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Appendices 1-18 to: Report on the Health Effects of Selected Pesticide Coformulants

51     Animal toxicity

51.1     Single dose toxicity

51.1.1     Inhalation

The LC₅₀-value reported for rats is greater than 480 mg/m³ (RTECS 2000).

Sodium ligninsulphonate may be irritating to mucous membranes and upper respiratory tract (Aldrich Chemical Co., Inc. 2001).

51.1.2     Oral intake

The oral LD₅₀-value reported for mice is 6 g/kg (RTECS 2000) and for rats greater than 40 g/kg (Luscombe & Nicholls 1973).

51.1.3     Dermal contact

Sodium ligninsulphonate may cause eye and skin irritation (Aldrich Chemical Co., Inc. 2001).

51.1.4     Other routes

The intraperitoneal LD₅₀-value reported for rats is 260 mg/kg (RTECS 2000).

Sodium ligninsulphonate has caused drowsiness and muscle weakness; species, route of exposure, and dose levels were not stated (Aldrich Chemical Co., Inc. 2001).

An anticoagulant effect of sodium ligninsulphonate has been demonstrated in mongrel dogs; route of exposure and dose levels were not stated. The anticoagulant activity of sulphonated lignins was related to their molecular weight with higher molecular weight fractions possessing greater anticoagulant activity than the lower molecular weight fractions. (Loomis & Beyer 1953 – quoted from Luscombe & Nicholls 1973 and Samson & Hollis 1992).

A European patent exists for a method of making a sodium ligninsulphonate with anti-thrombotic activity. Low doses (7.5-15 mg/kg b.w.) of this sodium ligninsulphonate administered by intravenous injection significantly decreased the incidence of thrombus formation and also the amount of thrombus formed in a White New Zealand rabbit thrombosis model despite the lack of anti-coagulant effect (as measured by lack of significant effect on prothrombin time, activated partial thromboplastin time, thrombin time, reptilase time, fibrinogen level and platelet count). At higher dosages (intravenous injection of 0.19 mg/ml blood), sodium ligninsulphonate caused significant changes in the blood coagulation with prolonged bleeding time in greyhound dogs. Within the first 15 minutes behavioural changes (increased salivation, unsteadiness and anxiety) were noted in the dogs. (Samson & Hollis 1992).

51.2     Repeated dose toxicity

51.2.1     Inhalation

No data have been found.

51.2.2     Oral intake

Groups of 20 male and 20 female Wistar rats were given AHR-2438B in their drinking water at levels of 0, 0.25, 2.5, 25 or 100 g/l (according to the authors equal to 0, 17, 168, 2830 or 10020 mg/kg b.w. per day in males and 0, 26, 283, 2420 or 9990 mg/kg b.w. per day in females) for 16 weeks. AHR-2438B is a purified sodium salt of a ligninsulphonate with an average molecular weight of 5000. No adverse effects on growth, organ weights, haematology, biochemistry, urine analysis and histopathology were observed at the three lowest dose levels. At the highest dose level, animals of both sexes showed skin lesions at the base of the tail. The lesions seemed to occur as a result of local irritation caused by adhering sticking faecal matter containing large quantities of the test material. Anaemia and raised leucocyte levels in the high dose animals was suggested to be a result of the presence of the tail lesions. In addition the high dose animals showed an increase in the absolute and relative weights of the liver, kidney and spleen, and male rats had a decreased weight gain. Histological changes were consistent with reticulo-endothelial activation in the liver and with vacuolar degeneration of the proximal convoluted tubules in the kidney. No ulcerative lesions were found in any section of the gastrointestinal tract. Blood coagulation times were unchanged throughout the period of dosing. (Luscombe & Nicholls 1973).

Groups of 5 male albino guinea pigs received as drinking fluid an aqueous solution of sodium ligninsulphonate at concentrations of 0, 10, 20, 50 or 100 g/l (according to the authors equal to 0, 1740, 2720, 1570 or 7780 mg/kg b.w. per day) for 1-5 weeks. At the end of the experiment, the stomach, duodenum and colon were examined histologically for ulcerations. Two animals in the 50 g/l dose group died after a week. All of the animals administered the two highest doses lost weight and some of them developed mild diarrhoea and had blood and mucus in the faeces. Animals receiving the two lowest doses gained less weight than controls but otherwise appeared clinically undisturbed. No ulcerations were found in the duodenum in any animal. However, ulcers of the upper part of the colon were found in 1-4 of the animals in each dosed group. The ulcers in the colon were more numerous (up to 100 or more) in the animals, which received the smaller concentrations of sodium ligninsulphonate. In the animals given higher concentrations, the ulcers numbered from 2 to 10. Ulcers of the upper two-thirds of the stomach developed in 4 animals in each of the two highest dosed groups. (Watt & Marcus 1976).

Groups of 8 male albino guinea pigs received as drinking fluid either water or a 1% aqueous solution of sodium ligninsulphonate (equivalent to 1700 mg/kg b.w. per day) for 2-6 weeks. None of the dosed animals developed diarrhoea. However, half of the dosed animals developed ulcers in the upper part of the colon. These animals had blood in the faeces and a lower weight gain than the rest of the group. One of the guinea pigs with ulcers died on the 13^th day of the experiment. (Marcus & Watt 1974).

Groups of 10 male Sprague-Dawley rats were fed either a control diet or a diet containing 3% of seven selected ligninsulphonate fractions for 14 days. In general, the diets containing ligninsulphonate were less digestible and caused a slightly lower pH value in the caecum and colon than the control diet. The caecum weighed more in rats fed ligninsulphonate than in control rats. Some of the ligninsulphonate fractions affected the short-chain fatty acid concentration and the concentration of two beneficial gastrointestinal tract bacteria. (Flickinger et al. 1998).

51.2.3     Dermal contact

A United States patent exist for a method of treating viral infections caused by Herpes simplex, types I and II, by topically applying a ligninsulphonate to the infected tissue. The inventors have examined different commercially available ligninsulphonates as well as fractions thereof. In general, the higher molecular weight fractions with the sugars removed are the most effective antiviral agents. The ligninsulphonates was shown to be effective against Herpes simplex virus in infected human cell lines in culture as well as in vaginal infections in female mice and guinea pigs. (Ward & Tankersley 1980).

51.2.4     Other routes

Female mongrel dogs with total gastric fistula were administered 500 mg of sodium ligninsulphonate (AHR-2438B) dissolved in 10 ml water twice during a two-hour period directly into the stomach through a cannula. Pepsin digestion was analysed using coagulated egg albumin as the substrate. AHR-2438B was an effective inhibitor of pepsin proteolysis. (Alphin et al 1971).

51.3     Toxicity to reproduction

No data have been found regarding reproductive and developmental effects following exposure by inhalation, oral administration, or dermal contact.

Sodium ligninsulphonate (as well as other surfactants) were tested for estrogenic activity in a recombinant yeast screen. The natural oestrogen 17b-oestradiol as well as other known chemicals with estrogenic activity was used as positive controls. Sodium ligninsulphonate did not possess estrogenic activity. (Routledge & Sumpter 1996).

51.4     Mutagenic and genotoxic effects

No data have been found.

51.5     Carcinogenic effects

No data have been found.

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