. . 1 .

. . I I  \1 p XYLENE :

DEVELOPMENT OF A BIOLOGIC STANDAIZD FOR THE INDUSTRIAL WORKER BY BREATH ANALYSIS PROPERR OF AYERSON POLYlECHNiC UNJVERSIR 350 VICTORIA SX, TORONTO, ONT. M58 2K3 ci) F B 000001 P XYLENE:

DEVELOPMENT OF A BIOLOGIC STANDARD FOR THE INDUSTRIAL WORKER BY BREATH ANALYSIS C. L. Hake, Ph. D.

R. D. Stewart, M. D., M. P. H.

A. Wu, Ph. d.

S. A. G r a f f , B. S.

H. V. F o r s t e r , Ph. D.

W. H. Keeler, M. D.

A .J . Lebrun, M. D.

P. E. Newton, M. S.

R. J. Soto, M. S.

Report No.: NIOSH MCOW ENVM XY 77 3 From t h e Department of Environmental Medicine, The Medical College of Wisconsin, Allen Bradley Medical Science Laboratory, 8700 West Wisconsin Avenue, Milwaukee, Wisconsin 53226.

This i n v e s t i g a t i o n w a s supported by Contract No. HSM 99 72 84 from t h e National I n s t i t u t e f o r Occupational Safety and Health. i i SYNOPSIS  ABSTRACT Adults of both sexes were exposed repetitively to p xylene vapor concentrations of 0, 20, 100, and 150 pprn for periods of 1, 3, and 7 1/ 2 hr in a controlled environment chamber for two purposes: 1) to develop a practical "biologic" test which could be used' to limit the magnitude of an industrial exposure; 2) to monitor the physiological response of healthy, sedentary adults to different vapor concentrations and durations of exposure, including the Threshold Limit Value (TLV) of 100 ppm, for five consecutive days.

Repetitive vapor exposure to the current TLV of 100 ppm produced no serious subjective or objective health responses in the 16 subjects,

neither were any elicited in the eight male subjects while being exposed for five consecutive days to 150, ppm p xylene vapor. There was an indication of the saturation of the metabolic pathway( s) of p xylene when four subjects exercised briefly while breathing 150 ppm; however,

the certainty and nature of this response requires confirmation.

Analysis of methyl hippuric ,acid metabolite in 24 hr urine samples,

and of p xylene in post exposure blood, saliva, and breath samples all revealed the certainty of p xylene vapor exposures. For the greatest practicality for routine biologic monitoring, combined with assurance of limiting p xylene exposures in workers, we recommend breath sampling.

An alveolar breath sample, obtained 15 min after the termination of a p

xylene exposure, should have a p xylene concentration of no greater than 4.5 ppm if from a male worker or 3.5 ppm if from a female worker.

Concentrations below these limits would give assurance that the workers had not been exposed during the previous 8 hr to deleterious concentra

tions of p xylene. 800003 5 $14" ** +,* e# .r 4 +) iii p XYLENE SYNOPSIS ABSTRACT ............................ ii ACKNOWLEDGEMENTS .............................. iv INTRODUCTION .............................

EXPERIMENTAL ............................. t Exposure Schedule ........................ Subjects ............................ Exposure Chamber .......................... Analysis of Exposure Chamber Atmosphere ............. Medical Surveillance ...................... Breath Sample Collection and. Analysis. ............. Blood Sampling and p Xylene Analysis in Blood .......... Analysis of p Xylene in Saliva Samples ............. Analysis of a p Xylene Metabolite in Urine: Methyl Hippuric Acid Neurological Studies ...................... Cardio Pulmonary Function Studies ................. Cognitive Testing ........................ Subjective Responses ...................... .. 1 .. 2 .. 2 .. 3 .. 4 .. 5 ... 6 .. 7 .. 8 .. 9 . . 10 . . 11 . . 1 3 . . 16 . . 18 RESULTS ................................. 19 Exposure Schedule .......................... 19 Subjects .............................. 20 Exposure Chamber ........................... 20 Analysis of Exposure Chamber Atmosphere ............... 2 1 Medical Surveillance ........................ 22 Breath Analysis ........................... 22 Blood p Xylene Concentrations .................... 23 Saliva p Xylene Concentrations ................... 24 Urinary Methyl Hippuric Acid Concentrations ............. 25 Neurological Studies ........................ 25 Cardio Pulmonary Function Studies .................. 26 Cognitive Testing .......................... 28 Subjective Responses ........................ 29 F DISCUSSION ................................ 3 1 !

REFERENCES ................................ 38 f APPENDICES ................................ 1 111 i Statement of Voluntary Consent ................... 1 Medical Examination Forms ...................... I1 &111 TABLES .................................. I LIV . f .. ..... FIGURES .. +; . . +" 'p;~. gt!. ........................... 1 3 5 *:*

000004 iv ACKNOWLEDGMENT A l l personnel i n t h e Department during t h e t i m e t h a t t h i s study was c a r r i e d o u t , including L. E b e r t , S. Kamke, L. Pearson, J .E . Peterson, Ph. D.,

D. Shekoski, K. S u s c h i l , and T. Stewart, provided t e c h n i c a l e x p e r t i s e i n c a r r y i n g out t h e study and/ or aided i n preparing t h i s r e p o r t .

t i c a l a n a l y s i s of d a t a from the b e h a v i o r a l s t u d i e s was c a r r i e d o u t w i t h t h e a i d of J. H. Kalbfleisch, Ph. D., A s s i s t a n t P r o f e s s o r , Department of Preventive Medicine. The statis

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INTRODUCTION p Xylene is a key r a w material i n t h e burgeoning p o l y e s t e r f i b e r and f i l m b u s i n e s s , and is one of t h e t h r e e isomers i n t h e mixed xylenes s o l v e n t , now f i n d i n g a new u s e i n low lead g a s o l i n e . Annual production and imports of p xylene i n 1974 t o t a l l e d 2,586 m i l l i o n lb, and t h i s f i g u r e i s expected t o i n c r e a s e t o 4,735 m i l l i o n lb i n 1980( 1). To p r o t e c t t h e American worker from harmful exposures t o t h e mixed xylenes s o l v e n t , a Threshold L i m i t Value of 100 ppm f o r an eight hr work day w a s e s t a b l i s h e d i n 1965") and readopted annually t h e r e a f t e r .

w a s made t o set separate v a l u e s f o r t h e i n d i v i d u a l isomers i n t h e m i x t u r e , and i t has been assumed t h a t none i n d i v i d u a l l y is more hazar

dous than t h e mixture of isomers. No attempt I n t h i s s t u d y , one isomer w a s chosen t o prevent any confounding e f f e c t of a mixture, and t o allow an e x a c t measurement of t h e exposure c o n c e n t r a t i o n s a t a l l t i m e s . p Xylene w a s chosen because of i t s h i g h e s t volume usage of t h e t h r e e isomers by American i n d u s t r y .

I n t h e series of experiments t o b e r e p o r t e d , 16 a d u l t s of both s e x e s w e r e exposed r e p e t i t i v e l y t o p xylene vapor concentrations of 0,

20, 100, and 150 ppm f o r varying p e r i o d s of t i m e i n an environmentally c o n t r o l l e d chamber. The g o a l s were t o : 1 ) observe t h e physiologic response of sedentary persons upon exposure t o p xylene vapor, and 2)

develop a p r a c t i c a l b i o l o g i c test u s e f u l f o r estimating t h e magnitude of exposure t o p xylene.

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EXPERIMENTAL Healthy adults of both sexes were exposed to known concentrations of p xylene vapor in a controlled environment chamber. These studies were designed to simulate the type of exposures encountered in the industrial setting and consisted of both steady, non fluctuating vapor concentrations as well as widely fluctuating vapor concentrations of p

xylene.

Exposure Schedule:

The vapor exposure sequence is presented in Table I. The sequence was initiated with male subjects who were exposed to p xylene vapor concentrations of 0, 20, 100, and 150 ppm for periods of 1, 3 , or 7 1/ 2

hr. The female subjects were exposed to 0 and 100 ppm for identical periods of time. The vapor concentrations in the controlled environment chamber were not permitted to fluctuate widely except for the male subjects' exposure during Week 5 when the wide fluctuation experiment was performed. The female subjects' exposure sequence occurred sub

sequent to the exposure of male subjects and duplicated Week 2 for males.

The widely fluctuating concentrations of p xylene vapor during Week 5 of exposure of male subjects was attained by varying the concentration of p xylene in the chamber from 50 to 100 to 150 ppm during equal periods of time. The sequence of the up and down concentrations was designed so that the last 15 min of exposure for all subjects was to a vapor concentration of 100 ppm p xylene. 3

Subjects :

The s u b j e c t s were s e l e c t e d from t h e Caucasian, middle class,

working population of t h e Milwaukee metropolitan area. They were r e c r u i t e d f o r t h i s study by a p r i v a t e employment agency. Each s u b j e c t who completed t h e study received $2.50 p e r h r spent a t t h e l a b o r a t o r y ,

p l u s overtime, w i t h a 3 hr minimum payment f o r t h e Saturday morning medical s u r v e i l l a n c e check. ,A f t e r t h e o b j e c t i v e s of t h e s t u d y and t h e n a t u r e of t h e procedures t o be used were f u l l y explained t o them, a l l s u b j e c t s signed a n informed consent form, a copy of which is a t t a c h e d as Appendix I.

Eleven h e a l t h y males volunteered f o r t h i s study. T h e i r ages ranged from 19 t o 55 y e a r s , h e i g h t from 1 7 3 t o 185 cm, and t h e i r weight from 62.7 t o 110.1 kg. The one v o l u n t e e r t h a t w a s obese, weight 110.1 kg and height 173 cm, dropped o u t of t h e s t u d y a f t e r t h e f i r s t day (0 ppm p xylene) and thus w a s n o t exposed t o t h e vapor of t h e chemical. O f 9 volunteer s u b j e c t s i n i t i a l l y a v a i l a b l e , 4 were assigned t o Group I (7

1/ 2 hr exposure), 2 t o Group I1 (3 hr exposure), and 3 t o Group I11 (1

h r exposure).

t h e study during t h e 0 ppm exposures, another Group I11 s u b j e c t dropped o u t a f t e r Day 1 of Week 2.

day a t 100 ppm. Two new v o l u n t e e r s j o i n e d Group I11 during Week 3. The l a s t s u b j e c t remaining of t h e 3 o r i g i n a l Group 111 s u b j e c t s dropped o u t a t t h e end of Week 3. I n a d d i t i o n t o t h e Group I11 s u b j e c t who dropped o u t of H i s exposure t o p xylene was l i m i t e d t o 1 The ages of t h e 7 p a r t i c i p a t i n g females ranged from 22 t o 39 y e a r s ,

t h e i r h e i g h t from 156 t o 172 cm, and t h e i r weight from 56.7 t o 93.5 kg.

One Group I s u b j e c t w a s obese. Two a d d i t i o n a l females volunteered b u t 000008 4

dropped o u t of t h e study a f t e r the f i r s t day (0 ppm p xylene). The d i v i s i o n of s u b j e c t s i n t o Groups I , 11, and I11 w a s 3 , 2 , and 2 , re

s p e c t i v e l y .

All s u b j e c t s were cautioned t o a b s t a i n from t h e use of drugs and t o l i m i t t h e i r use of a l c o h o l t o very moderate amounts.

smokers were n o t allowed t o smoke during t h e i r s t a y i n t h e c o n t r o l l e d  Subjects who were environment chamber. Subjects who underwent behavioral t e s t i n g (3 hr and 7 1/ 2 hr males) were asked t o r e f r a i n from consuming any c a f f e i n e p r i o r t o t h e end of each day's s t u d y (1 h r post exposure).

n Most of t h e s u b j e c t s had no o t h e r wage earning job during t h e t i m e of t h e s t u d y , and none experienced any exposure t o p xylene o u t s i d e of t h e l a b o r a t o r y .

Exposure Chamber:

All exposures t o t h e vapor of p xylene w e r e conducted i n a con

trolled environment chamber 20 x 20 x 8 f t i n s i z e , which was adjoined by a 3 x 5 x 8 f t t o i l e t f a c i l i t y and a 7 x 7 1/ 2'x 8 f t room s h i e l d e d . a g a i n s t electromagnetic r a d i a t i o n . Both t h e t o i l e t f a c i l i t y and t h e s h i e l d e d room were v e n t i l a t e d by a i r from t h e chamber.

complex had its independent a i r handling system and a l l o u t s i d e doors were s e l f s e a l i n g when closed.

imately 1500 cu f t p e r min and approximately 25% of t h i s flow w a s This t h r e e room A i r flow through t h e complex w a s approx

exhausted causing a s l i g h t negative p r e s s u r e w i t h i n t h e complex a t a l l times. A i r temperature w a s maintained a t 72 74' F while r e l a t i v e humidity ranged between 4555%.

sweeping t h e concentrated vapor from a warm f l a s k w i t h a stream of a i r The p xylene vapor w a s introduced by i P$ t? B<""{ f5 I s>.. 3 J *.. i ,r 808009 5

i n t o t h e chamber's c i r c u l a t i n g a i r . A r e c i p r o c a l dual piston pump maintained a s t e a d y flow of l i q u i d p xylene i n t o t h e f l a s k .

Analysis of Exposure Chamber Atmosphere:

Each 3 kg c o n t a i n e r of p xylene (Aldrich Chemical, p xylene, 99%)

used t o contaminate t h e chamber atmosphere was i n d i v i d u a l l y analyzed by gas chromatography f o r benzene contamination b e f o r e use. No benzene at l e v e l s g r e a t e r than t h e s e n s i t i v i t y of t h e instrument (1 ppm) w e r e found. .

Standards w e r e prepared by f i l l i n g s a r a n bags with room a i r pumped i n sequence through a charcoal column, a w e t test meter, a Drierite column, and a type N a l l s e r v i c e gas mask c a n n i s t e r .

bag with a known amount of c l e a n , dry air, a c a l c u l a t e d amount of p

xylene was i n j e c t e d i n t o t h e bag using a m i c r o l i t e r s y r i n g e . Necessary amounts of p xylene were c a l c u l a t e d t a k i n g i n t o account bag volume,

ambient temperature and barometric p r e s s u r e . C a l i b r a t i o n of a n a l y t i c a l devices w a s accomplished by a t t a c h i n g t h e s a r a n bag s t a n d a r d t o t h e necessary probe w i t h i n t h e chamber. At least t h r e e s t a n d a r d s were analyzed p r i o r t o allowing s u b j e c t s t o enter t h e chamber each day and then s t a n d a r d s were analyzed a t approximately 2 hr i n t e r v a l s throughout t h e day.

Two completely independent systems were used t o monitor t h e chamber A f t e r f i l l i n g a atmosphere. I n both c a s e s , a i r w a s withdrawn from t h e chamber through 1/ 4" I. D. polyethylene tubes at approximately 7R/ min, through o r p a s t t h e a n a l y t i c a l d e v i c e , to a small diaphragm pump which discharged back i n t o t h e chamber.

OOQO10 1 1 .

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I 7 d. 6

A Wilks MIMN I I n f r a r e d Analyzer w a s used as t h e primary moni

t o r i n g and chamber concentration c o n t r o l device. The 20 m c e l l w a s operated a t 13.5, 1 9 .5 , or 20 m path length and t h e a b s o r p t i o n band a t 12.65 P w i t h a 2 mm s l i t w a s used.

connected t o a s t r i p c h a r t r e c o r d e r , and a v o l t a g e p r o p o r t i o n a l t o t h e pen p o s i t i o n of t h a t recorder w a s conducted t o t h e a n a l o g t o d i g i t a l i n p u t of a, PDP 12 (DEC) computer. The computer sampled pen p o s i t i o n v o l t a g e each sec, averaged t h o s e v o l t a g e s every 30 sec, recorded the'

average on magnetic t a p e , and using the b e s t f i t i n v e r s e r e g r e s s i o n l i n e based on s t a n d a r d s wrote on a CRT t h e c o n c e n t r a t i o n over t h a t 30 sec i n t e r v a l and t h e cumulative o r time weighted average c o n c e n t r a t i o n s i n c e t h e beginning of t h e run. Voltage output of t h e MIRAN I w a s A gas chromatograph (GC) was used as t h e "backup" method of chamber The Varian Aerograph Model 940 GC was equipped w i t h a a i r a n a l y s i s .

column packed w i t h Apiezon L on Chromosorb W, 60/ 80 mesh, operated a t 140" C.

t o r operated a t 270 290" C .

chamber a i r i n t o t h e GC every 120 sec. Output of the GC was connected t o a s t r i p c h a r t r e c o r d e r . Peak height v a l u e s read nianually were t r a n s

formed i n t o concentrations based on t h e s t a n d a r d s t h a t had been analyzed during t h e day and compared w i t h t h e v a l u e s obtained using t h e i n f r a r e d spectrometer. Concentrations found by t h e two methods were i n agreement throughout t h e s t u d y . Nitrogen w a s used as t h e c a r r i e r gas t o a hydrogen flame detec

An automatic device i n j e c t e d a sample of Medical Surveillance:

Each s u b j e c t was given a comprehensive medical examination p r i o r t o t h e stu dy and a f t e r t h e l a s t exposure day of t h e s t u d y . These exam

+". .' ZL '2 $$$:. It:] ' J ,

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i n a t i o n s included a complete h i s t o r y and p h y s i c a l examination with t h e following laboratory s t u d i e s : complete blood count, complete panel of c l i n i c a l chemistries (23 values p l u s 2 c a l c u l a t e d ), and a 12 lead electrocardiogram (EKG). A complete blood count and t h e panel of c l i n i c a l chemistries were repeated a t least once p e r week during t h e weekly exposures. P r i o r t o each d a y `s exposure t h e s u b j e c t s w e r e given a b r i e f medical examination which included blood p r e s s u r e , temperature,

s u b j e c t i v e s i g n s o r symptoms, and u r i n a l y s i s (Labstix , Ames). During t h e t i m e t h a t they were i n t h e environmental chamber, each s u b j e c t ' s EKG (lead 11) was continuously monitored by telemetry and recorded a t hourly i n t e r v a l s .

personnel while they were i n t h e s t u d y . R The s u b j e c t s were under c o n t i n u a l s u r v e i l l a n c e by medical Breath Sample C o l l e c t i o n and Analysis:

Alveolar b r e a t h samples w e r e obtained d a i l y from each s u b j e c t p r i o r t o e n t r y i n t o t h e environmental chamber, immediately upon e x i t from t h e chamber, and a t t h e following t i m e s a f t e r e x i t i n g t h e chamber (p o s t ` exposure): 15 and 30 min; 1, 2, and 3 h r . These samples were each c o l l e c t e d i n 5 k s a r a n bags. The pre exposure sample from t h e following morning represented t h e 15 1/ 2, 20, o r 22 hr p o s t exposure sample f o r Group I, 11, o r 111, r e s p e c t i v e l y . Alveolar b r e a t h samples were ob

t a i n e d by e x p e l l i n g a b r e a t h which had been held f o r a t least 20 sec i n t o t h e s a r a n bag and stoppering t h e bag s e c u r e l y . Sampling of t h e b r e a t h i n t h e bag w a s accomplished by puncturing w i t h a s y r i n g e needle.

A l l samples, except t h e 2 and 3 hr p o s t exposure s a m p l e s , were analyzed t h e same day t h a t they were obtained. The 2 and 3 hr p o s t exposure 000012 f' p ~ (i ." % P L 8

s a m p l e s were c o l l e c t e d by t h e s u b j e c t s a f t e r leaving t h e l a b o r a t o r y , and they were analyzed t h e following day.

