**6. Toxicity**

188 Pesticides in the Modern World - Risks and Benefits

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

wine (Everall and Dowd 1978).

Endocrine Diabetes

Gastrointestinal Hemorrhage

**System Effect and symptoms** 

Skin Skin lesions (melanosis, keratosis)

respiratory Pulmonary insufficiency, emphysem

Cardiovascular Blackfoot disease, atherosclerosis, hypertension

Hematological Bone marrow depression (anemia, leucopenia, thrombocytopenia)

Renal Tubule degeneration, papillary and cortical necrosis Nervous Peripher and central neuropathy, encephalopathy

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

Hepatic Hepatomegaly, fibrosis, cirrhosis, altered heme metabolism

following table.

Naidu 2009).

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

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 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 Schneider 2009; Hughes 2002).

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

The order of toxicity of arsenicals is:

Monomethylarsonic acid (MMA III) > Arsenite (III) > Arsenate (V) > MMA(V) (Singh, Kumar, and Sahu 2007).

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.
