vu~ f- V
7 t P) eL 6^X"
OTHER NOXA
THE OTHER NOXA THAT ARE THE SUBJECT OF THIS TALK
TODAY ARE
PARTICULAR SMOKE COMPONENTS MENTIONED IN THE 3RD
REPORT OF THE
UNITED KINGDOM IMDEPENDENT SCIENTIFIC COMMITTEE ON
SMOKING AND
rriour'4T
HEALTH - 19S3. THEY WERE CITED AS BEING,'OF MAJOR
IMPORTANCE WITH
REGARD TO THE HAZARDOUS EFFECTS OF SMOKE. AND HERE
IS THE SHOPPING
'", 0
LIST I" SLIDE 1
HAVE T;1OU611T- Gr-A4WAY OF PUTTING THE ~LATIVE
HAZARD OF SMOKE
COMPONENTS LIKE THESE INTO PERSPECTIVE .* THIS IS
TO ASSESS WHETHER
THE INDIVIDUAL COMPONENTS WOULD BE PRESENT IN THE
SMOKERS LUNG AT
OCCUPATIONALLY ACCEPTABLE CONCENTRATIONS.
THE OCCUPATIONALLY ACCEPTABLE CONCENTRATION IS
DEFINED AS THAT WHICH
CAN BE RESPIRED, IN ISOLATION, FOR 8 HOURS A DAY,
5 DAYS A WEEK,
FOR A WORKING LIFETIME, WITH NO ADVERSE EFFECT.
THIS MAKES IT A
VALUABLE BENCH MARK FOR OUR THINKING IN SMOKING
AND HEALTH.
VIE CAN GROUP SMOKE COMPONENTS INTO TWO CATEGORIES
- THOSE PRODUCING
CONCENTRATIONS ABOVE THEIR OCCUPATIONALLY
ACCEPTABLE LEVELS, AND THOSE
AT OR BELOW THESE LEVELS. REGARDING CIGARETTE
DESIGN WE SHOULD GIVE
PRIORITY ATTENTION TO THOSE COMPONENTS WHOSE SMOKE
CONCENTRATIONS
ARE FOUND TO BE UNACCEPTABLY HIGH USING THESE
CRITERIA,
THIS OF COURSE HAS NOT TAKEN INTO CONSIDERATION
THE POSSIBLE
INTERACTION BETWEEN COMPONENTS. INTERACTION CAN BE
A COMPLICATING
FACTOR BUT IT IS LIKELY ONLY TO HAVE A SIGNIFICANT
EFFECT ON BORDERLINE
CASES.
BECAUSE OF THIS COMPLICATIONj AND OTHER WORKING
ASSUMPTIONSj THIS
APPROACH SHOULD NOT BE REGARDED AS DEFINITIVE
WITHOUT FURTHER STUDY.
HOPEFULLY HOWEVER IT WILL BE A HELPFUL GUIDE AND
PROVIDE A FRAMEWORK
FOR FURTHER STUDY, WHAT ARE THESE WORKING
ASSUMPTIONS ?
SLIDE 2
A ASSUME THAT A PUFF OF SMOKE IS DILUTED TO A
VOLUME OF 500cc IN
THE LUNG.
B-ASSUME THAT ALL SMOKE IS CLEARED FROM THZ LUNG
BETWEEIN-i"UfFS SO THAT
THERE IS NO BUILD UP OF SMOKE CONCENTRATION.
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3
1 F THE OCCUPATIONAL EXPOSURE LIMIT IS EL MG/M '
THEN THIS CAN BE
EXPRESSED AS EL UG/L, OR 1/2 EL UG/500cc,
I DEFINE THE OCCUPATIONAL EXPOSURE EQUIVALENT AS
THE YIELD PER PUPF
PRODUCING THE OCCUPATIONAL EXPOSURE LIMIT
CONCENTRATION IN 500cc OF
LUNG.
WITH THIS DEFINITION, THE OCCUPATIONAL EXPOSURE
EQUIVALENT IS
1/2 EL UG.