A Varian Aerograph Model 900 gas chromatograph (GC) equipped w i t h a hydrogen flame i o n i z a t i o n d e t e c t o r w a s used t o determine p xylene i n t h e b r e a t h samples. The GC w a s f i t t e d with a s t a i n l e s s steel column, 5 f t x 1 /3 i n , packed with 10% FFAP on Chromosorb W , 80/ 100 mesh. The column w a s preconditioned a t 220" C overnight p r i o r t o use.

a t i n g conditions of t h e GC were as follows: carrier gas (n i t r o g e n ) flow rate of 40/ ml p e r min; column temperature of 110" C; i n j e c t i o n p o r t ,

190" C; and d e t e c t o r , 240" C. Both hydrogen and a i r flow were kept a t 20 p s i g . The sample s i z e w a s u s u a l l y 1 m l . Standards a t 3 concentra The oper

t i o n s t o bracket t h e unknown levels were prepared with clean a i r as d i l u e n t .

r e p r o d u c i b i l i t y of t h e a n a l y s i s . The concentration of p xylene i n t h e A s i n g l e i n j e c t i o n from t h e s a r a n bags w a s used because of t h e unknowns w a s obtained by d i r e c t comparison of peak heights t o t h e standards.

method was 0.05 ppm with an accuracy of k O .1 ppm. The minimal amount of p xylene d e t e c t a b l e i n b r e a t h by t h i s Blood Sampling and p Xylene Analysis i n Blood:

Blood samples were withdrawn from an a n t e c u b i t a l vein of each s u b j e c t on Days 1 and 4 of each exposure week.

obtained pre exposure, immediately p r e e x i t from t h e chamber, 30 min,

and 60 min p o s t exposure, by s y r i n g e .

o u t on 2 m l of blood t h a t was introduced immediately upon withdrawal The blood samples w e r e Analysis of p xylene was c a r r i e d from t h e s u b j e c t i n t o a 40 ml saran lined capped g l a s s v i a l containing 1 m l aqueous s o l u t i o n of 5 pprn toluene as i n t e r n a l standard. The headspace 000013 9

technique w a s then employed f o r t h e a n a l y s i s .

e q u i l i b r a t i o n a t room temperature for a t l e a s t 1 h r , 1 m l of t h e head

space a i r w a s withdrawn and i n j e c t e d i n t o a gas chromatograph. After complete mixing and Samples were analyzed t h e same day t h a t they w e r e obtained.

A Varian Aerograph Model 2700 ModulineR gas chromatograph (GC)

equipped w i t h a hydrogen flame i o n i z a t i o n d e t e c t o r w a s used t o determine t h e p xylene levels i n t h e blood. The GC w a s f i t t e d with a s t a i n l e s s steel column 3 1/ 2 f t x 1/ 8 i n , packed w i t h 25% Apiezon L on Chromosorb W , 45/ 60 mesh. The column was preconditioned at: 200" C overnight p r i o r t o i t s use.

was baked a t 200" C when i t was n o t i n use. Throughout t h e a n a l y s i s f o r p xylene i n blood, t h e column The operating c o n d i t i o n s of t h e GC were: carrier gas (nitrogen} flow rate of 45/ min; column tempera

t u r e , 120" C; i n j e c t i o n p o r t , 235 C ; and d e t e c t o r , 250" C . A c a l i b r a t i o n curve (peak height r a t i o of p xylene t o toluene vs concentration) was prepared d a i l y . Samples were i n j e c t e d i n d u p l i c a t e and t h e concentra

t i o n of p xylene i n blood w a s obtained d i r e c t l y from t h e c a l i b r a t i o n curve.

while t h e accuracy w a s 50.02 ppm. The d e t e c t a b l e l i m i t of p xylene by this method was 0.001 ppm Analysis of p Xylene i n S a l i v a Samples:

To demonstrate p o t e n t i a l monitoring of another compartmental source where p xylene might be s t o r e d , a c u r s o r y study of p xylene l e v e l s i n saliva w a s c a r r i e d o u t .

Two m l of saliva were c o l l e c t e d i n a 35 ml saran lined capped g l a s s v i a l from both Group I male and female s u b j e c t s . The t i m e schedule f o r sample c o l l e c t i o n s included: p r i o r t o exposure, immediately upon e x i t ,

. i .* i, * "$" 2,% 8 :;: 00003.4 1 0

15 and 30 min post exposure. The analysis precedure for p xylene in saliva was identic a1 to that of blood, except that no internal standard was added.

Analysis of a p Xylene Metabolite in Urine: Methyl Hippuric Acid:

Methyl hippuric acid (p toluric acid) has been proposed as the major metabolite of p xylene in the urine of humans (3 9 4 ) . Twenty four , '

hr urine collections were made by all subjects on Days 1 and 4 of each week. Plastic jars placed in iced foam buckets were used. Daily excre

tion was measured prior to sampling for analysis of methyl hippuric acid.

A colorimetric method developed by Tomukuni and Ogata( 5) that mea

sures total hippuric acids was adopted with modification for the anal

ysis. A Coleman Junior I1 A Linear Absorbance Spectrophotometer Model 6 20A was used. One ml of urine was diluted with 4 ml of distilled water, 0.5 ml of this diluted urine was pipetted into a glass tube,

followed by 0.5 ml pyridine. The resulting solution was well mixed * before introducing a 0.2 rnl aliquot of benzenesulfonyl chloride (Aldrich Chemical Company). An orange color developed immediately. The colored solution was well mixed by means of gentle shaking and was allowed to stand at room temperature for 30 min. The sample was then diluted to 5 ml with 95% ethanol.

read against a 95% ethanol blank at 410 nm. At least two aqueous stan

dard solutions, e. g., 0.25 mg/ ml and 0.5 mg/ ml respectively, were used to bracket the unknown concentrations. All samples were determined in The concentration of hippuric acids in urine was duplicate with an accuracy of 2 0.05 mg/ ml. 11

Neurological S t u d i e s :

Within 5 min of e n t r y i n t o t h e environmental chamber on each exposure day, and w i t h i n 10 min p r i o r t o e x i t , each s u b j e c t performed a modified Romberg and heel to toe e q u i l i b r i u m test which was videotaped f o r later i n s p e c t i o n i f necessary.

each l e g s i n g l y with arms at t h e s i d e f o r a minimum of 3 sec, and walking heel to toe i n a s t r a i g h t l i n e f o r approximately 5 f t . This w a s f i r s t done with t h e eyes open and then repeated w i t h t h e eyes s. hut. The test c o n s i s t e d of s t a n d i n g upon Spontaneous electroencephalograms (EEG) and v i s u a l evoked responses (VER) were recorded 4 t i m e s each on Monday, Wednesday, and Friday on Group I (7 1/ 2 hr) s u b j e c t s . Recordings were normally made once during t h e f i r s t h r and 3 t i m e s a f t e r t h e f i f t h h r of exposure. A complete d e s c r i p t i o n and i l l u s t r a t i o n of t h e EEG VER monitoring system i s found i n a previous p u b l i c a t i o n (6 ) from t h i s l a b o r a t o r y . Gold plated s i l v e r d i s k e l e c t r o d e s were o r i e n t e d on t h e s c a l p according t o a modified 10 20 I n t e r n a t i o n a l Electrode System( 7). Grass EEG paste w a s used t o s e c u r e An 8 channel Grass polygraph f i t t e d w i t h 2 ,t h e e l e c t r o d e s t o t h e s c a l p .

EEG a m p l i f i e r s w a s u t i l i z e d f o r recording.

f o r 15 30 sec b e f o r e , d u r i n g , and 15 30 sec a f t e r a c q u i s i t i o n of t h e VER. EEG a c t i v i t y w a s recorded The EEG recordings were analyzed by v i s u a l examination.

The VER was recorded from t h e e l e c t r o d e a t t h e i n i o n , r e f e r r e d t o t h e l e f t ear. An EEG channel w a s used t o amplify t h e VERY and t h e output w a s f e d t o an on line averaging computer (Nuclear Chicago, 7100).

The VER w a s t r i g g e r e d by a s t r o b e f l a s h (3 psec) a t t h e rate of 1 p e r s e c f o r 100 sec.

c a n d l e s .a t 1 m from t@ e s u b j e c t ' s eyes, which were c l o s e d throughout t h e The s t r o b e w a s operated t o d e l i v e r 18 m i l l i o n beam " %! ,i f .)C `f 1 2

period of s t r o b e f l a s h i n g . Analysis t i m e w a s 250 msec. Flash delay from t h e synchronizing pulse which i n i t i a t e d t h e computer sweep w a s 25 msec. The computer averaged t h e response t o t h e 100 f l a s h e s , and t h e r e s u l t a n t VER w a s recorded on an X Y p l o t t e r f o r a n a l y s i s .

It has been shown t h a t VER amplitude can be a l t e r e d by varying l e v e l s of a t t e n t i o n , c o r t i c a l desynchronization, and s l e e p (8).

l y , standardized conditions were used throughout each exposure day,

s p e c i f i c a l l y immediately preceding t h e a c t u a l recordings.

t h e booth, t h e s u b j e c t w a s always allowed 3 5 min t o achieve a relaxed state, and then immediately p r i o r t o i n i t i a t i n g the s t r o b e f l a s h , i n an attempt t o standardize "a t t e n t i o n ," t h e s u b j e c t clapped h i s hands 5 times slowly and f o r c i b l y . According

A f t e r e n t e r i n g The most prominent and reproducible p o r t i o n s of the VER complex are the 3rd, 4 t h , and 5 t h waves (designation by Gastaut) (9) . Our a n a l y s i s was thus r e s t r i c t e d t o t h e s e waves.

i n a p o s i t i v e d i r e c t i o n 80 120 msec a f t e r i n i t i a t i o n of t h e s t r o b e f l a s h . Wave 3 w a s i d e n t i f i e d as proceeding Waves 4 and 5 were the succeeding negative and p o s i t i v e segments o f t h e VER. Our a n a l y s i s involved 1) measuring t h e amplitude of t h e s e waves and 2) measuring whether changes had occurred i n latency and wave form of t h e VER complex. A paired t test w a s used t o a s c e r t a i n whether t h e amplitude of any s i n g l e wave of each s u b j e c t d i f f e r e d s i g n i f i c a n t l y during p xylene exposure from 0 ppm exposure conditions. Furthermore,

each s u b j e c t ' s d a i l y mean t o t a l amplitude w a s c a l c u l a t e d , and then using paired t test, analyses of v a r i a n c e , ,and group t test methods, t h e O ppm d a t a was compared with t h e p xylene exposure d a t a (technique employed by (10) F o r s t e r e t a1 1. 1 3

Before and a f t e r each recording s e s s i o n t h e equipment w a s C a l i  i 1 b r a t e d as a system. Ten pv square waves, 100 msec i n d u r a t i o n , were f e d E 1 i n t o t h e a m p l i f i e r s , averaged over 100 t r i a l s , and recorded.

i t k I Cardio Pulmonary Function S t u d i e s :

b Minute v e n t i l a t i o n was measured under 0 ppm c o n d i t i o n s b e f o r e and a f t e r t h e p xylene exposure and on t h e 2nd and 4 t h days of each week of exposure t o p xylene. Measurements were made while i n t h e s i t t i n g p o s i t i o n during t h e last one half hour of exposure.

o f a breathing valve w a s connected via corrugated tubing (1 inch I. D.)

t o a 13 1L spirometer (W. E. C o l l i n s ). A f t e r approximately 5 min b r e a t h i n g on t h e v a l v e , v e n t i l a t i o n was c o l l e c t e d f o r 3 4 min and t h e average minute volume over t h i s t i m e period w a s t a b u l a t e d . The e x p i r a t i o n p o r t Measurements designed t o e v a l u a t e f u n c t i o n a l i n t e g r i t y of pulmonary airways, a l v e o l a r c a p i l l a r y gas exchange, and r e g u l a t i o n of pulmonary v e n t i l a t i o n and h e a r t rate were made on male Group I s u b j e c t s only.

Three maximum and p a r t i a l forced e x p i r a t o r y maneuvers were per

. formed by each male Group I s u b j e c t under r e s t i n g c o n d i t i o n s between t h e The components of t h e a ) i n series 5 t h and 6 t h exposure hours on Day 5 of each week.

system employed i n t h e s e forced e x p i r a t o r y maneuvers were:

a mouthpiece, a f l e x i b l e tube, a heated F l e i s c h No. 3 Pneumotachograph,

and a water spirometer, and b) t h e e s s e n t i a l s of a computer system f o r a n a l y s i s , i .e . PDP 12 mini computer, o s c i l l o s c o p e , t e l e t y p e , etc.

I n i t i a l l y , under c o n t r o l c o n d i t i o n s , each s u b j e c t ' s v i t a l c a p a c i t y (VC)

and f u n c t i o n a l r e s i d u a l c a p a c i t y (FRC) were determined on t h e water spirometer. For t h e a c t u a l maneuver, t h e s u b j e c t i n sequence: a)

J , ' *f 6) 06) 3) 13i8 . .,* ' 1 4 * , 14

breathed q u i e t l y on t h e system f o r 3 o r 4 b r e a t h s , b) i n s p i r e d t o h i s 70% VC mark on t h e spirometer (based on FRC), c) expired maximally, d)

i n s p i r e d maximally, and f i n a l l y , e> expired maximally. Step by step software a n a l y s i s of t h e acquired flow time d a t a included: a ) i n t e

g r a t i o n t o determine volumes, b) generation of flow volume curves, and c ) c a l c u l a t i o n and p r i n t o u t of such v a r i a b l e s as t o t a l e x p i r a t o r y volumes (VC), volume expired i n one second (FEV ), and flow rates a t 40% 1 and 25% of v i t a l c a p a c i t y f o r both t h e maximum and p a r t i a l e x p i r a t i o n .

It i s important t o n o t e t h a t i n our system, because expired flow r a t e was dependent on lung volume, necessary adjustments were made s o t h a t a l l flow rate determinations were a t t h e same a b s o l u t e lung volume.

Metabolic, pulmonary, c a r d i a c , and hematologic parameters were measured on Group I male s u b j e c t s a t rest and during two levels of dynamic muscular e x e r c i s e between t h e 5 t h and 7 t h hours of exposure on Day 4 of each week (Day 2 of Week 6 ). The e x e r c i s e was performed on a b i c y c l e ergometer for 11 consecutive min, 6 min a t 350 KPM followed by 5 min a t 750 KPM.

The e s s e n t i a l components of t h e expired gas c o l l e c t i o n and mea ,

surement system were a b r e a t h i n g v a l v e , corrugated tubing, a Parkinson

Cowan gas meter, a 150 R Douglas bag, and a Hewlitt Packard r e c o r d e r .

Minute v e n t i l a t i o n w a s q u a n t i t a t e d using t h e gas meter and r e c o r d e r .

Expired gas w a s c o l l e c t e d i n t h e Douglas bag f o r 1 min a t rest and 1 min a t each e x e r c i s e i n t e n s i t y (between 4.5 and 5.5, and 9.5 and 10.5 m i n of e x e r c i s e ). F i f t y m l of t h i s mixed expired a i r w a s s t o r e d i n a g l a s s syringe and subsequently analyzed f o r [COz] and [0 2 ] using a Quintron gas chromatograph.

l a t e cpt$, bcfJi%: fate and r e s p i r a t o r y q u o t i e n t . V e n t i l a t i o n and [CO,] and [0 ] were used t o calcu 2 000019 1 s

For sampling of blood, a 21 gauge needle was placed in a s u p e r

f i c i a l d o r s a l hand v e i n . The needle w a s a t t a c h e d t o a tubing stopcock arrangement whi. ch during non sampling periods w a s f i l l e d with heparin

i z e d s a l i n e .

approximately 42" C . For 5 min p r i o r t o sampling, t h e e n t i r e hand w a s heated t o This procedure s u f f i c i e n t l y "a r t e r i a l i z e d " t h e (11) venous blood s o t h a t P and pH were v i r t u a l l y i d e n t i c a l t o arterial . co2 Three t o 5 m l of blood were sampled over t h e 1 min period of expired air c o l l e c t i o n . The blood w a s analyzed w i t h i n 15 min f o r P and pH w i t h co2 t h e Radiometer e l e c t r o d e arrangement.

Alveolar capillary gas exchange w a s assessed by t h e s i n g l e b r e a t h carbon monoxide d i f f u s i o n technique( 12) (DLCO). Measurements were made twice on each s u b j e c t a t rest and a f t e r 5.5 and 10.5 min of exercise.

The previously described computerized system w a s used t o c a l c u l a t e i n s p i r e d , r e s i d u a l , and t o t a l lung volume and D CO. Neon w a s used as t h e i n e r t gas t o measure r e s i d u a l volume. Neon and CO c o n c e n t r a t i o n s i n L t h e c o l l e c t e d a l v e o l a r sample were analyzed using a Quintron chroma

tograph.

Heart rate w a s measured using t h e B i o t e l 170 ECG p a t i e n t telemetry system developed by Spacelabs, I n c . (Chatworth, C a l i f o r n i a ). Heart rate w a s measured during t h e 30 sec i n t e r v a l preceding i n i t i a t i o n of t h e e x e r c i s e and over t h e f i n a l 30 sec i n t e r v a l of each e x e r c i s e p e r i o d (350 and 750 KPM).

S y s t o l i c and d i a s t o l i c blood p r e s s u r e were measured by t h e auscul

t a t o r y method. Measurements were made at rest and a f t e r 4 and 9 minutes of e x e r c i s e . 10

Cognitive Tes Ling:

A b a t t e r y of c o g n i t i v e tests were performed i n a group s i t u a t i o n by t h e male Group I and I1 s u b j e c t s on days 1, 3, and 5 of each week. The t e s t i n g w a s c a r r i e d o u t 3 and 2 h r a f t e r t h e s t a r t of exposure f o r t h e 7 112 and 3 hr groups, r e s p e c t i v e l y .

performance p l a t e a u b e f o r e t h e s e tests w e r e used during exposures t o p

xylene. The s u b j e c t s were t r a i n e d t o a The s u b j e c t s sat i n comfortable c h a i r s a t i n d i v i d u a l carrels t o perform t h e c o g n i t i v e tests.

have access t o watches, food, s o f t d r i n k s , r a d i o s , etc. during t h e t e s t i n g . A l l i n s t r u c t i o n a l commands were made from o u t s i d e of t h e chamber via a n intercom system. The tests, i n o r d e r of performance, are described below. The s u b j e c t s were not permitted t o t a l k o r Ten and T h i r t y Second Time Estimation Test: Each s u b j e c t , upon v e r b a l s i g n a l (ready, begin) depressed a hand held, s i l e n t , push button micro switch f o r an i n t e r v a l of t i m e he estimated t o be 10 seconds.

This w a s repeated two a d d i t i o n a l t i m e s , and then t h r e e 30 second esti

' mates were made. The micro switches were connected t o t h e PDP 12 D i g i t a l computer which measured t h e t i m e i n t e r v a l s . This test took approximately 3 min t o perform.

Marquette Time Estimation T e s t : This t e s t c o n s i s t e d of a series of nine tone s t i m u l i followed by nine l i g h t s t i m u l i of approximately 1, 3,

and 5 seconds d u r a t i o n presented i n a random sequence b u t always w i t h t h r e e s t i m u l i of each t i m e i n t e r v a l . A t t h e termination of each stimu

Ius, t h e s u b j e c t depressed t h e push button f o r t h a t interval o f t i m e h e estimated t o be e q u a l i n l e n g t h t o t h e o r i g i n a l a u d i t o r y o r l i g h t stimulus., A d e t a i l e d d e s c r i p t i o n of t h e test and t h e i n s t r u m e n t a t i o n ~ &tr ;# ipP OQOO21 17

used t o c a r r y i t o u t has been described by Stewart, e t a1 (I3). T h i s t e s t took approximately 7 min t o perform.

