1068

depression, 2 patients with mania, and 1 patient withschizophrenia refused admission and were offered eitherday-patient or outpatient treatment as an alternative.Almost a third of the patients were referred back to theirgeneral practitioner with advice on treatment and man-agement.

6. Factors Precipitating ReferralThe reasons for urgent referral, based on information

from the referring sources, are shown in the accompany-ing table. The term "social stress" used in the tablerefers to the loss, or threatened loss, of one or moresocial supports in the patient’s life-e.g., marital break-down, separation, or loss of job or accommodation.

"Referring-agency anxiety" often appeared to stem frommanipulative or attention-seeking behaviour superim-posed on a long-standing problem.

DISCUSSION ’

Only 34% of patients were considered to warranturgent psychiatric assessment. Reviewing these 34 cases,three significant contributing factors emerged:

1. Clinical considerations.-An acute onset of a well-defined

psychiatric illness, either de novo or a relapse, or a patient pre-senting with complex and multiple symptoms which alarmedthe referring agency.

2. Patient’s behaviour.-This was either a patient’sexpressed intent of harming himself, or alarming and unpre-dictable behaviour which aroused anxiety within the patient’ssocial setting. In only two cases did patients threaten to harmothers.

3. Social stress factors.-Any breakdown of the patient’ssignificant social milieu, or social isolation per se, which preci-pitated action by the referring agent.

All 34 "urgent" patients demonstrated at least two ofthe above factors and, retrospectively, it is for this rea-son that we considered they warranted urgent assess-ment. The two commonest factors were clinical con-siderations and the patient’s behaviour. Significantsocial stress factors predominated in only 10 of the 34cases. In 29 of the 34 cases the patient’s behaviourappeared to be the single most important contributingfactor.The most important criteria for admission were be-

havioural and clinical considerations. All 10 patientsadmitted directly from the clinic were either a serioussuicidal risk or demonstrated unpredictable behaviourwhich could have been harmful. 8 of these 10 had a

clearly defined psychotic illness (either depressive orschizophrenic), and the other 2 had severe reactive

depression. In this respect our findings agree with thoseof Gleisner and others,S who showed that schizophreniaand affective psychoses were the commonest diagnosesamong psychiatric admissions.

CONCLUSIONS

Two-thirds of our sample were not considered to needurgent psychiatric assessment or treatment. It seemsthat one of the major functions of such a clinic is toidentify patients who are likely to respond to particularpsychiatric services, and to avoid unnecessary admis-sion.The study also shows that many referring doctors find

the significance of disturbed behaviour difficult to assess;an important function of the clinic, therefore, is to

depression, 2 patients with mania, and 1 patient withschizophrenia refused admission and were offered eitherday-patient or outpatient treatment as an alternative.Almost a third of the patients were referred back to theirgeneral practitioner with advice on treatment and man-agement.

6. Factors Precipitating ReferralThe reasons for urgent referral, based on information

from the referring sources, are shown in the accompany-ing table. The term "social stress" used in the tablerefers to the loss, or threatened loss, of one or moresocial supports in the patient’s life-e.g., marital break-down, separation, or loss of job or accommodation.

"Referring-agency anxiety" often appeared to stem frommanipulative or attention-seeking behaviour superim-posed on a long-standing problem.

DISCUSSION ’

Only 34% of patients were considered to warranturgent psychiatric assessment. Reviewing these 34 cases,three significant contributing factors emerged:

1. Clinical considerations.-An acute onset of a well-defined

psychiatric illness, either de novo or a relapse, or a patient pre-senting with complex and multiple symptoms which alarmedthe referring agency.

2. Patient’s behaviour.-This was either a patient’sexpressed intent of harming himself, or alarming and unpre-dictable behaviour which aroused anxiety within the patient’ssocial setting. In only two cases did patients threaten to harmothers.

3. Social stress factors.-Any breakdown of the patient’ssignificant social milieu, or social isolation per se, which preci-pitated action by the referring agent.