THUS THE CRITICAL YIELD PER PUFF IN US IS ONE HALF
THE OCCUPATIONAL
EXPOSURE LIMIT WHEN EXPRESSED A~. MU/M ,
AT OR BELOW THIS CRITICAL YIELD., LUNG
CONCENTRATIONS WOULD BE
OCCUPATIONALLY ACCEPTABLE FOR THE ISOLATED
COMPONENT.
PUBLISHED OCCUPATIONAL LIMITS ARE OF 2 TYPES -
LONG TERM EXPOSURE LIMIT
(8 HR TIME WEIGHTED AVERAGES), AND SHORT TERM
EXPOSURE LIMITS (10 OR
15 MINUTE TIME WEIGHTED AVERAGES). EXPOSURE AT
SHORT TERM LIMITS
MUST NOT TAKE PLACE MORE THAN 4 TIMES A DAY. SINCE
THE AVERAGE
SMOKER SMOKES MORE THAN 4 CIGARETTES A DAY, IT IS
ONLY REALISTIC
TO USE THE LONGER TERM LIMIT FOR DEFINING
ACCEPTABLE YIELDS PER PUFF.
IF WE USE MY CRITERIA, THEN THE PERMITTED
CONCENTRATION IN THE LUNG
NEVER EXCEEDS THE OCCUPATIONAL EXPOSURE
EQUIVALENT.
~ sc~'f-Dc'
ON THE OTHER HAND, CALCULATING;SO CALLED
ACCEPTABLE YIELDS BASED ON
THE MASS OF MATERIAL RESPIRED IN 8 HOURS AT THE
OCCUPATIONAL LIMIT
WILL ALWAYS GIVE A LUNG LEVEL EXCEEDING THE LONG
TERM LIMIT CONCENTRATI
THIS MUST BE THE CASE, BECAUSE THIS CALCULATION
INCORPORATES CONTINUOUS
EXPOSURE AT THE CRITICAL OCCUPATIONAL EXPOSURE
LIMIT, BUT THEN
VIOLATES THIS LIMIT BY ALLOWING AN ADDITIONAL LOAD
DURING SMOKING
COMPUTED FROM THE LOAD THAT CAN BE BREATHED WHILST
NOT SMOKING.
THIS IS CLEARLY A NONESENSEj YET I HAVE SEEN THE
OCCASSIONAL PAPER
FROM THE INDUSTRY, EVEN ADDRESSED TO GOVERNMENT,
WHERE ARGUMENTS OF
SAFETY HAVE BEEN BASED ON THIS TYPE OF
CALCULATION.
CHE LONG TERM LIMITS SET BY THE UK HEALTH AND
SAFETY EXECUTIVE
ARE LISTED IN THE NEXT SLIDE FOR THOSE COMPOUNDS
ON THE 3RD REPORT
CD
OTHER NOXA SHOPPING LIST CD
SLIDE 3
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November 1999


YOU WILL NOTE THAT NOT ALL THE OTHER NOXA HAVE
PUBLISHED OCCUPATIONAL
EXPOSURE LIMITS.
IF WE USE MY CALCULATION, WE CAN SEE HOW THE
TYPICAL PROFILE
OF A FLUE CURED CIGARETTE COMPARES WITH
OCCUPATIONAL LIMITS.
SLIDE,4
CLEARLY WITH THIS CIGARETTE, AMMONIA, NITRIC
OXIDE, PHENOL, SILICA,
AND ACETALDEHYDE ARE PRESENT IN SMOKE AT
OCCUPATIONALLY ACCEPTABLE
LEVELS. " 13~~ IATZ~t~~-T-tr- -ID
ACROLEINj CARBON MONOXIDE, FORMALDEHYDE, AND
HYDROGEN CYANIDE ARE
PRESENT AT UNACCEPTABLY HIGH LEVELS.