Coordination Test: This test w a s t h e Flanagan Aptitude Class

i f i c a t i o n Tests, 7A, Coordination, published by Science Research Assoc

i a t e s , I n c ., 259 East Erie Str, eet, Chicago, I l l i n o i s . This test asked t h e s u b j e c t t o r a p i d l y follow a s p i r a l pathway with a p e n c i l . The s u b j e c t w a s allowed 40 s e c t o complete each of 6 s p i r a l s . The f i r s t 2 were considered p r a c t i c e and t h e l a s t 4 were scored and t o t a l e d . The t o t a l s c o r e depended upon t h e lon8est d i s t a n c e a t t a i n e d i n each s p i r a l minus t h e number of t i m e s t h e s i d e s of t h e s p i r a l pathway were touched with t h e p e n c i l . This test took approximately 5 min t o perform.

Arithmetic Test: This test, which measured t h e s u b j e c t ' s a b i l i t y t o work with numbers, was divided i n t o 2 p a r t s . The f i r s t p a r t , l a s t i n g 5 min, c o n s i s t e d of simple a d d i t i o n and s u b t r a c t i o n problems while t h e second p a r t , l a s t i n g 3 min, c o n s i s t e d of m u l t i p l i c a t i o n and d i v i s i o n .

The maximum s c o r e a t t a i n a b l e i f a l l answers were c o r r e c t w a s 140;

however, no s u b j e c t completed t h e tests i n t h e a l l o t t e d t i m e . I n o r d e r t o minimize memorization of answers, 10 randomly generated problem tests were used.

Inspection T e s t : This test w a s a measure of t h e s u b j e c t ' s a b i l i t y t o s p o t t h e number "3" i n rows of random numbers on an 8 1/ 2" x 11"

page. The s u b j e c t w a s asked t o scan each row, beginning a t t h e top of t h e page, and s l a s h o u t with a r e d p e n c i l each "3" encountered. The s u b j e c t w a s given 2 min t o s t r i k e o u t as many as p o s s i b l e . No s u b j e c t ever f i n i s h e d t h e entilee page.

of 1 1 3 ' s ' 1 s t r u c k . A s u b j e c t ' s s c o r e w a s t h e t o t a l number !

S i x d i f f e r i n g pages with random numbers were u t i l i z e d 1 8

s o t h a t no s u b j e c t received an i d e n t i c a l number s h e e t on successive tests.

S u b j e c t i v e Responses:

Each s u b j e c t w a s asked t o n o t e on an i n d i v i d u a l i z e d form any s u b j e c t i v e responses occurring during t h e exposure i n t h e chamber o r during t h e f i r s t 3 h r p o s t exposure.

headache, nausea, d i z z i n e s s , abdominal p a i n , eye, nose, t h r o a t irri

t a t i o n , o t h e r , and odor, and columns f o r t h e "immediate", "l/ Z hr", and hourly periods of t i m e t h e r e a f t e r . The a d j e c t i v e s "mild, moderate, and strong" appeared on t h e s h e e t as cue words, and t h e phrase "only ab

n o r m a l i t i e s recorded" was prominently typed a t t h e bottom. The home telephone numbers of each of t h e Department physicians appeared on t h e form and t h e s u b j e c t s were encouraged t o phone i f they became ill w h i l e away from t h e l a b o r a t o r y . The form contained rows f o r n o t i n g 000023 RESULTS Exposure Schedule:

The exposure schedule for volunteer male subjects was designed in a manner that included two days of exposure to zero ppm concentration (control) of p xylene before and after actual exposure to the vapor of the chemical. A two day weekend separated these control days from the five day per week actual exposures. A s is customary in our studies, the chamber was contaminated with an odor level (approximately 10 ppm) of p

xylene when Groups I and I11 entered the environmental chamber on the two control days at the end of the study. Within 10 min the p xylene concentration was reduced to zero ppm. A pre exposure and a post

exposure control day were also carried out for the female exposures,

with initial odor contamination on the post exposure control day when the subjects readily recognized the odor of p xylene.

The 5 day weekly sequence of male subject exposures to p xylene vapor began with the TLV concentration, 100 ppm, at a steady level,

dropped to 20 ppm steady the second week, was increased to 150 ppm steady the third week, and finished with five days at 100 ppm fluctu

ating from 50 to 100 to 150 ppm. The female subjects were exposed to 4 100 ppm steady for five days.

centrations were within two percent of the desired concentrations as All time weighted average exposure con

shown in Table I.

Figure I demonstrates the planned execution of the fluctuating Concentration exposures wherein each group of subjects was to be exposed to a time weighted average of 100 ppm. The discrepancy in actual ..* I . , .; .\$ i .$ :i. ,;; ~

; .;,

800024 2 0

exposure concentrations of t h e two Group 111 s u b j e c t s (see Table I)

during t h i s week was due t o t h e one s u b j e c t ' s i n a b i l i t y t o be p r e s e n t a t t h e u s u a l t i m e reserved f o r t h e Group I11 s u b j e c t s .

Subjects:

Obtaining and r e t a i n i n g t e n v o l u n t e e r s u b j e c t s for each study (male, female) w i t h p xylene proved t o b e d i f f i c u l t . Although t e n s u b j e c t s passed t h e i r p h y s i c a l examination f o r each s t u d y , one in each study decided n o t t o p a r t i c i p a t e a f t e r o r i e n t a t i o n , and two from each study dropped o u t during t h e study. None of t h e drop outs d i d so be

cause of t h e exposure t o t h e vapor of p xylene. Because t h e study w i t h male s u b j e c t s w a s of longer d u r a t i o n , w e were a b l e t o add two s u b j e c t s t o t h e study a f t e r i t had begun. The number of s u b j e c t s exposed d a i l y #

by group is shown i n Table I.

Absenteeism w a s a l s o a problem i n t h e s t u d y w i t h male s u b j e c t s .

Again, t h i s could n o t be a t t r i b u t e d t o t h e chemical, t h e u s u a l excuse being a personal reason.

Cooperation of s u b j e c t s i n c a r r y i n g o u t t h e i r assigned t a s k s , and i n r e f r a i n i n g from over indulgence i n a l c o h o l or o t h e r d r u g s , was ex

c e l l e n t . A l l s u b j e c t s accepted t h e r e q u i r e d venipunctures, c o l l e c t i o n Of 24 hr u r i n e samples, and b r e a t h samples w i t h equanimity.

Exposure Chamber:

Because of t h e low odor t h r e s h o l d of p xylene (< 1 ppm), i t w a s p o s s i b l e t o d e t e c t t h e vapor when i t escaped from t h e environmental chamber. A i r sampling o u t s i d e of t h e chamber demonstrated t h a t 1 3 ppm 21

p xylene contaminated the subject lounge occasionally. Although this should have had no measurable effect upon breath sample concentrations,

as a precaution the subjects gave their pre exposure breath samples in the uncontaminated foyer immediately upon entry to the building.

The large size of the environmental chamber (20 x 20 x 8 ft) allowed freedom of movement and sufficient comfort for all subjects while in the chamber.

Group I male subjects on day 4 of each week, were sedentary during their stay in the chamber. Residence in the chamber for each group was con

tinuous on a daily basis. During the periods of time that they were not being tested, they read, played cards, watched TV, or occupied them

selves with other sedentary activities. The subjects, with the exception of the 11 min of exercise by Analysis of Exposure Chamber Atmosphere:

Use of the infrared analyzer connected to the computer allowed for precise control of the chamber's atmosphere with regard to p xylene vapor concentration. As shown in Table I, the standard deviation of continuous, repeated 30 sec samples during the weeks of steady concen

trations was never more than three ppm.

take place in the analyzer cell, however response to changes of 20 ppm e xylene concentration of standards was always complete in three min. Damping of rapid excursions did Agreement between the two assay methods, with a possible variance Of up to five percent, continually assured the avoidance of an acciden

tal over exposure of the subjects. 22

Medical Surveillance:

Comprehensive medical examination of each s u b j e c t a t l e a s t t h r e e days a f t e r t h e l a s t exposure t o p xylene r e v e a l e d t h a t a l l s u b j e c t s were i n good h e a l t h a f t e r t h e study. The a t t a c h e d forms (History Appendix 11, P h y s i c a l Examination Appendix 111) w e r e used and are r e t a i n e d i n each s u b j ect ' s personal f i l e .

complete blood counts revealed t h e u s u a l number (approximately 5%) of s l i g h t l y "out of normal range" v a l u e s ; however, none were considered s i g n i f i c a n t o r r e l a t e d t o t h e exposure.

revealed t h e u s u a l number of wintertime c o l d s . Daily u r i n a l y s i s by t h e d i p s t i c k technique, and c o n t i n u a l monitoring of EKG's (lead 11) while Weekly blood c l i n i c a l c h e m i s t r i e s and Daily medical s u r v e i l l a n c e s u b j e c t s were i n t h e environmental chamber, revealed no a b n o r m a l i t i e s .

No female became pregnant while a s u b j e c t i n t h i s study.

Breath Analysis :

p Xylene concentration i n b r e a t h samples obtained b e f o r e e n t e r i n g t h e chamber, upon e x i t , and a t s p e c i f i e d t i m e s p o s t exposure was d e t e r

mined by gas chromatography and r e p o r t e d as ppm (v/ v) i n t h e b r e a t h . Group means, r a n g e s , and s t a n d a r d d e v i a t i o n s were c a l c u l a t e d f o r each t i m e p e r i o d of each day. The r e s u l t s f o r t h e m a l e s u b j e c t s are l i s t e d i n Tables I1 through X I 1 1 and f o r t h e female s u b j e c t s i n Tables X V I I through X I X . P e r u s a l of t h e d a t a i n d i c a t e d no obvious d i f f e r e n c e s i n b r e a t h c o n c e n t r a t i o n s r e l a t e d t o t h e day of t h e week, and t h e r e f o r e , weekly d a t a f o r each group w a s pooled f o r Tables X I V , XV, and XVT, r e p r e s e n t i n g 7 1/ 2, 3 , and 1 hr 000027 23

exposures of male s u b j e c t s , while Table XX p r e s e n t s poolcd d a t a f o r each group of female s u b j e c t s .

breath concentrations as s u b j e c t s e x i t e d t h e chamber and before b r e a t h i n g OR each t a b l e , t h e 1 min p o s t e x i t values r e p r e s e n t non contaminated a i r , while t h e b a s e l i n e v a l u e s represent concentrations t h e morning following t h e exposure.

Breath l e v e l s of p xylene upon e x i t from t h e chamber were only a small f r a c t i o n of t h e level of t h e vapor i n t h e chamber. A t 20 ppm exposure, t h i s breath level averaged 5.1% of t h e exposure level, a t 100 pprn i t averaged 5.7%,

and a t 150 ppm, 6.4%. These low b r e a t h l e v e l s i n d i c a t e uptake by the body of 93 t o 95% o f t h e inhaled p xylene vapor from t h e a l v e o l a r spaces of t h e lungs.

Blood p Xylene Concentrations:

The concentrations of p Xylene found i n t h e pre exposure, p r e e x i t ,

30 min p o s t , and 1 hr p o s t exposure blood samples obtained on Days 1 and 4 of each exposure week are l i s t e d i n Tables XXI through XXIV.

values are reported i n ppm on a w/ w b a s i s , assuming blood t o have a s p e c i f i c g r a v i t y of 1.0. P e r u s a l of t h e v a l u e s found f o r t h e male s u b j e c t s on a l l Day 1 pre exposure blood samples reveals 0.0 t o 0.8 ppm p xylene. It is f e l t t h a t many of t h e high r e s u l t s found on Day 1 were due t o contamination, because from 0 .1 t o 0.5 ppm w a s found i n pre

exposure s a m p l e s from s u b j e c t s p r i o r t o any exposure t o p xylene. All This 800028 1 : was n o t t r u e of samples taken from female s u b j e c t s on Day 1 as shown i n Table XXIV. By t h i s t i m e t h e contamination problem had been s o l v e d , and t h e pre exposure values found f o r Day 4 are believed t o be real, i n d i

c a t i n g a s l i g h t build up of p xylene i n t h e blood of a l l s u b j e c t s upon f o u r consecutive days of exposure t o p xylene. Even though t h e r e may be a contamination e r r o r i n p xylene blood v a l u e s f o r males, t h e d a t a r e v e a l s a p o s i t i v e r e l a t i o n s h i p between exposure concentration and blood l e v e l , b u t no c l e a r r e l a t i o n s h i p between l e n g t h of d a i l y exposure and ,,, ___

blood level. '\

Table XXV demonstrates t h e e f f e c t of exercise on p xylene blood l e v e l s . On day 4 of each exposure week, Group I male s u b j e c t s exercised on b i c y c l e ergometers f o r a s h o r t t i m e (s e e Cardiopulmonary Function S t u d i e s ). A r t e r i o l i z e d venous blood w a s obtained from a c a t h e t e r i n the back of t h e hand, and a l i q u o t s were analyzed f o r p xylene i n t h e same manner as t h e o t h e r venous blood s a m p l e s . Average concentrations of p

xylene i n t h e blood increased two t o t h r e e f o l d during 11 min of mod

erate exercise. 24

S a l i v a p Xylene Concentrations:

Analysis of s a l i v a samples for p xylene revealed concentrations t h a t were very similar t o t h e concentrations of p xylene i n blood Sam

p l e s obtained a t approximately t h e same t i m e . Tables XXVI and XXVII l i s t t h e r e s u l t s of saliva a n a l y s i s f o r Group I male s u b j e c t s d u r i n g t h e weeks of exposure t o 150 ppm and 100 ppm f l u c t u a t i n g p xylene vapor concentrations, while Table XXVIII lists t h e r e s u l t s from Group I female s u b j e c t s during t h e i r week of exposure t o 100 ppm p xylene vapor. 000029 . ;;> ;; t! f: z. J 2 5

Rather wide ranges and v a r i a b i l i t y on d i f f e r e n t days of t h e same week I were noted. Again, as i n t h e blood a n a l y s e s , low grade contamination of t h e head space, or imprecision of t h e procedure, may have contributed t o t h e s c a t t e r of r e s u l t s .

the s a l i v a a n a l y s e s because, c o n t r a r y t o t h e blood a n a l y s e s , no i n t e r n a l standard w a s used. This could b e p a r t i c u l a r l y t r u e i n the case of Urinary Methyl Hippuric Acid Concentrations:

Twenty four h r u r i n e c o l l e c t i o n s w e r e analyzed f o r h i p p u r i c a c i d s ,

including methyl h i p p u r i c a c i d (p t o l u r i c a c i d ) concentration, on Days 1 and 4 of each week. Tables XXIX through XXXII list i n d i v i d u a l values f o r each s u b j e c t , n o t i n g both t h e u r i n a r y c o n c e n t r a t i o n i n mg/ ml, and t h e c a l c u l a t e d d a i l y e x c r e t i o n i n g /2 4 h r , based upon t h e measured volume of u r i n e excreted i n 24 h r . From t h e v a l u e s obtained i t i s apparent t h a t h i p p u r i c a c i d s e x c r e t i o n i s extremely v a r i a b l e due t o t h e presence of h i p p u r a t e s i n t h e u r i n e p r i o r t o any exposure t o p xylene.

A s a n example of t h e extreme v a r i a b i l i t y between two s u b j e c t s i n one group, female s u b j e c t s 264 and 265 e x c r e t e d 4.90 and 0.69 g of h i p p u r i c a c i d s , r e s p e c t i v e l y , d u r i n g Day 1 of i d e n t i c a l 1 hr exposures t o 100 ppm p xylene. I n t e r e s t i n g l y , t h e h i g h e s t excreters of a group were gen

e r a l l y h i g h e s t on every day, and conversely t h e lowest w a s g e n e r a l l y always lowest, even on a non exposure day.

Neurological S t u d i e s :

No s i g n i f i c a n t n e u r o l o g i c a l a b n o r m a l i t i e s occurred during t h e exposures of t h e s e s u b j e c t s t o p xylene. Equilibrium as measured sub

4 `f *,,Q "*

Q``  i 3 ..*

000030 2 0

j e c t i v e l y on a twice d a i l y b a s i s by t h e modified Romberg test and heel

to toe test remained normal a t a l l t i m e s . EEG recordings were analyzed v i s u a l l y f o r changes from t h e normal alpha rhythm, and only an increased incidence of l a r g e amplitude waves i n t h e d e l t a frequency range (5 8 hz)

were noted. Examples of EEG recordings made during 0 ppm exposures p r i o r t o a c t u a l exposure and some showing increased d e l t a a c t i v i t y during exposures t o 100 ppm p xylene are shown i n Figures 2 through 9.

Although a l l Group I s u b j e c t s demonstrated t h i s trend t o increased d e l t a a c t i v i t y , i t w a s n o t evident i n any s u b j e c t during every exposure, i t s incidence w a s poorly c o r r e l a t e d w i t h exposure concentration, and some s u b j e c t s admitted t h a t they were drowsy or sleepy during some EEG re

cordings (condition characterized by increased d e l t a a c t i v i t y ). How

e v e r , t h e s e abnormal rhythms were n o t noted on t h e 0 ppm day a f t e r exposures t o p xylene were complete. The general s t a b i l i t y of VER t r a c i n g s throughout exposures t o p xylene vapor is demonstrated i n Figure 10, a compilation of t r a c i n g s from female s u b j e c t 258 taken from days b e f o r e , during, and a f t e r exposure t o 100 pprn p xylene vapor.

Tables XXXIII and XXXIV l i s t t h e d a i l y summed amplitudes and t h e means of t h e weekly exposures f o r t h e 3, 4 , and 5 complex of t h e VERs f o r a l l Group I s u b j e c t s . Values s i g n i f i c a n t l y d i f f e r e n t (p< 0.05) from pre

exposure by t h e p a i r e d t test were spurious and n o t thought t o be re

l a t e d t o t h e breathing of a i r w i t h p xylene vapor a t a concentration of up t o 150 ppm. I Cardiopulmonary Function Studies :

Pulmonary v e n t i l a t i o n (V ) values i n R /m i n (B. T. P. S., body tern E Perapre ,and p r e s s u r e , s a t u r a t e d ) are l i s t e d f o r i n d i v i d u a l s u b j e c t s i n *.*%.* I F u p 7 ,. y p 00003i 2 7

Table XXXV.

u a l s , probably r e f l e c t i n g a heightened emotional state; however, i n g e n e r a l t h e v a l u e s were c o n s i s t e n t from day t o day.

females were g e n e r a l l y lower than t h o s e of males, r e f l e c t i n g t h e gen

e r a l l y lower metabolic rate of females.

expected from s u b j e c t s i n t h e s e a t e d p o s i t i o n There were some s p u r i o u s high v a l u e s f o r s e v e r a l i n d i v i d

Also, v a l u e s of The v a l u e s are a l l i n t h e range (14) .

