1070

8. Simmons, R. L., Thompson, E. J., Yunis, E. J., Noreen, H., Kjellstrand,C. M., Fryd, D. S., Condie, R. M., Mauer, S. M., Buselmeier, T. J.,Najarian, J. S. Am. J. Med. 1977, 62, 234.

9. Opelz, G., Terasaki, P. I. Lancet, 1976, ii, 380.10. See British Medical Journal 1977, i, 66.11. Gore, Sh. M., Jones, I, G., Rylter, E. C. ibid. p. 85.

Points of View

TESTING OF INDUSTRIAL CHEMICALS

SOME five hundred new chemicals are introduced intocommerce each year.’ Until now it has been quite usualfor the toxicity of a new chemical to remain undis-covered until the workers fell ill or died, as happenedwith beryllium, vinyl chloride, asbestos, nitrosamines,and -naphthylamine.2 This is clearly intolerable. TheHealth and Safety Commission and its Executive

(H.S.E.) have the duty of working towards health andsafety at work, and have put forward a scheme in whichall new chemicals should be tested before use.3 Thescheme is, so far, limited to new chemicals made or im-ported in amounts of one tonne a year or more. The sug-gested procedures comprise the following:

1. Observation of the effects on rats of a single dose in thelethal range (acute toxicity test and L.D.,,).

2. Irritancy to the skin and eye, and sensitisation test.3. Effects of 30 days of exposure.4. Mutagenic potential to bacteria and tissue-culture cells

(as tests of carcinogenicity).5. Effects on the fetus in pregnant rats.6. Effects on one fish species and stability in soil or sewage.The results of these tests would have to be sent to

H.S.E. with the notification of intention to use the newchemical. The information on toxicity would permit thefactory inspectorate and other H.S.E. staff to warn in-tending users of possible dangers in transport, labelling,and industrial use.The scheme seems sensible-an excellent, humane,

socially desirable move to ensure that members of theworking population are protected from new hazards atwork. But there are underlying drawbacks. Firstly, thescheme takes no account of consumer or environment.These are not a target of H.S.E. attention, but bothEuropean Economic Community and U.K. legislationwill certainly move towards consumer and environmen-tal protection against new chemicals. So shall we havethree bodies examining chemicals, each with its ownrules? The Pesticide Safety Precautions Scheme

(P.S.P.S.) deals with all three aspects-worker, con-sumer, and natural environment- and has had consi-derable success in dealing with these intrinsically dan-gerous chemicals. But P.S.P.S. can insist on full testingof a new pesticide, at a cost of perhaps 1 million,because of the great economic importance of successfulnew pesticides. The H.S.E. scheme is a "mini" toxicitytest, costing about c5000 per chemical. Is this enough?Or is it too much, in that it is k5000 spent with littleuseful information at the end, but a cost that might pre-vent some useful chemicals from ever starting? More-over, the information gathered by H.S.E. will be kept

TESTING OF INDUSTRIAL CHEMICALS

SOME five hundred new chemicals are introduced intocommerce each year.’ Until now it has been quite usualfor the toxicity of a new chemical to remain undis-covered until the workers fell ill or died, as happenedwith beryllium, vinyl chloride, asbestos, nitrosamines,and -naphthylamine.2 This is clearly intolerable. TheHealth and Safety Commission and its Executive

(H.S.E.) have the duty of working towards health andsafety at work, and have put forward a scheme in whichall new chemicals should be tested before use.3 Thescheme is, so far, limited to new chemicals made or im-ported in amounts of one tonne a year or more. The sug-gested procedures comprise the following:

1. Observation of the effects on rats of a single dose in thelethal range (acute toxicity test and L.D.,,).

2. Irritancy to the skin and eye, and sensitisation test.3. Effects of 30 days of exposure.4. Mutagenic potential to bacteria and tissue-culture cells

(as tests of carcinogenicity).5. Effects on the fetus in pregnant rats.6. Effects on one fish species and stability in soil or sewage.The results of these tests would have to be sent to