All 34 "urgent" patients demonstrated at least two ofthe above factors and, retrospectively, it is for this rea-son that we considered they warranted urgent assess-ment. The two commonest factors were clinical con-siderations and the patient’s behaviour. Significantsocial stress factors predominated in only 10 of the 34cases. In 29 of the 34 cases the patient’s behaviourappeared to be the single most important contributingfactor.The most important criteria for admission were be-

havioural and clinical considerations. All 10 patientsadmitted directly from the clinic were either a serioussuicidal risk or demonstrated unpredictable behaviourwhich could have been harmful. 8 of these 10 had a

clearly defined psychotic illness (either depressive orschizophrenic), and the other 2 had severe reactive

depression. In this respect our findings agree with thoseof Gleisner and others,S who showed that schizophreniaand affective psychoses were the commonest diagnosesamong psychiatric admissions.

CONCLUSIONS

Two-thirds of our sample were not considered to needurgent psychiatric assessment or treatment. It seemsthat one of the major functions of such a clinic is toidentify patients who are likely to respond to particularpsychiatric services, and to avoid unnecessary admis-sion.The study also shows that many referring doctors find

the significance of disturbed behaviour difficult to assess;an important function of the clinic, therefore, is to

provide such assessment for general practitioners.By having students attend the clinic as part of their

undergraduate course in psychiatry we hope that theywill feel more able to cope with the psychiatric problemsthey will encounter in their clinical practice.

Requests for reprints should be addressed to D. A. S.

provide such assessment for general practitioners.By having students attend the clinic as part of their

undergraduate course in psychiatry we hope that theywill feel more able to cope with the psychiatric problemsthey will encounter in their clinical practice.

Requests for reprints should be addressed to D. A. S.

REFERENCES

1. Robin, A. Br. J. Psychiat. 1976, 128, 138.2. Shepherd, M., Cooper, B., Brown, A. C., Kalton, G. Psychiatric Illness in

General Practice. London, 19663. Brothwood, J. Br. J. Psychiat. 1965, 111, 631.4. Mindham, R. H. S., Kelleher, M. J., Birley, J. L. T. Lancet, 1973, i, 1169.5. Gleisner, J., Hewett, S., Mann, S. Evaluating a Community Psychiatric Ser-

vice. The Camberwell Register, chap. 13, p. 199. London, 1972.

Occasional Survey

EVALUATING THE TREATMENT OF RENALFAILURE BY DIALYSIS AND

TRANSPLANTATION

MARTIN S. KNAPP

Renal Unit, City Hospital, Nottingham NG5 1PD

EVALUATION of drug treatment was very imprecisebefore proper attention was given to patient selection,observer bias, and other variables. New drugs are nowevaluated by objective methods. Any new treatment canbe judged with similar techniques, but these have notbeen applied to the treatment of renal failure by dialysisor transplantation.

In Britain most patients treated receive home dialysis. Thereis some evidence’ that home dialysis is associated with a lowermortality and that it is cheaper; but this conclusion is notbased on trials of the standard used to assess drugs. The maincriticism is that there may have been biased allocation to thetwo treatment groups. Many patients treated by hospital di-alysis will probably have adverse prognostic features. Roberts’report on the results of home dialysis in twelve U.S.A. centres,2is one of the very few to provide details of the patients com-pared. Roberts found that 5-year mortality varied betweencentres from 28% to 82%. Certain features significantly in-fluenced survival--e.g., age, nature of renal disease, and"health status" at the start of dialysis. Any study of the treat-ment of renal failure must provide the percentages of patientswith such adverse features. This is rarely done, although someworkers have adjusted for certain factors (e.g. for age, by com-paring results in restricted age-groups). The ideal is a prospec-tive randomised trial of two treatments with no change inmanagement. After the trial, the patients in each group wouldbe compared to ensure that the random allocation had, ashoped, provided two matched groups. Factors thought to in-fluence the outcome of treatment by dialysis or transplantationinclude:

Factors Possibly Influencing Dialysis Mortality

AgeDiagnosis

Associated disorders (e.g., diabetes mellitus, hypertension)Clinical state at start of dialysis

Socioeconomic statusType of unit providing treatment (e.g., size, experience inyears, patients treated, population needing treatment).

EVALUATION of drug treatment was very imprecisebefore proper attention was given to patient selection,observer bias, and other variables. New drugs are nowevaluated by objective methods. Any new treatment canbe judged with similar techniques, but these have notbeen applied to the treatment of renal failure by dialysisor transplantation.

