Annex 1 to the Interim Report



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Persistence


No hydrolysis of endosulfan occurs under acidic conditions, while hydrolytic half-lives have been determined to a few weeks in neutral medium, and to about 1 day in alkaline medium (1,2). Thus, hydrolysis is important especially in marine environments (1). Endosulfan diol is the main metabolite (1,2). In study of biotic transformation in water/sediment system, endosulfan sulfate and endosulfan hydrocarboxylic acid were identified as main metabolites, but reliable half-lives have not been presented as yet (2).
Endosulfan does not seem to exceed the criteria for persistence in itself. The -isomer appears to be more rapidly degraded than the -isomer (1,2), however, most results are given for the sum of isomers. Half-lives determined in laboratory studies in soil at 20C (+) range from 26 to 128 days, with a mean value of 79 days (2). From field studies on dissipation in soil, carried out in Germany and the US (Georgia and California), DT50s of 16-93 days are reported (for +), with a mean value of 63 days (2). The main metabolite in soil is endosulfan sulfate (1,2). From a field study in Germany half-lives of this metabolite were reported to 655 days (planted soil) and 2 210 days (bare ground), while field studies in Spain and Greece resulted in shorter half-lives; 75 and 47-161 days, respectively (1). Thus, the criterion for persistency is considered to be met for endosulfan when also considering endosulfan sulfate.

Bioaccumulation


Reported log Kow values for endosulfan are 2.2-4.8 (1) and 4.9 at pH 4, 4.6-4.8 at pH 7 and 5.6 at pH 10 (2). Thus, a high potential for bioconcentration is indicated. This is confirmed by at least some studies on bioconcentration in fish. Reported bioconcentration factors (BCFs) range from 350 to

11 580 (1,2). Half-life for depuration in fish has been reported as 2-4 days. In mussel, a BCF of 600 was reported, with a half-life for clearance of about 1 day (1).


Endosulfan and endosulfan residues have been found in numerous food products such as vegetables (0.5-13 µg/kg), seafood (0.0002-1.7 µg/kg), milk and tobacco (1). In 1995-98 endosulfan and endosulfan sulfate were found in 0.1-9.9% of meat samples and in fish, crab and mollusc samples in Germany (1). In recent samples of blue mussel from the south Swedish coast, 0.03-0.06 mg -endosulfan/kg lipid was measured (lipid content of the mussels being approx. 1 %) (5).
In mammals, excretion rate seems to be rapid after a single oral dose. Following repeated dosing in rat, the residues reached maximum values after about 3 weeks, with the highest concentrations in kidneys (2). These residues consisted of polar compounds, whereas endosulfan sulfate was the major component in the residues in fat. Following cessation of dosing, the residues in all tissues fell significantly over the next 5 days to levels which for most tissues were similar to those seen 24 hours after a single oral dose (2). Residue levels in reproductive organs were not higher than in general organs. In mammals, endosulfan is converted to the following metabolites: endosulfan sulfate, endosulfan diol, endosulfan ether, endosulfan hydroxyether, endosulfan lactone, and a number of polar metabolites which probably are the conjugates of the metabolites (2).
Although some of the reported BCF values exceed 5000, it is not clear whether endosulfan meet the criterion for bioaccumulation. It is clear that varying degree of bioaccumulation occurs in organisms having relatively low metabolic capacity. In mammals however bioaccumulation or biomagnification is not likely to occur because metabolism in mammals seems to be fairly rapid. Also, no data on measured concentrations in mammals was found.

Toxicity


Endosulfan is highly toxic for aquatic organisms, with several EC/LC50 values in the µg/l range reported for fish and aquatic invertebrates (1,2). Lowest LC50 value from acute toxicity test was 0.04 µg/l for the marine crustacean Penaeus duorarum (1,2). The -isomer seems to be more toxic than the -isomer. In carp, LC50 (96 h) was 0.75 µg/l for -endosulfan, > 3.1 µg/l for -endosulfan (2). In daphnids, EC50 (48 h) was 224 µg/l for -endosulfan, 528 µg/l for -endosulfan (2). In a pond study, fish mortality was observed at water concentrations of 0.4 and 1 µg/l (2).
Some NOEC values reported from long-term studies on aquatic organisms are: 21-d and 28-d NOEC in fish 0.05 µg/l (1,2); 21-d NOEC in daphnids 63 µg/l (2) and 14-d NOEC in daphnids 49 µg/l (1).
Short-term toxicity of metabolites have also been investigated in fish (carp) and daphnids (2):

endosulfan sulfate: LC50 (96 h) fish 2.2 µg/l, EC50 (48 h) daphnids 300 µg/l,

endosulfan lactone: LC50 (96 h) fish 570 µg/l, EC50 (48 h) daphnids >1 300 µg/l,

endosulfan ether: LC50 (96 h) fish > 1 650 µg/l, EC50 (48 h) daphnids 580 µg/l,

endosulfan hydroxyether: LC50 (96 h) fish 2 300 µg/l, EC50 (48 h) daphnids 1 600 µg/l.
Endosulfan is also toxic to birds; Acute LD50 was 28 mg/kg bw; Short-term dietary LC50 was 805 ppm, and NOEC for effects on reproduction was as low as 30 ppm (2).
To mammals, endosulfan is highly toxic via the oral route (1), with LD50 values of 10-23 mg/kg bw reported for female rat (2). Lowest relevant NOAEL has been established as 0.6 mg/kg bw/d for neurotoxic effects observed in a 1-year study in dog (2). In rat and mouse, 90-d NOAEL was 3.8 mg/kg bw/d (male rat) and 2.3 mg/kg bw/d (mouse) (2). Stimulation of the central nervous system is the major characteristic of endosulfan poisoning (1). Sheep and pigs grazing on fields sprayed with endosulfan showed lack of muscle coordination and blindness; reversible blindness has also been reported for cows grazing in contaminated fields (1).
Endosulfan has no carcinogenic potential (1,2). The substance is not mutagenic in vitro and in vivo in somatic ells, but some positive results have been reported in in vivo studies in germ cells (2). There are no evidence of teratogenicity or effects on reproduction in mammals (1,2). Several data suggest that endosulfan as well as endosulfan sulfate are endocrine disrupters (estrogenic action), however, as yet it seems as if there is no clear consensus on this topic (1).
The toxicity of metabolites has also been tested in mammals (2):

For endosulfan sulfate an LD50 of 568 mg/kg bw was reported for male rat, 25-50 mg/kg bw for females. For endosulfane lactone, male rats were more sensitive than females, with LD50 < 200 mg/kg bw. Acute oral toxicity for endosulfan hydroxyether was 1750 mg/kg bw in female rat. A low acute oral toxicity was reported for endosulfan ether and endosulfan diol. For endosulfan sulfate, lowest 90-d NOAEL was reported for dog, 0.75 mg/kg bw/d (males and females). For endosulfan diol 90-d NOAEL was about 8-9 mg/kg bw/d in rat and dog.


From all these data it is clear that endosulfan as well as some of its metabolites meet the criterion for adverse effects.



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