2001 Membership Contributions are Due Now

In the envelope containing this Newsletter, Medichem Members will receive an invoice for the payment of the 2001 Medichem Membership Dues. They have remained unchanged at USD 50 per year.

Details concerning Medichem's bank connection and possible modes of payment can be found on the invoice form.

The Secretary-Treasurer is extremely grateful to those who pay their dues promptly and thus help avoid unnecessary cost and effort for reminders later in the year.

I would like to thank you already now for your co-operation.

For those who, because of their personal circumstances, find it difficult to pay the full membership contribution, Medichem has set aside a limited amount of funds to subsidise a scheme of reduced membership fees. An application must be made in writing to the Secretary-Treasurer. The reduction is 50 per cent. The exact rules governing the scheme can be found in the Medichem Handbook and are also available from the Secretary.

Dr. Andreas Flückiger, Basel (Switzerland)

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Medichem 2001 Board Elections – Call for Candidates

This year, several Medichem Board Members arrive at the end of their terms of office: Noel Humphry, Leo Miksche, Kalle Ahlberg, Teo Popov, Hugo Rüdiger, Abed Bin Onn and Andreas Flückiger. Furthermore, there are two vacancies on the Medichem Board that can be filled.

The following Board members have stated that they are willing to be a candidate for a further term of office as Board Members: Teo Popov, Hugo Rüdiger, Abed Bin Onn and Andreas Flückiger (who will however hand over the Secretariat to a successor).

According to Article 5, Section 4.1 of the Medichem Constitution, every country can only be represented by one Board Member. As an exception from this rule, there can be two Board Members from one country if one of them holds an office.

Members are now asked to nominate candidates for the Board if they so wish.

Any member in good standing can nominate a candidate. This year, candidates for Board membership may not be from Canada, the Czech Republic, Japan, the Netherlands, Singapore, South Africa, the US nor the UK.

(continued on page 2)


Honorary President:

Prof. Dr.med. Dr.h.c. Alfred M. Thiess

Chairman:

Dr. Noel F. Humphry

Dow Chemical (Australia) Ltd.

Kororoit Creek Road

Altona, Vic. 3018 (Australia)

Phone: +61-3-9226 3787

Fax: +61-3-9226 3798

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Secretary-Treasurer:

Dr. Andreas Flückiger

Corporate Medical Director

F.Hoffmann-La Roche Ltd.

CH-4070 Basel (Switzerland)

Phone:+41-61-688 37 38

Fax: +41-61-688 16 51

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Board Members:

Dr. R.W. Ahlberg (Finland)

Dr. A. Bin Onn (Malaysia)

Dr. L.J.N.G.M. Bloemen (Netherlands)

Prof. M. Cikrt (Czech Republic)

Dr. W.M. Coombs (South Africa)

Dr. S. S. Guirguis (Canada)

Prof. Y. Kudo (Japan)

Dr. L. W. Miksche (Germany)

Dr. T. Wai-Hoong Phoon (Singapore)

Prof. T. Popov (Bulgaria)

Dr. A. R. Reid (U.K.)

Prof. H. W. Rüdiger (Austria)

Dr. Leslie M. Yee (USA)

Medichem Newsletter February 2001Pg 1

(continued from Page 1)

All candidates must be Medichem members in good standing, and in addition members in good standing of the ICOH or agree join ICOH before the election. Furthermore, the nomination shall only be valid if it is sent in along with written acceptance of the nomination from the candidate herself or himself. Nominations must be sent to the Secretary of Medichem, Dr. Andreas Flückiger, by mail or fax. They must be in possession of the Secretary no later than April 30th, 2001.

Dr. Andreas Flückiger, Basel (Switzerland)

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PVC Softeners Suspected of Causing Allergies

Softeners of PVC-plastics are suspected of increasing the risk of respiratory allergies in children. This is the finding of a recently published Norwegian study of 3000 children during two years in Oslo. Research at the Danish Institute of Working Life show that some phthalates heighten allergic reactions in mice.

