1070 so we will not be able to look at the way in which decisions 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 consumers, but not with workers or natural environment. So each manufacturer will have to assemble data, and may have to submit it to several bodies. Who will decide whether a new chemical should be used or not? We are in danger of losing valuable new products and processes, not because they are hazardous, but because our efforts to reduce hazard have produced a jungle of office work through 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.
secret,
Points of View TESTING OF INDUSTRIAL CHEMICALS SOME five hundred new chemicals are introduced into each year.’ Until now it has been quite usual for the toxicity of a new chemical to remain undiscovered until the workers fell ill or died, as happened with beryllium, vinyl chloride, asbestos, nitrosamines, and -naphthylamine.2 This is clearly intolerable. The Health and Safety Commission and its Executive (H.S.E.) have the duty of working towards health and safety at work, and have put forward a scheme in which all new chemicals should be tested before use.3The scheme is, so far, limited to new chemicals made or imported in amounts of one tonne a year or more. The suggested procedures comprise the following:
commerce
1. Observation of the effects on rats of a single dose in the lethal 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 new chemical. The information on toxicity would permit the factory inspectorate and other H.S.E. staff to warn intending 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 the working population are protected from new hazards at work. But there are underlying drawbacks. Firstly, the scheme takes no account of consumer or environment. These are not a target of H.S.E. attention, but both European Economic Community and U.K. legislation will certainly move towards consumer and environmental protection against new chemicals. So shall we have three bodies examining chemicals, each with its own rules? The Pesticide Safety Precautions Scheme (P.S.P.S.) deals with all three aspects-worker, consumer, and natural environment- and has had considerable success in dealing with these intrinsically dangerous chemicals. But P.S.P.S. can insist on full testing of a new pesticide, at a cost of perhaps 1 million, because of the great economic importance of successful new pesticides. The H.S.E. scheme is a "mini" toxicity test, costing about c5000 per chemical. Is this enough? Or is it too much, in that it is k5000 spent with little useful information at the end, but a cost that might prevent some useful chemicals from ever starting? Moreover, the information gathered by H.S.E. will be kept 1.
Page, N. P. in Environmental Cancer (edited by H. F. Kraybill and 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 Toxic Properties of Substances. H. M. Stationery Office. 1977.
M. A.
of the
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.
Toxicity is measured. Model systems are set up. We meainjurious effects of known doses of the chemical to animals living in controlled conditions. Or else we use bacteria to 1.
sure
see if the substance causes mutations, tissue culture to look at chromosome breaks, and birds, beasts, plants, and activated sludge to measure interactions with living systems. In particular the relation of dose to response, and the mechanism and tissues affected are sought. 2. Hazard is assessed. When we know the intended use, we can estimate exposure of people who may be in contact with the chemical in the factory or working as farm sprayers. Using the estimated dose to man, and the measured toxicity in our animal and model systems, we try to infer whether there is likely to be any ill-effect on the exposed population. This requires knowledge of the engineering processes. How much of a toxic gas such as vinyl chloride will escape from the polymeriser pots where it is turned into P.v.c.? How well ventilated is the factory floor? What protective clothing do farm workers really wear? 3. Risk is evaluated. Essentially all activity carries risk. Lying in bed dissolves bones; motor cycling and climbing mountains lead to broken bones. We have to decide whether the risks involved in the use of a new chemical are justified by the potential benefits, to process workers and to society. This is a political, not a medical, decision. The role of doctor and scientist is to give the best advice about risks, benefits, and alternatives. 4. Epidemiological follow-up-Because species differ, and no animal tests can go on as long as the human lifespan, and because human exposure includes men who drink too much or smoke cigarettes, or pregnant women or men with atheromatous arteries, our predictions of hazard are insecure. We have to monitor our population to see if unanticipated risks turn up. The side-effects of new drugs remind us of the wide variety of unexpected ill-effects that show up when large numbers of
people 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 that step 1 (toxicity measurement) be carried out in a small way and without reference to intended use of the new chemical. As a result the wrong tests may well be done. If a substance is to be used as a spray it must be tested by inhalation; if it will be a residue on food, it must be tried by mouth. But, in particular, the scheme does not make it clear to industry that the evaluation of hazard from new chemicals can be done only in a series of steps which must culminate in careful observation and recording 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 toxicologists in this country is probably not sufficient to do the testing, quite apart from the need for people to look at the data and evaluate its meaning. False-negative results will harm
