Endosulfan in human

Limited information is available regarding the effects of endosulfan in humans and animals after inhalation exposure. The reports of effects in humans are limited to case reports of adverse effects noted in workers exposed to large quantities of endosulfan during its manufacture. Exposures in these reports are likely to be a combination of inhalahon and dermal exposures. Therefore, the findings from these case reports are also presented in the section on dermal exposures (Section 2.2.3). 

No studies were located regarding the distribution of endosulfan in humans and animals after inhalation exposure to endosulfan. 

Dermal Effects. There have been no reports of adverse dermal effects associated with exposure to endosulfan in humans. When tested in farmers, endosulfan did not cause contact dermatitis (Schuman and Dobson 1985). Studies in experimental animals have shown that dermal exposure to endosulfan is only slightly to moderately irritating at relatively high doses (Hoechst 1983b, 1985c, 1985d, 1989b Industria Prodotti Chimici 1975). 

Acute clinical signs of neurotoxicity, manifested by hyperexcitability, dyspnea, decreased respiration, tremors, and convulsions, were identified in the available literature as effects caused by high doses of endosulfan. Exposure to high levels of endosulfan in humans may possibly be associated with permanent brain damage as manifested by cognitive and emotional deterioration, memory impairment, and... 

Most of the hterature reviewed concerning the health effects of endosulfan in humans described case reports of occupational exposure and accidental or intentional ingestion of endosulfan. The cases of occupational exposure to endosulfan concerned exposures of acute-to-intermediate durations, and the cases of oral exposure were exclusively acute-duration exposure situations. The predominant route of exposure in the occupational case reports is believed to be inhalation, but the possibility of some degree of dermal exposure cannot be ruled out. The information on human exposure is limited because the possibility of concurrent exposure to other pesticides or other toxic substances cannot be excluded. In addition, the precise duration and level of exposure to endosulfan generally cannot be quantified from the information presented in these reports. 

No information is available regarding the metabolism of endosulfan in humans. However, the metabolic pathway of this chemical has been well characterized in several species of experimental animals (Deema et al. 1966 Dorough et al. 1978 Gorbach et al. 1968 WHO 1984). The data indicate that metabolism of endosulfan occurs in both the liver and kidney (Agarwal et al. 1978 Deema et al. 1966 Hoechst 1987 ... 

Children s Susceptibility. The information on health effects of endosulfan in humans is derived mainly from cases of accidental or intentional exposure of adults to high amounts of the pesticide, and the main adverse effect is neurotoxicity. No reports of adverse effects in endosulfan-exposed children were found, but it is reasonable to assume that children will exhibit similar signs and symptoms to those in adults under similar exposure conditions. Some studies in animals have provided evidence that young animals respond to endosulfan differently than adult animals (Kiran and Varma 1988 Lakshmana and Raju 1994 Sinha et al. 1995,1997 Zaidi et al. 1985), but there is no conclusive evidence to suggest that young animals are more susceptible than older ones. Further studies that evaluate a number of different end points in young as well as older organisms would provide valuable information. 

Positive identification of low-ppb (pg/L) levels of endosulfan in human blood has been achieved by GC equipped with a microcoulometric detector (GC/MC) (Griffith and Blanke 1974). Although GC/MC is specific and nearly as sensitive as GC/ECD for detecting endosulfan in blood, GC/MC is more difficult to operate. Both isomers of endosulfan can be measured in blood using a method described by Guardino et al. (1996). According to the authors, endosulfan can be recovered and measured with an approximate limit of quantitation (LOQ) of 0.2 pg/L (sub-ppb). 

GC/MS has been employed by Demeter et al. (1978) to quantitatively detect low-ppb levels of a- and P-endosulfan in human serum, urine, and liver. This technique could not separate a- and P-isomers, and limited sensitivity confined its use to toxicological analysis following exposures to high levels of endosulfan. More recently, Le Bel and Williams (1986) and Williams et al. (1988) employed GC/MS to confirm qualitatively the presence of a-endosulfan in adipose tissue previously analyzed quantitatively by GC/ECD. These studies indicate that GC/MS is not as sensitive as GC/ECD. Mariani et al. (1995) have used GC in conjunction with negative ion chemical ionization mass spectrometry to determine alpha- and beta-endosulfan in plasma and brain samples with limits of detection reported to be 5 ppb in each matrix. Details of commonly used analytical methods for several types of biological media are presented in Table 6-1. 

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