PVC-plastics are used in a large number of buildings, mainly in floor coverings, but also in some furniture, wall coverings and other furnishings. PVC is also found in packaging. Floor coverings can contain up to 40% of phthalates. Moisture in flooring is suspected of increasing the emission of phthalates.

The Danish Institute of Working Life has now found that certain mono-phthalates, primarily DBP and DEHP, appear both in the form of gas and as particles in floor dust in Danish homes, offices, classrooms and day care nurseries. During the coming year, results from new studies will be presented.

The number of Danish children with allergies has, as in most other Northwestern European countries, more than doubled in the past 25 years.

"The reasons for this can be many, among them changes in the immune system due to changing eating habits", says Leif Aringer, Chief Medical Officer at the Swedish National Board of Occupational Safety and Health.

The Swedish Chemicals Inspectorate has recently banned the use of phthalates in toys for children under the age of three. The Institute of Analytical Chemistry at Stockholm University is planning to undertake a study of softeners in PVC.

There is still controversy among researchers as to the role of phthalates in cancer and hormone disorders.

(From the Newsletter of the Joint Industrial Safety Council, Stockholm, Sweden, Dec. 2000 issue).

Dr. Andreas Flückiger, Basel (Switzerland)

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Fire Fighters at Risk for Cancer?

Research undertaken in New Zealand has identified that fire fighters are three times more likely to get testicular cancer than the average male. The study was conducted by the Wellington School of Medicine in conjunction with the Institute if Environmental Science and Research. Details from

From: Hazmat & Enviroment Notes, November 2000, submitted by

Jeff Simpson, Haztech Environmental, Ashburton, Vic. (Australia)

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26th Conference of the ICOH in Singapore

A modest ~2000 participants attended the 26th Conference of the ICOH which took place Aug 27th-Sept. 1st in Singapore.

The main topic of the conference was the impact of globalisation on safety and health at the workplace.

The degree of industrialisation is steadily decreasing in the so-called "industrialised" nations. The service sector is growing rapidly and the occupational health issues related to this sector differ from the traditional occupational diseases. "Soft factors" such as job satisfaction are important determinants of health at work. Organisations have been shrunk and the workload for those remaining has continuously increased. In Finland, 8% of the working population work 80 or more hours a week. The average European believes that each week should have an extra 20 hours to enable him to do all the things he should do. This lifestyle has adverse effects on exercise, and often nutrition is not adapted to the limited physical activity either.

Workers in this sector who are not satisfied with their jobs are often not very productive although they show up at work every day. The term "presenteeism" has been coined for this phenomenon. In Scandinavia, it has been estimated that productivity could be increased by as much as 50% if health at work in the broadest sense was tackled effectively.

Large firms with traditionally good safety and health practices at work tend to concentrate on what they consider to be their "core business". Other activities such an maintenance and cleaning are out-sourced to contractors. It was suspected and has now been confirmed that health protection of the workforce of these usually small contract firms is generally inferior to health protection that was offered for the same jobs when they were still integrated in a large company.

The quality of occupational health practices has been influenced in different ways, depending on the region of the world. In the past 10 years, the general health of the workforce has improved in most OECD countries as well and China and India, but remained unchanged or even deteriorated in Latin America, Africa, the Arab countries and in most countries of the former Eastern Block.

Women, children, the elderly and the handicapped are particularly vulnerable.

Among the traditional health problems affecting productivity, allergies, affections of the musculo-skeletal system and infectious diseases are on the increase.

Whilst the terms "occupational illness" and "occupational disease" have been used almost synonymously, preference being given to one or the other depending on the country, the point was made that maybe the term "occupational disease" should be used when describing the traditional and well established health problems arising from the workplace whereas "occupational illness" would describe those affections where the causal link between the affection and workplace seemed plausible or even clear, but the ailment was not recognised by the country's legal system as a work-related health impairment. This implies that the work-related health problems that we see these days in the countries of the so-called first world often no longer correspond to those work-related health problems that are legally recognised.