In Britain most patients treated receive home dialysis. Thereis some evidence’ that home dialysis is associated with a lowermortality and that it is cheaper; but this conclusion is notbased on trials of the standard used to assess drugs. The maincriticism is that there may have been biased allocation to thetwo treatment groups. Many patients treated by hospital di-alysis will probably have adverse prognostic features. Roberts’report on the results of home dialysis in twelve U.S.A. centres,2is one of the very few to provide details of the patients com-pared. Roberts found that 5-year mortality varied betweencentres from 28% to 82%. Certain features significantly in-fluenced survival--e.g., age, nature of renal disease, and"health status" at the start of dialysis. Any study of the treat-ment of renal failure must provide the percentages of patientswith such adverse features. This is rarely done, although someworkers have adjusted for certain factors (e.g. for age, by com-paring results in restricted age-groups). The ideal is a prospec-tive randomised trial of two treatments with no change inmanagement. After the trial, the patients in each group wouldbe compared to ensure that the random allocation had, ashoped, provided two matched groups. Factors thought to in-fluence the outcome of treatment by dialysis or transplantationinclude:

Factors Possibly Influencing Dialysis Mortality

AgeDiagnosis

Associated disorders (e.g., diabetes mellitus, hypertension)Clinical state at start of dialysis

Socioeconomic statusType of unit providing treatment (e.g., size, experience inyears, patients treated, population needing treatment).

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AdditionalFactors Possibly Influencing Transplantation

Age of donorWarm-time of donor kidney

HistocompatibilityNumber of transfusions given to recipients

Duration of pre-transplant dialysisAvailability of dialysis if transplant fails

Retrospective studies of series of patients, the standardmethod in most analyses to date, usually fail to establish thatthe way the method of treatment was decided on had notresulted in critical differences between the groups, other thanthe difference being considered.Transplantation is now an acceptable alternative to dialysis.

There are financial and social reasons for favouring this

approach, but mortality figures tend to favour dialysis, espe-cially in older patients. These comparisons are, however, opento the criticism levelled at comparisons between results ofhome dialysis and hospital dialysis. Clinical decisions are in-fluenced by these published comparisons, despite the strongpossibility that there are important differences between thetypes of patients receiving transplantation and those receivingdialysis only. The result is that a treatment is chosen that willproduce results confirming the early trends, because "goodrisk" patients are not subjected to an apparently more dan-gerous treatment. If transplantation is chosen, problems arisewith tissue-typing. The choice of a recipient for an availablecadaver kidney will be influenced by the opinions of the renalphysician and the transplant team. Doctors who feel that tis-sue-typing is important tend to decline a poorly matched kid-ney for a patient doing well on dialysis but they might acceptsuch a kidney for a patient doing less well. It is probable thatthe factors which contribute to good progress after transplan-tation are similar to those which result in prolonged survivalon dialysis. Decisions taken on clinical grounds rather than byrandom allocation are, therefore, likely to result in one group(probably that treated by transplantation with a poorlymatched kidney) having an excess of patients with a poor prog-nosis. The onus of proving that this has not happened shouldbe on those, such as Festenstein et al.,3 who publish apparentlystatistically significant evidence that tissue-typing is impor-tant.

It is ten years since HLA typing was introduced, and largesums of money have been spent on its application to renaltransplantation, but convincing evidence for the benefit ofHLA typing in cadaver-kidney transplantation has yet to

appear. More detailed analysis of data already collected or aproperly organised trial are needed to prove that histocompati-bility typing is clinically important for first cadaver trans-

plants. Considerable savings can be achieved by kidney trans-plantation earlier in the course of severe renal failure,’ but thisis not usually possible unless HLA typing is given a low pri-ority. This has been the policy in Nottingham for first trans-plants, and the results are almost identical to U.K. averages,’except that the mean waiting-time for cadaver transplantationis less than 4 months.

Many units have now collected enough data to pub-lish reviews of their experience with transplantation orregular dialysis. These provide material that allows com-parisons between units using different policies and alsoallow important conclusions about treatment. The highsuccess-rate in certain units (e.g., in Australia6) whichdo not rely extensively on histocompatibility results isone fact that supporters of tissue-typing find difficult toexplain. Comparisons between units, made possible bypublication of their results, are likely to be valid only ifdata on likely prognostic factors are included. Anotheruseful statistic, especially for units serving a definedpopulation, is the number of transplants per million ofpopulation per year, especially if the numbers put on

regular dialysis and/or transplantation are also

AdditionalFactors Possibly Influencing Transplantation

Age of donorWarm-time of donor kidney

HistocompatibilityNumber of transfusions given to recipients

Duration of pre-transplant dialysisAvailability of dialysis if transplant fails

Retrospective studies of series of patients, the standardmethod in most analyses to date, usually fail to establish thatthe way the method of treatment was decided on had notresulted in critical differences between the groups, other thanthe difference being considered.Transplantation is now an acceptable alternative to dialysis.

