ozone chemistry and technology - ACS Publications

Factors Modifying Toxicity of Ozone HERBERT E. STOKINGER

Downloaded by AUBURN UNIV on September 12, 2017 | http://pubs.acs.org Publication Date: January 1, 1959 | doi: 10.1021/ba-1959-0021.ch048

Occupational Health Program, Public Health Service, U. S. Department of Health, Education, and Welfare, 1014 Broadway, Cincinnati, Ohio

O z o n e in single, acute exposure is a highly poisonous substance to laboratory animals. N o experimental evidence was found that this toxicity is modified to a significant degree by the presence of nitrogen oxides that may accompany ozone production. Seven factors have been experimentally found that may modify the toxicity of ozone. Four of t h e s e — youth, physical exertion, alcohol, a n d respiratory infection—tend to augment the injurious response or act to the detriment of the host; intermittent exposure, premedication, a n d pre-exposure either reduce or eliminate the injurious effects of ozone. Consideration has been given these factors in the evaluation of possible hazards to populations from ozone-containing smogs.

^ ) z o n e h a s been e s t a b l i s h e d w i t h o u t q u e s t i o n t o be a c o m p o n e n t of L o s A n g e l e s s m o g {6, lJf). A s a n agent of distress a n d p o t e n t i a l disease, ozone h a s b e e n w e l l d o c u m e n t e d (IS). W h e t h e r ozone of i t s e l f is c a p a b l e of b e c o m i n g a h e a l t h h a z a r d i n u r b a n a t m o s p h e r e s is less c e r t a i n , h o w e v e r . N e w i n f o r m a t i o n d e r i v e d f r o m a n i m a l e x p e r i m e n t a t i o n o n ozone a t m o s p h e r e s a n d n i t r o g e n o x i d e - o z o n e a t m o s p h e r e s u n d e r v a r y i n g c o n d i t i o n i s p r e s e n t e d here i n t h e h o p e t h a t i t w i l l p e r m i t a m o r e exact e v a l u a t i o n of t h e p o t e n t i a l h a z a r d s t o u r b a n a n d w o r k i n g p o p u l a t i o n s exposed t o ozone. T h i s becomes e s p e c i a l l y i m p o r t a n t i n t h e l i g h t of t h e recent r e p o r t of K l e i n f e l d (8) o n ozone i n j u r y of t h e l u n g s a m o n g w e l d e r s u s i n g t h e n e w i n e r t g a s - s h i e l d e d a r c process. T h e s e r e p r e sent t h e f i r s t i n s t a n c e s of h u m a n i n j u r y f r o m ozone ever r e p o r t e d . Lethal

Doses

A m p l e evidence h a s been p r e s e n t e d (15) t o s h o w t h a t ozone i n a c u t e exposures is a h i g h l y t o x i c a n d l e t h a l s u b s t a n c e . T h e LD v a l u e s f o r t h r e e r o d e n t species a r e g i v e n i n T a b l e I . T h e LD v a l u e is t h e dose of a s u b s t a n c e t h a t w i l l o n t h e a v e r a g e k i l l 5 0 % of a s i g n i f i c a n t n u m b e r of a n i m a l s e x p o s e d u n d e r specified c o n d i t i o n s . S e v e r a l e x p e r i m e n t a l l y s i m p l e a n d s t a t i s t i c a l l y s o u n d m e t h o d s of o b t a i n i n g LD values are available ; t h e one u s e d i n t h i s w o r k is t h a t of W e i l (19). T h e s u s c e p t i b i l i t y o r n a t u r a l t o l e r a n c e v a r i e s c o n s i d e r a b l y w i t h t h e species, t h e h a m s t e r b e i n g t h e l e a s t s u s c e p t i b l e of t h e species t e s t e d . A l t h o u g h insufficient n u m b e r s of o t h e r species h a v e b e e n e x p o s e d t o ozone t o d e t e r m i n e a c c u r a t e LD values, the dog w o u l d appear to resemble t h e h a m 50

50

50

50

360

OZONE CHEMISTRY AND TECHNOLOGY Advances in Chemistry; American Chemical Society: Washington, DC, 1959.