H.S.E. with the notification of intention to use the newchemical. The information on toxicity would permit thefactory inspectorate and other H.S.E. staff to warn in-tending users of possible dangers in transport, labelling,and industrial use.The scheme seems sensible-an excellent, humane,

socially desirable move to ensure that members of theworking population are protected from new hazards atwork. But there are underlying drawbacks. Firstly, thescheme takes no account of consumer or environment.These are not a target of H.S.E. attention, but bothEuropean Economic Community and U.K. legislationwill certainly move towards consumer and environmen-tal protection against new chemicals. So shall we havethree bodies examining chemicals, each with its ownrules? The Pesticide Safety Precautions Scheme

(P.S.P.S.) deals with all three aspects-worker, con-sumer, and natural environment- and has had consi-derable success in dealing with these intrinsically dan-gerous chemicals. But P.S.P.S. can insist on full testingof a new pesticide, at a cost of perhaps 1 million,because of the great economic importance of successfulnew pesticides. The H.S.E. scheme is a "mini" toxicitytest, costing about c5000 per chemical. Is this enough?Or is it too much, in that it is k5000 spent with littleuseful information at the end, but a cost that might pre-vent some useful chemicals from ever starting? More-over, the information gathered by H.S.E. will be kept

1. Page, N. P. in Environmental Cancer (edited by H. F. Kraybill and M. A.Mehlman); p. 88. New York, 1977.

2. Hunter, D. The Diseases of Occupations. London, 1977.3. Health and Safety Executive. Proposed Scheme for the Notification of the

Toxic Properties of Substances. H. M. Stationery Office. 1977.

secret, so we will not be able to look at the way in whichdecisions about risks to the working public are made.The Department of Health’s committees on Safety of

Chemicals in Food and the Environment deal with con-

sumers, but not with workers or natural environment.So each manufacturer will have to assemble data, andmay have to submit it to several bodies. Who will decidewhether a new chemical should be used or not? We arein danger of losing valuable new products and processes,not because they are hazardous, but because our effortsto reduce hazard have produced a jungle of office workthrough which only the largest firms can hack a path.How can we decide that a new chemical is fit for use

in industry, or as a drug, food additive, or pesticide?There are four essential steps in the process of decision.

1. Toxicity is measured. Model systems are set up. We mea-sure injurious effects of known doses of the chemical to ani-mals living in controlled conditions. Or else we use bacteria tosee if the substance causes mutations, tissue culture to look atchromosome breaks, and birds, beasts, plants, and activatedsludge to measure interactions with living systems. In particu-lar the relation of dose to response, and the mechanism and tis-sues affected are sought.

2. Hazard is assessed. When we know the intended use, wecan estimate exposure of people who may be in contact withthe chemical in the factory or working as farm sprayers. Usingthe estimated dose to man, and the measured toxicity in ouranimal and model systems, we try to infer whether there is like-

ly to be any ill-effect on the exposed population. This requiresknowledge of the engineering processes. How much of a toxicgas such as vinyl chloride will escape from the polymeriser potswhere it is turned into P.v.c.? How well ventilated is the fac-

tory floor? What protective clothing do farm workers reallywear?

3. Risk is evaluated. Essentially all activity carries risk.

Lying in bed dissolves bones; motor cycling and climbingmountains lead to broken bones. We have to decide whetherthe risks involved in the use of a new chemical are justified bythe potential benefits, to process workers and to society. Thisis a political, not a medical, decision. The role of doctor andscientist is to give the best advice about risks, benefits, andalternatives.