SLIDE 5
OTHER DATA FROM A RANGE OF CIGARETTES INDICATES
THAT CADMIUM IS AT
ACCEPTABLE LEVELS IN SOME BRANDS AND UNACCEPTABLY
HIGH IN OTHERS,
NICKLE IS PROBABLY PRESENT AT OCCUPATIONALLY
ACCEPTABLE LEVELS,
ESPECIALLY IF IT IS DELIVERED IN AN INSOLUBLE
FORM, IT WOULD BE
IN THE INDUSTRY'S - INTERESTS TO ESTABLISH THAT
NICKEL IS
PRESENT IN SMOKE IN THE INSOLUBLE FORM.
CRESOLS ARE LARGELY PRESENT AT OCCUPATIONALLY
ACCEPTABLE LEVELS.
SLIDE 6
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November 1999


- Ll -
THE ANALYSIS WE HAVE JUST DONE CONCLUDES THAT WITH
REGARD TO
THE "OTHER NOXA' OF THE 3RD REPORT WHICH HAVE
OCCUPATIONAL LIMITS
ASSIGNED, THE GROUP CONTAINING ACROLEIN, CARBON
MONOXIDE, FORMALDEHYDE,
HYDROGEN CYANIDEj AND AT TIMES CADMIUMj DESERVES
PRIORITY ATTENTION
BY RESEARCH MANAGERS. THE ANALYSIS ALSO PROVIDES
YIELD TAFGETS
TO ATTEMPT TO ACHIEVE.
SLIDE 7
A MORE RELAXED ATTITUDE COULD BE TAKEN WITH
AMMONIA, NITRIC OXIDE,
SILICA AND ACETALDEHYDEj WHERE IN TYPICAL FLUE
CURED SMOKE, THEY
ARE WITHIN OCCUPATIONALY ACCEPTABLE LEVELS, I DONT
THINK THEY SHOULD
BE FORGOTTEN, BUT THEY ARE OF LOW PRIORITY. I DONT
THINK RESEARCH
MANAGERS SHOULD BE QUITE SO RELAXED WITH CADMIUM,
NICKELj PHENOL,
AND(RESOLS, DESPITE THEIR OCCUPATIONALY ACCEPTABLE
LEVELS, BECAUSE
THEY ALL POTENTIALLY CONTRIBUTE TO THE
CARCINOGENIC ACTIVITY OF
SMOKE.
I WOULD LIKE TO SAY A FEW WORDS ABOUT SOME KEY
ASPECTS OF THESE
OTHER NOXA.
CADMIUM
INHALATION OF CADMIUM DUSTS, SALTS AND FUME OVER A
NUMBER OF YEARS
RESULTS IN CHRONIC CADMIUM POISONING, A DISEASE
CHARACTERISED BY A
DISTINCTIVEj NON HYPERTROPHIC EMPHYSEMA WITH OR
WITHOUT RENAL
TUBULAR INJURYj IN WHICH URINARY EXCRETION OF A
PROTHIN OF MOLECULAR
WEIGHT OF MOW TO 30,000 OCCURS.
THIS PROTEIN DOES NOT REACT TO ROUTINE PROTEINUREA
TESTS, AND IS BY
ITSELF AN INDICATIVE SIGN OF EARLY BUT REVERSIBLE
CHRONIC POISONING.
I THINK IT WOULD BE A GOOD IDEA TO SEEK FOR THIS
PROTEIN IN SMOKERS
IN ORDER TO RULE OUT OR CONFIRM ANY SIGNIFICANT
ROLE OF CADMIUM IN
SMOKERS' LESESIONSi EMPHYSEMA AND POSSIBLY LUNG
CANCER. THE ACCUMULATED
BODY BURDEN OF CADMIUM IN HEAVY SMOKERS CAN BE
TWICE THAT FOR NON
SMOKERS, AND IS THOUGHT TO DERIVE FROM CADMIUM IN
PHOSPHATE
FERTILISERS USED TO FEED THE TOBACCO PLANT.
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THE INTERNATIONAL AGENCY FOR RESEARCH ON CANCER,
IN A RECENT
PUBLICATION q5D CONSIDER CADMIUM AND ITS COMPOUNDS
AS PROBABLY
CARCINOGENIC TO HUMANS; CARCINOMA OF THE LUNG AND
PROSTATE HAS
BEEN ASSOCIATED WITH OCCUPATIONAL EXPOSURE TO
CADMIUM OXIDE DUST.