There are financial and social reasons for favouring this

approach, but mortality figures tend to favour dialysis, espe-cially in older patients. These comparisons are, however, opento the criticism levelled at comparisons between results ofhome dialysis and hospital dialysis. Clinical decisions are in-fluenced by these published comparisons, despite the strongpossibility that there are important differences between thetypes of patients receiving transplantation and those receivingdialysis only. The result is that a treatment is chosen that willproduce results confirming the early trends, because "goodrisk" patients are not subjected to an apparently more dan-gerous treatment. If transplantation is chosen, problems arisewith tissue-typing. The choice of a recipient for an availablecadaver kidney will be influenced by the opinions of the renalphysician and the transplant team. Doctors who feel that tis-sue-typing is important tend to decline a poorly matched kid-ney for a patient doing well on dialysis but they might acceptsuch a kidney for a patient doing less well. It is probable thatthe factors which contribute to good progress after transplan-tation are similar to those which result in prolonged survivalon dialysis. Decisions taken on clinical grounds rather than byrandom allocation are, therefore, likely to result in one group(probably that treated by transplantation with a poorlymatched kidney) having an excess of patients with a poor prog-nosis. The onus of proving that this has not happened shouldbe on those, such as Festenstein et al.,3 who publish apparentlystatistically significant evidence that tissue-typing is impor-tant.

It is ten years since HLA typing was introduced, and largesums of money have been spent on its application to renaltransplantation, but convincing evidence for the benefit ofHLA typing in cadaver-kidney transplantation has yet to

appear. More detailed analysis of data already collected or aproperly organised trial are needed to prove that histocompati-bility typing is clinically important for first cadaver trans-

plants. Considerable savings can be achieved by kidney trans-plantation earlier in the course of severe renal failure,’ but thisis not usually possible unless HLA typing is given a low pri-ority. This has been the policy in Nottingham for first trans-plants, and the results are almost identical to U.K. averages,’except that the mean waiting-time for cadaver transplantationis less than 4 months.

Many units have now collected enough data to pub-lish reviews of their experience with transplantation orregular dialysis. These provide material that allows com-parisons between units using different policies and alsoallow important conclusions about treatment. The highsuccess-rate in certain units (e.g., in Australia6) whichdo not rely extensively on histocompatibility results isone fact that supporters of tissue-typing find difficult toexplain. Comparisons between units, made possible bypublication of their results, are likely to be valid only ifdata on likely prognostic factors are included. Anotheruseful statistic, especially for units serving a definedpopulation, is the number of transplants per million ofpopulation per year, especially if the numbers put on

regular dialysis and/or transplantation are also

recorded. A 30% mortality-rate in a unit treating 50patients per million of population per year may reflecta more satisfactory policy than a 15% mortality-rate inan area where only 25 patients per million of populationper year are being treated. An impressive feature of theAustralian series6 is that most, if not all, "possible" can-didates in one community were treated and manypatients with poor prospects must have been included.The increasing cost of dialysis (over 13 million a

year in the U.K.) creates an urgent need for unequivocalinformation on the type of patient for whom long-termregular dialysis would be justified.Those responsible for analysing data--e.g., the

National Organ Matching Service in the U.K.’ and theEuropean Dialysis and Transplant Registration Commit-teel-may provide more useful information now thatthey are considering fuller analysis of selected subgroupsinstead of their previous policy of less complete analysisof larger numbers. Simmons et al.8 have used this

approach in analysing the results of a single transplantunit, but by excluding certain subgroups from analysisthey have reduced the size of their series. Since donorkidneys were allocated in an unbiased manner to all

patients in end-stage renal failure, high-risk patientsshould have featured equally in any two groups analysedfor a variable such as tissue-typing; confirmation of thiswould have increased the value of their report. Reportssuggesting a critical role for previous blood-transfusionin preventing rejection 1,3, 7,9 may alter clinical policy butthey too lack adequate analyses, although we have triedto provide this in our own small series. Blood-transfu-sion for a patient in renal failure may be more likely incertain types of patients. Only when sufficient publica-tions with clinical details of the two groups (with andwithout transfusion) become available will it be reason-able to conclude that improved results are due to thetransfusions. Many complex and expensive clinical andlaboratory trials could be organised in an attempt toestablish the importance of blood-transfusion. However,analysis of data already collected could probably providemost of this information.