4. Epidemiological follow-up-Because species differ, andno animal tests can go on as long as the human lifespan, andbecause human exposure includes men who drink too much orsmoke cigarettes, or pregnant women or men with atheroma-tous arteries, our predictions of hazard are insecure. We haveto monitor our population to see if unanticipated risks turn up.The side-effects of new drugs remind us of the wide variety ofunexpected ill-effects that show up when large numbers ofpeople are exposed to a new chemical.When we have examined the four stages of hazard

evaluation we see that the H.S.E. scheme requires thatstep 1 (toxicity measurement) be carried out in a smallway and without reference to intended use of the newchemical. As a result the wrong tests may well be done.If a substance is to be used as a spray it must be testedby inhalation; if it will be a residue on food, it must betried by mouth. But, in particular, the scheme does notmake it clear to industry that the evaluation of hazardfrom new chemicals can be done only in a series of stepswhich must culminate in careful observation and record-

ing of the health of exposed workers.If the scheme is to be effective in protecting workers,

then the data must be reliable. The number of toxicol-

ogists in this country is probably not sufficient to do thetesting, quite apart from the need for people to look atthe data and evaluate its meaning. False-negative resultswill harm workers, in the particular factory or process;

secret, so we will not be able to look at the way in whichdecisions about risks to the working public are made.The Department of Health’s committees on Safety of

Chemicals in Food and the Environment deal with con-

sumers, but not with workers or natural environment.So each manufacturer will have to assemble data, andmay have to submit it to several bodies. Who will decidewhether a new chemical should be used or not? We arein danger of losing valuable new products and processes,not because they are hazardous, but because our effortsto reduce hazard have produced a jungle of office workthrough which only the largest firms can hack a path.How can we decide that a new chemical is fit for use

in industry, or as a drug, food additive, or pesticide?There are four essential steps in the process of decision.

1. Toxicity is measured. Model systems are set up. We mea-sure injurious effects of known doses of the chemical to ani-mals living in controlled conditions. Or else we use bacteria tosee if the substance causes mutations, tissue culture to look atchromosome breaks, and birds, beasts, plants, and activatedsludge to measure interactions with living systems. In particu-lar the relation of dose to response, and the mechanism and tis-sues affected are sought.

2. Hazard is assessed. When we know the intended use, wecan estimate exposure of people who may be in contact withthe chemical in the factory or working as farm sprayers. Usingthe estimated dose to man, and the measured toxicity in ouranimal and model systems, we try to infer whether there is like-

ly to be any ill-effect on the exposed population. This requiresknowledge of the engineering processes. How much of a toxicgas such as vinyl chloride will escape from the polymeriser potswhere it is turned into P.v.c.? How well ventilated is the fac-

tory floor? What protective clothing do farm workers reallywear?

3. Risk is evaluated. Essentially all activity carries risk.

Lying in bed dissolves bones; motor cycling and climbingmountains lead to broken bones. We have to decide whetherthe risks involved in the use of a new chemical are justified bythe potential benefits, to process workers and to society. Thisis a political, not a medical, decision. The role of doctor andscientist is to give the best advice about risks, benefits, andalternatives.

4. Epidemiological follow-up-Because species differ, andno animal tests can go on as long as the human lifespan, andbecause human exposure includes men who drink too much orsmoke cigarettes, or pregnant women or men with atheroma-tous arteries, our predictions of hazard are insecure. We haveto monitor our population to see if unanticipated risks turn up.The side-effects of new drugs remind us of the wide variety ofunexpected ill-effects that show up when large numbers ofpeople are exposed to a new chemical.When we have examined the four stages of hazard

evaluation we see that the H.S.E. scheme requires thatstep 1 (toxicity measurement) be carried out in a smallway and without reference to intended use of the newchemical. As a result the wrong tests may well be done.If a substance is to be used as a spray it must be testedby inhalation; if it will be a residue on food, it must betried by mouth. But, in particular, the scheme does notmake it clear to industry that the evaluation of hazardfrom new chemicals can be done only in a series of stepswhich must culminate in careful observation and record-

ing of the health of exposed workers.If the scheme is to be effective in protecting workers,

then the data must be reliable. The number of toxicol-

ogists in this country is probably not sufficient to do thetesting, quite apart from the need for people to look atthe data and evaluate its meaning. False-negative resultswill harm workers, in the particular factory or process;