THE OCCUPATIONAL EXPOSURE LIMIT IS SUFFICIENT TO
PREVENT
PROTEINUREA, PULMONARY EDEMA AND EMPHYSEMA.
THEREFORE WITH
THOSE CIGARETTE STYLES WHICH PRODUCE CADMIUM
YIELDS BELOW
THE OCCUPATIONAL EQUIVALENT, A CADMIUM INVQJ\EMENT
IN SMOKING
ASSOCIATED EMPHSEMA IS LESS LIKELY.
NICKEL
NICKEL IN SOME COMPOUND FORMS HAS BEEN ASSOCIATED
WITH INCREASED
RISK OF DEVELOPING LUNG AND SINUS CANCER IN NICKEL
REFINERY
WORKERS. THE INTERNATIONAL AGENCY FOR RESEARCH ON
CANCER i~o~
CONSIDER NICKEL AND ITS COMPOUNDS IS PROBABLY
CARCINOG:--'NIC
TO HUMANS.
PHENOL
LABORATORY ANIMAL EXPERIMENTATION SHOWS THAT
INHALATION OF PHENOL
VggLIZ-AT 5 TO 10 TIMES THE OCCUPATIONAL LIMIT CAN
RESULT IN
LUNG, HEART, LIVER AND KIDNEY DAMAGE. HOWEVER, THE
OCCUPATIONAL
LIMIT IS CONSIDERED TO PROVIDE A SUFFICIENTLY
LARGE SAFETY
FACTOR PREVENTING SYSTEMIC POISONING.
SOME AUTHORS CITE THE PHENOLS AS A MAJOR GROUP OF
TUMOUR PROMOTING
AGENTS IN SMOKE. INTERESTINGLY THE INTERNATIONAL
AGENCY FOR RESEARCH
ON CANCER DO NOT APPEAR TO TAKE THIS VIEW IN
THATjOF THE FIVE
PHENOLS AND PHENOL ETHERS THEY CITE (CATECHOL,
EUGENOL, HYDROQUINONE,
RESOURCINOLi CHOLESTEROL) THEY CONSIDER THE
EVIDENCE FOR CARCINOGENicr
IS EITHER INADEQUATE OR LIMITED.
CRESOLS /T"IC
THE CRESOLS HAVE A CLOSELY ANALOGOUS AMON TO
PHENOL.
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6
FORMALDEHYDE
FORMALDEHYDE IS VERY SOLUBLE IN WATER, AND HENCE
IS READILY
ABSOR3ED BY THE UPPER RESPIRATORY TRACT, WITH ONLY
SMALL AMOUNTS
REACHING THE LUNGS.
ONCE ABSORBED IT IS RAPIDLY METABOLISED TO FORMIC
ACID, WHICH IS
MORE SLOWLY ELIMINATED.
IN MANj FORMALDEHYDE IS AN UPPER RESPIRATORY TRACT
IRRITANT,
ALTHOUGH IRRITATION IS SLIGHT BELOW I PPM (HALF
THE OCCUPATIONAL
EXPOSURE LIMIT) AND ADAPTION OCCURS. OCCUPATIONAL
EXPOSURE
CAN RESULT IN BOTH ACUTE AND CHRONIC AIR FLOW
OBSTRUCTION, AND IN
ASTHPA.A. IT 13 PARTICULARLY IRRITANT TO THE EYES.
FORMALDEHYDE, LIKE ACROLEIN, ACETALDEHYDE AND
AMMONIA, IS CILIA
TOXIC., AND INHIBITS LUNG CLEARANCE AFTER SMOKE
INHALATION. IT
WOULD BE HELPFUL_TF A VAPOUR THRESHOLD FOR THIS
EFFECT COULD
BE ESTABLISHED
SLIDE 8 1 ONLY HAVE A SYNOPSIS OF THIS
DATA, BUT ILLUSTRATES THE POINT
NOTE WITH THIS DATA THE "THRESHOLDS" ARE ME
CALCULATE
TO BE THE EXPECTED LUNG CONCENTRATIONS. OTHER
DATAj ON RABBIT
TRACHEAj SHOWED FORMALDEHYDE TO BE MUCH MORE
CILIATOXIC THAN
ACROLEIN, COMPARING THE AEROSOL FORMS.