The r e s u l t s of t h e e x t e n s i v e cardiopulmonary t e s t i n g c a r r i e d o u t .on Day 4 of each week on t h e Group I, m a l e s u b j e c t s are given i n Tables XXXVI through XXXVIII.

rates were measured t h r e e times each day, and t h e means of t h e t h r e e trials were used t o c a l c u l a t e t h e d a i l y means f o r t h e f o u r s u b j e c t s Maximum and p a r t i a l e x p i r a t o r y volumes and flow (Table XXXVI). Table XXXIX demonstrates t h e within day t r i a l t o t r i a l v a r i a b i l i t y of each parameter, and except for t h e flow rates during maximum e x p i r a t i o n t h e i n t e r t r i a l v a r i a b i l i t y was less than 5%. Flow rates during t h e second and t h i r d maximum e x p i r a t i o n of each day w e r e s i g n i f i c a n t l y higher (two tailed t test) than the f i r s t e x p i r a t i o n (11 t o 1 7 %). One p o s s i b l e explanation of t h i s d i f f e r e n c e i s t h a t , with t h e i n i t i a l e x p i r a t i o n , r e s i d u a l bronchomotor tone w a s a l l e v i a t e d . Hence,

during t h e subsequent e x p i r a t i o n s t h e flow rates were increased (15)

Taking i n t o account t h e above r e l i a b i l i t y of t h e meaned t r i a l s , t h e d a i l y means found i n Table XXXVI i n d i c a t e t h a t t h e r e w a s no decrement i n e x p i r a t o r y volumes and flow rates due t o t h e p xylene vapor.

,,

Metabolic r a t e , pulmonar, y, c a r d i a c , and hematologic d a t a as ex

Pressed i n mean v a l u e s of f o u r s u b j e c t s a t rest and a t two l e v e l s of exercise (work 1 = 350 KPM f o r 6 min, work 2 = 750 KPM f o r 5 min) during Day 4 of each exposure week are found i n Tables XXXVII and XXXVIII. The 2 8

results demonstrate that there was no consistent effect of p xylene vapor on mechanisms regulating pulmonary ventilation, alveolar capillary gas exchange, metabolic rate, heart rate, peak systolic and diastolic blood pressure, and arterial acid base status. Alveolar capillary gas exchange (I) seemed to increase with p xylene exposure each week, but the increases were not dose related, and the mean values did not return %o to pre exposure values, indicating the possibility of spuriously low .

pre exposure values, or an actual prolonged effect of p xylene upon this parameter.

Cognitive Testing:

Extensive data accumulated from the battery of cognitive tests given to Group I and I1 male subjects on Days 1, 3 , and 5 of each week.

The daily means (+ one standard deviation, S. D.) of the test results vs.

the day performed, along with bar graphs showing the concentration of p

xylene, were graphed for rapid visual assessment. Figures 11 through 20 contain the data for Group I subjects while Figures 21 through 30 are for Group I1 subjects. In order to assess the significance of the exposure t o p xylene on test results, analysis of variance for the Group scores were made for the parameters measured in each test. There were insufficient test subjects in Group I1 to make such an assessment fea

sible. Results of the analysis of variance are shown in Tables XL through L. Significant variance (p< 0.05), other than that attributed to learning (linear day trend) and people, was noted only in the effect of P xylene exposure upon the Flanagan coordination test. Figures 31 and 32 show the test performance means (2 S. D.) versus exposure level for 2 9

Day's and Days 1 ,3 , and 5 combined, r e s p e c t i v e l y . These graphs show a decrement i n performance a t t h e 150 ppm exposure l e v e l . Table L I p r e

s e n t s t h e i n d i v i d u a l d a i l y test s c o r e s throughout t h e s t u d y , and i t can ,,,.; t: yl($ >.

be Seen t h a t t h e decrement i n performance a t 150 ppm i s due almostrjy;.:.

wholly t o one s u b j e c t (# ll7). This s u b j e c t had been ill, consequently a b s e n t , on Days 1 and 3 of t h e previous week during t h e 20 ppm exposure,

and d i d poorly on t h e coordination test on Day 5. Therefore, i t appears t h a t h i s poorer than normal performance d u r i n g t h e exposures t o 150 ppm could have been r e l a t e d t o h i s i l l n e s s . A second s u b j e c t (11248) a l s o had a poorer than normal performance on Day 3 of t h i s week, and t h i s occurred s h o r t l y a f t e r he had noted eye i r r i t a t i o n on h i s s u b j e c t i v e response s h e e t . The o t h e r two s u b j e c t s s c o r e s were unaffected. Un

f o r t u n a t e l y , t h e r e s u l t s of t h e t e s t i n g of only one o r two s u b j e c t s from Group I1 during t h i s week sheds l i t t l e l i g h t on t h e e f f e c t of 150 ppm p

xylene on t h i s test. It i s evident from t h e Group I test s c o r e s t h a t 100 ppm, s t e a d y o r f l u c t u a t i n g , had no d e t r i m e n t a l e f f e c t upon t h e performance of t h i s test. .. , .~, ., ..

;;, j . *

' .? ?,\

S u b j e c t i v e Responses:

S u b j e c t i v e responses t o t h e vapor of p xylene are summarized i n Table L I I as t o t a l mentions by m a l e o r female s u b j e c t s a t each exposure concentration. Of t h e s i x s p e c i f i c responses from t h e male s u b j e c t s ,

only ENT i r r i t a t i o n appeared t o be r e l a t e d t o t h e concentration of p

xylene, and t h i s w a s p r i m a r i l y because one 7 1/ 2 hr s u b j e c t who wore c o n t a c t l e n s e s noted eye i r r i t a t i o n on almost a d a i l y b a s i s , and he w a s j o i n e d by one o t h e r s u b j e c t t w i c e a t 100 ppm and 3 t i m e s a t 150 ppm. % 3 3 0

There w a s no v i s i b l e reddening of t h e eyes o r conjunctiva in t h e s e s u b j e c t s . No male 3 hr s u b j e c t s ever l i s t e d ENT i r r i t a t i o n , and only once (a t 150 ppm) d i d a 1 hr s u b j e c t mention i t . I n t e r e s t i n g l y , ENT i r r i t a t i o n w a s a l s o mentioned very o f t e n by females during t h e week of exposure t o 100 ppm p xylene, b u t i n t h e s e mentions i t w a s almost always nose o r t h r o a t i r r i t a t i o n . It appears t h a t p xylene has a weakly irri

t a t i n g e f f e c t on s o f t t i s s u e s a t a c o n c e n t r a t i o n of 100 ppm, and may .

p a r t i c u l a r l y i r r i t a t e t h e eyes of persons wearing c o n t a c t l e n s e s .

The odor of p xylene w a s noted by a l l s u b j e c t s upon e n t e r i n g t h e environmental chamber a t a l l t i m e s when t h e vapor w a s p r e s e n t . It w a s g e n e r a l l y judged t o be moderate i n i n t e n s i t y a t a c o n c e n t r a t i o n of 100 ppm, and s t r o n g a t 150 ppm, upon f i r s t c o n t a c t . Usually w i t h i n one h r t h e i n t e n s i t y r a t i n g w a s reduced by a t least one (s t r o n g t o moderate t o mild t o none). No s u b j e c t complained t h a t t h e odor w a s completely o b j e c t i o n a b l e . 3 1

DISCUSSION The Threshold L i m i t Value (TLV) of 100 ppm f o r t h e mixed xylene isomers w a s s e l e c t e d p r i m a r i l y due t o eye i r r i t a t i o n and p o s s i b l e i m

pairment of r e a c t i o n t i m e i n some workers a t 200 ppm( 16). The s t u d i e s described i n t h i s r e p o r t tend t o confirm t h e v a l i d i t y of t h e TLV of 100 ppm f o r one of t h e isomers, p xylene.

exposed t o vapor concentrations of p xylene t h a t bracketed t h i s TLV,

s p e c i f i c a l l y 20 and 150 ppm, f o r up t o 7 1/ 2 h r p e r day, f i v e days p e r week f o r one week, i n a d d i t i o n t o two weeks of exposure t o t h e TLV.

Also, female s u b j e c t s were exposed t o t h e TLV f o r one week t o compare t h e i r responses t o t h e male s u b j e c t s .

comprehensive study of s u b j e c t responses w a s made on i n d i v i d u a l s who were u s u a l l y sedentary during t h e exposure p e r i o d s .

d i t i o n s , only eye, nose, and/ or t h r o a t i r r i t a t i o n could be d i r e c t l y '

r e l a t e d t o t h e p xylene exposure.

t a t i o n w a s one s u b j e c t who wore c o n t a c t lenses.

were s u g g e s t i v e of changes a t 100 and 150 ppm exposure l e v e l s were changes from a l p h a t o d e l t a EEG a c t i v i t y on some occasions and a de

crease i n c o o r d i n a t i o n i n one s u b j e c t as measured by t h e Flanagan Sedentary m a l e s u b j e c t s were It must b e pointed o u t t h a t t h i s Under t h e s e con

E s p e c i a l l y s e n s i t i v e t o eye irri

Other responses t h a t Coordination test.

a s s o c i a t e d without q u e s t i o n t o p xylene exposure. Furthermore, the decrement i n c o o r d i n a t i o n e x h i b i t e d by t h e one m a l e s u b j e c t w a s n o t However, n e i t h e r of t h e s e changed responses could be .

2. '

c o r r e l a t a b l e w i t h i n c r e a s e d d e l t a EEG a c t i v i t y .

There is a d e a r t h of r e c e n t l i t e r a t u r e r e g a r d i n g t h e t o x i c i t y of any xylenes i n man o r animal. Of some i n t e r e s t t o t h i s study is a paper 3 2 ,

by Mikulski, e t a l . (I7) wherein u r i n a r y h i p p u r i c a c i d s concentration,

which a l s o included methyl h i p p u r i c a c i d , w a s c o r r e l a t e d t o combined toluene and xylene exposure i n s h i p ' s p a i n t e r s . The c o r r e l a t i o n between t o t a l h i p p u r i c a c i d concentration and exposure l e v e l s somewhat d i f f e r e n

t i a t e d <lo0 ppm from >200 pprn exposures, though t h e r e w a s considerable overlap. I n t h i s p a p e r , t h e a u t h o r s r e p o r t a decrease i n u r i n a r y u r i c a c i d c o n c e n t r a t i o n i n v e r s e l y p r o p o r t i o n a l t o t h e amount of h i p p u r i c a c i d excreted. They a t t r i b u t e d t h i s decrease t o t h e "contribution of t h e glycine pool t o t h e e x c r e t i o n of toluene and xylene metabolites."

s u b j e c t s i n our s t u d y , though u r i n a r y u r i c a c i d w a s n o t measured, d i d not experience a n i n c r e a s e i n blood u r i c a c i d c o n c e n t r a t i o n , as shown i n Table L I I I .

l e v e l s , though t h e decreases were n o t of g r e a t magnitude. I f t h e ex

c r e t i o n of u r i n a r y u r i c a c i d , as r e p o r t e d by Mikulski, e t al., is i n f a c t decreased upon toluene and xylene exposure, our d a t a would support t h e theory t h a t t h e r e d u c t i o n is n o t caused by g r e a t e r r e t e n t i o n of u r i c a c i d i n t h e blood, b u t p o s s i b l y by a decrease i n t h e formation of u r i c The Almost a l l s u b j e c t s had a mild decrease i n blood u r i c a c i d . a c i d . Glycine i s a precursor of endogenous u r i c a c i d , however, i t seems improbable t h a t t h e g l y c i n e needed f o r h i p p u r i c a c i d e x c r e t i o n would decrease t h e l a r g e g l y c i n e pool s u f f i c i e n t l y t o cause a decrease i n u r i c a c i d b i o s y n t h e s i s , as p o s t u l a t e d by Mikulski and coworkers. It would seem more l i k e l y t h a t a n as y e t unknown mechanism f o r t h i s a l l e g e d r e d u c t i o n i n u r i n a r y u r i c a c i d e x c r e t i o n should be p o s t u l a t e d .

Moeschlin( 18) i n h i s review of poisoning by aromatic hydrocarbons lumps benzene, t o l u e n e , and xylene t o g e t h e r as myelotoxic a g e n t s , though i n none of h i s examples of xylene and toluene i m p l i c a t i o n w a s a previous 33

exposure t o benzene excluded. In o u r s t u d y , every p xylene c o n t a i n e r was assayed f o r benzene t o e n t i r e l y prevent any benzene exposure.

blood p i c t u r e of all s u b j e c t s who were r e p e a t e d l y exposed t o p xylene remained normal. The white blood count of a l l male s u b j e c t s who were exposed f o r more than one week t o p xylene vapor are l i s t e d i n Table from Moeschlin's own l a b o r a t o r y , LIV. I n a more r e c e n t p u b l i c a t i o n s t u d i e s w i t h r a b b i t s convinced t h e a u t h o r s t h a t p u r e xylene, uncontami

nated w i t h benzene, lacked myelotoxicity. The (19)

(3 ,4 ) Ogata and co workers have published d a t a r e l a t i n g u r i n a r y methyl h i p p u r i c a c i d and h i p p u r i c a c i d c o n c e n t r a t i o n s of p a i n t e r s t o exposures t o toluene and p xylene. A s experienced w i t h our s u b j e c t s ,

c o r r e l a t i o n of u r i n a r y m e t a b o l i t e e x c r e t i o n w i t h exposure w a s only v a l u a b l e as a g r o s s measure of exposure. Other b i o l o g i c measures t h a t w e found t o b e u s e f u l as gross measures of exposure were p xylene con

c e n t r a t i o n i n blood and i n s a l i v a . Concentrations of t h e chemical i n both of t h e s e b i o l o g i c f l u i d s were measurable by gas chromatography of headspace samples taken from an enclosed c o n t a i n e r . However, contami

n a t i o n w a s a problem i n o u r hands, and t h e i n t e r s u b j e c t v a l u e s obtained were q u i t e v a r i a b l e . 1 3 4

Sedivec and Flek (2" ' 21) reported on the absorption, metabolism, and excretion of xylenes in man in papers published after our study was completed. These authors developed a chromatographic procedure for the analysis of the methyl hippuric acids which has the advantage of speci

ficity for quantifying the metabolite of p xylene. They found that 95.1% of the p xylene taken up by the body was excreted in the urine as the p toluric acid, and only 0.05% as the 2,5~ ylenol. Most of the remainder, or 3.5% was primarily excreted in the breath. These authors propose (21) the measurement of toluric acids in an 8 or 24 hr urine sample, and expression of the results in mg excreted per 1 kg of body weight, as the most suitable measure of determining the magnitude of an exposure. They suggest a range Of from 4.29 to 7.1 mg/ kg as acceptable for a worker doing light physical work for an 8 hr day while exposed to the Czechoslovakian MAC of 200 ug/ R (46 ppm).

Our reported concentrations of p toluric acids excreted for a 24 hr period including exposure cannot be favorably compared with the results reported by Sedivec and Flek (21) because our colorimetric procedure was . not as specific for the metabolite of p xylene as was their chromato

graphic procedure. For instance, our 7 1/ 2 hr subjects excreted from 0.77 to 2.19 gm of methyl hippuric acid during exposures to 20 ppm p

xylene, while they report a range of 0.46 to 0.85 gm from 8 hr exposures t o 46 ppm.

employed by Sedivec and Flek" ') It is reasonable to assume that the more specific procedure though technically more difficult to carry out, would result in lower, and more consistent, concentrations of metabolite. .; I .< %

800039 35

Another apparent d i f f e r e n c e noted between o u r s t u d i e s and t h o s e reported by Sedivec and Flek (20) is t h a t of p o s t exposure b r e a t h concen

t r a t i o n s of xylene. Although t h e i r d a t a are shown f o r only one s u b j e c t who w a s exposed t o 86 ppm of m xylene f o r 8 h r , i t appears from t h e f i g u r e t h a t they were obtaining much higher b r e a t h ' levels a t a l l p e r i o d s than w e obtained w i t h p xylene a t 100 ppm. It i s most l i k e l y t h a t t h i s d i f f e r e n c e i s due p r i m a r i l y t o t h e method of sampling. Whereas w e used a 20 second b r e a t h holding technique and measured t h e c o n c e n t r a t i o n i n a l v e o l a r a i r .s a m p l e s , they simply captured a sample of exhaled a i r and measured t h e xylene concentration. The d i f f e r e n c e p o i n t s o u t t h e neces

s i t y of d e f i n i n g t h e procedure when recommending b r e a t h sampling as a t o o l f o r e v a l u a t i n g exposures.

Upon p e r u s a l of t h e mean p xylene p o s t exposure b r e a t h concentra

t i o n s i n Tables XIV, XV, XVI, and XX f o r 7 1/ 2, 3, and 1 hr exposures t o i d e n t i c a l concentrations of p xylene i n t h e chamber a i r , i t i s obvious t h a t c o n c e n t r a t i o n and d u r a t i o n of exposure w e r e n o t d i r e c t l y c o r r e l a t a b l e Although t h e b r e a t h concentrations from 7 1/ 2 hr exposures were g e n e r a l l y somewhat higher than those from 1 hr exposures, t h e d i f f e r e n c e s were u s u a l l y s m a l l and t h e r e was c o n s i d e r a b l e overlap i n i n d i v i d u a l v a l u e s .

The d i f f e r e n c e s between 7 1/ 2 and 3 hr s u b j e c t s were even less, w i t h means from t h e latter o f t e n h i g h e r than t h e former.

t o n o t e t h a t t h e same p i c t u r e is p r e s e n t i n t h e comparison of blood and saliva c o n c e n t r a t i o n s after 7 1/ 2, 3, o r 1 hr exposures as s e e n i n Tables XXI through XXVIII. It i s i n t e r e s t i n g Comparison of b r e a t h c o n c e n t r a t i o n s a f t e r 150, loo, o r 20 ppm exposures revealSa s l i g h t l y b e t t e r c o r r e l a t i o n of b r e a t h t o exposure :: ;; <> G. f fJ Ir QQW40. ;, y,

3 3 0

concentrations. Figure 33 p r e s e n t s t h e means and ranges of b r e a t h c o n c e n t r a t i o n s a f t e r t h e f o u r 7 1/ 2 hr s u b j e c t s were exposed t o t h e t h r e e s t e a d y concentrations on a weekly b a s i s . Hand drawn curves repre

s e n t t h e b r e a t h a n a l y s i s decay curves.

v e r y l i t t l e overlap i n v a l u e s when o n l y t h e s e t h r e e weeks are considered.

However, when t h e values from t h e week of 100 ppm f l u c t u a t i n g concentra

t i o n s (between 50 and 150 ppm p xylene) w e r e considered, t h e r e w a s c o n s i d e r a b l e overlap with t h e 150 ppm week.

t h a t a n e q u i l i b r i u m e x i s t s between f r e e p xylene and e i t h e r bound o r metabolized product, w i t h t h e e q u i l i b r i u m i n favor of t h e bound o r metabolized product.

t h a t approximately 72% of t h e xylenes were excreted as t h e bound metabo It can be noted t h a t t h e r e i s These d a t a seem t o i n d i c a t e From t h e work of Sedivec and Flek (20) who found l i t e s d u r i n g 8 h r of exposure, i t is probabLe t h a t a t t h e levels of exposure s t u d i e d a m e t a b o l i t e of p xylene w a s being formed almost as r a p i d l y as t h e blood could c a r r y t h e f r e e chemical t o t h e l i v e r .

metabolized product w a s conjugated w i t h g l y c i n e , i t w a s being e x c r e t e d r a p i d l y by t h e kidneys. Only d u r i n g exercise and exposure t o 150 ppm P

xylene d i d t h e blood c o n c e n t r a t i o n rise d r a m a t i c a l l y , as shown i n Table XXV. This i n d i c a t e s t h a t a s a t u r a t i o n of t h e metabolic mechanism, plus t h e shunting of more blood away from t h e l i v e r t o t h e musculature, w a s t a k i n g p l a c e during t h e h i g h exposure w i t h exercise.

