to US Air Force Operation Ranch Hand herbicide records [3] and 3.2 million liters of Agent Blue was sprayed as part of Khai Quang program [2]. Agent Blue, also applied by the RV military and the US Navy and Army worked rapidly defoliating or desiccating a wide variety of plant species of grasses and grains. It works by uncoupling phosphorylation in plants [14]. It was used in situations requiring rapid defoliation, causing browning or discoloration within one day, with maximum desiccation and leaf fall occurring within two to four weeks [14]. By starving rice plants of moisture, the enemy and millions of rice-growing villagers could be denied their most basic food source. This formed an essential part of the RV and U.S. government’s “rice-killing operations” [15]. The term “Agent Blue” was first applied to cacodylic acid in powder form that was mixed with water. Cacodylic acid is a highly soluble organic arsenic compound that readily breaks down in soil [29]. It is considered to have very low toxicity for mammals [30].

The original commercial form of Agent Blue was so common and so profitable that it was among 10 toxic insecticides, fungicides and herbicides partially deregulated by the US Environmental Protection Agency (EPA) in February 2004, and specific limits on toxic residues in meat, milk, poultry and eggs were removed [31] [44] [45]. However, in 2009, the U.S. Environmental Protection Agency issued a cancellation order to eliminate and phase-out the use of organic arsenical pesticides by 2013, with one exception – monosodium methanearsonate (MSMA), a broadleaf weed herbicide for use in defoliation of cotton. Small amounts of cacodylic acid (or disodium methanearsonate) were historically applied as herbicides in cotton fields, golf courses, backyards and other areas, but its use is now prohibited under the USEPA 2009 organic arsenical product cancellation [25] [38]. Other organic arsenicals (e.g. roxarsone, arsanilic acid and its derivatives) are used as feed additives for poultry and swine to increase the rate of weight gain, improve feed efficiencies, pigmentation, and to treat and prevent disease [14] [40] [44] [45].

The highest exposure in insecticide manufacturing was usually found at the mixing, screening, drying, bagging, and drum-filling operations (Figure 30). During these operations, reported arsenic concentrations in air ranged from 0.5 - 45 mg/m³ [25]. The World Health Organization (WHO) guideline for the safety limit of arsenic is 10 μg/L in drinking water [32]. In Vietnam, the legal arsenic concentration limit is five times higher than in the WHO guidelines [31]. The groundwaters of the Red River alluvial tract in Hanoi are anoxic and rich in iron due to naturally occurring organic matter in the sediments [34]. The problems were caused largely by the “tube wells”, which draw water from depths of between approximately 10 and 40 m. The wells, designed to provide safe drinking water by avoiding polluted surface waters, inadvertently tapped into arsenic laden underground aquifers [19]. The use of Agent Blue during the Vietnam War and other industrial developments caused the levels of bio-available arsenicals to spike dangerously [35]. The arsenic contamination levels varied from 1 - 3050 μg/L, with an average arsenic concentration of 159 μg/L in rural groundwater samples from private small-scale tube wells. In a highly affected rural area, the groundwater used directly as drinking water had an average concentration of 430 μg/L [44]. Analysis of raw groundwater pumped from the lower aquifer for the Hanoi water supply yielded arsenic levels of 240 - 320 μg/L in three of eight water treatment plants and 37 - 82 μg/L in another five plants. Aeration and sand filtration applied in the treatment plants to remove iron lowered the As concentrations to 25 - 91 μg/L, but 50% remained above the Vietnamese standard of 50 μg/L.

During the Vietnam War (1962-1971), herbicides were sprayed by RV and US militaries at a rate of an order of magnitude greater than amounts used for domestic weed control [14] [32]. The herbicides were stored and shipped in 208-liter barrels, and named after the colored band painted on each barrel. They were mostly sprayed over the forests and rice paddies of southern Vietnam to kill the mature rice crop in order to deprive the NVA troops of food, and to remove the vegetative cover used for concealment, making ambushes more difficult [15]. Agent Blue was used as a contact herbicide in southern Vietnam for rapid defoliation, grassy plant control and rice destruction. Blue (and later Agent Blue) was the agent of choice used by the RV and U.S. militaries for the destruction of rice crops.