FORMALDEHYDE VAPOUR HAS INDUCED NASAL CARCINOMAS
IN RATS, AND
IS THEREFORE A SUSPECTED CARCINOGEN IN MAN.
ACROLEIN
ACROLEIN IS STRIKINGLY IRRITANT. THE OCCUPATIONAL
EXPOSURE
LIMIT MINIMISES, BUT DOES NOT ENTIRELY PREVENTj
IRRITATION
TO ALL EXPOSED INDIVIDUALS,
ACROLEIN IN A PUFF OF CIGARETTE SMOKE (64 FOLD
ABOVE THE
OCCUPATIONAL EXPOSURE EQUIVALENT) WOULD BE
EXPECTED TO BE
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- 7 -
INTENSELY IRRITATING TO THE UPPER RESPIRATORY
TRACT AND TO
THE EYES, AND TO BE LACRIMATORY. ACROLEIN MUST BE
A MAJOR
CONTRIBUTOR TO THE IRRITANT QUALITY OF CIGARETTE
SMOKE.
ACROLEIN IS CILIA TOXIC, AS ILLUSTRATED IN THE
SLIDE,
ACETALDEHYDE
HIGH LEVELS OF ACETALDEHYDE CAN CAUSE IRRITATION,
NARCOSIS,
BRONCHITIS, ALBUMINURIEA: FATTY LIVER AND LUNG
EDEMA. HOWEVER
ACETALDEHYDE IN A PUFF OF CI nETTE SMOKE IS AT THE
OCCUPATIONAL
EXPOSURE EQUIVALENT; THIS IS CONSIDERED
SUFFICTENTLY LOW TO
PREVENT POTENTIAL INJURY TO THE RESPIRATORY TRACT
WITH LESS
THAN 8 HRS/DAY CONTINUOUS EXPOSURE,
ACETALDEHYDE IS METABOLISED RAPIDLY. IT IS PRESENT
IN VERY
SMALL AMOUNTS IN NORMAL BLOOD. IT IS CILIATOXICj
BUT LESS
POTENT THAN FORMALDEHYDE AND ACROLIEN.
EERON AND OTHERS REPORTED ACETALDEHYDE VAPOUR CAN
ENHANCE THE
CARCINOGENIC EFFECT OF BENZO(A) PYRENE IN THE
SYRIAN HAMSTER,
AT A CONCENTRQTION 16-25 TIMES THE OCCUPATIONAL
EXPOSURE
LIMIT, THE INTERNATIONAL AGENCY FOR RESEARCH ON
CANCER CONSIDER
THERE IS SUFFICIENT EVIDENCE THAT ACETALDEHYDE IS
A CO-CARCINOGEN.
LABORATORY ANIMAL EXPERIMENTS HAVE SHOWN THAT
ACETALDEHYDE VAPOUR,
AT CONCENTRATIONS GREATER THAN 16 TIMES THE
OCCUPATIONAL LIMIT,
PRODUCES MARKED INCREASES IN BLOOD PRESSURE, AN
EFFECT ALSO
SEEN USING IV INJECTION
IN HUMANS
WHEN ACETALDEHYDE IN BLOOD WAS RAISED TO 0.2-0.7
MG'/." BY
INTRAVENOUS INJECTIONj INCREASED HEART RATE AND
RESPIRATORY
VENTILATION WAS NOTED.