Because of t h e overlap and r e s u l t a n t l a c k of c l a r i t y of b r e a t h As t h e a n a l y s i s decay curves t h a t could b e drawn from t h e data obtained, and because of t h e r a p i d drop of b r e a t h c o n c e n t r a t i o n s w i t h t i m e a f t e r exposure, b a r graphs of means and ranges of p xylene b r e a t h c o n c e n t r a t i o n s immediately and 15 min p o s t exposure w e r e drawn and are p r e s e n t e d i n 37

Figures 34 and 35, r e s p e c t i v e l y . Female s u b j e c t s g e n e r a l l y gave lower b r e a t h p xylene c o n c e n t r a t i o n s than d i d male s u b j e c t s exposed t o i d e n t i c a l concentrations of p xylene. I n n e i t h e r male nor female sedentary s u b j e c t s exposed f o r 7 1/ 2 h r p e r day f o r f i v e consecutive days w a s t h e r e any clear c u t evidence of d e l e t e r i o u s response t o 100 ppm of p xylene. Even a t 150 ppm f o r t h e same t i m e p e r i o d , m a l e s u b j e c t s evidenced no d e l e t e r

i o u s responses, w i t h only a p o s s i b l e s a t u r a t i o n of t h e metabolic pathways as a p o t e n t i a l i n d i c a t i o n of d e l e t e r i o u s e f f e c t . Because of t h e need f o r a r e l a t i v e l y simple method of a s s e s s i n g t h e body burden of p xylene as r e l a t e d t o a s a f e exposure f o r 7 1/ 2 o r 8 h r we recommend a n a l v e o l a r b r e a t h sample be obtained e x a c t l y 15 minutes a f t e r termination oY t h e exposure.

ppm i f a m a l e worker and no more than 3.5 ppm i f a female worker. I f The c o n c e n t r a t i o n of p xylene should be no g r e a t e r than 4.5 t h i s s t a n d a r d i s m e t , a l l workers should b e p r o t e c t e d from any d e l e t e r i o u s e f f e c t s of p xylene vapor exposure.

000042 , 3 8

li E F E R ENC E S 1. Greek, B. F.: Polyester Raw Materials Allow F i b e r Growth, C& EN, p . 11,

September 29, 1975 2. Threshold Limit Values f o r 1965, American Conference of Governmental I n d u s t r i a l Hygienists, Adopted a t t h e 27th Annual Meeting, Houston, Texas,

May 2 4, 1965.

3. Ogata, M., Tomokuni, K ., and Takatsuka, Y .: Urinary Excretion of Hippuric Acid and  m o r 2 Plethylhippuric Acid i n t h e Urine of Persons Exposed t o Vapors of Toluene and  m o r 2 Xylene as a T e s t of Exposure,

I n d u s t r . Med.,  27: 43 50, 1970. B r i t . J.

4 . Ogata, P i ., Takatsuka, Y ., and Tomokuni, K.: Excretion of Hippuric Acid and 5 o r 2 Methylhippuric Acid i n t h e Urine of Persons Exposed t o Vapors of Toluene and  m o r E Xylene i n an Exposure Chamber and i n WorksHops,

With S p e c i f i c Reference t o Repeated Exposures, B r i t . J . I n d u s t r . Med.,

 28~ 382 385, 1971.

5. Tomokuni, K., and Ogata, M.: Jap. J. Ind. Health, 14: 103, 1972.

6 . Hosko, M .J .: The E f f e c t of Carbon Monoxide on t h e Visual Evoked Response i n Man, Arch. Environ. Health, 21: 174 180, 1970.

7 . J a s p e r , H. H.: The 10 20 Electrode Systems of I n t e r n a t i o n a l Federation,

EEG C l i n . Neurophysiol.,  10: 371 375, 1958.

8. Bergamasco, B.: E x c i t a b i l i t y Cycle of t h e V i s u a l Cortex i n Normal Subjects During Psychosensory R e s t and Cardiozolic Activation, Brain  R e s ., 2: 51 60, 1966.

9. Gastaut, H ., and Regis, H .: Visually Evoked P o t e n t i a l s Recorded T r a n s c r a n i a l l y i n Man, in P r o c t e r , L .D ., and Adez, W. R. (e d s .): Symposium 000043 7 :'

10.

11.

12.

13.

14.

15'.

16.

17. 3 9

on the Analysis of CNS and cu Data Using Computer Methods, publication SP 72, National Aeronautics and Space Administration, Washington, D. C.,

1964.

Forster, H. V., Soto, R. J., Dempsey, J. A., and Hosko, M .J .: The Effect of Sojourn at 4300m Altitude on the Electroencephalogram and the Visual Evoked Response, J. Appl. Physiol., 39: 109 113, 1975.

Forster, H. V., Dempsey, J. A., Thomson, J. , Vidruk, E., and do Pico, G. A. :

Estimation of Arterial Po2, Pco2, pH, and Lactate from Arterialized Venous Blood, J. Appl. Physiol., 32: 134 137, 1972.

Forster, R. E.: Diffusion of Gases, Handbook of Physiology, Sec. 3, V O l . 1,

American Physiological Society, Washington, D. C., 1964, pp. 839 872.

Stewart, R. D., Peterson, J. E., Baretta, E. D., Bachand, R. T., Hosko, M .J .,

and Herrmann, A. A.: Experimental Human Exposure to Carbon Monoxide, Arch.

Environ. Health, 21: 154 164, 1970.

Rasmussen, B., and Lammert, 0.: Ventilation and Ventilatory Responses to C02 During Static and Dynamic Exercise at Equal Oxygen Uptake, Acta Physiol. Scand., In Press.

Green, M., and Mead, J.: Time Dependence of Flow Volume Curves, J. Appl.

Physiol., 37: 793 797, 1974.

Documentation of the Threshold Limit Values for Substances in Workroom  Air, 3rd Edition, American Conference of Governmental Industrial Hygienists,

Cincinnati, Ohio, 1971, pp. 281 282.

Mikulski, P. I., Wiglusz, R., Bublewska, A., and Uselis, J.: Investigation of Exposure of Ship's Painters to Organic Solvents, Brit. J. Industr.

Med., 2: 450 453, 1972.

000094 40

18. Moeschlin, J.: Poisoning Diagnosis and Treatment, 1st American E d i t i o n ,

Grune & S t r a t t o n , New York, 1965, pp. 329 345.

19. Speck. B ., and Moeschlin, S.: [The Action of Toluene, Xylene, Chlor

amphenicol and T h i o u r a c i l on t h e Bone Marrow.] (German) Schweiz. Med.

Wschr., 98: 1684 1686, 1968.

Sedivec, V ., and Flek, J.:

of Xylenes i n Man, I n t . Arch. Occup. Environ. H l t h ., 37: 205 217, 1976. 20. The Absorption, Metabolism, and Excretion ~ A .

21. I b i d ., Exposure T e s t f o r Xylene, 219 232.

(800045 TABLE XLIX.

Analysis of Variance for the Coordination Test During Exposure to p Xylene (7 1/ 2 Hr/ Day)

 SOURCE OF SUM O F SQUARES MEAN SQUARE MSR ( F 1 TOTAL 55 27841.84 D A Y S 1 3 9 8 5 .4 3  LINEAR 1 D A Y TREND C INEAR P XYLENE 1 34.99 233.29 0.60 c 34.99 ~

7 5 .8 0 233.29 11 743.16 67.56 1.27 OTHER 3 24784.13 8261.38 PEOPLE RESIDUAL 39 2072.29 53.14 * Significant p 2 .OS . 000046 TABLE LIT.

SUBJECTIVE RESPONSES TO p XYLENE VAPOR 8 MALES 0 PPm 4 days Headache 3  Nausea 0 Dizziness 3 Abdominal Pain 0 Chest Pain 0 ENT Irritation 3 Other 0 20 PPm 5 days 100 ppm 5 days (Mentions)

7 FEMALES _ I_

i 0 PPm 100 ppm i 2 days 5 days i i (Mentions)

Headache 1 8 Nausea 0 1 Di z zines s 3 6 Abdominal Pain 0 0 I ,

i i I ! Chest Pain 1 ENT Irritation 5 Other 3 , 0 17 0 3 0 3 0 0 7 i.

2 100 ppm (fluctuating) 5 days 150 ppm 5 days 3 1 b 1 0 0 8 ' .7.

2 000047 API'ENDCX I STATEMENT OF VOLUNTARY CONSENT FOR RESEARCH INVESTIGATION OF HUMAN EXPOSURE TO:

p XYLENE I 1, subject, in a program of research investigation under the direction and , hereby agree t o participate as a of Dr. R. D. Stewart.

m e general purpose of this research is t o determine r a t e s of uptake, excretion and metabolism of p XYLENE ,

The studies have been described to m e and the known r i s k s involved in this experimental procedure have been explained t o me. frequently described known r i s k s are: I understand that the most none known a t this level of expo s u r e .

Iunderstand a l s o that it is not possible t o identify all potential r i s k s in experimental procedures which involve controlled exposures t o the chemical in a specially designed chamber.

I further understand that reasonable precautions and safeguards have been and will. be taken to remove and reduce both the known and the potential but unknown risks and to provide for my safety and comfort.

I also understand that, while the program will be under the direction and super vision of Dr. R. D. Stewart, other professional persons who work with him may be designated to assist him o r to a c t f o r him,

Inview of those considerations, I hereby authorize Dr. R, D. Stewart and his representatives to proceed with the investigation on the understanding that I may terminate my service a s a subject in this research at any time I so desire. Ialso authorize Dr. R. D. Stewart to u s e any type of data', pictures, films @tc. for use in any scientific report o r publication.

Iarn offering my service freely, in consideration of s i m i l a r actions on the p a r t of other subjects involved in like voluntary efforts t o improve our society through r e 8 ear ch. 000048 W i ~k g d b <j 20 Signed Investigator Subject Date I *

r %

. I . I .+ 000049 PART 2 DATE <

z t + GOUT 0 I MEDICATION

IMMUNIZATIONS RELIG. ED.

VOCAT. SMALLPOX TETANUS DIPTH.

MARITAL POLIO 2 INFLU. Id j TYPH.

HABITS SLEEP COFFEE CIG. ALCOL. MEAS.

WK. HRS./ WK.

I 1 W/ H 0. MELL CA I ASTHMA LARGE IClFAtJ7S STILLBORN HAY FEVER F TBC EPILEPSY i I 1 li HEART INSANITY ' = NORMAL, YES 0 ABSENT EXAMINAIIUIV DATE I B. P. P. HT. WT. ST. WT.

POSTURE COLOR TEXTURE OISTRI8UTION / ICLEAN ERUPTION ALOPECIA $LULL / PALSIES EXPRESSION LIPS FACE 1 CERUMEN TYM MEME WATCH HEARD TOPHI / EARS R L DISCHARGE OBSTRUCTION PERFORATION HOSE MOUTH / BREATH ULCERS AE. PIGMENTATION _

 x I CARIOUS 0 ABSENT R E 7 6 5 4 3 2 1 1 2 3 4 5 6 7 8 L R E 7 6 5 4 3 2 1 1 2 3 4 5 6 7 8 L TEETH CLEAN ADEQUATE CHEWING SURFACE  RETRACTION PYORRHEA GUMS /

PROTRUDED MIDLINE TREMOR ATROPHY STATUS ENLARGED INJECTION EXUDATE TONGUE  TONSILS PHARYNX GAG REFLEX INJECTIDN EXUDATE I COLOR ARCUS SENlLlS PERRLA NEOM NY STAGMUS I E XOP HTH AL L I D LAG PTOSIS PERIORBITAL EDEMA VISION NEAR FAR FIELDS OPHTHAL Dl SC H GR. A CR. TONOMETER EYES R L R L V O I ~~R M A C R L MIDLINE TUG , TRACHEA LARYNX NECK $PINE THORAX PALP ABL E STI F FN ESS NODES VEINS CAROTID THYROIO TENDERNESS RIGIDITY AB. CURVATURE SYMMETRICAL CVA TENDERNESS STERNAL TENDERNESS RATE REGULAR DEPTH SYMMETRICAL FORCED RESPlRA COUGH SPUTUM PERCUSSION RESONANT BREATH SOUNDS VESICULAR LUNGS TACTILE FREMITUS VOICE SOUNDS RALES t k HEAVE SHOCK THRILL TO L. OF M. C. L.

I. C. S. E. C. D. EXTENDS Chi. TO L. OF M. S. L. HEART APEX IMPULSE PALPABLE IN I. C. 5. CM. FROM M. PL.

SOUNDS A2 p 2 M1 M2 RHYTHM MURMUR SIZE NORMAL TENDERNESS MASSES  ASCITES SYMMETRICAL DILATE0 VEINS PALPABLE LIVER SPLEEN KIDNEY MASSES D DO MEN TENDERNESS RIGIDITY SOUNDS HERNIA \

DISCHARGE SKIN LESION TESTES LENIT.

PELVIC  I 44MS RAD1 AL PULSE TREMOR CLUBBING CYANOSIS JOINTS ;KIN ?ECTAL 'ROSTATE .( EURO

[UNOERLINE I F NORMAL. OTHERWISE ENCIRCLE AND CHART) JOINT SENSE TOUCH PAIN STEREOGNOSIS TEMPERATURE TRACE0 FIGURES DEEP PAIN TWO POINT VIBRATION #

AB. PIGMENTATION i ERUPTION ODLOR JAUNDICE HEMORRHOIDS . im COLOR FECES MASSES TENDERNESS  4 MASS I 4 ENLARGED TENDER /

TOUCH. ARABIC; PAIN. ARABIC IN CIRCLE; TEMP. ~ ROMAN R PROGRAM:

1 000053 _... .. , A 465 (3 ) (11/ 71) TABLE I p XYLENE EXPOSURE SCHEDULE ACTUAL TIME WEIGHTED AVERAGE VAPOR CONCENTRATION, PPM ' Desired Conc . of Week Group I, 7 1/ 2 h r Group 11, 3 h r Group 111, 1 h r PPM ek Day No. of No. of No. of Subj. Mean 2S. D. Subj. Mean +S. D. Subj. Mean fS. D. /

FEMALE 000054 5 0 4 0 3 0 2 0 _

1 100 3 100 2 2 99 1 2 99 1 2 100 3 99 1 2 98 1 2 98 1 3 100 3 100 1 2 1 2 99 2 4 1 , . '10 0 1 :,! 3 100 1 2 1 2 99 1 100 100 1 3 100 1 2 99 1 2 99 5 100 0  0 3 0 2 _ 1_ 0  2  TABLE I1 DAILY p XYLENE BREATII CONCENTRATION OF SEDENTARY MALES Exposure T i m e : 7 1/ 2 Hours  Chainber Concentration: 100 PPm GROUP I Time

Fay I: 1 min., post e x i t 1 c 11 11 11 J 2 I1 11 II 11 I t li 11 30 'I 1 hour 2 3 B a s e l i n e Day 2 : 1 min., p o s t exit II 11 15 'I II 11 11 11 II I 1 11 30 'I 1 hour 2 I'

3 B a s e l i n e Day 3: 1 min., p o s t e x i t I 1 I t 15 'I' I 1 11 I1 11 11 11 I1 30. 1 hour 2 I'

3 Baseline Day 4 : 1 min., p o s t e x i t I 1 ' I 1 11 I1 I 1 II 11 I t I t 15 If 30 'I 1 h o u r I'

2 If 3 B a s e l i n e Day>: 1 min., p o s t exit 15 ' ' 11. L 2 9rg & 11 1 f I t 30 'I I 1 I 1 11 11 11 1 hour 'I 2 3 B a s e l i n e .' Mean (i n p p d 6.25 1.98 1.69 1.15 0.40 0,30 0.20 3.91 1.56 1.28 0 .9 1 0.75 0.48 0.30 4.78 1.90 1.05 0.68 0.44 0 .4 1 0.20 5.08 2.34 1 .8 1 1.33 1.02 0.63 0.30 4.99 0.99 0.70 0.56 0.65 0.36 0.19 5 '< Range (i n ppm)

5.90  6.90 1 .8 0  2.20 1.58  1 .8 0 1.00  1 .3 0 0.22  0.59 0.18  0.39 0.13  0.26 2.93  4.98 1 ,5 1  1.57 1.12  1.33 0.84  1.05 0.70  0.80 0.40  0.50 0.20  0.40 3.40  6.50 1.80  2.20 0.90  1.50 0.60  0.80 0.40  0.55 0.38  0.50 0.20 3.70  5.70 2.02  2.90 1.65  2.02 1.20  1.50 0.81  1.38 0.40  0 .7 0 0.22  0 .3 8 3 .2 2  8 .1 1 0.95  1.00 0.61  0.95 0.51  0 .6 1 0.60  0 .8 1 0.30  0.45 0.10  0.30 Standard 5 Deviation 0.47 0.17 0.13 0.13 0.17 0.09 0.08 0.92 0.03 0.11 0.10 0.06 0.05 0.08 1.28 0.20 0.30 0.10 0.08 0.06 0 0.93 0.40 0.19 0.13 0.25 0.15 0.07 2.23 0.03 0.17 0.06 0.11 0.08 0.09 Number of S u b j e c t s 4 4 .4 4 4 ' 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 000055 TABLE 111 DAILY p XYLENE BREATH CONCENTRATION OF SEDENTARY MALES Exposure Time : 3 Hours  Chamber Concentration: 100 ppm T i m e  e: 1 m i n ., post exit 11 I 1 11 11 11 I 1 11 I t I 1 15 30 I'

1 hour 2 I'

3 Bas e line Day 2: 1 m i n ., post exit 11 11 I 1 11 I t I1 I1 11 I t 15 I'

30 1 hour 2 I t 3 Baseline Day 3: 1 min., post exit '1 c I t 11 I 1 I t 11 I t I f 11 11 11 30 1 hour 2 '! 3 j Baseline Day 4: 1 min., post exit I t I t 15 I1 I1 I t 11' 11 I t 11 30 I'

1 hour 'I 2 3 Baseline u: 1 min., post exit (1 I1 I1 I t 11 I 1 I 1 11 (1 30 1 hour 2 I'

3 Baseline Mean (in ppm)

7.65 3.25 2.40 1.65 0.38 0.30 0.13 5.87 1.84 1.23 0.77 0.40 0.20 0.20 7.40 2.30 1.25 0.90 0.70 0.60 0.16 9.25 2.43 1.73 1.25 0.67 0.53 0.30 7.60 1.73 1 .3 1 0.90 0.60 0.38 0.10 GROUP I1 Range (in ppm)

6.90  8.40 3.10  3.40 1.50  1.80 0.21  0.54 0.12  0.47 2.40 0.13 4.64  7.09 1.68  2.00 1.10  1.35 0.77  0.20  0.60 0.20 0.20 5.50  9.30 1.70  2.90 1 .2 0  1.30 0.80  1.00 0.70 0.60 0.12  0.20 7.30 11.20 2.30  2.55 1 .5 0  1.95 1.05  1.45 0.60  0.74 0.45  2.60 0.30 5.70  9.50 1.55  1 .9 1 0.91  1 .7 1 0.72  1 .0 8 0.60 0.30  0.45 0.10 Standard *Deviation 1.06 0 .2 1 0 0 .2 1 0.23 0.25 0 1 .7 3 0.23 0.18 0 0.28 0 0 2.69 0.85 0.07 0.14   0.06 2.76 0.18 0.32 0.28 0.10 0.11 0 2.69 0.25 0.57 0.25 0 0.11  Number of Subjects 2 .2 2 2 2 2 2 2 2 2 2 1 1 2 2 2 2 2 2 2 2 2 2 2 2 2 2 \ 1 0010056 TABLE IV p XYLENE BREATH CONCENTRATION OF DAILY SEDENTARY MALES 1 Hours  Chamber Concentration: 100 P P ~ Exposure Time :

I11 GROUP Number of Subjects Mean (in ppm)

3.80 1.85 1.20 0.75 0.22 0.11 0.13 1.47 1.33 0.52 0.45   0.20 Standard  +Deviation Range (i n ppm)

3.60  4.00 1.80  1.90 1.00  1.40 0.70  0.80 0.22 0.11 0.13 Time Day 1: 1 min., post exit 1 E 11 I 1 I 1 0.28 0.07 0.28 0.07 2 .2 2 2 1 1 1 IJ I 1 I 1 11 I 1 11 11 I 1 30 1 hour 2 3 Baseline Day 2: 1 m i n ., post exit I 1 t I 11 11 I1 I 1 I1 11 I1 15 30 I'

1 hour 2 3 Baseline 1.47 1.33 0.52 0.45  0.20 1 1 1 1 I I !