361

STOKINGER—FACTORS MODIFYING TOXICITY

ster i n n a t u r a l t o l e r a n c e t o ozone o n t h e basis of t h e evidence has a t o l e r a n c e b e t w e e n t h a t of t h e r a t a n d the h a m s t e r . Table I.

at h a n d ; the r a b b i t

Lethal O z o n e Doses for Small Animals (Duration of exposure, 4 hours)

Animal Species Mouse, albino, male Rat, albino, male Hamster (Cricetus auratus), male a

Av. Body Wt., G . 22 250

Ozone LDw* P.p.m. by Vol. 3.8 4.8

Range, P.p.m. by Vol. 3.6-4.1 3.6-6.4

75

10.5

9.1-12.1

a

Determined by method of Weil (19).

C o m p a r i s o n of t h e LD v a l u e s f o r ozone w i t h those f o r t h e i n d u s t r i a l l y w e l l k n o w n a n d h i g h l y t o x i c gas, p h o s p h i n e , shows a v a l u e f o r p h o s p h i n e (10) of 60 p . p . m . f o r t h e r a t u n d e r s i m i l a r c o n d i t i o n s of e x p o s u r e , i n d i c a t i n g ozone to be a p p r o x i m a t e l y 12 t i m e s m o r e t o x i c i n single a c u t e doses. T h e h i g h t o x i c i t y of ozone is a l l t h e m o r e r e m a r k a b l e w h e n i t is n o t e d t h a t b u t one q u a r t e r of t h e i n h a l e d ozone reaches t h e lungs (7), where i t produces p u l m o n a r y edema, hemorrhage, a n d eventual death. T a k i n g t h i s i n t o a c c o u n t , t h e a b s o l u t e a m o u n t of ozone k i l l i n g t h e r a t is b u t 0.025 m l . of p u r e ozone gas a t s t a n d a r d t e m p e r a t u r e a n d p r e s s u r e , or 50 γ ; a s i m i l a r v a l u e for t h e m o u s e is 4 γ of ozone. T h i s assumes a r e s p i r a t o r y m i n u t e v o l u m e ( v o l u m e of a i r i n s p i r e d d u r i n g 1 m i n u t e b y a n a n i m a l w h i l e a t rest) of 100 m l . f o r t h e r a t a n d 10 m l . f o r t h e m o u s e . T h e o r d e r of 1000 γ of p h o s p h i n e is r e q u i r e d t o k i l l t h e r a t , a s s u m i n g t h a t 5 0 % of t h e i n h a l e d gas reaches t h e l u n g s . T h e s e figures p r o v i d e s t r i k i n g evidence of t h e h i g h l y l e t h a l c h a r a c t e r of ozone.


50

I n a l l e x p e r i m e n t s r e p o r t e d here ozone w a s d e t e r m i n e d b y t h e a l k a l i n e - p o t a s s i u m i o d i d e m e t h o d of S m i t h a n d D i a m o n d (13) as m o d i f i e d b y B y e r s , S a l t z m a n , a n d H y s l o p (2). T h e t o t a l oxides of n i t r o g e n w e r e d e t e r m i n e d b y t h e p h e n o l d i s u l f o n i c a c i d m e t h o d ; n i t r o g e n d i o x i d e b y t h e specific m e t h o d of S a l t z m a n (11). T h e a c c u r a c y of t h e ozone m e t h o d is s t i l l u n d e r e x p e r i m e n t a l s c r u t i n y . I t is possible t h a t some f a c t o r i a l u p w a r d r e v i s i o n of t h e ozone v a l u e s r e p o r t e d here m a y h a v e t o be m a d e a t a f u t u r e d a t e . A c o r r e c t i o n f a c t o r of a p p r o x i m a t e l y 2 a p p e a r s p r o b a b l e a t t h i s d a t e . The m e t h o d , h o w e v e r , was t h e best a v a i l a b l e a t the t i m e these e x p e r i m e n t s were p e r f o r m e d . T o x i c i t y of