More than 4.6 million liters of Agent Blue (also known as Phytar 560-G), were dispensed in the Operation Ranch Hand herbicide program, according to Air Force herbicide spraying records [3]. This was in addition to approximately, 3.2 million liters of Agent Blue (468,008 kg As) was sprayed or dumped by the RV military, with the support of the US military, during the extended Khai Quang Program (1962 to 1971). Agent Blue works by rapidly defoliating or desiccating a wide variety of plant species of grasses and grains [14]. It works by uncoupling phosphorylation in plants [32]. It was used in situations requiring rapid defoliation, causing browning or discoloration within one day, with maximum desiccation and leaf fall occurring within two to four weeks [33]. By starving rice plants of moisture, the enemy soldiers and millions of rice-growing southern Vietnamese villagers would be starved of their most basic food. This formed an essential part of the US government’s “rice-killing operations” [15]. The term “Agent Blue” was first applied to cacodylic acid in powder form that was mixed with water in the field. Cacodylic acid is a highly soluble organic arsenic compound that readily breaks down in soil [36]. It was considered, at the time, to have very low toxicity for mammals [30].

Agent Blue affects plants by causing them to dry out (Figure 3). As rice is highly dependent on water to live, using Agent Blue on these paddies can destroy an entire field and leave it unsuitable for further planting. This is why Agent Blue was also used where food was not a factor, but the foliage was. The Communist insurgents (RVA) had an advantage while fighting in southern Vietnam because they were used to the abundance of plant life on the battlefield. The U.S. found themselves at a disadvantage and based on the precedent set by the British in Malaya [46] decided that the best retaliation would be to take the enemy’s advantage away from them by removing their cover. Along roads, canals, railroads, and other transportation networks, Ranch Hand cleared several hundred yards using the herbicides to make ambushes more difficult for their enemies. In Laos, the herbicide removed the jungle canopy from the roads and trails used for infiltrating men and supplies, making them more vulnerable to attack from the air.

Although the acute and chronic effects of organic arsenicals are not as severe as those of inorganic arsenicals, organic arsenicals still have a significant impact on human health. Additional studies many uncover more currently unproven or unknown health effects. The present public health concern to human exposure to arsenic was linked with the consumption of arsenic-rich drinking water. This is a result of the alluvial sediments on the floodplains being rich in arsenic [47] [48]. Current epidemiological and experimental studies have attempted to elucidate the specific mechanism of arsenic carcinogenicity. This has led to the question of whether it is an epigenetic carcinogen. Due to the complexity of the mechanism of toxicity on the molecular level, and because of genetic polymorphism in the human population, both options continue to remain plausible [28]. However, recent studies show that the trivalent organic arsenicals that are metabolic products of inorganic arsenic could possibly be more toxic that the parent compound [29] [30]. The mechanism of arsenic includes inhibition and oxidative stress, as well as immune, endocrine, and epigenetic effects [31].

Analytical determination of arsenic poisoning may be made by examining arsenic levels in human urine, hair and toenails. Kapaj and Pederson [20] found communities and individuals relying, on groundwater sources for drinking water, need to measure arsenic levels to ensure their water supplies are safe. Communities with arsenic levels greater than 5 ug/L in drinking water should consider a program to document arsenic levels [20].

Since arsenic poisoning of humans can occur by gradual accumulation of small doses until lethal levels are reach, the use of Agent Blue (during the Vietnam War) and other organic arsenicals pose a long-term danger [18]. Neurological symptoms are usually more frequent than gastrointestinal effects over prolonged exposure of organic arsenicals [26]. Cacodylic acid may cause paresthesia and/or weakness in the hands and feet [42]. Repeated skin contact may cause hyper pigmentation and keratosis. Malnourished people are more susceptible to arsenic-related skin lesions [20].