1071

false-positives will harm society as a whole, in prevent-ing improved production methods.There are no university departments of toxicology in

the U.K., so the shortage of thoughtful toxicologists islikely to continue. Perhaps some aspects of toxicologyshould become part of undergraduate courses in medi-cine, chemistry, and biology.The difficult decision is how best to spend society’s

resources to improve the quality of life for all of us, inour capacities as workers and consumers. P.v.c. is madeby process workers some of whom have to climb into thebig pressure vessels to clean up after the vinyl chloridegas has been polymerised. In the past around 3% ofthese men got bone disease and perhaps 0-1% got liverdisease or liver cancer after about ten years of exposureto 200 parts per million or more of v.c. gas in the in-

spired air. By spending some z1000 per worker theexposure of all the process workers can be greatlyreduced (less than 20 p.p.m.) with a resulting increaseof about 2 per tonne in the price of P.v.c. There are200 deaths per annum on the building sites in the U.K.There has been perhaps one death per annum fromvinyl-chloride disease. Should we spend equivalentamounts to improve safety in building? It is fashionableto work on chemical hazards, but are we looking toomuch at insidious poison and not enough at the dangersof falling bricks and of tractors that turn over? About1% of the gross national product is expended on mea-sures to combat environmental pollution.4 Is it beingspent in the right way? ,

false-positives will harm society as a whole, in prevent-ing improved production methods.There are no university departments of toxicology in

the U.K., so the shortage of thoughtful toxicologists islikely to continue. Perhaps some aspects of toxicologyshould become part of undergraduate courses in medi-cine, chemistry, and biology.The difficult decision is how best to spend society’s

resources to improve the quality of life for all of us, inour capacities as workers and consumers. P.v.c. is madeby process workers some of whom have to climb into thebig pressure vessels to clean up after the vinyl chloridegas has been polymerised. In the past around 3% ofthese men got bone disease and perhaps 0-1% got liverdisease or liver cancer after about ten years of exposureto 200 parts per million or more of v.c. gas in the in-

spired air. By spending some z1000 per worker theexposure of all the process workers can be greatlyreduced (less than 20 p.p.m.) with a resulting increaseof about 2 per tonne in the price of P.v.c. There are200 deaths per annum on the building sites in the U.K.There has been perhaps one death per annum fromvinyl-chloride disease. Should we spend equivalentamounts to improve safety in building? It is fashionableto work on chemical hazards, but are we looking toomuch at insidious poison and not enough at the dangersof falling bricks and of tractors that turn over? About1% of the gross national product is expended on mea-sures to combat environmental pollution.4 Is it beingspent in the right way? ,

Laboratory of Toxicology,Department of Clinical Pharmacology,University College HospitalMedical School,

London WC1E 6JJ. A. E. M. MCLEAN

4. The Times, Oct 25, 1977, p. 19.

Round the World

United States

SCREENING FOR BREAST CANCER

Early detection has been hailed by the American CancerSociety and the National Cancer Institute as the answer tocancer. The first enthusiasts maintained that routine mammo-

graphy would halve the death-rate from breast cancer over thenext 20 years. But the initial flush of evangelism has nowwaned, and the National Institutes of Health recently calledtogether a special panel, headed by Dr Samuel Thier, chair-man of the department of medicine at Yale University, to holdpublic hearings on the federal programme for the early detec-tion of breast cancer. The panel has paid particular attentionto routine mammography and its application as a screeningprocedure, and though its recommendations are intended forthe federal programme, it is hoped that private practitionerswill likewise adopt them. The panel agreed that screeningwomen over 50 is useful in the detection of breast cancer, and

they also felt it was probably beneficial, although some epidem-iologists doubt this. But they decided that screening womenunder the age of 50 has not been shown to be effective, andindeed, that there was evidence to suggest that mammographyin this group was likely to be harmful and might induce malig-nant disease at a later date. Moreover, in their opinion thebreast-cancer detection demonstration project devised by theNational Cancer Institute had been poorly designed. Out of the1850 women diagnosed as having breast cancer, no less than

