**5.1 Acute effects**

After acute poisoning studies show that the highest concentration of arsenic is in the kidney and liver (Benramdane et al. 1999). Most cases of acute arsenic poisoning occur from accidental ingestion of insecticides or pesticides. Acute exposure to arsenic arise symptoms like abdominal pain, vomiting, diarrhea. The abdominal pain may mimic an acute abdomen (Mueller and Benowitz 1989). Other clinical features are muscular weakness and cramping, erythematous skin eruptions like diffuse skin rash and swelling of acrals. A progressive deterioration in the motor and sensory responses and toxic cardiomyopathy may also result 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 monomethylarsoonic acid (Hopenhayn-Rich, Smith, and Goeden 1993).

### **5.2 Chronic effects**

186 Pesticides in the Modern World - Risks and Benefits

Yamauchi, and Fan 2004). The skin is very sensitive to As and skin lesions, which are As-

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

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

**Country Daily dietary intake of total arsenic from diet (µg/d)** 

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;

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

The biological activity of arsenic in the body covers a broad spectrum from toxic to therapeutic agent. Not to forget- Arsenic is a human carcinogen (IARC 2004). A number of studies show that arsenic is an essential element for humans. Other studies have attempted to show that arsenic has not been demonstrated to be essential to humans (Ohtake 2000). The major routes of arsenic absorption in the general population are ingestion and inhalation. Meat, fish and poultry account for 80 % of dietary arsenic intake (Edmonds and Francesconi 1987). Arsenic is absorbed in the small intestine by an electrogenic process involving a proton gradient. The absorbed arsenic undergoes hepatic biomethylation. The products are less toxic but not completely innocuous. About 50 % of the ingested dose may be eliminated in the urine in 3-5 days. Metabolism of As involves reduction of As V to a

After acute poisoning studies show that the highest concentration of arsenic is in the kidney and liver (Benramdane et al. 1999). Most cases of acute arsenic poisoning occur from accidental ingestion of insecticides or pesticides. Acute exposure to arsenic arise symptoms like abdominal pain, vomiting, diarrhea. The abdominal pain may mimic an acute abdomen (Mueller and Benowitz 1989). Other clinical features are muscular weakness and cramping, erythematous skin eruptions like diffuse skin rash and swelling of acrals. A progressive deterioration in the motor and sensory responses and toxic cardiomyopathy may also result

Saipan and Ruangwises 2009; Sorvari et al., 2007; Watanabe et al. 2004)

trivalent state and subsequent oxidative methylation.

induced, are the early effects to chronic As exposure.

arsenate insecticide.

raised in the soil.

**5.1 Acute effects** 

**5. Effects on human** 

Bangladesh 515 Japan 182 USA 20-130 Spain 245 French 62 Germany 52 UK 66 Denmark 64

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

#### **5.3 Skin symptoms**

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

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

Arsenic – Pesticides with an Ambivalent Character 189

Arsenic compounds or arsenic-containing compounds vary in toxicity to mammalian cells. Arsenic does not directly react with DNA or cause gene mutations, except to a small extent at high dose. As can cause gene amplification and chromosomal damage at lower doses and can enhance mutagenesis by other agents, apparently by inhibiting DNA repair. The

following table gives an overview over the modes of carcinogenic action of arsenic.

Table 5. Modes of carcinogenic action of arsenic (Schuhmacher-Wolz, Dieter, Klein, and

sulphydryl groups makes keratin-rich cells a target for arsenic.

The binding with sulfhydryl groups by arsenite compounds has the potential to influence a wide range of metabolic activities. Arsenic toxicity inactivates up to 200 enzymes. The effects of As occur through indirect alteration of gene expression via disruption of DNA methylation, inhibition of DNA repair, oxidative stress, or altered modulation of signal transduction pathways. Another indirect mechanism is the influence of growth-stimulating chemicals or cytokinesed generated in response to arsenic exposure. Biotranformation is the major metabolic pathway for inorganic arsenic in humans. Toxic inorganic arsenic species can be biomethylated by bacteria, algae, fungi and humans. The high affinity of arsenic for

Monomethylarsonic acid (MMA III) > Arsenite (III) > Arsenate (V) > MMA(V) (Singh,

In arsenic biotransformation the intermediate product MMA III is highly toxic than other arsenical, which might be responsible for the arsenic-induced carcinogenesis and other effects (Styblo et al. 2000). As III binds thiol or sulfhydryl groups in tissue proteins of the liver, lungs, kidney, spleen, gastrointestinal mucosa and keratin-rich-issues (skin, hair, nails). By binding a wide range of metabolic activities are influenced including cellular glucose uptake, gluconeogenesis and fatty acid oxidation (Jones 2007). Many other toxic effects of arsenic compounds are detailed by Abernathy et al in 1999 (Abernathy et al. 1999). The acute toxicity is related to its chemical form and oxidation state. In the human adult the lethal range of inorganic arsenic is estimated at a dose of 1-3 mg As / kg (Schoolmeester and White 1980). The characteristics of acute arsenic toxicity in humans include gastrointestinal discomfort, vomiting, diarrhea, bloody urine, anuria, shock, convulsions, coma and death.

Arsenic has been used therapeutically for over 2000 years. During the 18th- 20th centuries arsenic compounds have been used as medicines, including arsphenamine and arsenic

**6. Toxicity** 

Genotoxicity Oxidative damage

Tumor promotion

**Modes of carcinogenic action of arsenic** 

Modification of cell signalling Influence on DNA repair Influence on DNA methylation Changes in cell proliferation

Schneider 2009; Hughes 2002).

The order of toxicity of arsenicals is:

Kumar, and Sahu 2007).

**7. Pharmaceutical use** 

Co-mutagenesis and transformation

Fig. 6. Blackfoot diseases after chronic arsenic exposure (Better Life Laboratories, USA)

from 20 to 50 years (Haque et al. 2003). It is described that the latent period after exposure can be as long as 60 years, which has been reported in patients treated with Fowler´s solution, in vineyard workers using arsenical pesticides and from drinking contaminated wine (Everall and Dowd 1978).

Many different systems within the body are affected by chronic exposure. Some of these systems and their associated toxic effects from chronic arsenic exposure are listed in the following table.


Table 4. Human effects after chronic arsenic exposure (Singh, Kumar, and Sahu 2007; Schuhmacher-Wolz et al. 2009; Hughes 2002; Balakumar and Kaur 2009; Rahman, Ng, and Naidu 2009).
