Molluscicide

NOMENCLATURE

niclosamide

Common name niclosamide (BSI, E-ISO, (m) F-ISO, BAN, Germany (for veterinary use))
IUPAC name 2',5-dichloro-4'-nitrosalicylanilide
Chemical Abstracts name 5-chloro-N-(2-chloro-4-nitrophenyl)-2-hydroxybenzamide
CAS RN [50-65-7]

niclosamide-olamine

Common name niclosamide-olamine (BSI, E-ISO, (m) F-ISO, BAN); clonitralid (Germany, for public health use)
CAS RN [1420-04-8] Development codes SR73

PHYSICAL CHEMISTRY

niclosamide

Mol. wt. 327.1 M.f. C13H8Cl2N2O4 Form Almost colourless crystals. M.p. 230 oC V.p. <1 mPa (20 oC) KOW logP = 1 (pH 9.6) Solubility In water 1.6 (pH 6.4), 110 (pH 9.1) (both in mg/l, 20 oC). Soluble in common organic solvents such as ethanol and diethyl ether. Stability Hydrolysed in aqueous solution, DT50 (20 oC) c. 7 d (pH 6.9), 18.8 d (pH 13.3). Stable to heat. Decomposes under u.v. irradiation. Hydrolysed by concentrated acid or alkali.

niclosamide-olamine

Mol. wt. 388.2 M.f. C15H15Cl2N3O5 Form Yellow, crystalline solid. M.p. Decomposes at 208 oC V.p. <<1 mPa (20 °C) Solubility In water 0.1 g/l (20 oC). In n-hexane, toluene <0.1, dichloromethane 0.015, isopropanol 0.25 (all in g/l, 20 oC).

COMMERCIALISATION

History Molluscicidal properties described by R. G?nnert & E. Schraufst?tter (Proc. Int. Conf. Trop. Med. Malar., 1958, 2, 5) and development discussed by R. G?nnert et al. (Z. Naturforsch., Teil B, 1961, 16, 95). The olamine salt introduced as a molluscicide by Bayer AG. Patents DE 1126374; US 3079297; US 3113067

APPLICATIONS

Mode of action Molluscicide with respiratory and stomach action. Uses Control of golden apple snail in rice. Control of schistosomiasis and fascioliasis in man by killing fresh-water snails which act as intermediate hosts. Also used for veterinary control of tapeworm infestations. Formulation types EC.

niclosamide

Compatibility Incompatible with acidic materials. Selected tradenames: 'Bayluscide' (EC250) (Bayer) Formulation types WP.

niclosamide-olamine

Selected tradenames: 'Bayluscide' (WP70) (Bayer)

ANALYSIS

Product analysis by redox titration (WHO Specifications Pesticicides Used in Public Health, p. 309). Residues in water measured by colorimetry (R. Strufe, Pflanzenschutz-Nachr. (Engl. Ed.), 1962, 15, 42) or by titration (details from Bayer AG).

MAMMALIAN TOXICOLOGY

niclosamide

Oral Acute oral LD50 for rats ?5000 mg/kg. Skin and eye Acute percutaneous LD50 for rats >1000 mg/kg (EC250). Strong eye irritant; skin reacts after repeated and long-lasting exposure (rabbits). Inhalation LC50 for rats (1 h) 20 mg/l air. NOEL (2 y) for male rats 2000, female rats 8000, mice 200 mg/kg diet; (1 y) for dogs 100 mg/kg b.w. ADI (proposed) 3 mg/kg b.w. Other No relevant mutagenic or embryotoxic effect. Toxicity class WHO (a.i.) III (Table 5); EPA (formulation) II

niclosamide-olamine

Oral Acute oral LD50 for rats >5000 mg tech./kg. Skin and eye Acute percutaneous LD50 for rats >2000 mg (as 70% WP)/kg. Inhalation LC50 (4 ? 1 h) 3630-8224 mg/m3 air (as 70% WP).

ECOTOXICOLOGY

niclosamide

Birds LD50 for mallard ducks >500 mg/kg. Fish LC50 (96 h) for golden orfe 0.1 mg/l. Daphnia LC50 (48 h) 0.2 mg/l. Bees No significant mortality effects.

ENVIRONMENTAL FATE

Animals Following oral administration, 14C-niclosamide was absorbed and metabolised in the rat. The major metabolite in the urine was the reduced compound 2',5-dichloro-4'-aminosalicylanilide ([10558-45-9]); several labile conjugates were also detected. The major constituent in the faeces was unchanged niclosamide, although considerable amounts of 2',5-dichloro-4'-aminosalicylanilide were also present; parent compound is present not only because of non-absorption, but also because of release from the biliary conjugate by ?-glucuronidase of the intestinal microflora (L. A. Griffiths & V. Facchini, "The major metabolite of niclosamide: Identification by mass spectrometry" in Recent Developments in Mass Spectrometry in Biochemistry and Medicine, 2, 121-126 (1979)). Another study indicates that niclosamide is very poorly absorbed after dermal application. Radioactivity in the urine and faeces after application of 14C-niclosamide accounted for <2% and 10% of the labelled compound applied to pig and rat skin, respectively; c. 20% was recovered from the area of application (P. Brennan et al., "Dermal absorption of niclosamide in rats and minipigs" in Biopharmaceutics & Drug Disposition, Vol. 12, 547-556). Studies in fish with niclosamide and its 2-aminoethanol salt, indicate that niclosamide is rapidly excreted, as the glucuronide conjugate, and that there is little biomagnification; see D. P. Schultz & P. D. Harman, J. Agric. Food Chem., 26, 1226-1230 (1978); J. L. Allen et al., "Excretion of the Lampricide Bayer 73 by Rainbow Trout", Special Technical Publication, Philadelphia, 667, 52-61 (1979); and M. S. M. Marzouk, "Laboruntersuchungen an Karpfen über Rückst?nde von Bayluscid und dessen Einwirkung auf das Karpfenblut", PhD Thesis, Univ. Munich, Germany (1981). Soil/Environment There was a rapid decline in niclosamide residues in paddy water; degradation followed pseudo-first order kinetics, DT50 0.3 d. At harvest, niclosamide residues were below the detection limit of 0.03 mg/kg in rice leaves, stalk and grain, indicating that the use of niclosamide as a molluscicide in rice production does not lead to persistent residues in the rice paddy ecosystem (S. M. F. Calumpang et al., Bull. Environ. Contam. Toxicol., 55, 494-501 (1995)). An aqueous solution of 14C-niclosamide was 95% degraded after 14 d exposure to long-wavelength u.v. light. No degradation occurred within 56 days either in buffered solution (pH 5.0, 6.9 and 8.7) or in pond water (initial pH 7.8) (D. P. Schultz & P. D. Harman, U.S. Fish and Wildlife Service: Investigations in Fish Control, 83, 1-5 (1978)).