United States

SCREENING FOR BREAST CANCER

Early detection has been hailed by the American CancerSociety and the National Cancer Institute as the answer tocancer. The first enthusiasts maintained that routine mammo-

graphy would halve the death-rate from breast cancer over thenext 20 years. But the initial flush of evangelism has nowwaned, and the National Institutes of Health recently calledtogether a special panel, headed by Dr Samuel Thier, chair-man of the department of medicine at Yale University, to holdpublic hearings on the federal programme for the early detec-tion of breast cancer. The panel has paid particular attentionto routine mammography and its application as a screeningprocedure, and though its recommendations are intended forthe federal programme, it is hoped that private practitionerswill likewise adopt them. The panel agreed that screeningwomen over 50 is useful in the detection of breast cancer, and

they also felt it was probably beneficial, although some epidem-iologists doubt this. But they decided that screening womenunder the age of 50 has not been shown to be effective, andindeed, that there was evidence to suggest that mammographyin this group was likely to be harmful and might induce malig-nant disease at a later date. Moreover, in their opinion thebreast-cancer detection demonstration project devised by theNational Cancer Institute had been poorly designed. Out of the1850 women diagnosed as having breast cancer, no less than

66 turned out to be false-positives and in a further 22 womenthe pathologists were uncertain as to whether the tumour wasmalignant. All the women in these two groups had had surgery-in many instances a radical mastectomy. The suggestionwas put forward that carcinoma of the breast might occur "insitu" in the same fashion that non-invasive carcinoma of the

prostate is often found at a routine necropsy.The N.I.H. hierarchy have throughout the years avoided

any activity that might be construed as technology assessmentor instrument testing. This seems a not unreasonableapproach, the fear being that their research efforts would bediluted and compromised by such involvement. But Congres-sional pressures are making it more and more difficult for themto avoid entanglement in the evaluation of technology. Therecent hearings on the early detection of breast cancer haveclearly established a precedent.

ACCESS TO INFORMATION

THE latest craze in this country is the demand for free accessto information in the day-to-day files of all sorts of official andunofficial institutions. This has come to be regarded as a con-stitutional right, legally enforceable and socially desirable. Thefiles of F.B.I. and the C.I.A. and of various governmental regu-latory agencies have been raked over by journalists, writers,lawyers, and members of the public. As a result attempts havebeen made to reopen long-decided legal cases, to re-try con-victed, even executed, individuals, and to try to discover injus-tices, illegalities, and malfeasances, especially those allegedlycommitted by Government agencies. Unpleasant allegationshave been made against scientists and others, some of themlong dead and unable to defend themselves, some living, whohave been dragged out of retirement to be questioned and har-ried by Congressional committees for advice given and actionstaken long, long ago and in a very different social, political,and economic climate. The astonishing thing is that there hasbeen little general opposition to the doctrine that public accessto all information should be unrestricted.

All the evil consequences of free access have yet to revealthemselves, but there have been some quite ludicrous situ-ations. As is often the case, these become evident in mattersmedical. The Board of Regents in New York State have madea new rule on a patient’s rights of access to personal medicalrecords, a ruling that the State’s Medical Society is now con-testing. The society’s legal advisers interpret the rule as mean-ing that, on the patient’s demand, a physician is compelled toreveal to the patient, and to someone designated by the pa-tient, the total medical record of the patient. This would beobligatory, regardless of whether the patient had or had notpaid for the services rendered. The effects of this rule can wellbe imagined: physicians will simply give up recording their fullfindings and opinions. They will not dare to say anything ques-tionable or which might adversely reflect on a third party. Ifthe doctors are right to be chary with their sane, well-balancedpatients, what of the neurotic, the alcoholic, the malicious, thepsychotic? What will be their reactions on reading their ownmedical records? It is very hard to see how the patient will ben-efit from this new right, and the danger is that in the prevail-ing atmosphere the right will not for long be restricted to thepatient and his or her designee.