In most of these countries, on paper, the costs of occupational accidents by far exceed the costs of occupational illnesses. However, some countries such as the UK have taken a closer look at the situation and are convinced that the real situation is the other way around: occupational illnesses actually have a far greater impact on a nation's economy than is expressed by the figures of recognised occupational diseases.

Medichem was present at the conference with a session of proffered papers on occupational health in the chemical industry and a mini-symposium on "Occupational and environmental effects on the reproduction process". Four speakers presented papers: Rob Taalman of CEFIC's Endocrine Modulators Steering Group, Ron Miller, toxicologist of Dow Chemical, Sin-Eng Chia of the U. of Singapore and John Jackson of Jackson-Hocking in the UK.

The mini-symposium was very well attended and feed-back from the audience was very positive.

ICOH will hold its next conference in Foz do Iguaçú, Brazil from February 23-28, 2003.

Dr. Andreas Flückiger, Basel (Switzerland)

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Manganese

In the February 2000 Medichem Newsletter, a summary was given on research conducted at the Chemical Industry Institute of Toxicology (CIIT) in the US on the mechanisms of manganese neurotoxicity.

In the past year, manganese has been under particular scrutiny by the occupational health authorities in a number of countries, in particular also the UK. Manganese is used in the making of steel and welding rods, but it is also of interest to those companies in the chemical industry who consider themselves to be players in the field of the health sciences. Manganese is a trace element in animal feed and fertilisers where it is used in relatively large quantities.

A review of manganese toxicity seems to indicate that health-based occupational exposure limits (OELs) for this material would have to be lower than existing limits in many countries. In many countries, the OEL for manganese compounds (as Mn) is 0.5 mg/m³, but in some, it is still as high as 5 mg/m³. However, epidemiological studies show that men exposed to workplace levels around 1 mg/m³ (inhalable dust) suffered from neurological effects. A human no-effect-level has never been clearly identified, but is likely to be well below 1 mg/m³, probably also at less than 0.5 mg/m³. The ACGIH have already had their manganese TLV at 0.2 mg/m³ for a number of years and this seems a reasonable order of magnitude.

Blend plants in the feed industry are not exactly dust-free, and even under good conditions, exposures of 1 to 2 mg/m³ are typical.

Compliance with exposure limits of 0.2 mg/m³ or possibly less should be achieved primarily by means other than personal protective equipment. One possibility to real this goal would be to make the form or manganese used less dusty.

The feed industry handles other trace elements which can be hazardous to health, such as selenium and cobalt. The quantities of Co and Se used are much smaller than those of Mn, and the cost of these elements is higher than the cost of manganese. In practice, that means that making selenium and cobalt preparations inherently safer by bringing them into a low dustiness granulated form is a feasible solution. The added cost of granulation is relatively small and absorbed by the market without great difficulty.

This may not be the case for manganese which is relatively inexpensive and used in much greater volumes.

It will be interesting to track further developments in good occupational hygiene practice in the handling of manganese, both the possible setting of new and lower OELs but also means of ensuring compliance with these new limits.

Dr. Andreas Flückiger, Basel (Switzerland)

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Occupational Toxicology Roundtable 2000

The historic Mohawk Mountain Hotel in Upstate New York was the impressive venue for the October 2000 Occupational Toxicology Roundtable, an informal gathering of occupational toxicology and industrial hygiene specialists coming mainly from the US but also from the European pharmaceutical industry.

Although the meeting is the one of an informal group and participation is only by invitation, the Occupational Toxicology Roundtable now has a long-standing tradition and a high reputation in the industry.

Topics discussed are best practises of occupational hygiene in the pharmaceutical industry, principles of setting in-house occupational exposure limits for therapeutic substances, categorisation systems for such compounds and information given in those sections of safety data sheets that relate to health hazard characterisation, occupational handling, toxicology and classification.

Since a fair amount of professional judgement is involved in dealing with these subjects, exchanging views and opinions and benchmarking is considered indispensable.