workers, in the particular factory
or
process;
1071
false-positives will harm society as a whole, in preventing improved production methods. There are no university departments of toxicology in the U.K., so the shortage of thoughtful toxicologists is likely to continue. Perhaps some aspects of toxicology should become part of undergraduate courses in medicine, chemistry, and biology. The difficult decision is how best to spend society’s resources to improve the quality of life for all of us, in our capacities as workers and consumers. P.v.c. is made by process workers some of whom have to climb into the big pressure vessels to clean up after the vinyl chloride gas has been polymerised. In the past around 3% of these men got bone disease and perhaps 0-1% got liver disease or liver cancer after about ten years of exposure to 200 parts per million or more of v.c. gas in the inspired air. By spending some z1000 per worker the exposure of all the process workers can be greatly reduced (less than 20 p.p.m.) with a resulting increase of about 2 per tonne in the price of P.v.c. There are 200 deaths per annum on the building sites in the U.K. There has been perhaps one death per annum from vinyl-chloride disease. Should we spend equivalent amounts to improve safety in building? It is fashionable to work on chemical hazards, but are we looking too much at insidious poison and not enough at the dangers of falling bricks and of tractors that turn over? About 1% of the gross national product is expended on measures to combat environmental pollution.4 Is it being spent in the right way? ,
Laboratory of Toxicology, Department of Clinical Pharmacology, University College Hospital Medical School, London WC1E 6JJ. 4. The Times, Oct
A. E. M. MCLEAN
25, 1977, p. 19.
Round the World United States
66 turned out to be false-positives and in a further 22 women the pathologists were uncertain as to whether the tumour was malignant. All the women in these two groups had had surgery -in many instances a radical mastectomy. The suggestion was put forward that carcinoma of the breast might occur "in situ" 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 assessment or instrument testing. This seems a not unreasonable approach, the fear being that their research efforts would be diluted and compromised by such involvement. But Congressional pressures are making it more and more difficult for them to avoid entanglement in the evaluation of technology. The recent hearings on the early detection of breast cancer have clearly established a precedent.
ACCESS TO INFORMATION craze in this country is the demand for free access information in the day-to-day files of all sorts of official and unofficial institutions. This has come to be regarded as a constitutional right, legally enforceable and socially desirable. The files of F.B.I. and the C.I.A. and of various governmental regulatory agencies have been raked over by journalists, writers, lawyers, and members of the public. As a result attempts have been made to reopen long-decided legal cases, to re-try convicted, even executed, individuals, and to try to discover injustices, illegalities, and malfeasances, especially those allegedly committed by Government agencies. Unpleasant allegations have been made against scientists and others, some of them long dead and unable to defend themselves, some living, who have been dragged out of retirement to be questioned and harried by Congressional committees for advice given and actions taken long, long ago and in a very different social, political, and economic climate. The astonishing thing is that there has been little general opposition to the doctrine that public access to all information should be unrestricted. All the evil consequences of free access have yet to reveal themselves, but there have been some quite ludicrous situations. As is often the case, these become evident in matters medical. The Board of Regents in New York State have made a new rule on a patient’s rights of access to personal medical records, a ruling that the State’s Medical Society is now contesting. The society’s legal advisers interpret the rule as mean-
THE latest
to
the patient’s demand, a physician is compelled to the patient, and to someone designated by the patient, the total medical record of the patient. This would be obligatory, regardless of whether the patient had or had not paid for the services rendered. The effects of this rule can well be imagined: physicians will simply give up recording their full findings and opinions. They will not dare to say anything questionable or which might adversely reflect on a third party. If the doctors are right to be chary with their sane, well-balanced patients, what of the neurotic, the alcoholic, the malicious, the psychotic? What will be their reactions on reading their own medical records? It is very hard to see how the patient will benefit from this new right, and the danger is that in the prevailing atmosphere the right will not for long be restricted to the patient and his or her designee. If the legal decision comes down on the side of restricting the patient’s right of access to medical records, perhaps there will be a backlash against the more ridiculous aspects of this mania for free access to information, which will re-establish the right of Government agencies, and institutions of all sorts, to solicit and receive confidential advice. The value of protecting this right has become evident even in the academic world, where students have become vociferous in insisting on their right to see all statements made about them. The result has been that no-one has felt free to make unfavourable comments, and reports about students have become so non-committal as to be useless.
