Formulations and adjuvants

The full extent of the toxicity of pesticides to aquatic life is not known. Although chronic toxicity testing is required for new substances, little is known about the long-term effects of older pesticides. Also, very little is known about the toxicity and occurrence of the products formed when pesticides break down (metabolites) or the many non-pesticidal additives (co-formulants and adjuvants) used in pesticide formulations. However, the future is looking brighter. New modelling techniques, EQS development, and the involvement of the NRA in the pesticide registration process, coupled with the development of newer, less persistent pesticides with lower dose rates, all should help to reduce the risk of pesticide pollution. 

Kudsk P and Mathiassen SK Influence of formulations and adjuvants on the rainfastness of maneb and mancozeb on pea and potato, Pesticide Science, 33 57-71 (1991). 

Florida, Illinois, Louisiana, Massachusetts, New Jersey, Pennsylvania, and Rhode Island (43). 1-Propanol is allowed as a flavoting substance and adjuvants according to 21 CFR 172.515 (48), and is exempted from the requirement of tolerance when used as a solvent or cosolvent iu pesticide formulations (49) (see Flavors AND spices Pesticides). 

Release profiles of these immunogens ean be improved through their formulation with adjuvants (Chapters 14, 15), and the immunogenieity of certain purified baeterial eomponents such as polysaccharides ean be improved by their conjugation to a carrier. 

The mathematics involved with calculating the amount of active ingredient, formulated product, adjuvants, and water to put in a spray tank to achieve the application rate specified in the protocol should be addressed prior to arrival at the field for the first application. This is also true for the calibration method. The author has found that if eight agronomists are involved in a spray application, one will encounter eight distinct calibration methods. If a calibration SOP is not written for the spray equipment to be used, the precise steps in the calibration process should be documented in the field notebook. 

Surfactants are often used in agrochemical formulations as adjuvants, e.g. as wetting agents to improve the physico-chemical characteristics of the solution and to increase the uptake of active ingredients (e.g. pesticides) [6-8]. The surfactants can be included in pesticide products and/or added to the tank mix prior to use however, they rarely exceed 1% of the total applied spray. Examples of typical surfactants used in agrochemical formulations are shown in Table 2.8.3 [9]. 

To analyze newly developed vaccines, it is of interest to study the pharmacological and immunostimulatory effects of the dehvery system (adjuvant) and to compare them to the effects of the combination between the adjuvant and the antigen of interest. This is accomplished by comparing three groups of mice (n = at least 6) Mice immunized with the vaccine (antigen formulated with adjuvant VAC) (to study efficacy aud type of immune response) mice administered with the adjuvant only ADJ) (to elucidate the contribution of the adjuvant on immune response, mechanism of action, and possible side effects) and nonimmunized mice (N). 

Very often whole-killed vaccines are formulated with adjuvants, which are designed to enhance vaccine persistence and induction of immune responses. However, the only adjuvant currently approved by FDA for clinical use is alum, in the form of vaccines complexed with aluminum hydroxide or aluminum sulfate. Even with the help of alum adjuvants, inactivated vaccine antigens are presented to APC extracellularly, as opposed to intracellularly, leading to a bias toward antibody-mediated responses. Little or no cell-mediated response to whole-killed vaccines with alum adjuvant renders some vaccines ineffective. 

Liposomes are phospholipid vesicles that have been evaluated both as adjuvants and as vehicles for antigens and adjuvants (17). A liposomal hepatitis A (Hep A) vaccine (virosomes) has been extensively evaluated in the clinic and is currently licensed for a Hep A vaccine (18). Alternative adjuvants that have been used in a few products include L-tyrosine (allergy vaccine) and MPL (cancer treatment). The various adjuvants (mainly alum salts) used in vaccine formulations and their quantities per dose are listed in Table 1. 

No adjuvant is licensed as a medicinal product in its own right, but only as a component of a particular vaccine. Therefore preclinical and toxicology studies need to be designed on a case-by-case basis to evaluate the safety profile of the adjuvant and adjuvant/ vaccine combination [60], Evaluation in preclinical studies is important for identifying the optimum composition and formulation process and also for allowing development of tests for quality control [61]. Data from these studies also helps plan protocols for subsequent clinical trials from which safety and efficacy in humans can be evaluated. 

Rogiers, L.M. (1995). Adjuvants and efficacy, in New Trends in the Formulation of Adjuvants, Proceedings of the 4th International Symposium on Adjuvants for Agrochemicals, 3-6 October, 1995, Melbourne, Australia, Forest Research Institute Bulletin, No. 193, R.E. Gastein (Ed.), New Zealand Forest Research Institute, Toturua, New Zealand,... 

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