**4. Epidemiology**

184 Pesticides in the Modern World - Risks and Benefits

Through the centuries Arsenic was a common method of homicide. The death of the French emperor Napoleon Bonaparte, on 5 May 1821 was believed to be a victim after drinking arsenic-tainted wine that was served him (Leslie and Smith 1978; Lin, Alber, and Henkelmann 2004). Arsenic was a popular murder weapon because of the odorless and tasteless properties and the poisoning result in symptoms that can be confused with other natural disorders. In the Middle ages arsenic was a favorite poison and has been called the

Arsenic was also used as healing agents. The Greek physicians such as Hippocrates and Galen popularized it use for treating skin ulcers and tumors such as superficial epitheliomas. Arsenic has been used as topical pastes, as vapor inhalation, intravenous injection, orally in liquid or in solid form. A paste of the sulfides were used for treatment of neuralgia, rheumatism, arthritis and skin disease (Shen et al. 1997). Also Fowler´s solution, a 1% arsenic trioxide preparation, was widely used during the 19th century. Fowler´s original recipe was described as "64 grains arsenic oxide, 64 grains purest vegetable alkali, distilled water half pound. Heat until clear. Cool. Add half pound spirit of lavender and make up to

Poison of Kings and the King of Poison (Vahidnia, van, V, and de Wolff 2007).

15 oz with water." (Cullen 2008).

Deutschmark banknote.

Fig. 3. Fowler´s Solution made by Wisconsin Pharmacal Co

It was used to treat diseases like leukemia, Hodkin´s disease and pernicious anemia.

Fig. 4. German 200 Deutschmark banknote with hologram and Paul Ehrlich

The first organic arsenical used therapeutically was Salvarsan, which was developed by Paul Ehrlich 1907. It was used to treat syphilis, until penicillin became available in the 1940s. A model representation from Salvarsan and a picture of Ehrlich adorned the 200 Arsenic exposure occurs from inhalation, absorption through the skin and by ingestion. Arsenic is mainly transported in the environment by food, which contains both organic and inorganic As, but mostly accrue as relatively no-toxic organic compounds (arsenobentaine and arsenocholine). Seafood, fish and algae are the richest organic sources (Edmonds and Francesconi 1987). The following table shows an overview of the arsenic content of various foods.


Table 2. Estimated of daily arsenic intake from diet (Sorvari et al. 2007)

Concentrations of arsenic vary in the environment, e.g. 0,03-025 ppm in soil, 0,023-0,35 ppm in plants, up to 55 ppm in groundwater, 0,0001-0,08 ppm in seawater, 4-170 ppm in fish, 0,008-0,85 ppm in wine and up to 0,00049 or 0,63 mg/m³ in urban air (2004; Jones 2007; Rahman 2006; Basu et al. 2001). Contamination of arsenic in ground water is a global problem and millions of people are at a risk of arsenicosis. People from countries in Asia (Taiwan, Bangladesh, West Bengal (India) and South America (Chile and Córdoba) get presented to inorganic arsenic in ground water with very high concentration. The arsenic poisoning from drinking As-contaminated underground water was often triggered by the introduction of deep tube-pump wells to replace surface water. The World health organization (WHO) and US environment protection agency (EPA) had set up the standard for drinking water known as maximum contamination level (MCL) which is 10 µg/l (Effelsberg 1992). The WHO recommended 0.01 mg/l of arsenic in drinking water as an allowable ranger for human consumption. Millions of people are compelled to use the drinking water higher arsenic level than MCL worldwide. In addition there are industrial exposures for workers, e.g. semiconductor workers and famers handle with arsenical herbicides. Arsenic has been used as feed additives e.g. poultry feeds.

It was found an increase in the prevalence of skin lesions at 0,005 mg As/l in the drinking water, which is a lower level than the drinking water quality standard of WHO (Yoshida,

Arsenic – Pesticides with an Ambivalent Character 187

leading to shock and death. Depending on the quantity of arsenic, death usually occurs within 1-5 days. In acute poisoning the best indicator of recent ingestion (1-2 days) is urinary arsenic concentration. Dimethylarsinic acid is the dominant urinary metabolite compared with

Chronic ingestion of inorganic arsenic causes multisystem adverse health effects. The clinical features of chronic arsenic toxicity vary between individuals, population groups and geographic areas. In chronic arsenic ingestion, arsenic accumulates in the liver, kidneys, heart and lungs and smaller amounts in the gastrointestinal tract, spleen and muscles (Benramdane et al., 1999). High doses of arsenic cause characteristic skin manifestation, vascular, renal and neurological diseases, cardiovascular and chronic lung diseases and cancer of skin, lungs, liver, kidney and bladder. After about two weeks arsenic is deposited in the hair and nails. Levels between 0,1 and 0,5 mg/kg on a hair sample indicate chronic poisoning. Various epidemiological studies have reported that arsenic exposure is associated with hypertension, atherosclerosis and endothelial dysfunction (Yang et al. 2007) (Chen et al. 2007) (Kwok et al. 2007). Increasing exposure of arsenic is also associated with non insulin dependent diabetes mellitus (Wang et al. 2003). Studies reported that arsenic is

Skin manifestation is the most common and initial sign of chronic arsenic exposure. Chronic ingestion of arsenic causes characteristic melanosis, keratosis, basal cell carcinoma and squamous cell carcinoma (Maloney 1996). Melanosis includes hyperpigmentation, spotted pigmentation, depigmentation and leucomelanosis. Keratosis is a late feature of arsenicaldermatosis and appears especially on palm as a uniform thickening or as discrete nodules (Wong, Tan, and Goh 1998b). Both palmar and solar keratosis are significant diagnostic criterion. Bowen´s disease is a precancerous lesion and predisposed to an increased incidence of the squamous cell carcinoma. Chronic ingestion of arsenic lead to accumulate in keratin rich areas of body and appears as white lines in the nails, called Mee´s lines (Fincher and Koerker 1987). The latency period of skin lesions of arsenic after first exposure varies

monomethylarsoonic acid (Hopenhayn-Rich, Smith, and Goeden 1993).

associated with the growth retardation in children (Wang et al. 2007).

Fig. 5. Patient with plantar keratosis (2004; Wong, Tan, and Goh 1998c).

**5.2 Chronic effects** 

**5.3 Skin symptoms** 

Yamauchi, and Fan 2004). The skin is very sensitive to As and skin lesions, which are Asinduced, are the early effects to chronic As exposure.

Arsenic is released to the atmosphere from both natural and anthropogenic sources.

Tobacco smoke may contain arsenic, especially when the plants have been treated with arsenate insecticide.


Table 3. Estimated daily intake of arsenic by the general population ((Devesa et al. 2001; Jelinek and Corneliussen 1977; Leblanc et al. 2005; Mohri, Hisanaga, and Ishinishi 1990; Saipan and Ruangwises 2009; Sorvari et al., 2007; Watanabe et al. 2004)

The principal natural source is volcanic activity, with minor contribution by exudates from vegetation and wind-blow dust. Man-made emissions to air arise from the smelting of metals, the combustion of fuels, especially of low-grade brown coal, and the use of pesticides. Because of the use of numerous arsenical pesticides the arsenic concentration raised in the soil.