ing that,
reveal
SCREENING FOR BREAST CANCER
Early detection has been hailed by the American Cancer Society and the National Cancer Institute as the answer to cancer.
The first enthusiasts maintained that routine
mammo-
graphy would halve the death-rate from breast cancer over the next 20 years. But the initial flush of evangelism has now waned, and the National Institutes of Health recently called together a special panel, headed by Dr Samuel Thier, chairman of the department of medicine at Yale University, to hold public hearings on the federal programme for the early detection of breast cancer. The panel has paid particular attention to routine mammography and its application as a screening procedure, and though its recommendations are intended for the federal programme, it is hoped that private practitioners will likewise adopt them. The panel agreed that screening women over
50 is useful in the detection of breast cancer, and
they also felt it was probably beneficial, although some epidemiologists doubt this. But they decided that screening women under the age of 50 has
not been shown to be effective, and evidence to suggest that mammography in this group was likely to be harmful and might induce malignant disease at a later date. Moreover, in their opinion the breast-cancer detection demonstration project devised by the National Cancer Institute had been poorly designed. Out of the 1850 women diagnosed as having breast cancer, no less than
indeed, that there
was
to
on
secret,
Points of View TESTING OF INDUSTRIAL CHEMICALS SOME five hundred new chemicals are introduced into each year.’ Until now it has been quite usual for the toxicity of a new chemical to remain undiscovered until the workers fell ill or died, as happened with beryllium, vinyl chloride, asbestos, nitrosamines, and -naphthylamine.2 This is clearly intolerable. The Health and Safety Commission and its Executive (H.S.E.) have the duty of working towards health and safety at work, and have put forward a scheme in which all new chemicals should be tested before use.3The scheme is, so far, limited to new chemicals made or imported in amounts of one tonne a year or more. The suggested procedures comprise the following:
commerce
1. Observation of the effects on rats of a single dose in the lethal 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 new chemical. The information on toxicity would permit the factory inspectorate and other H.S.E. staff to warn intending 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 the working population are protected from new hazards at work. But there are underlying drawbacks. Firstly, the scheme takes no account of consumer or environment. These are not a target of H.S.E. attention, but both European Economic Community and U.K. legislation will certainly move towards consumer and environmental protection against new chemicals. So shall we have three bodies examining chemicals, each with its own rules? The Pesticide Safety Precautions Scheme (P.S.P.S.) deals with all three aspects-worker, consumer, and natural environment- and has had considerable success in dealing with these intrinsically dangerous chemicals. But P.S.P.S. can insist on full testing of a new pesticide, at a cost of perhaps 1 million, because of the great economic importance of successful new pesticides. The H.S.E. scheme is a "mini" toxicity test, costing about c5000 per chemical. Is this enough? Or is it too much, in that it is k5000 spent with little useful information at the end, but a cost that might prevent some useful chemicals from ever starting? Moreover, the information gathered by H.S.E. will be kept 1.