Ozone

Prepared from Air

and

Oxygen

B e c a u s e of t h e p o s s i b i l i t y t h a t ozone p r e p a r e d b y electric d i s c h a r g e ( V i t a a i r o z o nizer, V i t a A i r e Process Co., M i l w a u k e e , Wis.) f r o m laboratory, oil-compressed air m i g h t h a v e t o x i c q u a l i t i e s different f r o m t h a t p r e p a r e d f r o m o x y g e n , a series of t o x i c i t y tests i n m i c e was m a d e a t v a r y i n g c o n c e n t r a t i o n s of ozone a n d p e r i o d s of e x p o s u r e u t i l i z i n g t h e f o u r p o s s i b l e c o m b i n a t i o n s of a i r , o x y g e n , a n d a i r c l e a n e d b y s c r u b b i n g with chromic acid and sodium hydroxide (Table I I ) . N o c o n s p i c u o u s difference i n t o x i c i t y t o m i c e o c c u r r e d f r o m a n y of t h e different m e a n s of p r e p a r a t i o n of ozone w h e n t e s t e d a t c o n c e n t r a t i o n s b e t w e e n 4 a n d 10 p . p . m . ; i f a n y t e n d e n c y w a s e v i d e n t , t h e ozone p r e p a r e d f r o m o x y g e n a n d s c r u b b e d d i l u t i n g a i r was s l i g h t l y less t o x i c t h a n t h a t from air and diluted with unwashed air. Effect of Concentration a n d T i m e . A s t u d y w a s m a d e i n m i c e t o d e t e r m i n e w h e t h e r ozone o b e y e d t h e t o x i c o l o g i c r u l e t h a t t h e p r o d u c t of t h e c o n c e n t r a t i o n a n d t i m e of e x p o s u r e p r o d u c e d a c o n s t a n t , t o x i c o l o g i c response, CT = K, o v e r a c o n c e n t r a t i o n r a n g e of f r o m 1 t o 50 p . p . m . I f a p o s i t i v e c o r r e l a t i o n is f o u n d , s u c h i n f o r m a t i o n p e r m i t s i n t e r p o l a t i o n a n d e x t r a p o l a t i o n of t h e v a r i a b l e s of e x p o s u r e w i t h o u t t h e l a b o r of e x p e r i m e n t a l d e t e r m i n a t i o n . A p l o t of t h e v a l u e s i n T a b l e I I f r o m 2.5 t o 50 p . p . m . of ozone shows r e a s o n a b l y g o o d l i n e a r i t y , w i t h t h e e x c e p t i o n of t h e single response t o 4 p . p . m . of ozone p r e p a r e d f r o m a i r . W h e n t h e e n t i r e e x p e r i e n c e of t h e o t h e r t h r e e tests a t t h i s l e v e l was u s e d , h o w e v e r , close a g r e e m e n t t o l i n e a r i t y was f o u n d . N o f a t a l


362

A D V A N C E S IN CHEMISTRY SERIES

Table II. Mortality of Mice Following Exposure to O z o n e at V a r y i n g Concentrations and Times and Prepared by Different Means

Ozone Concn., P.p.m. 1 1 2.5 4 6 8 10 24 50


a b

Ozone from Air Diluted with

Exposure Concn. X Time, CT Value P.p.m.-Hr. 15 1200b 6 10 37 16 24 48 20 72 72 25

Unwashed air 0/10» 0/25 0/5 3/10 4/5 6/10 12/20 10/10 5/10 10/10 10/10

Ozone from Oxygen Diluted with

Washed air or oxygen

Unwashed air

Washed air

2/10

5/10 8/10

2/20

6/10

5/10

4/10

Numerator: Number of animals that died. Denominator: Discontinuous exposure for 6 hours daily, 5 days per week.

10/20 Number of animals exposed.

