The theoretical considerations on the effects of the chemical composition of water on the effectiveness of the molluscicide 5,2' -dichloro- 4' -nitrosalicylic anilide (Bayluscide-R)

• WORLD HEALTH ORGANIZATION ORGANISATION MONDIALE DE LA SANTE THEORETICAL CONSIDERATIONS ON THE EFFECTS OF THE CHEMICAL COMPOSITION OF WATER ON THE EFFECTIVENESS OF THE MOLLUSCICIDE 5,2'-DICHLOR0-4 1 -NITROSALICYLIC ANILIDE (BAYLUSCIDER)l by WHO/SCHIST0/71.10 WHO/VBC/71.296 ORIGINAL: ENGLISH ,·,· ij ti -. 'f ~ R. Meredl.. th '\ ,.;:;., •)"-, ·/'·,. ,., ... Tropical Pesticides Research Headquarters and Information Unit ':._'·' ' London, United Kingdom .z:,_; The molluscicide Bayluscide is the ethanolamine salt of 5,2'-dichloro-4'-nitrosalicylic anilide (niclosamide). The hypothetical structure of this is shown below: + - NH -CH -CH OH 0 3 2 2 p-CO-NH-b- NO 2 Cl Since 5,2'-dichloro-4 1 -nitrosalicylic anilide (nicOH) is a weak acid and ethanolamine a weak base, the salt is only likely to exist extensively in this form in solution at a pH close to pH 7. At higher pH the ethanolamine ion will be displaced to give NH2-cH2-cH20H and at ~ower pH the 5,2'-dichloro-4 1 -nitrosalicylic anilide will be present as the free undissociated acid. Thus, in solution the niclosamide will be in equilibrium between a number of forms, the position of this equilibrium being dependent on the pH of the solution. This equilibrium, in a generalized form, is shown in Fig. 1. Under natural conditions the niclosamide could exist extensively in any of the Forms I to VI (see Fig. 1). As these forms may well have very different toxicological properties, it is important that a detailed study of this equilibrium be conducted in order to arrive at the most economical conditions for applying the molluscicide in the field. The conditions under which these various forms could exist, with their possible implications, are given below: Form I: Undissolved ethanolamine salt of niclosamide is only likely to exist in the slurry made up in the dispenser before application to the water under treatment. Form II: Dissolved ethanolamine salt of niclosamide will be found both in the dispenser and the water under treatment and should be the preponderant form in solution under natural conditions. Form III and Form IV: Under conditions of increasing acidity, Form II will be converted to Form III. As nicOH is only slightly soluble in distilled water (5-8 ppm) and is probably far less soluble under acid conditions, Form III could be largely present in very low 1 R Bayluscide = Registered trade mark of Farbenfabriken Bayer AG, Leverkusen. The issue of this document does not constitute formal publication. It should not be reviewed, abstracted or quoted witlfout the agreement of the World Health Organization. Authors alone are responsible for views expressed in signed articles. Ce document ne constitue pas une publication. II ne doit faire l'objet d'aucun compte rendu ou resume ni d'aucune citation sans l'autorisation de !'Organisation Mondiale de la Sante. Les opinions exprimees dans les articles signes n'engagent que leurs auteurs. WHO/SCHIST0/71.10 WHO/VBC/71. 296 page 2 Form V and Form VI: concentration in equilibrium between Forms II and IV. However, if the water contains an ion which results in the formation of an insoluble salt of ethanolamine, or if ethanolamine forms a salt with strongly acidic groups on mud particles, the equilibrium would be shifted strongly in favour of Form IV. Under conditions of increasing alkalinity Form II will be converted to Form V resulting in an equilibrium condition between II and V. Form VI is only likely to be found in the slurry in the dispenser, unless the niclosamide forms an insoluble salt with another substance dissolved in the water or reacts with strongly basic groups on mud particles. In this case the equilibrium will be shifted in favour of Form VI. If it is assumed (a) that Forms II, III and V are all toxic to snails (although these toxicities may differ) and (b) that Forms IV and VI are harmless as they are unable to enter the snails, then any water condition which favours the formation of Forms IV and VI is likely to seriously lower the efficiency of the molluscicide and conditions favouring Form III or VI are likely to give results differing considerably from those expected. The pH of the water is clearly the most important factor in determining the form in which the niclosamide will be found, and thus the effects of pH on the molluscicidal activity justifies considerable laboratory investigation. This should be by means of a bio-assay technique and, if possible, the chemical isolation and characterization of the various forms of niclosamide. Work along these lines has already been initiated and is the subject of another recent paper by Meredith. 1 FIG. l, DIAGRAM OF THE GENERALIZED EQUILIBRIUM BETWEEN 5,2'-DICHLOR0-4 1 -NITROSALICYLIC ANILIDE AND ITS VARIOUS SALTS AS COULD EXIST UNDER FIELD CONDITIONS -+ . (nic 0) NH3CH2ctt20H (s)(I) -+ 1 l (nic 0) NH3ctt2CH20H (aq)(II) -+ ~~ A NH3CH2CH20H + n;c OH (1t (III) I , (nic 1\ B (aq)(V) + NH2CH2CH20H - + nic OH (s) (IV) (nic O) B (s) (VI) acid conditions basic conditions (s) - undissolved niclosamide; (nic 0) - niclosamide ion; (aq) - dissolved niclosamide; nicOH - free acid niclosamide. 1 Unpublished document WHO/SCHIST0/71.12-Wtto/vsc/71.297.