Page, N. P. in Environmental Cancer (edited by H. F. Kraybill and 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 Toxic Properties of Substances. H. M. Stationery Office. 1977.
M. A.
of the
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.
Toxicity is measured. Model systems are set up. We meainjurious effects of known doses of the chemical to animals living in controlled conditions. Or else we use bacteria to 1.
sure
see if the substance causes mutations, tissue culture to look at chromosome breaks, and birds, beasts, plants, and activated sludge to measure interactions with living systems. In particular the relation of dose to response, and the mechanism and tissues affected are sought. 2. Hazard is assessed. When we know the intended use, we can estimate exposure of people who may be in contact with the chemical in the factory or working as farm sprayers. Using the estimated dose to man, and the measured toxicity in our animal and model systems, we try to infer whether there is likely to be any ill-effect on the exposed population. This requires knowledge of the engineering processes. How much of a toxic gas such as vinyl chloride will escape from the polymeriser pots where it is turned into P.v.c.? How well ventilated is the factory floor? What protective clothing do farm workers really wear? 3. Risk is evaluated. Essentially all activity carries risk. Lying in bed dissolves bones; motor cycling and climbing mountains lead to broken bones. We have to decide whether the risks involved in the use of a new chemical are justified by the potential benefits, to process workers and to society. This is a political, not a medical, decision. The role of doctor and scientist is to give the best advice about risks, benefits, and alternatives. 4. Epidemiological follow-up-Because species differ, and no animal tests can go on as long as the human lifespan, and because human exposure includes men who drink too much or smoke cigarettes, or pregnant women or men with atheromatous arteries, our predictions of hazard are insecure. We have to monitor our population to see if unanticipated risks turn up. The side-effects of new drugs remind us of the wide variety of unexpected ill-effects that show up when large numbers of
people 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 that step 1 (toxicity measurement) be carried out in a small way and without reference to intended use of the new chemical. As a result the wrong tests may well be done. If a substance is to be used as a spray it must be tested by inhalation; if it will be a residue on food, it must be tried by mouth. But, in particular, the scheme does not make it clear to industry that the evaluation of hazard from new chemicals can be done only in a series of steps which must culminate in careful observation and recording 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 toxicologists in this country is probably not sufficient to do the testing, quite apart from the need for people to look at the data and evaluate its meaning. False-negative results will harm
workers, in the particular factory
or
process;
1071
false-positives will harm society as a whole, in preventing improved production methods. There are no university departments of toxicology in the U.K., so the shortage of thoughtful toxicologists is likely to continue. Perhaps some aspects of toxicology should become part of undergraduate courses in medicine, chemistry, and biology. The difficult decision is how best to spend society’s resources to improve the quality of life for all of us, in our capacities as workers and consumers. P.v.c. is made by process workers some of whom have to climb into the big pressure vessels to clean up after the vinyl chloride gas has been polymerised. In the past around 3% of these men got bone disease and perhaps 0-1% got liver disease or liver cancer after about ten years of exposure to 200 parts per million or more of v.c. gas in the inspired air. By spending some z1000 per worker the exposure of all the process workers can be greatly reduced (less than 20 p.p.m.) with a resulting increase of about 2 per tonne in the price of P.v.c. There are 200 deaths per annum on the building sites in the U.K. There has been perhaps one death per annum from vinyl-chloride disease. Should we spend equivalent amounts to improve safety in building? It is fashionable to work on chemical hazards, but are we looking too much at insidious poison and not enough at the dangers of falling bricks and of tractors that turn over? About 1% of the gross national product is expended on measures to combat environmental pollution.4 Is it being spent in the right way? ,
Laboratory of Toxicology, Department of Clinical Pharmacology, University College Hospital Medical School, London WC1E 6JJ. 4. The Times, Oct
A. E. M. MCLEAN
25, 1977, p. 19.