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November 1999


W
bR/K) WIKH, I SQLA`~ED 90C-'HEART HA~ HOW _p ~Fy C
T~11' ~ID E ~HD E
0 .A
,REASE HEAR
I N
,yNT
A,~ Ty~ kT~ AkR24T-E A
HYDROGEN CYANIDE
THE FLUE CURED SMOKE LEVEL is 4.8 FOLD HIGHER THAN
THE OCCUPATIONAL
EXPOSURE EQUIVALENT, CORRESPONDING TO A
CONCENTRATION OF HYDROGEN
CYANIDE WHICH COULD BE TOLERATED CONTINUOUSLY FOR
1/2 HR TO 1 HR
WITHOUT I."14EDIATE OR LATE EFFECTS (ACCORDING TO
PATTY)
SLIDE 9
AS i-YOU CAN SEE, THERE IS QUITE A SPECTRUM OF HCN
DELIVERY
ACROSS CIGARETTE STYLES, WITH SOME BELOW
OCCUPATIONAL LEVELS,
BUT MOST ABOVE THOSE LEVELS. HOWEVER, IT INDICATES
REDUCTIONS
COULD BE POSSIBLE, AND IT ALSO INDICATES THAT THE
OCCUPATIONAL
LEVEL APPROACH CAN TELL THE CIGARETTE DESIGNER
WHERE FURTHER
EFFORT 15 NOT REALLY CALLED FOR. FOR INSTANCE, WAS
IT REALLY
NECESSARY TO DRIVE THE YIELD DOWN TO 0.4 UG WHEN
THE NEED FOR
REDUCING OTHER COMPONENTS HAS BECOME RELATIVELY
MORE PRESSING ?
HYDROGEN CYANIDE IS RAPIDLY ABSORBED BY THE LUNGSj
SKIN AND
MUCOUS MEMBRANES, THE MAJOR DETOXIFICATION PATHWAY
IS BY OXIDATION
TO THIOCYANATE, REACTION WITH CYSTINE AND WITH
HYDROXYCOBALAMINE.
CYANIDE CAN BE DETECTED IN THE BLOOD OF HEALTHY
INDIVIDUALS.
AT LETHAL DOSES, CYANIDE CAUSES ALMOST
INSTANTANEOUS CESSATION
OF RESPIRATIONj BY COMPLEXING METAL ATOMS IN
ENZYMES AND CO-
ENZYMES. SUB LETHAL DOSES WELL ABOVE THE
OCCUPATIONAL LIMIT AND
ABOVE CIGARETTE DOSAGE STIMULATE OR DEPRESS
RESPIRATIONj DEPRESS
THE CNS, AND INCREASE FREQUENCY OF ECTOPIC HEART
BEATS, IT
PROBABLY HAS A SMALL, IF ANY, EFFECT ON CILIA.
TOBACCO AMBLYOPIA WAS A TERM USED TO DESCRIBE A
RANGE OF VISUAL
DEFECTS IN SOME HEAVY CONSUMERS OF PIPE TOBACCO.
THE DISEASE
RESULTS FROM VITAMIN B12 DEFICIENCY AND AN
INHERENT DEFECT IN
THE MECHANISM OF CYANIDE METABOLISM IN THE
INDIVIDUALS AFFECTED, j-,
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CARBON MONOXIDE
CARBON MONOXIDE IS A CHEMICAL ASPHYRIANT GAS WHOSE
PRIMARY
TOXIC ACTION IS A DIRECT RESULT OF THE HYPOXIA
PRODUCED BY
A GIVEN DOSE. IT RAPIDLY DIFFUSES ACROSS THE
ALVEOLAR
MEMBRANE AND IS RL4&49=4;9~ BOUND TO ONE OF THE
HAEME PROTEINS.
80-907- COMPLEXES WTIH HAEMOGLOBIN RESULTING IN A
REDUCTION
IN THE OXYGEN CARRYING CAPACITY OF THE BLOOD, THE
REMAINDER
OF THE CO BINDS WITH MYOGLOBIN, CYTOCHROME
OXIDASE, CYTOCHROME
P-450 AND THE HYDROPEROXIDASES.