Recent articles which expressed concern about themisuse of statistics in medical papers, 10, 11 could wellhave included, as examples, the reports on dialysis andtransplantation. Most of the errors are not mathemati-cal. They are mainly caused by comparing two groupswhich are not demonstrated -to be homogeneous or tohave a comparable heterogeneity-i.e., there is no evi-dence that biased allocation has not taken place.Many thousands of patients with renal failure have

now been treated, and nearly all have been recorded onnational and supranational registers. It is unsatisfactorythat the analyses required to make rational plans for anindividual unit, or for individual patients, are still notavailable.

recorded. A 30% mortality-rate in a unit treating 50patients per million of population per year may reflecta more satisfactory policy than a 15% mortality-rate inan area where only 25 patients per million of populationper year are being treated. An impressive feature of theAustralian series6 is that most, if not all, "possible" can-didates in one community were treated and manypatients with poor prospects must have been included.The increasing cost of dialysis (over 13 million a

year in the U.K.) creates an urgent need for unequivocalinformation on the type of patient for whom long-termregular dialysis would be justified.Those responsible for analysing data--e.g., the

National Organ Matching Service in the U.K.’ and theEuropean Dialysis and Transplant Registration Commit-teel-may provide more useful information now thatthey are considering fuller analysis of selected subgroupsinstead of their previous policy of less complete analysisof larger numbers. Simmons et al.8 have used this

approach in analysing the results of a single transplantunit, but by excluding certain subgroups from analysisthey have reduced the size of their series. Since donorkidneys were allocated in an unbiased manner to all

patients in end-stage renal failure, high-risk patientsshould have featured equally in any two groups analysedfor a variable such as tissue-typing; confirmation of thiswould have increased the value of their report. Reportssuggesting a critical role for previous blood-transfusionin preventing rejection 1,3, 7,9 may alter clinical policy butthey too lack adequate analyses, although we have triedto provide this in our own small series. Blood-transfu-sion for a patient in renal failure may be more likely incertain types of patients. Only when sufficient publica-tions with clinical details of the two groups (with andwithout transfusion) become available will it be reason-able to conclude that improved results are due to thetransfusions. Many complex and expensive clinical andlaboratory trials could be organised in an attempt toestablish the importance of blood-transfusion. However,analysis of data already collected could probably providemost of this information.

Recent articles which expressed concern about themisuse of statistics in medical papers, 10, 11 could wellhave included, as examples, the reports on dialysis andtransplantation. Most of the errors are not mathemati-cal. They are mainly caused by comparing two groupswhich are not demonstrated -to be homogeneous or tohave a comparable heterogeneity-i.e., there is no evi-dence that biased allocation has not taken place.Many thousands of patients with renal failure have

now been treated, and nearly all have been recorded onnational and supranational registers. It is unsatisfactorythat the analyses required to make rational plans for anindividual unit, or for individual patients, are still notavailable.

REFERENCES

1. Gurland, H. J., Brunner, F. P., Chantler, C., Jacobs, C., Scharer, K., Sel-wood, N. H., Speis, G., Wing, A. J. Proc. Eur. Dialysis Transplant Ass.1976, 13, 3.

2. Roberts, H. Kidney Int. 1976, 9, 363.3. Festenstein, H., Sachs, J. A., Paris, A. M. I., Pagrum, C. D., Moorhead,

J. F. Lancet, 1976, i, 157.4. Blamey, R. B., Knapp, M. S. Unpublished.5. Blamey, R. B., Salisbury, M., Knapp, M. S. British Transplantation Society

Abstracts. July 1977.6. Mathew, T. H., Marshall, V. C., Vibraman, P., Hill, A. V. L., Johnson, W.,

McOmish, D., Morris, P. J., Kincaid-Smith, P. Lancet, 1975, ii, 137.7. Report of National Organ Matching Service, Bristol, 1976.

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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;