response t o quiescent e x p o s u r e t o o z o n e a t 1 p . p . m . w a s o b s e r v e d , n o m a t t e r w h a t t h e d u r a t i o n (cf. T a b l e V I I ) . Negative Role of Nitrogen Oxides i n O z o n e Toxicity. T h e r e i s a n e r r o n e o u s i m p r e s s i o n , u n f o r t u n a t e l y w i d e s p r e a d , g a i n e d f r o m t h e m i s i n t e r p r e t a t i o n of c e r t a i n s t u d i e s (16, 17) t h a t " t h e c o n t a m i n a t i o n of ozone w i t h oxides of n i t r o g e n h a s b e e n p a r t l y r e s p o n s i b l e f o r t h e o b s e r v e d t o x i c i t y a n d t h a t ozone i s n o t n e a r l y so t o x i c as i t has b e e n t h o u g h t t o b e " (1). T h e r e a r e a t least t w o reasons f o r t h i s m i s i m p r e s s i o n . 1. T h e r e p o r t e d a n i m a l t o x i c i t y d a t a w e r e insufficient t o p e r m i t t h e c o n c l u s i o n t h a t n i t r o g e n oxides a s s o c i a t e d w i t h ozone p r o d u c t i o n c o n t r i b u t e d t o t h e o v e r - a l l t o x i c i t y . 2. T h e r e p o r t e d e x p e r i m e n t s d e a l t w i t h a b n o r m a l l y h i g h c o n c e n t r a t i o n s of n i t r o g e n oxides ( a p p r o x i m a t e l y 5 0 % of t h e ozone c o n c e n t r a t i o n ) . I n a l l o r d i n a r y m e t h o d s of ozone p r o d u c t i o n b y e l e c t r i c d i s c h a r g e t h e a m o u n t s of n i t r o g e n oxides a r e r e l a t i v e l y i n s i g n i f i c a n t (12). T h e evidence s u r r o u n d i n g this q u e s t i o n (15) w e i g h e d h e a v i l y a g a i n s t t h e c o n c l u s i o n t h a t n i t r o g e n oxides c o n t r i b u t e d s i g n i f i c a n t l y t o t h e t o x i c i t y of ozone, b u t l e f t t h e m a t t e r o p e n t o f u r t h e r e x p e r i m e n t a t i o n . T h e q u e s t i o n w a s finally r e s o l v e d i n f u r t h e r e x p e r i m e n t s i n w h i c h m i c e were s u b j e c t e d t o v a r i o u s m i x t u r e s of o z o n e a n d oxides of n i t r o g e n , a n d t h e r e s u l t a n t t o x i c i t y was c o m p a r e d w i t h t h a t f r o m ozone alone ( T a b l e I I I ) . A l t h o u g h a u n i f o r m l y i n c r e a s i n g degree of m o r t a l i t y i n m i c e i s o b s e r v e d w i t h a n i n c r e a s i n g c o n c e n t r a t i o n of ozone alone, n o such increase was demonstrated i n mice exposed to increasing concentrations of n i t r o g e n oxides m i x e d w i t h o z o n e . N o t u n t i l t h e t o t a l c o n c e n t r a t i o n of i r r i t a n t gases f a r exceeded t h e LD f o r ozone alone (4 p . p . m . ) w e r e c o m p a r a b l e l e t h a l effects p r o d u c e d b y t h e m i x t u r e (10 p . p . m . of n i t r o g e n oxides a n d 4 p . p . m . of o z o n e ) . O t h e r s i m i l a r e x p e r i m e n t s h a v e b e e n p e r f o r m e d o n s e v e r a l occasions w i t h s i m i l a r r e s u l t s . T h u s , c o n t r a r y t o p a s t assertions, n o e v i d e n c e w a s f o u n d f o r a s c r i b i n g t h e t o x i c effects of ozone t o n i t r o g e n oxides. 50

I n d e e d n o basis f o r s u c h a v i e w i s k n o w n , i f one c o n s i d e r s t h e t o x i c i t y of t h e i n d i v i d u a l n i t r o g e n oxides i n r e l a t i o n t o t h a t of o z o n e . T h e e x p e r i m e n t a l e v i d e n c e i s t h e following : 1. P u r e ozone, p r e p a r e d f r o m p u r e t a n k o x y g e n a n d m i x e d w i t h a i r p u r i f i e d b y c a r e f u l s c r u b b i n g , is of i t s e l f h i g h l y t o x i c . 2. T h e l o w e r n i t r o g e n oxides, N 0 a n d N O , a r e n o t s i g n i f i c a n t l y t o x i c (18) n o r w o u l d t h e y be l i k e l y c o n t a m i n a n t s i n o z o n e - g e n e r a t i n g sources. 3. N 0 h a s a n L D v a l u e f o r r a t s of 65 t o 7 5 p . p . m . f o r a 4 - h o u r e x p o s u r e (4), a t o x i c i t y of a l o w e r o r d e r of m a g n i t u d e t h a n ozone. 4. N i t r o g e n p e n t o x i d e , t h e r e a c t i o n p r o d u c t of N O a n d N 0 i n t h e presence of ozone, i s f a r less t o x i c t h a n ozone, as s h o w n b y t h e l o w t o x i c i t y g i v e n i n T a b l e I I I 2

2

5

0

2


363

STOKINGER—FACTORS MODIFYING TOXICITY

T a b l e III. (4-hour exposures. Total Nitrogen Oxides Concn., P.p.m. by Vol.

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