If the legal decision comes down on the side of restrictingthe patient’s right of access to medical records, perhaps therewill be a backlash against the more ridiculous aspects of thismania for free access to information, which will re-establishthe right of Government agencies, and institutions of all sorts,to solicit and receive confidential advice. The value of protect-ing this right has become evident even in the academic world,where students have become vociferous in insisting on theirright to see all statements made about them. The result hasbeen that no-one has felt free to make unfavourable comments,and reports about students have become so non-committal asto be useless.

66 turned out to be false-positives and in a further 22 womenthe pathologists were uncertain as to whether the tumour wasmalignant. All the women in these two groups had had surgery-in many instances a radical mastectomy. The suggestionwas put forward that carcinoma of the breast might occur "insitu" in the same fashion that non-invasive carcinoma of the

prostate is often found at a routine necropsy.The N.I.H. hierarchy have throughout the years avoided

any activity that might be construed as technology assessmentor instrument testing. This seems a not unreasonableapproach, the fear being that their research efforts would bediluted and compromised by such involvement. But Congres-sional pressures are making it more and more difficult for themto avoid entanglement in the evaluation of technology. Therecent hearings on the early detection of breast cancer haveclearly established a precedent.

ACCESS TO INFORMATION

THE latest craze in this country is the demand for free accessto information in the day-to-day files of all sorts of official andunofficial institutions. This has come to be regarded as a con-stitutional right, legally enforceable and socially desirable. Thefiles of F.B.I. and the C.I.A. and of various governmental regu-latory agencies have been raked over by journalists, writers,lawyers, and members of the public. As a result attempts havebeen made to reopen long-decided legal cases, to re-try con-victed, even executed, individuals, and to try to discover injus-tices, illegalities, and malfeasances, especially those allegedlycommitted by Government agencies. Unpleasant allegationshave been made against scientists and others, some of themlong dead and unable to defend themselves, some living, whohave been dragged out of retirement to be questioned and har-ried by Congressional committees for advice given and actionstaken long, long ago and in a very different social, political,and economic climate. The astonishing thing is that there hasbeen little general opposition to the doctrine that public accessto all information should be unrestricted.

All the evil consequences of free access have yet to revealthemselves, but there have been some quite ludicrous situ-ations. As is often the case, these become evident in mattersmedical. The Board of Regents in New York State have madea new rule on a patient’s rights of access to personal medicalrecords, a ruling that the State’s Medical Society is now con-testing. The society’s legal advisers interpret the rule as mean-ing that, on the patient’s demand, a physician is compelled toreveal to the patient, and to someone designated by the pa-tient, the total medical record of the patient. This would beobligatory, regardless of whether the patient had or had notpaid for the services rendered. The effects of this rule can wellbe imagined: physicians will simply give up recording their fullfindings and opinions. They will not dare to say anything ques-tionable or which might adversely reflect on a third party. Ifthe doctors are right to be chary with their sane, well-balancedpatients, what of the neurotic, the alcoholic, the malicious, thepsychotic? What will be their reactions on reading their ownmedical records? It is very hard to see how the patient will ben-efit from this new right, and the danger is that in the prevail-ing atmosphere the right will not for long be restricted to thepatient and his or her designee.

If the legal decision comes down on the side of restrictingthe patient’s right of access to medical records, perhaps therewill be a backlash against the more ridiculous aspects of thismania for free access to information, which will re-establishthe right of Government agencies, and institutions of all sorts,to solicit and receive confidential advice. The value of protect-ing this right has become evident even in the academic world,where students have become vociferous in insisting on theirright to see all statements made about them. The result hasbeen that no-one has felt free to make unfavourable comments,and reports about students have become so non-committal asto be useless.