1 . i I Day 3: 1 min., post exit II 11 I t 11 11 11 I 1 11 II 15 'I 30 1 hour If 2 3 ' Baseline 2.60 1.10 0.80 0.60 0.58 0.28 0.12 4.00 1.50 1.05 0.80 0.40 0.40 0.10 3.82 1.47 0.82 0.61 0.60 0.15 0.10 1 1 1 1 1 1 1 1 1 1 1 1 1 1 2.60 1.10 0.80 0.60 0.58 0.28 0.12 Day 4 : 1 min., post exit 11 I1 I 1 11 11 I t 11 I 1 I 1 15 30 '' 1 hour I t 2 3 Baseline 4.00 1.50 1.05 0.80 0.40 0.40 0.10 _Day 5 : 1 min., post exit I1 I t 11 t t 11 11 11 11 II 15 I '

30 I'

1 hour "

2 If 3 I'

Baseline 3.82 1.47 0.82 0.61 0.60 0.15 0.10 1 1 1 1 I 1 1 000057 TABLE V DAILY p XYLENE BREATH CONCENTRATION OF Exposure Time: 7 1 /2 Hours  Chamber C o n c e n t r a t i o n : 20 ppm GROUP I Number of S u b j e c t s Rang e (in ppm) Standard  + D e v i a t i o n Time  e: 1 rnin., p o s t e x i t 11 11 11 11 11 11 11 I1 I 1 15 "

30 "

1 hour 2 3 B a s e l i n e 1.37 0.49 0 .3 1 0.20 0.12 0.08 0.05 1.20  1.68 0.43  0.53 0.16  0.22 0.05  0.16 0.05  0.12 0.05 0.31 0.27 0.05 0 0.03 0.06 0.04 0 Day 2: 1 min., p o s t e x i t I 1 11 15 I' 0.89 0.30 0.17 0.14 0.12 0.05 0 0.83  0.93 eO. 22  0.41 0.15  0.18 0.12  0.15 0.11  0.13 0.05 0 0.05 0.09 0.02 0.02 0.01 0 0 11 11 11 11 11 I1 11 30 1 hour 2 3 l1 B a s e l i n e Day: 1 min., p o s t e x i t 11 11 15 l1 0.65 0.37 0.27 0.27 0.21 0.14 0.08 0.62  0.70 0.36  0.40 0.26  0.30 0.24  0.30 0.19  0.25 0.12  0.15 0.05  0.10 0.04 0.02 0.02 0.03 0.03 0.02 0.02 3' 3 3 3 3 3 4 . I 1 11 11 30 "

1 hour . 2 3 I j a s e l i n e I1 11.

11 11 Day 4 : 1 min., p o s t e x i t 1 5 " 11 I t 1.16 0.49 0.31 0.18 0.17 0.03 0.10 1.00  1.30 0.48  0.50 0.21  0.40 0.15  0.24 0.14  0.24 0.08  0.10 0.02  0.05 0.13 0.01 0.08 0.04 0.06 0.01 0.02 11 11 11 I 1 11 11 11 30 l1 1 h o u r ' 2 3 B a s e l i n e +: 1 m i n ., post e x i t 15 I1 II 30 " 11 11 1 h o u r " 11 2 3 l1 B a s e l i n e 11 11 11 11 0.90 0.70  1.05 0.16 4 0.32 0.26  0.41 0.06 4 0.27 0.21  0.36 0.07 4 0.22 0.19  0.31 0.06 4 0.25 0.19  0.34 0.07 3 0.15 ,0.10  0.20 0.06 4 0.05 0.05  0.06 0.01 4 000058 TABLE V I DAILY p XYLENE BREATH CONCENTRATION OF SEDENTARY E U E S Exposure Time: 3 Hours  Chamber Concentration: 20 ppm T i m e  e: 1 rnin., post e x i t 1 hour 'I 2 l1 3 Baseline I 1 11 11 11 11 11 11 11 11 15 I t 30 lay: 1 min., post e x i t 11 I 1 11 11 11 15 I'

30 I '

1 hour 2 1s 11 11 3 Baseline 11 11 G3: 1 min., post e x i t I 1 11 11 11 I 1 I 1 11 I 1 11 15 30 I'

1 hour 2 ,3 Baseline 11 c: 1 min., post e x i t 11 I 1 11 11 15 30 1 hour 11 2 3 Baseline I 1 I 1 11 11 CQ: 1 rnin., post e x i t 15 I' 11 11 30 '' 11 I t 1 hour 11 2 3 Baseline 11 11 I1 11 Me an (in p p d 1.45 0.34 0.28 0.20 0.16 0.12 0.05 1.55 0.31 0 .2 1 , 0.12 0.11 0.05 0 0.74 0.49 0.33 0.24 0.20 0.12 0.05 1.11 0.50 0.24 0.18 0.11 0.07 0.02 1.10 0.28 0.19 0.12 0.13 0.09 0 8 4.

1 >. 1.36  1.54 0.31  0.36 0.25  0.31 0.16  0.23 0.16 0.12 0.05 1.55 0.31 0.21 0.12 0 .1 1 0.05 0 0.70  0.77 0.47  0.50 0.30  0.36 0.22  0.25 0.19  0.20 0.12 0.05 1.00  1.22 0.50 0.22  0.25 0.16  0.20 0.10  0.12 0.05  0.09 0.02 0.85  1.35 0.25  0.31 0.17  0.20 0.11  0.12 0.12  0.14 0.08  0.10 0 Standard 2 Deviation 0.13 0.04 0.04 0.05

0.05 0.02 0.04 0.02 0.01 0 0 0.16 0 0.02 0.03 0.01 0.03 0 0.35 0.04 0.02 0.01 0.01 0.01  Number of Subjects .2 2 2 2 1 1 1 2 2 2 2 2 . 2 2 2 2 2 2 2 2 2 000059 TABLE V I 1 DAILY p X YLENE BREATH CONCENTMTIOM OF SEDENTARY MALES Exposure T i m e : 1 Hours  Chamber Concentration: 20 PPm GROW 111 Mean (in p p d d: 1 min., post e x i t 1.31 0.36 0.24 0.16 1 hour I'

0.14 2 0.11 3 Baseline 0.05 11 I1 I I I1 11 I 1 I1 I I 11 15 30 I'

iay: 1 n i n ., post e x i t 1.00 0.26 I 1 I I 15 . ~

'I 0.15 0.09 30 I t 1 hour I t 0.05 0 2 I t 3 Baseline 0 I I It I t I I II (I lay: 1 min., post e x i t 0.63 15 I' 11 I I . 0.32 II I t 0.27 I I 0.23 1 hour I'

I I I1 0.12 11 I t 0.12 2 3 It Baseline 0.05 30 If 4: 1 min., post e x i t 1.00 0.30 0.18 1 hour 'I 'I 0.14 2 I1 I I 0.10 3 It I 1 I t 0.08 Baseline 0 I t I 1 I t I I 15 I'

30 It 1 min., post e x i t 0.95 0.19 0.16 0.09 1 hour 'I 0.09 0.07 2 I t 3 If Baseline 0.02 I I 11 I 1 I1 11 I I l t II 11 15 .

30 Range (i n ppm)

0.90  1.71 0.22  0.50 0.17  0.30 0.10  0.21 0.10  0.18 0.10  0.11 0 05 0.85  1.15 0.20  0.29 0.12  0.17 0.08  0.10 0.05 0 0 0.54  0.70 0.30  0.36 0.25  0.30 0.22  0.25 0.10  0.15 0.08  0.18 0.05 1.00 0.19  0.41 0.15  0.19 0.12  0.15 0.08  0.12  0.04  0.10 0 0.91  1.00 0.17  0.20 0.15  0.17 0.08  0.10 0.08  0.10 0.05  0.08 0.02 Standard Deviation 0.57 0.20 0.09 0.08 0.06 0.01 0 0.15 0.05 0.03 0.01 0 0 0 0.08 0.03 0.03 0.02 0.03 0.05 0 0 0.11 0.02 0.02 0.02 0.03 0 0.05 0.02 . 0.01 ' 0.01 0.01 0.02 0 Number of Sub j e c t s 2 .2 2 2 2 2 2 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 3 2 2' '2 000060 TABLE VI11 DAILY p XYLENE BREATH CONCENTRATION OF SEDENTARY W E S Exposure Time: 7 1 /2 Hours  Chamber Concentration: 150 ppm GROUP I Time  &: 1 min., p o s t exit 1 hour "

2 3 l1 Baseline 11 11 11 11 11 11 11 11 11 15 "

30 "

G2: 1 min., p o s t exit 15 "

30 'I 1 hour "

2 l1 3 Baseline I 1 I t 11 11 11 11 t l 11 11 u3: 1 min., post e x i t 11 11 15 I' I 1 11 11 II II 11 11 30 "

1 hour 'I 2 3 Baseline G: 1 min., p o s t e x i t 11 11 11 11 11 11 11 II 11 15 30 "

1 hour "

2 3 Baseline u: 1 min., p o s t exit 11 11 II I 1 11 I t 11 11 11 15 30 "

1 hour 'I 2 3 'I Baseline Mean (i n ppm)

9.33 4.40 3.78 2.55 1.27 0.78 0.39 9.03 3.58 3.10 2.21 1.88 0.87 0.63 8.88 3.99 2.77 2.20 1.50 0.80 0.46 12.88 6.26 4.75 3.85 1.87 1 .1 9 0.66 10.55 5.00 3.83 3.00 1.85 1.15 0.88 Range (i n ppm)

8 .2 1 11.01 4.20  4.80 3.50  4.00 2.22  2.84 0.55  1.65 0.55  0.90 0.38  0.40 6.30 11.81 .3.20  4.10 2.60  3.50 2.08  2.30 1.75  2.05 0 .8 1  0.95 0.55  0.65 8.00 10.81 3.71  4.35 1 .9 1  3.71 1 .9 1  2.30 1 .3 1  1.60 0.50  0.95 0.32  0.50 11.80 14.50 5.65  7.30 4.30  5.50 3.50  4.10 1.80  2.00 1.15  1.20 0.60  0.70 8.20 12.00 4.80  5.30 3.55  4.20 2.60  3.60 1.75  2.00 0.95  1.50 0.50  1.00 Standard ~t Deviation 1.37 0.28 3.78 0.28 0.50 0.16 0.01 2.25 0.38 0.39 0.11 0.13 0.07 0.05 1.30 0.32 0 .7 4 0.20 0.13 0.21 0.09 1.16 0.75 0.52 0.27 0.10 0.03 0.05 1.67 0.25 0.33 0.49 0.13 0.34 0.25 Number of Sub j e c t s 4 4 4 4 4 4 4 4 4 4 4 3 3 .4 Time  TABLE IX DAILY p XYLENE BREATH CONCEN" RAT1ON OF SEDENTARY MALES Exposure Time : 3 Hours  Chamber Concentration: 150 ppm d: 1 rnin., post exit I1 11 11 11 I 1 I I 11 11 11 15 'I 30 1 hour 2 3 I'

Baseline e: 1 rnin., post e x i t I 1 I I 11 I t 11 11 11 II I9 15 30 1 hour 'I 2 3 I t Baseline fl: 1 m i n ., post e x i t I c I I I I I 1 .lJ I I I1 I I I I I t II I I 30 1 hour 'I 2 l t 3 I1 Baseline u: 1 min., p o s t e x i t 11 I 1 11 II I 9 I I 11 11 11 15 30 'I 1 hour  I'

2 I'

3 Baseline u: 1 min., post e x i t 11 I 1 11 I 1 11 11 II 91 I I 15 ' I 30 1 hour 2 l1 3 (1 Bas e line GROUP Mean (i n p p d 8.45 3.86 2.64. 1.90 0.98 0.67 0.38 8.68 3.01 1.83 1.61 1.12 0.76 0.55 8.03 2.55 2.51 1.75 1.05 0.95 0.48 9.43 2.30 2.35 1.88 1.61 1.35 0.65 11.40 3.55 2.70 2.00 1.75 1.50 0.20 I1 Range (i n ppm)

7.46  9.44 3.72  4.00 2.55  2.72 1.90 0.90  1.05 0.65  0.68 0.35  0.40 7.55  9.80 .2.76  3.25 1.61  2.05 1.60  1.61 1.03  1.21 0.72  0.80 0.52  0.58 6.66  9.40 1.80  3.30 2.21  2.80 1.40  2.10 0.95  1.15 0.95 0.48 8.85 10.00 1.80  2.80 2.20  2.50 .1 .8 5  1.90 1.61 1.35 0.65 11.40 3.55 2.70 2.00 1.75 1.50 0.20 . Standard 2 Deviation 1.40 0.20 0.12 0 0.11 0.02 0.04 1.59 0.35 0.31 0.01 0.13 0.06 0.04 1.94 1.06 0.42 0.50 0.14 0  ' Number of Subjects 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 2 1 2 0.81 2 0.71 2 0.21 2 0.04 2 000062 +; 1 1 1 1 1 1 '1 TABLE X DAILY p XYLENE BREATH CONCENTRATION OF SEDENTARY EULES Exposure Time: 1 Hours  Chamber Concentration:

GROUP I11 Mean  Time (i n p p d 1 min., post e x i t 7.58 2.10 1.86 15 1 .4 1 30 1 hour "

0.65 2 3 Baseline 0.35 I 1 11 11 I 1 I 1 11 I 1 0.90 II I1 lay: 1 rnin., post exit 9.16 2.11 1.54 1.35 1 hour I 1 II 0.94 I 1 I t 0.61 2 3 Baseline 0.43 11 I t 11 I1 I 1 15 30 I'

lay: 1 min., post e x i t 8.65 I' . 2.26 I t 15 I 1 I1 I 1 11 I 1 f I I1 30 I'

1 hour 2 'l 3 I'

Baseline e: 1 min., p o s t e x i t 11 I t I 1 I1 l f I 1 I1 I f I 1 15 30 1 hour 2 3 I'

Baseline 1 min., post e x i t 11 I t 11 11 11 I 1 I 1 I 1 I I 15 30 I'

1 hour "

2 3 f t Baseline 2.00 1.40 0.55 0.35 0.25 10.25 2.18 1.93 1.53 0.92 0.70 0.60 9.48 2.78 2.03 1.61 1.10 0.75 0.38 Rang e (i n ppm)

6.10  9.05 2.10 1.50  2.21 1.28  1.54 0.90 0.65 0.28  0 .4 1 7.80 10.51 n1.81  2.41 1.27  1.81 1.08  1.61 0.72  1.16 0.50  0.72 0.38  0.48 8.10  9.. 20 2.21  2.30 1.80  2.20 1.20  1.60 0.30  0.80 0.20  0.50 0.20  0.30,

9.70 10.80 2.10  2.25 1.90  1.95 1.15  1.90 0.79  1.05 0.61  q. 79 0.60 8,70 10.25 2.60  2.95 1.65  2.40 1.41  1.80 0.80  1.40 0.50  1.00 0.38 Standard Deviation 2.09 0.50 0.18

  0.09 1.92 0.42 0.38 0.38 0.31 0.16 0.71 0.78 0.06 0.28 0.28 0.35 0.21 0.07 0.78 0.11 0.04 0.53 0.92 0.13 0 1.10 0.25 0.53 0.28 0.42 0.35 0 150 ppm Number of Subjects 2 .1 2 2 1 1 2 000063 2 2 2 2 2 2 2 2 2 2 2 2 2 2 TARLE X I DAILY p XYLENE BREATH CONCENTRATION OF SEDENTARY k L E S Exposure Time: 7 1 /2 Hours  Chamber Concentration:

GROUP I Time  e: 1 min., post e x i t 1 hour 'I 2 3 I t Baseline I 1 I 1 I 1 11 11 I t II I1 II 15 30 'I lay: 1 m i n ., post e x i t 11 11 I1 I 1 I1 11 I I 11 11 15 30 'I,

1 hour 2 3 Baseline 'ay: 1 m i n ., post e x i t I 1 I t 15 " I 1 11 I1 I1 11 I1 I1 30 1 hour 2 3 Baseline 4: 1 min., p o s t e x i t I1 I t 15 I' I1 I 1 I 1 I 1 11 11 I1 30 It 1 hour 'I 2 3 Baseline u: 1 min., post e x i t I 1 I f 15 " Mean (in p p d 6.33 2.65 2.27 1.82 1 .5 2 0.62 0.27 6.88 2.53 2.00 1.63 1.36 0.60 0.30 7.17 3.24 2.48 1.75 1.78 1.01 0.57 7.50 4.13 2.84 '2.20 1.50 0.90 0.45 6.43 3.72 2.55 1.83 1.07 0.78 0.28 Range (i n p p d 5.80  7.20 2.20  3.21 2 1 0  2.50 1.66  2.00 1.40  1.70 0.55  0.72 0.10  0.40 6.30  7.80 2.30  2.80 1.75  2.25 1.41  1.75 1.22  1.45 0.55  0.65 0.25  0.35 5.10  9.96 3.00  3.55 2.30  2.90 1.70  1.80 1.60  1.90 1.00  1.04 0.50  0.70 5.10 11.60 3.50  4.75 2.42  3. '15 1.92  2.42 1 .3 5  1 .8 0 0.70  1.10 0.45 5.70  7.00 3.55  3.80 2.45  2.70 1.75  2.00 0.80  1.30 0.75  0.80 0.25  0.35 Standard 5 Deviation 0.76 0 .5 1 0 .2 1 0.17 0.16 0.09 0.14 0.65 0.21 0.20 0.16 0.11 0.06 0.04 2.04 0.28 0.29 0.06 0.15 0.02 0.10 2.85 0.62 0.34 0.23 0.26 0.20 0 0.67 0.14 0.13 0.14 0.25 0.03 0.06 Fluct. 50 150 ppm Number of Subjects 4 4 4 4 4 4 4 4 4 4 4 4 4 3 3 3 3 3 3 3 ' ' 3 000064 15 11 I 1 2.93 2.30  3.55 0.88 2 30 I 1 11 1.89 1.67  2.10 0.30 2 1 hour ' I I 1 1.50 1 .3 0  1.70 0.28 2 2 'I 1 1 I 1 I1 1.50 1.50   1 1 1 1 1 1 1 1 1 1 3.50 3.50 1 1.89 1.80 1 1 0.80 0.80 1 0.80 '3.80  Bas d i n e 0.79 3.70 %: 1 min., p o s t e x i t 7.40 7 .4 0   3.10 3.10 1 h o u r 11 2.00 2.00 2 3 B a s e l i n e 0.48 3.48 I 1 I t 15 30 I t I 1 2.60 2.60

11 I 1 1.25 1.25

I1 I 1 0.30 0.90

3 ~: 1 min., p o s t e x i t 7.80 7.80   11 I 1 15 30 I' I 1 I 1 2.20 2.20  11 I 1 I 1 I 1 I 1 1 hour 2 3 I t   TABLE XI11 DAILY p XYLENE BREATH CONCENTRATION OF SEDENTARY MALES Exposure Time: 1 Hours  Chamber Concentration:

GROUP 111 Time  ly: 1 rnin., post e x i t 11 I 1 I 1 11 11 I1 11 I 1 11 15 "

30 1 hour 2 "

3 I'

Baseline 3y: 1 min., post e x i t I 1 I1 11 I 1 I 1 I1 11 I1 I 1 15 I'

30 I t 1 hour 2 3 Baseline e: 1 min., post e x i t 11 I I I 1 11 11 I1 I 1 11 I1 15 'I 30  2 'I ' 3 'I 1 hour Baseline *: 1 min., p o s t e x i t I 1 !I 'I I 1 15 I'

30 I t i t 1 hour 2 I'

3 Baseline I 1 11 11 I1 M e an (i n p p d 7.10 2.20 1.72 1.43 0.53 0.45 0.25 6.50 1.80 1.35 1.10 0.80 0.23 0.23 5.15 2.06 1.30 1.13 0.94 0.65 0.40 9.20 3.10 2.10 1.45 NO DATA NO DATA 0.30 5.95 2.35 1.88 1.48 0.70 0.45 0.20 6.70  7.50 2.15  2.25 1.55  1.89 1.40  1.45 0.45  0.60 0.40  9.50 0.25 5.60  7.40 *1.50  2.10 1.20  1.50 0.90  1.30 0.80 0.20  0.25 0.20  0.25 5.00  5.30 1.67  2.45 1.15  1.45 9.99  1.35 0.70  1.18 3.45  0.85 0.40 9.20 3.10 2.10 1.45 0.25  0.35 6.90  7.30 2.30  2.40 1.80  1.95 1.30  1.65 0.40  1 90 0.30  0.60 0.20 Standard + Deviation I 0.57 0.07 0.24 0.04 0.11 0.07 0 1.27 0.42 0.21 0.28 0.04 0.04 0.21 0.55 0.21 0.32 3.34 0.28 0

0.07 0.07 0.07 0.11 0.25 0.42 0.21  Fluct. 50 150 ppm.