A SMALL AMOUNT OF CO IS PRODUCED ENDOGENOUSLYj
MAINLY FROM
THE CATABOLISM OF HEMOGLOBIN,
WHETHER THE EFFECT CO IS HARMFUL DEPENDS ON THE
DOSE AND THE
STATE OF HEALTH OF THE EXPOSED INDIVIDUAL. THE
BODY COMPENSATES
FOR THIS HYPOXIC STRESS BY INCREASING CARDIAC
OUTPUT AND BLOOD
FLOW TO SPECIFIC ORGANS SUCH AS THE BRAIN OR
HEART. WHEN THIS
ABILITY TO COMPENSATE IS OVERPOWERED OR IS LIMITED
BY DISEASEj
TISSUE INJURY RESULTS,
EXPOSURE TO CO SUFFICIENT TO PRODUCE COHB
SATURATION IN THE
3 -nRANGE IMPAIRS CARDIOVASCULAR FUNCTION IN
PATIENTS WITH
CARDIOVASCULAR DISEASE AND IN NORMAL SUBJECTS.
COHB SATURATIONS
IN THE 4 - 6 % RANGE SIGNIFICANTLY REDUCE THE
VENTRICULAR FIBRILLATION
THRESHOLD IN NORMAL ANESTHETISED DOGS, AND THOSE
WITH ACUTE
MYOCARDIAL INJURY.
THE OCCUPATIONAL EXPOSURE LIMIT IS A CONCENTRATION
WHICH SHOULD
NOT RESULT IN BLOOD CO LEVELS ABOVE 101'.. HEALTHY
WORKERS CAN
COMPENSATE FOR THE HYPOXIC STRESS UNDER THESE
CONDITIONS BY
INCREASING CARDIAC OUTPUT, BUT . THOSE WITH
SIGNIFICANT DISEASEj
BOTH DETECTED OR UNDETECTED, MAY NOT BE ABLE TO
COMPENSATE
ADEQUATELY AND ARE AT RISK OF SERIOUS INJURY. FOR
SUCH WORKERS
AN OCCUPATIONAL EXPOSURE LIMIT THAT SHOULD NOT
RESULT IN BLOOD
COHE ABOVE 4% MIGHT BE NECESSARY
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SMOKERS ARE THE MOST HEAVILY EXPOSED NON
INDUSTRIAL
SEGMENT OF THE POPULATION. COHB SATURATION$ IN
SMOKERS RANGE-
FROM 4 To 20'%, WITH A MEAN FOR ONE PACK PER DAY
OF 5-6';..
AMMONIA
NO DETECTABLE IRRITATION IS EXPECTED AT THE
OCCUPATIONAL
EXPOSURE LIMIT. INDEED AT THIS LIMIT, THE ODOUR OF
AMMONIA
IS NOT DETECTABLE.
NITRIC OXIDE
THE FLUE CURED NITRIC OXIDE YIELD IS ABOUT HALF
THE OCCUPATIONAL
EXPOSURE EQUIVALENT. THE CHIEF TOXIC EFFECT OF NO
HAS BEEN
ASCRIBED TO THE FORMATION OF METHAEMOGLOBIN.
EPTDEMIOLOGICAL
STUDIES CONCERNED WITH THIS FACTOR HAVE NOT SHOWN
SMOKERS TO
HAVE HIGHER METHEMOGLOBIN LEVELS THAN NON SMOKERS.
SILICA
IN MY ANALYSIS THE/Kk+RT OF SMOKE IS ASSUMED TO BE
CRYSTALLINE
QUARTZ, TO GIVE A SAFETY MARGIN OVER ANYAMORPHOUS
SILICA,
WHICH HAS A MUCH HIGHER OCCUPATIONAL LIMIT.
TYPICAL SILICA YIELDS
IN SMOKE ARE BELOW THE OCCUPATIONAL EXPOSURE
EQUIVALENT.
INHALATION OF CRYSTALLINE QUARTZ IS ASSOCIATED
WITH LUNG
FIBROSIS - SILICOSIS. SILICOSIS IS NOT ASSOCIATED
WITH SMOKING,
OTHER THAN AS A COMPLICATING FACTOR. pC Vgd
THE LIST OF"OTHER NOXA' ALSO INCLUDES
TWOAPTEASHAVE NO
ASSIGNED OCCUPATIONAL LIMITS. THESE ARE THE
POLYCYCLIC AROMATIC
HYDROCARBONSi AND THE NITROSAMINES.