Whilst pharmaceutical production equipment is validated again and again for its GMP (good manufacturing practice, i.e. product-safety related) performance, this not so much the case for its performance in terms of industrial hygiene. A manufacturer of a particular piece of equipment can seldom say reliably what e.g. the dust leakage rate of his equipment is. However, such information would be very important to compare one piece of equipment with another and to decide what product can or needs to be produced on what sort of equipment. Standardised validation procedures need to be developed to attain this goal. Representatives of the Occupational Toxicology Roundtable are working together with the International Society of Pharmaceutical Engineers (ISPE) to develop such standards.

Dr. Andreas Flückiger, Basel (Switzerland)

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COSHH Essentials

The so-called COSHH (Control of Substances Hazardous to Health) regulations were published in the UK about a decade ago. These regulation call for a systematic approach to dealing with hazardous substances at all workplaces:

  • collection of all information available on the hazards (the compounds) and the workplace where they are handled
  • assessment of exposures to these hazards
  • conclusion as to magnitude of the health risk present according to the formula: risk = hazard x exposure
  • decision on managing this risk appropriately

It was soon recognised that particularly small and medium-sized enterprises had great difficulties implementing the COSHH regulations. To assist these companies in putting in place the right measures to control exposures at their workplaces as often as possible without specialist advice, the UK Health and Safety Executive developed "COSHH Essentials", a guidance document that has gained a great deal of applause and has become a standard reference far beyond the UK.

In a nutshell, COSHH essentials is about achieving good industrial hygiene whenever possible without specialist advice and without measuring.

You determine the toxicity of the product based on its EU risk phrases and check on the safety data sheet whether skin absorption might occur. This information is then combined with quantity handled and the level of dustiness or volatility of the product. This information leads up to recommendations for the engineering controls and containment needed.

Sixty control guidance sheets have been developed, each covering a particular activity, e.g. transfer, filling/emptying, weighing, mixing.

"COSHH Essentials" is designed to allow small businesses to get on with implementing reasonable industrial hygiene practices without being blocked before even starting by too complex a task.

COSHH Essentials – Easy Steps to Control Chemicals. 32 pages and 60 guidance sheets. ISBN 0-7176-2421-8. Price: about GBP 25.

Source: HSE Books. Phone +44-1787-88 11 65, Fax: +44-1787-31 39 95.

Dr. Andreas Flückiger, Basel (Switzerland)

and Jeff Simpson, Haztech Environmental, Ashburton, Vic. (Australia)

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Insecticide Diazinon to be Phased Out in the US

The US Environmental Protection Agency has announced plans to phase out, by the end of 2004, the home and garden use of the insecticide Diazinon, the last widely used pest-control product made from the organophosphate class of chemicals, which are linked to health risks for children. Source: USA Today, Dec. 5, 2000 (Reuters). Sent in by

Jeff Simpson, Haztech Environmental, Ashburton, Vic. (Australia)

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Cancer Risk from Occupational Handling of Cytostatics

Many cytostatics have a genotoxic mechanism of action. They are therefore classified as carcinogens. Individuals handling these compounds in the health sector, e.g. in hospitals, are exposed to a certain health risk.

The German BIA (Institute for Occupational Safety of the Occupational Accident Liability Insurance Fund – in German: "Berufsgenossenschaften") reviewed the epidemiological and toxicological literature to determine the cancer risk from occupational exposure to six selected cytostatics. The risk was calculated for 35 years of daily handling of these antineoplastic agents.

The agents evaluated were:

  • cyclophosphamide
  • melphalan
  • methotrexate
  • 5-fluoro-uracil
  • cisplatin
  • etoposide

The database seems best for cyclophosphamide. Biological monitoring studies showed that during the preparation of 2000 mg for patient application, a nurse will typically absorb anywhere between 2 and 60 mcgr of the compound. It was calculated that these exposures (if present 5 days a week, 35 years long) lead to an excess cancer risk of 2:100,000 to 7:10,000.

Figures for melphalan (Alkeran®) are less good, but the cancer risk per mg absorbed is at least 10 times higher than for cyclophosphamide. On the other hand, therapeutic doses for melphalan are lower than those of cyclophosphamide which may reduce the exposures of the hospital personnel to some extent.