Number of Subjects 2 .2 2 2 2 2 2 2 2 2 2 2 2 2 1 1 1 1 000066 TABLE X I V WEEY~ Y p XYLENZ BREATH COXCEhTZWTION OF SEDEXTARY MALES Exposure Time: 7 1/ 2 Hours  Chamber Concentration:

Chamber Time Conc. in ppm 7 I min., p o s t e x i t If I 1 II 11 t t I 1 I t II #I It 15 30 'I 1 hour 2 "

3 "

Baseline 1 min., post exit II 11 11 I1 11 11 If II I t 15 'I 30 'I I hour I'

2 IS 3 Baseline 2 min., post e x i t . I 1 I t II 18 t t II I1 15 'I .

30 'I 1 hour 2 I' 3 ' j ' I t Baseline 1 min., post e x i t II . I f I 1 I S I! 11 I t 11 I t 11 15 I'

30 1 hour 2 . 3 Baseline 100 20 15 0 Fluc. 50  150 Kean Range (in ppm) (in ppm)

5.00 1.75 1.30 0.92 0.65 0.43 I 0.24 0.99 0.39 0;. 26 0.20 0.16 0.11 0.05 10.13 4.65 3.62 2.76 1.67 0.95 0.60 6.91 3.26 2.43 1.85 1.46 0.79 0.38 2.93  8.17 0.95  2.90 0.61  2.02 0.51  1.33 0.22  1.38 0.18  0.70 0.10  0.38 0.63  1.68 .0.22  0.53 0.15  0.36 0.12  0.31 0.05  0.33 0.05  0.15 0.02  0.10 6 .3 0 '14.50 3.20  7.30 1.91.  5.50 1.91  4.10 0.55  2.05 0.50  1.50 0.32  1.00 5.10 11.60 2.20  4.75 1.75  3.15 1.41  2.42 0.80' 1.90 0.55  1.10 0.10  0.70 Standard Deviation 1.39 0.50 0.45 0.31 0.27 0.14 0.08 0.27. 0.10 0.07. 0.06 0.08 0.04 0.02 2.09 . 1.04 0.82 0.69 0.34 0.24 0.21 1.60 0.73 0.37 0.25 0.29 ' 0.18 0.15' Nunber of Subjects 4 4 ' 4 4 4 . 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 4 .

8 TABLE XV WEEKLY p XnCYXE BREATH CONCENTRATION OF SEDEKTARY MALES Exposure Time: 3 Hours  Chamber Concentration:

5 1 min., post e x i t Fluc t . 6.97 4.75  9.50 1.58 2 50 150 2.66' 1.80  3.55 0.65 2 1.92 1.50  2.60 0.36 2 1.56 1.30  2.00 0.25 2 1 hour 2 . II 11 1.07 0.79  1.50 0.28 2 3 11 I1 0.75 0.40  1.20 . . 0.30 2 Baseline 0.36 0.20  0.70 0.17' 2 II I t II II 11 II 15 30 b 000068 e;$ fl4$ gQ ' GROUP I1 Chamber Mean Rang e Standard T i m e Cone. i n ppm (i n ppn) (i n pun) + Deviation  1 rnin., post exit 100 11 . 11 I t ;f i ., II 18 I t l t 11 II I t 30 "

1 hour 2 3 Baseline 7.55 2.31 1.58 1.09 0.53 0.38 0.19 5.50 11.20 2.05 1.55  3.40 0.65 0.91  2.40 0.52 0.72  1.80 0.37 0.20  0.74 0.19 0.12  0.60 0.18 0.10  0.30 0.07 1 min., post e x i t 20 1.15 0.70  1.55 0.33. 0.39 0.25  0.47 0.10 0.25 0.17  0.36 0.06 0.17 . 0.11  0.25 0.05 0.14 0.11  0.19 0.04 0.09 0.05  0.12 0.03 11 I1 II II 11 81 I 1 11 I1 ' 15 I'

30 1 hour 'I 2 3 Baseline 0.04 0.02  0.05 0.02 1 min., post e x i t 15 0 8.95 6.66 * 11.40 1.49 . 3.00 1.80  4.00 . 0.79 2.37 1 .6 1  2.80 0.39 ' 15 "

1.81 1.40  2.10 0.22 30 "

1 hour 'I 1.21 0.90  1.75 0.31 2 '1 0.95 0.65  1.50 0.34 Baseline 0.46 0.20  0.65 0.14 II I 1 I1 11 11 11 * 3 8' 11 1) Number of Sub j ects 2 2 2 2 2 . 2 2 2 2 . 2 2 2 2 2 2 2 2 2 2 ' 2 2 7 TABLE X V I WEEI; LY p XYLEXE BREATH COXCENTRATION OF SEDEXTARY MALES Exposure Time: 1 Hours  Chamber C o n c e n t r a t i o n :

GROUP 111 Time  1 min., p o s t e x i t I I I I I1 I t 11 11 15 . 30 1 hour 'I n II 11 I t Baseline 1 min., post exit I1 I I II I1 I I I t 15 "

30 'I 1 hour 'I 2 I t 3 I' SI t1 ?t Baseline 1 rnin., p o s t e x i t If . I1 I1 I1 I 1 I t I 1 I1 IS ' 15 'I 30 'I 1 hour I t 2 . 3 1'

Baseline Chamber Me an Conc. i n ppm (in ppm)

100 3.25 1.52 0.93 0.66 0.45 0.24 0.13 1 min., post e x i t II 11 IC . I t I t I t I I. I 1 I1 I1 15 30 I'

1 horrr 2 . 3 Baseline 20 0.96 0.27 0.19 0.14 0.10  0.09 0.05 15 0 9.02 2.30 1.87 1.46 0.88 0.61 '0.40 Fluc. 6.73 1.62 1.30 0.73 0.44 0.28 50 150 2121 Range (in ppm)

1.47  4.00 1.10  1.90 0.52  1.40 0.45  0.80 0.22  0.60 0.11  0.28 0.10  0.20 0.54  1.71 0.17  0.50 0.12  0.30 0.08  0.25 0.05  0.18 0.04  0.18 0.05 6.10 10.80 1.81  2.95 1.27  2.40 1.08  1.90 0;. 30  1.40 0.20  1.00 0.20  0.60 5.00  9.20 1.50  3.10 1.15  2.10 0.90  1.65 0.40  1.18 0.20  0.85 0.20  0.40 Standard 2 Deviation .. .

1.02 0.30 0.30 0.13 0.18 0.13 0.04 0 .. 27 0.10 0.06 0.06 0.04 0.04 ' 0 1.43 0.34 0.28 0.31 0.22 0.13 . 0.33 1.30 0.46 0.33 0.25 0.28 0.21 0.08 Number of S u b j e c t s 2 2 2 2 ' 1 .I * 1 1 2 2 2 2 2 . 2 2 2 2 2 2 2 2 2 6 000069' . TABLE X V I I DAILY p XYLENE BREATH CONCENTRATION OF SEDENTARY FFPULES Exposure Time: 7 1/ 2 Hours  Chamber Concentration: 100 ppm GROUP I Mean Time (in P P d Range  (i n ppm) Numb e r Standard of It Deviation Subjects e: 1 min., p o s t e x i t 4.73 3.90  5.50 0.80 3 11 I 1 11 11 11 11 1 1 11 1 1 1.90 1.70  2.05 0.18 3 15 1.28 1.20  1.40 0.10 3 30 1.10 1.10 0 3 1 hour It 0.53 0.50  0.55 0.03 3 2 0.40 0.30  0.50 0.10 3 3 If Baseline 0.03 0.00  0.10 0 3 I , Lay 2: 1 min. , p o s t e x i t II 11 15 I 1 I 1 I 1 I 1 II I 1 I 1 30 'I 1 hour "

2 3 Baseline Day 3: 1 min., post e x i t I 1 I1 15 " 1 1 I f I 1 11 I 1 11 I t 30 If 1 hour 'I 2 If 3 I t Baseline 5.17 1.95 1.50 1.08 0.80 0.60 0.23 6.00 2.10 1.62 1.28 0.73 0.50 0.28 4.60  5.50 1.70  2.35 1.40  1.60 1.05  1.10 0.80 0.60 0.20  0.25 4.80  7.10 1.90  2.40 1.40  1.80 1.15  1.40 0.70  0.75 0.45  0.55 0.25  0.30 0.49 0.35 0.10 0.03 0 0 0.03 1.15 0.27 0.20 0.13 0.03 0.05 0.03 Day 4 : 1 min., post e x i t 6.20 3.08 I1 I 1 I 15 It 5.10  7.30 1.10 2.65  3.50 0.43 3 3 11 30 "

1 hour ' I 2 3 'I Baseline 11 I 1 2.57 2.45  2.65 0.10 3 2.00 1.80  2.20 0.20 3 0.75 0.70  0.80 0.07 3 II 0.53 0.50  0.55 0.04 2 0.30 0.30 0 3 11 I 1 I 1 Day 5 : 1 rnin., p o s t e x i t 4.70 4.30  5.00 0.36 3 II 1.63 1.40  1.80 0.21 3 1.25 1.05  1.50 0.23 ,

11 1 .1 2 1.05  1.20 0.08 3 1 hour 2 It I1 11 0.82 0.75  0.90 0.08 3 3 I t 11 0.65 0.55  0.70 0.09 3 Baseline 0.35 0.35 0 3 I 1 11 I 1 15 I'

30 I'

000070 TABLE XVIII DAILY p XnENE BREATH CONCENTRITION OF SEDENTARY FEMALES Exposure Time: 3 Hours  Chamber Concentration:

GROUP e: 1 min., p o s t e x i t I 1 I 1 I 1 I 1 I 1 I 1 ll 11 11 15 30 "

1 hour ' I

2 If 3 Baseline e: 1 min., p o s t e x i t 11 11 15 11 I 1 I 1 11 I t I 1 I 1 30 1 hour It 2 It 3 (I Baseline Day 3: 1 min., p o s t e x i t I 1 I 1 I t 11 11 11 11 I t I1 15 I'

30 I '

1 hour 2 It 3 Baseline Day 4 : 1 rnin., p o s t e x i t 11 11 I t 11 11 I 1 I t I 1 II 1 5 30 I'

1 hour It 2 I'

3 Baseline Day 5: 1 min., p o s t e x i t 11 11 11 I 1 I 1 I 1 8 1 I 1 I 1 15 It 30 I'

1 hour "

2 3 Baseline Mean (i n ppm)

4.90 1.55 1.08 0.75 0.35 0.25 0 5.48 1.35 0.85 0.55 0.43 0.30 0.08 4.78 1.25 0.80 0.60 0.35 0.40 0.13 4.75 1.18 0.88 0.68 0.50 0.50 0.10 4.00 1.23 0.88 0.55 0.50 0.20 0.15 I1 Range Standard (i n ppm) Deviation 4.60  5.20 1.40  1.70 1.05  1.10 0.70  0.80 0.35 0.00  0.50 0 3.95  7.00 1.20  1.50 0.80  0.90 0.55 0.40  0.45 0.30 .O. OO  0.15 3.25  6.30 1.10  1.40 0.70  0.90 0.60 0.35 0.40 0.10  0.15 4.20  5.30 1.15  1.20 0.80  0.95 0.65  0.70 0.50 0.40  0.60 0.10 3.00  5 0 0 1.20  1.25 0.80  0.95 0.50  0.60 0.50 0.20 0.15 0.42 0.21 0.35 0.07 0 0 0 2.16 0.21 0.07 0 0.04 0 2.16 0.21 0.14 0

  0.04 0.78 0.04 0.11 0.04 0 0.141 0 1 .4 1 0.04 0.11 0.07   100 ppm Number of Subjects 2 2 2 2 1 1 2 2 2 2 2 2 2 2 800071   f TABLE X I X DAILY p XYLENE BREATH CONCENTRATION OF SEDENTARY FEllALES Exposure Time: 1 Hours  Chamber Concentration: 100 ppm Time

gay 1: 1 min., p o s t e x i t 15 11 11 30 I f 11 11 1 hour 'I 11 2 I' 11 I f 3 11 I 1 B a s e l i n e p y 2: 1 min., p o s t exit 15 I 1 I 1 ?I II 11 VI 11 I1 11 30 1 hour 2 3 It Baseline Day 3: 1 min., p o s t e x i t I t I t 15 'I I 1 11 11 I 1 I 1 I 1 11 30 1 hour , "

2 2 3 Baseline Day. 4: 1 rnin., p o s t e x i t II 11 1 5 I '

30 I' I 1 11 2 1 1 I 1 3 .'? I 11 Baseline , 1 hour "/ I 1 Mean (i n ppm)

3.40 1.20 0.98 0.68 0.10 ,0.10 0 5.83 1.10 0.73 0.63 0.35 0.20 0 5.45 1.38 0.95 0.65 0.28 0.10 0.03 3.75 1.15 0.80 0.63 0.40 0.30 0.10 4.60 1.15 0.88 0.58 0.40 0.20 0.10 GROUP I11 Range (in ppm)

3.20  3.60 1.10  1.30 0.90  1.05 0.65  0.70 0.10 0.10 0 3.90  7.75 0.90  1: 30 0.55  0.90 0.55  0.70 0.30  0.40 0.20 0 4.40  6.50 1.05  1.70 0.80  1.10 0.50  0.80 0.20  0.35 0.00  0.20 0.00  0.05 3 00  4.50 1.00  1.30 0.70  0.90 0.55  0.70 0.40 0.30 0.10 3.60  5.60 1.00  1.30 0.80  0.95 0.55  0.60 0.40 0.20 0.10 Standard +Deviation 0.28 0.14 0.11 0.04 0 0 2.72 0.28 0.25 0.11 0.07 0 0 1.49 0.46 0 .2 1 0.21 0.11 0 0 1.06 0.21 0.14 0.11 0 0 0 1.41 0 .2 1 0.11 0.04

  0 Number of S u b j e c t s 2 2 2 2 1 1 2 000072 3 {OUP / 11:

sin., post e x i t II I 1 I 1 I 1 I 1 11 II I t I 1 1 1 l l I t II hoilr '1 d i n e .OUP 111 : TABLE XX WEEKLY p XYLENE BREATH CONCENTRATION 'OF SEDENTARY FEMALES Chamber Concentration: 100 ppm Number Mean Range Standard of f (in ppm) (in ppm) Deviation Sub j ects 5.03 2.13 1.64 1.32 0.73 0.54 0.24 3.90  7.30 1.40  3.50 1.05  2.65 1.05  2.20 0.50  0.90 0.30  0.70 0.00  0.35 / 4.78 3.00' 7.00 1.31 1.14  1.70 0.90 0.70  1.10 0.63 0. SO  0.80 0.43 0. '35  0.50 0.40 A ;O O  0.80 0.07 0.00  0.15 min., post exit 4.61 1.20 0.87 hour If 0.63 0.32 0.18 e l i n e 0.04 II 1 1 II I 1 11 ll I 1 I 1 t l I 1 I f I 1 I 1 3.00  7.75 . 0.90  1.70 0.55  1.10 0.50  0.80 0.10  0.40 0.00  0.30 0.00  1.00 1.63 0.58 0.52 0.37 0.12 0.11 0.12 1.26 0.19 0.12 0.09 0.07 0.25 0.07 1.55 0.23 0.16 0.10 0.11 0.10 0.05 000073 1 X:

e n n .I

..

.,

.'

.

..

n ..

.a .I .'

..

n .. .. .:

.'

n .,

.I n 4, Wk 1 ?? y

J" h r post exit 1.

Da  ,

& exposure p exit 30 min post exit 1 h r post exit 4, wk 2 pre exposure pre exi t 30 min post exit 1 hr post exit y .4 ,w k 3 pre exposure ?re exi t 30 min post exit 1 h r post exit lay 1 ,I\% 4 ?re exposure ?re exi t 10 min post exit L ,hr post exit lay 4, Wk 4 're exposure 're exi t IO min post exit L h r post exit )3y l, Wk 5 ire exposure Pre exi t 30 m i n post exit 1 hr post exit Day 4, Wk  5 Pre exposure Pre exit 30 min post exit 1 hr post exit TABLE XXI p XYLENE LEVELS IN Bl. OOD FOR MALE SUBJECTS GROUP 1 7 1 /2 1IR EXPOSURE  Mean Range:,

I i Chamber concentration; zero Chamber Concentration! 100 ppm 0 .3 1 0.25 j .i ,o 0 .8 9  0.2& 1.10 1.29 1 .0 5 ,. 1.55 0.48 0.40  0.60 0 .1 3 0.97 0 .4 5 0 .2 9 0.09  0.17 0.83  1.11 0.35  0 .5 2 0.26  0 .3 1 Chamber Concentration: 20 ppm 0 .1 3 0 .1 2  0 .1 3 0 .4 2 0 .4 0  0 .4 5 0.29 0.27  0 .3 0 0.19 0.15  0.22 0.00 0.51 0.49 0 .4 0 0 .0 0 0.43  0.60 0.26  0.80 0.21  0.55 Chamber Concentration: 1 5 0 ppm 0 .3 4 0.24  0.47 3.86 3.11  4.67 1.9G 1.75  2.99 .

1 .2 9 1.24  1 .4 3 0 .9 9 5.99 3.76 2.77 0.65  1.35 5.09  6.88 3.38  4 .6 2 2.49  2.95 +S .D.

0.08 0 .2 1 '

0.27 0.09 0 .3 3 0.16 0.09 0.02 N.

