Review
Risk assessment of the use of deltamethrin on bednets for the prevention of malaria

https://doi.org/10.1016/S0278-6915(00)00152-6Get rights and content

Abstract

Risk assessments covering the use of the pyrethroid, deltamethrin, on bednets for the prevention of malaria have been conducted The toxicity of deltamethrin in humans and animals is reviewed following both dermal and oral exposure. The no-adverse-effect level (NOEL) for exposure via the dermal route was 1000 mg/kg body weight/day. From this an acceptable exposure level (AEL) of 10 mg/kg body weight/day has been derived. The NOEL for exposure via the oral route was 1 mg/kg body weight/day, with exposures above this causing neurotoxic effects in animals. This NOEL has been used to derive margins of safety compared with predicted exposures. While direct skin contact does not seem to cause systemic toxicity in humans, it can cause burning, numbness and tingling of the skin, which is a local effect. This too is taken into account in the risk assessments. The risk assessments cover those treating bednets, on an intermittent or regular basis, the washing of treated nets, sleeping under treated nets (infants, children and adults). Worst case scenarios for each of these situations show that dermal exposures are low (one-tenth or less of the AEL) and the margins of safety for systemic exposure derived from oral data are acceptable, ranging from 10 to 3300. The benefits of the use of treated bednets in reducing morbidity and mortality from malaria are considerable and it can be concluded that the risk:benefit ratio is very favourable.

Introduction

The use of bednets impregnated with insecticides has become an important part of vector control strategy in the prevention of malaria in affected regions of the world (WHO, 1995). The type of insecticide used to impregnate bednets has usually been a pyrethroid. Pyrethroid-treated bednets have been effective in reducing malaria mortality and morbidity, in particular, neonatal and infant mortality, and may, in addition, reduce transmission of the malaria parasite when used on a large scale (WHO, 1995).

Pyrethroids are generally of low toxicity to humans including those occupationally exposed. However, their use on bednets presents quite different exposure situations from those normally encountered when pyrethroids are used for agricultural and other non-agricultural purposes. There is the potential for prolonged use of treated nets by large sectors of the population including infants, children and adults, both healthy and sick. Nets need to be re-impregnated at intervals by dipping in dilute solutions of insecticide. This may be done commercially, communally, or in the home, and young and/or untrained individuals may perform the dipping on a regular basis. Access to protective clothing may be limited and, even when available, it may not be used correctly. These special situations point to the need for human risk assessments to be carried out, both for those with regular use of nets during sleep, and also for those treating nets at intervals. The success of public health programmes to encourage the use of insecticide-impregnated bednets depends, in part, on adequate reassurance of safety. A brief review of the safety of bednets treated with the pyrethroids currently approved by the WHO has recently been published (Zaim et al., 2000).

Acute effects such as skin and nasal irritation have been reported in association with the use of pyrethroid-impregnated bednets. These and other potential toxic effects will be reviewed and an assessment made of the likelihood of acute and longer-term effects, using both average and “worst case” exposure scenarios for deltamethrin, one of the active ingredients commonly used. For risk assessment of the dipping process, the form in which the active ingredient, deltamethrin, is marketed is relevant. Concentrates in liquid form have been used in various field trials. More recently, a dispersible tablet of deltamethrin has been developed for the treatment of mosquito nets, which may offer some advantages over the use of liquid formulations. Acceptability and efficacy trials using deltamethrin tablets have been conducted in Africa (Jones and Miller undated, Darriet et al.,). The risk assessment that follows is based on use of deltamethrin tablets. The risk assessment is preceded by a brief review of published and unpublished data on the chemistry and toxicity of deltamethrin in experimental animals and humans. This information is used to derive exposure levels likely to be without toxic effects in humans. These no-effect levels are then compared with estimated exposure levels that may occur during dipping and use of deltamethrin-impregnated bednets to assess any risks and derive margins of safety. In any risk assessment there are usually a number of uncertainties, both in the toxicological data available and in the estimates of exposure. While a precautionary approach has been taken using worst case scenarios, there can be no absolute certainty of safety.

