26 Analytical Aspects: A Summary WILLIAM HORWITZ
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Food and Drug Administration, HFF-101, 200 C Street, NW, Washington, DC 20204
Modern toxicology is a multidiscipline approach to providing information on materials to which consumers are exposed. The primary test for safety is s t i l l a long-term animal study which must be monitored at every stage by the techniques of analytical chemistry. Dr. Cairns described a unique and probably never to be repeated experiment involving almost 25,000 mice handled over a 33-month period, requiring the services of analytical chemistry from beginning to end, including: 1. Identity, purity, properties, and stability of the test substance; 2. Handling and storage of the test substance; 3. Analysis of the feed and other essential bioassay supplies for essential and deleterious ingredients; 4. Homogeneity, stability, and proper concentration of the test substance in the dosage form; 5· Safety surveillance of personnel and work areas; 6. Safe disposal of the test chemical and contaminated experimental material. For monitoring the test, environmental, and experimental systems, both Dr. Fishbein and Dr. McKinney described some of the powerful tools which can be applied to explore, interpret, and understand situations affecting our health and safety. These tools are applied to nitrosamines and dioxins, which are families of toxic chemicals isolated, purified, and characterized by chemical and physical techniques operating at levels of parts per billion and below. (Remember that 1 part per billion is one second in 33 years; 1 teaspoonful of vermouth in a 40,000 gallon tank of gin.) Yet when we operate at such e x q u i s i t e l y low l e v e l s , as w e l l as i n a l l o f our s c i e n t i f i c work, we are c o n s t a n t l y confronted by the f a c t o f v a r i a b i l i t y . Dr. Tiede described s t a t i s t i c a l t o o l s which have been found u s e f u l to d e s c r i b e and summarize this v a r i a b i l i t y . But the purpose o f s t a t i s t i c s i s to manage data; s t a t i s t i c s cannot e l i m i n a t e v a r i a b i l i t y . S t a t i s t i c s can
This chapter not subject to U.S. copyright. Published 1981 American Chemical Society Bandal et al.; The Pesticide Chemist and Modern Toxicology ACS Symposium Series; American Chemical Society: Washington, DC, 1981.
THE
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PESTICIDE
CHEMIST
A N DM O D E R N
TOXICOLOGY
Concentration Figure 1.
Variation of the interlaboratory coefficient of variation (relative standard deviation X 100) withconcentration
Bandal et al.; The Pesticide Chemist and Modern Toxicology ACS Symposium Series; American Chemical Society: Washington, DC, 1981.
Downloaded by CORNELL UNIV on August 5, 2016 | http://pubs.acs.org Publication Date: August 10, 1981 | doi: 10.1021/bk-1981-0160.ch026
26.
HORWITZ
Analytical
Aspects: A
Summary
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help us s o r t out important v a r i a b l e s from unimportant ones. One of the speakers i n another s e s s i o n provided a u s e f u l i n s i g h t i n t o the uses o f s t a t i s t i c s . He s a i d , " I f you have to use numbers to answer questions regarding your statistics, you haven't adequately i n t e r p r e t e d your data " (1)< In my a n a l y t i c a l chemistry paper I t r i e d to give you some practical information about the variability of analytical systems at the trace l e v e l s where t o x i c o l o g i s t s and r e s i d u e chemists must operate. The lower you go, the more v a r i a b l e w i l l be the r e s u l t s . A copy o f my curve r e l a t i n g p r e c i s i o n to concent r a t i o n i s repeated below. E v e n t u a l l y , and probably before the p a r t s per t r i l l i o n l e v e l , at the present s t a t e of the a r t (picograms), the r e s u l t s become so bad that the f a l s e p o s i t i v e s and f a l s e negatives w i l l determine the l i m i t o f d e t e c t i o n and determination. Nevertheless, despite the high v a r i a b i l i t y o f our a n a l y t i c a l chemistry values at trace l e v e l s , they are i n f i n i t e l y b e t t e r and more s t a b l e than the r e s u l t s o f our b i o l o g i c a l t e s t s . Therefore both Dr. Cairns and Dr. McKinney a s p i r e to be able to p r e d i c t b i o l o g i c a l p r o p e r t i e s from chemical structure. T h i s i s an a s p i r a t i o n we hope can be accomplished. But the b a s i c data f o r such a deduction w i l l have to be r e l i a b l e and accurate b i o l o g i c a l measures o f t o x i c i t y f o r c o r r e l a t i o n purposes. These papers have shown that the a n a l y t i c a l chemist has served the t o x i c o l o g i s t w e l l i n i d e n t i f y i n g compounds and d e t e r mining t h e i r amounts. However, do not tempt him to push h i s a r t and science too f a r or your reward may be the r e c e i p t o f f a u l t y data without even r e c o g n i z i n g t h i s f a c t . As Dr. C a i r n s described trace a n a l y s i s i n one o f h i s papers, "The a n a l y t i c a l chemist has h i s feet f i r m l y planted i n m i d a i r . "
Literature Cited 1. Oiler, William L.; Gough, Bobby; Littlefield, Neal A. Chemical surveillance and quality assurance for preparation of dosed (2-AAF) animal feed (ED study). J. Environ. Pathol. Toxicol. 1980, 3, 203-210. 10
RECEIVED February 20,
1981.
Bandal et al.; The Pesticide Chemist and Modern Toxicology ACS Symposium Series; American Chemical Society: Washington, DC, 1981.