4 4 4 4 4 4 4 4 0.01 3 0 .0 3 3 0.02 3 0 .0 4 3 0.00 4 0.07 4 0.26 4 0.15 4 0.10 4 0 .6 5 4 0.15 4 0.09 4 0.35 4 0.90 4 0.58 4 0.22 4 Chamber Concentration: Fluct. 50 150 pprn 0 .3 2 0.20  0 .4 0 0.1.1 3 3.02 2.80  3.25 0.23 3 1 .4 3 1 .2 0  1 6 0 0 .2 0 3 1.45 1 00  1 .9 2 0.46 3 0.31 1.68 0.81 0.67 0.27  0.40 1.40  2 .0 3 0.70  1.00 0 .4 9  1.01 "4 Day 6. q<>{>.") Chamber Concentration: zero 0.061 4 0 .3 0 4 0.14 *4 0 .2 4 4 000074 1 Y TABLE XXLI p XYLENE LEVELS IN BLOOD FOR MALE SUBJECTS GROW 11 3 HR EXPOSURE +S .D. N.  Mean Range Chamber Concentration: zero Day 4, Wk 1 Chamber Concentration: 100 ppm 0.48 0.45  0.50 1.65 1.30  2.00 0. 78 0.65  0.90 0.58 0.50  0.65 Day 1, Wk 2 Pre exposure Pre exit 30 rnin post exit 1 hr post exit .O. 04 0.50 0.18 0.11 Day 4, Wk 2 Pre exposure Pre exit 30 rnin post exit 1 hr post exit 0.12 0.95 0.44 0.37 0.09  0.14 0.90  0.99 0.44 0.35  0.39 0.04 , 0.06 0.00 0.03 2 2 !

2 1 2 Chamber Concentration: 20 ppm 0.12 0.11  0.12 0.41 0.34  0.47 0.24 0.24 0.24 0.24 Day 1, Wk 3 Pre exposur e Pr e exi t 30 rnin post exit 1 hr post exit 0.01 0.09 0.00 0.00 2 2 2 2 1 Day 4, Wk 3 Pre exposure 0.08 Pr e exi t 0.43 30 min post exit 0.24 1 hr post exit 0.26 0.00  0.08 0.40  0.46 0.23  0.25 0.15  0.36 0.00 2 0.04 2 0.01 2 0.15 2 Chamber. Concentration: 150 ppm 0.22  0.57 0.25 3.10  3.25 0.11 1.50  1.60 0.07 0.97  1.25 0.20 Day 1, Wk 4 Pre exposure 0.40 Pre exit 3.18 30 rnin post exit 1.55 1 hr post exit 1.11 Day 4 , 4 Pre exposure 0.53 Pre exi t 6.19 30 rnin post exit 2.18 1 hr post exit 1.80 0.46  0.59 4.05  8.32 1.97  2.38 1.73  1.86 0.09 3.02 0.29 0.09 Chamber Concentration: Fluct. 50 150 ppm 0.40  0.50 0.07 3.09  3.73 0.45 1.27  1.45 0.13 1.00  1.13 0.09 Day 1, Wk 5 Pre exi t 3.41 30 min post exit 1.36 1 hr post exit 1.07 Pre exposure 0.45 Day 4, Wk 5 Pre exposure 0.26 Pre exit 1.33 30 min post exit 0.67 1 hr post exit 0.59 0.26 1.33 0.59 0.67 Chamber Concentration: zero 000075 Day 4, Wk 1 Day 1, Wk 2 Pre exposure Pre exit 30 min post exit 1 hr post exit Day 4, Wk 2 Pre exposure Pr e exi t 30 min post exit 1 hr post exit Day 1, Wk 3 Pre exposure Pre exit 30 m i n post exit 1 hr post exit Day 4, Wk 3 Pre exposure Pr e exi t 30 min post exit 1 h r post exit Day 1, Wk 4 Pre exposure Pr e exi t 30 min post exit 1 <hr post exit Day 4; Wk 4 Pr e expo sur e Pre exi t 30 min post exit 1 h r post exit Day 1 ,W k 5 Pre exposure Pre exi t 30 rnin post exit 1 h r post exit Day 4, Wk 5 Pr e exposur e Pre exit 3 0 min post exit 1 hr post%&%< j Day 1, Wk 6 TABEE XXIII p XYLENE LEVELS IN BLOOD FOR MALE SUBJECTS GROW 111 1 HR EXPOSURE Mean

0.18 1.23 0.55 0.33 0.12 0.69 0.35 0.23 0.00 0.24 0.18 0.00 0.00 0.58 0.25 0.26 0.30 2.04 0.77 0.67 0.38 3.37 1.45 1.12 0.49 2.93 1.25 0.82 0.15 1.30 0.78 0.41 Range Chamber Concentration: zero 2S. D.

Chamber Concentration: 100 ppm 0.10 , 0.25 0.11 1 10  1.35 0.18 0 4 5  0.65 0.14 0.30  0.35 0.04 0.12 0.69 0.35 0.23 Chamber Concentration: 20 ppm 0.00 0.24 0.18 0.00 0.00 0.27  0.76 0.15  0.40 0.12  0.48 IO0 0.27 0.13 0.19 Chamber Concentration: 150 ppm 0.15  0.45 0.21 1.50  2.57 0.76 0.67  0.87 0.14 0.60  0.73 0.09 0.38 3.35  3.38 1.35  1.54 1.05  1.19 0, oo 0.02 0.13 0.10 Chamber Concentration: Fluct. 50 150 ppm 0.18  0.80 0.44 2.55  3.30 0.53 1.25 0.00 0.73  0.90 0.12 0.15 1.30 0.78 0.41 N.

1 000076 Chamber Concentration: zero 2 2 2 2 .

1 1 1 1 1 1 1 1 3 3 3 3 2 2 2 2 2 2. 2 2 2 2 2 2 1 1 1 1 TABLE XXIV p XYLENE LEVELS IN BLOOD FOR FEMALE SUBJECTS Chamber Concentration: 100 ppm Ran EI e Me an  N. i 5S. D.

Day 1, Week 2 Group I, 7 1/ 2 h r exposure .

0.00 1.48  1 .7 9 0.49  0.72 0.46  0.58 0.00 3 0.18 3 0.12 3 0.07 3 Pre exposure 0.00 Pre exi t .1 .5 9 30 min pos t e x i t 0.59 1 h r pos t e x i t 0.50 Group 11, 3 h r exposure Pre exposure 0.00 Pre exi t 0.95 30 min p o s t e x i t 0.38 1 h r p o s t e x i t 0.29 0.00 0.85  1 .0 5 0 .2 6  0.49 0.27  0.31 0.00 2 0.14 2 0.16 2 0.03 2 Group 111, 1 h r exposure Pre exp os u r e 0.00 Pre exi t 0.88 30 min p o s t e x i t 0.46 1 h r p o s t e x i t 0.26 0.00 0.82  0.93 0.39  0.52 0.17  0.34 0.00 2 0.08 2 0.09 2 0.12 2 Day 4 , Week 2 Group I, 7 1 /2 h r exposure Pre exposure 0.50 Pre exi t 2.28 30 min p o s t e x i t 1.07 1 h r p o s t e x i t 0 .9 1 0.38  0.59 2.01  2.47 0.98  1. '16 0.74  1.25 0.11 0.24 0.09 0.29 Group 11, 3 h r exposure Pre exposure 0.36 Pre exi t 1.86 30 min p o s t e x i t 0.73 1 h r p o s t e x i t 0.62 0 .3 1  0.41 1.79  1.92 0.71  0.74 0.57  0.67 0.07 0.09 0.02 0.07 Group 111, 1 h r exposure Pre exposure 0.39 Pre exi t 1.74 30 min p o s t e x i t 0.60 1 h r p o s t e x i t 0.48 0.37  0.40 1.41  2.06 0.57  0.62 0.45  0.50 2 2 2 2 0.02 0.46 0.04 0.04 .. TABLE XXV EFFECT OF EXERCISE ON p XYLENE LEVELS IN BLOOD GROUP I MALE SUBJECTS Restin. g . 0.79 6 min exercise 1.25 11 min exercise 1.83 Resting 0.51 6 min exercise 0.71 11 min exercise 1 .6 1 Res t ing 4.64 6 min exercise 7 .1 2 11 min exercise 12.52 Resting 1.23 6 min exercise 1.87 11 min exercise 3.13 Range Chamber Concentration: 100 ppm +S. D.

0 .7 1  0.90 0.08 0.96  1.53 0.40 1.53  2.35 0.45 Chamber Concentration: 20 ppm 0.40  0.68 0.12 0.55  0.87 0.13 1.49  1.67 0.08 Chamber Concentration: 150 ppm 4.07  5.95 0.88 5.95  8.55 1.32 11.06  14.61 1.86 Chamber Concentration: 50 150 ppm Fluct.

0.84  1.74 1 .4 1  2.22 1.95  4.46 0.40 0.42 1.04 N.

4 2 3 4 4 4 4 3 3 4 3 4 000078 PROPERV OF RYERSON POLYT'Et7i; ': iiC UNlMRSrrV 350 VICTORIA ST., TORCNTO. ONT. M5B a Pr e exposure E x i t 15 min p o s t e x i t 30 min p o s t e x i t , pre exposure Exit 15 min p o s t e x i t 30 min p o s t e x i t , Pre exposure Exit: 15 min p o s t e x i t 30 min p o s t e x i t , Pre exposure ' Exit 15 min p o s t e x i t 30 min p o s t e x i t : Pre exposure ' Exit 15 min p o s t e x i t 30 min p o s t e x t t Mean 1.64 2.69 1 .6 3 5. a3 TABLE XXVI DAIJJY p XYLENE LEVELS I N SALIVA FOR SEDENTARY MALE SUBJECTS G R O W I 7 1/ 2 FIR EXPOSURS Chamber Concentration: 153 ppm WEEK. 4 0.72 2. a7 1.58 0.99 0.71 5.52 1.99 1 .4 2 0.41 3.54 1 .2 7 1. a7 0.36 3.35 2.08 1.81 Range 1.23  1 .9 4 5.50  6.13 1.50  1.75 2.38  2.88 .

0.50  1.06 2.31  4.06 1.25  1.88 9.88 . 1.13 0.33  1.30 3.63  7.25 1.81  2.13 1.25  1.63 0.19  0.73 2.50  4 .2 5 1 58  2.33 1.33  1.58 0.16  3.52 3.13  3.53 1.90  2.30 1.63  1.93 +S .D.

0.30 3 3 1 0.24 9.10 0.25 0.312 ' 0.107 '3.42 1.59 0.13 0.18 0.23 0.76 0.34 3.29 0.154 0.20 0.17 0.16 0 . a15 N.

4 4 4 4

.. TABLE XYVII DAILY p XYLENE LEVELS IN SALIVA FOR SEDEXTARY X A L ~ SUBJECTS GROW I 7 1/ 2 HR EXPOSURE Chamber Concentration: 50 150 ppm flnctuating WEEK 5 pre exposure 15 min post exit 30 ,min post exit 5: Exit .

pre expo sure 1: Exit .1 5 rnin post exit 30 min post exit Pre exposure Exit 15 min post exit 30 rnin post exit !:

,: Pre exposure . Exit 15 rnin post exit 30 rnin post exit : Pre exposure Exit ,

15 min post exit 30 rnin post exit Mean 0.22 2.03 0.99 0.65 0.25 3.26 1.53 1.07 0.55 3.28 1.85 1.08 0.16 3.56 1 .6 1 1.02 3.16 1 .2 1 0.75 0.47 __. Range 0.19  0.28 1.52  2.61 9.78  1 .1 3 3.53  3.75 0.16  0 .3 1 2.67  4.24 1 .3 1  1 .8 1 0.75  1.38 9.39  3.79 2.76  4.33 1.83  1.97 1.00  1.25 0.39  3.22 3.13  4.40 1.43  2.00 3.93  1.13 0.11  0.24 1 .0 8  1.43 0.68  0.81 3.41 ' 0.54 +S. D.

0.05 0.. 55 0.19 3.13 0. (17 0.69 0.21 0.27 0.18 .O . 6 1 0.08 0.12 0.05 0.57 0.26 0.10 9.07 . 0.19 0.37 0.07  N. 3 3 3 3  TABLE XXVIII DAILY p XYLENE LEVELS IN SALIVA FOR SEDENTARY FEMALE SUBJECTS GROUP I 7 1/ 2 HR EXPOSURE Chamber Concentration: 100 ppm pre exposure 1 min post exit 15 min post exit 30 min post exit Pre exposure 1 min post exit 15 rnin post exit 30 min post exit Pre exposure 1 min post exit 15 rnin post exit 30 rnin post exit Pre exposure 1 min post exit 15 rnin post exit 30 rnin post exit Pre exposure 1 min post exit 1 5 rnin post exit 30 rnin post exit Mean 0.21 0.79 0.37 0.25 0.34 1.26 0.51 0.42 0.52 1.07 0.57 0.39 0.51 1.. 15 0.95 0.60 0.33 1.96 1.00 0.69 Range 0619  0.22 0.56  1.10 0.33  0.42 0.19  0.28 0.31  0.41 1.04  1.37 0.41  0.56 0.37  0.46 0.32  0.71 0.85  1.35 0.47  0.65 0.35  0.41 0.48  0.55 0.65  1.45 0.93  0.98 0.50  0.75 0.17  0.52 1.60  2.45 0.95  1.05 0.60  0.76 2S. D.

0.02 0.28 0.05 0.05 0.06 0.19 0.09 0.05 0.20 0.26 0.09 0.03 0.04 0.44 0.03 0.13 0.18 0.44 0.05 0.08 N.

3 3 3 3  Date Day 4, Wk 1

Day 1, Wk 2 Day 4, Wk 2 Day 1, Wk 3 Day 4, Wk 3 Day 1, Wk 4 Day 4, Wk 4 Day 1, Wk 5 Day 4, Wk 5 " 3. Day 1, Wk &'" r.$ q 117 248 249 250 TAULE xxrx DAILY METHYL HIPPURIC ACID EXCRETION GROUP I MALE SUBJECTS Exposure T i m e : 7 1/ 2 HR Subject 117 248 249 250 117 248 249 250 117 248 249 250 117 248 249 250 117 248 249 250 117 248 249 250 117 249 *250 117 248 250 "" 117 248 249 250 248 Urine Concentration Vol m1/ 24 h r mg/ ml g/ 24 hr 6 50 1400 900 1050 600 1050 1000 1175 `

2350 1400 1300 800 Absent 1350 1100 1100 950 1150 625 500 950 1000 650 800 * Subject voided once i n 24 h r p e r i o d ** Snrnnlr 1 ~7 3 ~ n o t r e f r i s p r a t p d 1050 1200 650 170 1100 1025 750 1150 1125 500 650 1425 1300 650 850 1.81 0.84 0.77 0.94 4.11 4.64 1.78 1.71 1.17 1.70 1.45 2.65  0.57 0.78 1.24 2.30 1.28 1.44 2.38 3.57 2.82 3.57 3.28 3.53 2.22 2.69 2.25 2.77 1.67 2.67 0.72 1.89 3.90 3.06 2.32 1 10 2.60 1.20 1: 18 1.17 0.70 0.98 2.46 4.87 I. 78 2.00 2.74 2.38 1.89 2.12  0.77 0.86 1.37 2.19 1.48 0.90 1.19 3.39 2.82 2.32 2.62 3.70 2.66 1.75 0.38 3.05 1.71 2.00 0.83 2.13 1.95 1.98 3.31 1.43 1.69 1.02 p xylene Chamber Conc: ppm 0 100 100 20 20 150 150 F l u c t . 50 150 F l u c t . 50 150 0 000082 17 I. . ,, __i __..

 .

TABLE XXX DAILY METHYL HIPPURIC ACID EXCRETION GROUP 11 MALE SUBJECTS Exposure Time: 3 HR Date  Day 4, Wk 1 Day 1, Wk 2 Day 4, Wk 2 Day 1, Wk 3 Day 4, Wk 3 Day 1, Wk 4 Day 4, Wk 4 Urine Concentration Subject Vol m1/ 24 h r mg/ ml g /2 4 h r 251 800 0.62 0.50 25 2 1925 0.64 1.24 251 1125 0.75 0.85 252 1750 0.66 1.16 251 1000 1.09 1.09 25 2 1400 0.43 0.60 251 550 0.66 0.36 252 15 25 0.62 0.94 251 750 0.54 0.41 25 2 1275 1.05 1.34 251 550 0.73 0.40 252 1350 0.96 1.30 251 600 1.61 0.97 252 1100 1.12 1.23 Day 1, Wk 5 I 251 252 600 900 1.31 0.79 1.11 1.00 25 2 1300 0.82 1.07 1 Day 4, Wk 5 Day 1, Wk 6 251 1150 0.83 0.95 p xylene Chamber Conc: ppm 0 100 100 20 20 ' 150 150 F l u c t . 50 150 F l u c t . 50 150 0 Date P Day 4, Wk 1 Day 1, Wk 2 Day 4, Wk 2 Day 1, Wk 3 Day 4, Wk 3 Day 1, Wk 4 Day 4, Wk 4 Day 1, Wk 5 Day 4, Wk 5 .Day 1, Wk 6 TABLE XXXI DAILY METHYL HIPPURIC ACID EXCRETION GROUP 111 MALE SUBJECTS Exposure Time: 1 HR Urine Concentration Subject Vol m1/ 24 h r mg/ ml g/ 24 h r 253 254 255 255 254 255 255 255 *256 *257 256 25 7 256 257 256 257 257 256 257 775 15 75 . 375 375 1500 1100 9 75 750 1100 1520 1400 1050 1100 1100 1050 1450 850 1100 1025 0.74 1.05 0; 36 1.16 0.76 0.67 0.62 0.23 0.62 1.23 0.44 1.09 0.61 0.87 1.42 1.61 1.76 0.53 1.24 * Entered study during progress  no b a s e l i n e d a t a . 0.58 1.65 0.13 0.44 1.14 0.74 0.61 0.17 0.68 1.87 0.62 1.14 0.68 0.95 1.45 2.33 1.49 0.58 1.27 p xylene Chamb. er Conc: ppm 0 100 100 20 20 150 150 Fluc t . 50 150 Fluc t . 50 150 0 000084 TABLE X X X I I DAILY METHYL HIPPURIC ACID EXCRETION FOK FEMALE SUBJECTS Date Day 1, Wk 2 Day 4, Wk 2 Day 1, wk 3 Day 4, Wk 1 Day 1, Wk 2 Day 4, Wk 2 'Day 1, Wk 3 Day 4, Wk 1 Day 1, Wk 2 Day 4, Wk 2 Day 1, Wk 3 Urine Concentration Subject Vol m1/ 24 h r mglml g/ 24 h r Group I , Exposure Time: 7 1/ 2 h r 95 1900 0.85 25 8 1300 0.79 259 1450 1.46 95 15 00 2.29 258 1525 2.32 259 1350 2.65 95 2000 2.32 258 1350 1.85 259 950 2.76 95 1190 2 .1 1 258 1480 0.70 259 960 1 .1 2 Group 11, Exposure Time: 3 h r 261 1000 0.56 262 1200 1.55 26 1 650 0.92 262 1100 3.70 26 1 800 1.36 262 1450 2.76 261 1210 0.48 262 1140 1.32 Group 111, Exposure Time: 1 h r 264 850 1.60 265 750 1.07 264 600 8.20 265 850 0.81 264 750 6.19 265 450 1.86 264 860 2.09 265 1200 1.22 1.62 1.03 2.12 3.44 3.54 3.58 4.64 2.50 2.62 2.51 1.03 1.08 0.56 1.86 0.60 4.07 1.09 4.00 0.58 1.50 1.36 0.80 4.90 0.69 4.64 0.84 1.80 1.46 p xylene Chamber Conc: ppm 0 100 100 0 0 100 100 0 0 100 100 0 000085 I 1 rr: W 3 W E D4 0 X w $

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