Section snippets

Chemistry and mode of action as an insecticide

The commercial product, deltamethrin, contains the cis isomer, (S)-α-cyano-3-phenoxybenzyl, (1R,3R)-3-(2,2-dibromovinyl)-2,2-dimethylcyclopropanecarboxylate.

Technical deltamethrin has greater than 98% purity. Deltamethrin is chemically stable and exposure to breakdown products is therefore not an issue. It has a low vapour pressure (2.0×10−6 Pa or 1.5×10−8 mm Hg) and is considered to be practically non-volatile; inhalation risks are thus likely to be low (see later). It is lipophilic (log Po/w

Identification of NOELs and derivation of acceptable exposure levels for human risk assessment

In order to utilise the studies described above for risk assessment, the critical NOELs for dermal and systemic exposure have been identified. The NOELs and effect levels from the individual studies are summarised in Table 1.

Few data were available from human studies or poisoning cases. Similarly, there were few animal studies using inhalational or dermal routes of exposure. However, the latter is the principle route of exposure encountered in the dipping and use of treated bednets. In the

Background parameters

The parameters given below have been used in the risk assessments that follow.

Product:Foil-wrapped tablet (K-O TAB®, AgrEvo)
Deltamethrin content:0.4 g
Treatment:1 tablet/net
Net size:15 m2
Target dose:25 mg/m2 for average net size 15 m2
Volume of suspension:Synthetic net 0.5 l, cotton net 2.0 l
Loss of deltamethrin on first wash:20–30% (Duffield and Hordle, 1997)
Loss on further washes:2–3% (Duffield and Hordle, 1997)
Frequency of washing nets:4-week intervals (Jones and Miller, undated)
Frequency of

Conclusions

The pyrethroid insecticides are considered to be of relatively low toxicity compared to other insecticides such as the organophosphorus-containing compounds. The main effects observed in those exposed occupationally are skin irritation, sneezing, runny nose and abnormal facial sensations of numbness and tingling. The oral, experimental toxicity data on deltamethrin are extensive but there are few data relating to human exposure or exposure of animals via inhalation or dermal routes. The data

Acknowledgements

This paper was prepared at the request of the Malaria Consortium, London School of Hygiene and Tropical Medicine and the Liverpool School of Tropical Medicine. This work was partly supported by the UK Department for International Development. We are grateful to Michael Faust of Aventis Environmental Science (formerly Hoechst Schering AgrEvo Environmental Health) for access to unpublished reports used in the preparation of this paper.

References (33)

  • FAO Plant Production and Protection Paper 49. Pesticide Residues in Food: 1982 Evaluations of Some Pesticide Residues in Food

    (1983)
  • Garrod, A.N.I., Phillips, A.M., Pemberton, J.A. 2001. Potential exposure of hands inside protective gloves — a summary...
  • V Go et al.

    Estrogenic potential of certain pyrethroid compounds in the MCF-7 human breast carcinoma cell line

    Environmental Health Perspectives

    (1999)
  • F He et al.

    Effects of pyrethroid insecticides on subjects engaged in packaging pyrethroids

    British Journal of Industrial Medicine

    (1988)
  • F He et al.

    Clinical manifestations and diagnosis of acute pyrethroid poisoning

    Archives of Toxicology

    (1989)
  • F.S He et al.

    Changes of nerve excitability and urinary deltamethrin in sprayers

    International Archives of Occupational and Environmental Health

    (1991)
  • Cited by (115)

    • In-utero exposure to DDT and pyrethroids and child behavioral and emotional problems at 2 years of age in the VHEMBE cohort, South Africa

      2022, Chemosphere
      Citation Excerpt :

      In accordance with the Stockholm Convention on Persistent Organic Pollutants, eight malaria-endemic sub-Saharan African countries continue to use dichlorodiphenyltrichloroethane (DDT) for IRS (World Health Organization, 2016). Pyrethroid insecticides, particularly deltamethrin and cypermethrin, are commonly used for IRS due to their rapid elimination in humans (half-lives on the order of hours or days instead of years for DDT) (Barlow et al., 2001). DDT and pyrethroids are neurotoxic chemicals, interfering with voltage-gated sodium ion channels in insects, inducing excessive excitation of neurons and cell death.

    View all citing articles on Scopus
    View full text