POLYCYCLIC AROMATIC HYDROCARBONS
MORE THAN 200 SUCH COMPOUNDS HAVE BEEN ISOLATED
FROM TOBACCO
SMOKE CONDENSATE, THE MOST FREQUENTLY CITED, BENZ
A PYRENEj
HAS BEEN REPORTED AT 0.5 - 8 UG/100 CIGARETTES IN
MAINSTREAM
SMOKE, THE POLYCYCLIC AROMATIC HYDROCARBONS ARE
CONSIDERED
TO BE THE MAIN GROUP OF TUMOUR INITIATORS IN
TOBACCO SMOKE.
HOWEVER THE PAH CONTENT OF TOBACCO SMOKE DOES NOT
EXPLAIN ITS C:D
TUMOUROGENICITY TO MOUSE SKIN OR/INJECTED
SUBCUTANEOUSLY IN RATS. C:'
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NITROSAMINES
NITROSAMINES DETECTED IN TOBACCO AND SMOKE ARE OF
TWO TYPES;
VOLATILE-AND NON VOLATILE. THE VOLATILE GROUP ARE
ALSO
FOUND IN THE'ENVIRONMENT, BEVERAGES_AND FOOD,
OFTEN AT
HIGHER LEVELS THAN IN SMOKE. THE N-6N VOLATILE
GROUP ARE
UNIQUE TO TOBACCO, AND TERMED THE TOBACCO SPECTFIC
NITROSAMINES,
THOSE DETECTED IN SMOKE ARE N-NITROSONORNICOTINE
(NNN),
N-NITROSOANATABINE (NATB) AND
4-(METHYLNITROSOAMINO)-I-(3-
PYRIDYL)-1-BUTANONE (NNK). THE FOLLOWING LEVELS IN
SMOKE
HAVE BEEN REPORTED
SLIDE 10
YOU WILL NOT~THAT THERE IS A CONSIDERABLE
VARIATION BETWEEN
CIGARETTE STYLES, WITH UK CIGARETTES PARTICULARLY
LOW.
THERE APPEARES TO BE A RELATIONSHIP BETWEEN THE
NITRATE CONTENT
OF THE CIGARETTE BLEND AND THE DELIVERY OF THE
TOBACCO SPECIFIC
NITROSAMINES,
THE INTERNATIONAL ASSOCIATION FOR RESEARCH ON
CANCER
CONSIDER THER IS SUFFICIENT EVIDENCE THAT NNN AND
NNK ~~E
CARCINOGENIC, BUT THAT THE EVIDENCE FOR NATB IS
INADEQUATE.
ALL THE EVIDENCE IS FROM EXPERIMENTAL ANIMALS.
THERE IS
NO EVIDENCE IN MAN.
SUMMARY
IN SUMMARY7AN- APPROACH TO PLACING CIGARETTE SMOKE
NOXA INTO
PERSPECTIVE ... . BY RELATING THEM TO YIELDS WHICH
WOULD BE OCCUPATIONALY ACCEPTABLE GIVEN CERTAIN
WORKING ASSUMPTIONS.
THIS APPROACH ALSO GIVES THE CIGARETTE DESIGNER
QUANTITATIVE TARGETS
TO ACHIEVE A MORE ACCEPTABLE SMOKE PROFILE IN
HEALTH TERMS, "'INDICATES
COMPONENTS ARE MORE DESIGN EFFORT IS NEEDED, AND
ALLSO COMPONENTS
#jolt
WHICHj RELATIVELYj DOW JUSTIFY FURTHER EFFORT. IT
SHOULD BE
RECOGNISED THAT OCCUPATIONAL LIMITS CAN CHANGE
THROUGH TIME WITH NEW
KNOWLEDGE AND CHANGING RISK PERCEPTIONS.
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November 1999