Round the World United States
66 turned out to be false-positives and in a further 22 women the pathologists were uncertain as to whether the tumour was malignant. All the women in these two groups had had surgery -in many instances a radical mastectomy. The suggestion was put forward that carcinoma of the breast might occur "in situ" 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 assessment or instrument testing. This seems a not unreasonable approach, the fear being that their research efforts would be diluted and compromised by such involvement. But Congressional pressures are making it more and more difficult for them to avoid entanglement in the evaluation of technology. The recent hearings on the early detection of breast cancer have clearly established a precedent.
ACCESS TO INFORMATION craze in this country is the demand for free access information in the day-to-day files of all sorts of official and unofficial institutions. This has come to be regarded as a constitutional right, legally enforceable and socially desirable. The files of F.B.I. and the C.I.A. and of various governmental regulatory agencies have been raked over by journalists, writers, lawyers, and members of the public. As a result attempts have been made to reopen long-decided legal cases, to re-try convicted, even executed, individuals, and to try to discover injustices, illegalities, and malfeasances, especially those allegedly committed by Government agencies. Unpleasant allegations have been made against scientists and others, some of them long dead and unable to defend themselves, some living, who have been dragged out of retirement to be questioned and harried by Congressional committees for advice given and actions taken long, long ago and in a very different social, political, and economic climate. The astonishing thing is that there has been little general opposition to the doctrine that public access to all information should be unrestricted. All the evil consequences of free access have yet to reveal themselves, but there have been some quite ludicrous situations. As is often the case, these become evident in matters medical. The Board of Regents in New York State have made a new rule on a patient’s rights of access to personal medical records, a ruling that the State’s Medical Society is now contesting. The society’s legal advisers interpret the rule as mean-
THE latest
to
the patient’s demand, a physician is compelled to the patient, and to someone designated by the patient, the total medical record of the patient. This would be obligatory, regardless of whether the patient had or had not paid for the services rendered. The effects of this rule can well be imagined: physicians will simply give up recording their full findings and opinions. They will not dare to say anything questionable or which might adversely reflect on a third party. If the doctors are right to be chary with their sane, well-balanced patients, what of the neurotic, the alcoholic, the malicious, the psychotic? What will be their reactions on reading their own medical records? It is very hard to see how the patient will benefit from this new right, and the danger is that in the prevailing atmosphere the right will not for long be restricted to the patient and his or her designee. If the legal decision comes down on the side of restricting the patient’s right of access to medical records, perhaps there will be a backlash against the more ridiculous aspects of this mania for free access to information, which will re-establish the right of Government agencies, and institutions of all sorts, to solicit and receive confidential advice. The value of protecting this right has become evident even in the academic world, where students have become vociferous in insisting on their right to see all statements made about them. The result has been that no-one has felt free to make unfavourable comments, and reports about students have become so non-committal as to be useless.
ing that,
reveal
SCREENING FOR BREAST CANCER
Early detection has been hailed by the American Cancer Society and the National Cancer Institute as the answer to cancer.
The first enthusiasts maintained that routine
mammo-
graphy would halve the death-rate from breast cancer over the next 20 years. But the initial flush of evangelism has now waned, and the National Institutes of Health recently called together a special panel, headed by Dr Samuel Thier, chairman of the department of medicine at Yale University, to hold public hearings on the federal programme for the early detection of breast cancer. The panel has paid particular attention to routine mammography and its application as a screening procedure, and though its recommendations are intended for the federal programme, it is hoped that private practitioners will likewise adopt them. The panel agreed that screening women over
50 is useful in the detection of breast cancer, and
they also felt it was probably beneficial, although some epidemiologists doubt this. But they decided that screening women under the age of 50 has
not been shown to be effective, and evidence to suggest that mammography in this group was likely to be harmful and might induce malignant disease at a later date. Moreover, in their opinion the breast-cancer detection demonstration project devised by the National Cancer Institute had been poorly designed. Out of the 1850 women diagnosed as having breast cancer, no less than
indeed, that there
was
to
on
