Health hazards in pharma industry

Vinay Pathak

Little is known about the health risks of working in the pharmaceutical industry. On the surface, the industry looks clean. The production of medicinal demands a carefully maintained and sterile working environment and the white lab coats worn by workers add to the illusion of safety. The appearances are deceptive, though. Producing drugs and other medicinal may involve exposure to toxic industrial chemicals. And while the finished products may be lifesaving medications for sick people, they can be dangerous to healthy workers who are inhaling or absorbing them during the production process.

Some general health hazards

General health hazards in the manufacture of pharma products include: dust and noise exposures, repetitive motion disorders, exposure to formaldehyde, and exposure to ultraviolet radiation.

Dust becomes airborne during manufacture and is a problem for operators; in addition, filling and packaging of the finished product may pose an allergic hazard from dust.

Ensuring sterility of the product often involves exposure to formaldehyde and ultraviolet radiation. Formaldehyde may cause lung cancer, Hodgkins disease, and prostate cancer. Acute exposures can cause pulmonary edema (lungs fill with fluid, making breathing impossible) and pneumonia leading to death. Formaldehyde also causes allergic dermatitis.

Ultraviolet lamps used to maintain sterility pose a problem too. Although non-ionising (meaning the radiation does not have an electrical charge and therefore causes less damage to cells), ultra-violet radiation is dangerous and can cause skin cancer. The first sign of overexposure is dry, inelastic, and wrinkled skin. Various localised skin sores may develop and should be interpreted as a warning signal. Light-skinned people are most susceptible since their skin lacks pigments that would protect them from overexposure.

The constant repetitive motion associated with packaging and filling could lead to carpal tunnel syndrome or tendinitis. Tendinitis is most commonly caused by repetitive and twisting hand motions. Tendinitis symptoms usually are pain and tenderness in the affected area – hand, wrist, or forearm. Swelling can also be a symptom. The ability to use the hand is often greatly reduced, with exertion only causing greater pain. Tendinitis can be effectively treated with rest, perhaps in combination with heat and use of a splint. But the cause must be eliminated or tendinitis will develop again.

Carpal tunnel syndrome is usually caused by repeated bending and twisting of the wrist, especially when force is applied. Carpal tunnel symptoms include pain in the hand, numbness, tingling, and burning sensations, a dry shiny palm, and clumsiness of the hands. The symptoms often are most acute at night and usually are confined to one side of the hand. Carpal tunnel syndrome can best be treated by eliminating the twisting and bending that caused it in the first place, by switching jobs or changing the way a job is done. Medical treatments include wearing a wrist splint at night and physical therapy.

In some cases, anti-inflammatory drugs are prescribed, and surgery may be required in very severe cases. It is very important to remember that treatments for tendinitis and carpal tunnel syndrome will not work unless the cause of the problem, the job or tool design, is changed to eliminate the twisting and bending of the hand and wrist.

Some specific health hazards

Hazards specific to the pharma industry result from exposure to the active drug which usually takes place during the last phase of production.

Hormones

Health impairment due to pharma products has been described and observed mainly in hormone and antibiotics production workers.

The effects of occupational exposure to hormones may be severe. For male workers, exposure to estrogens may give rise to breast development; for female workers, there may be menstrual disorders, abnormal overgrowth of the endometrium and excessive bleeding during menopause.

Exposure of male workers to progestogen may bring about a lack of sexual drive and testicular pain. On the other hand, exposure of female workers to androgens is known to cause menstrual and ovarian function disorders, diminished fertility, increased frequency of spontaneous abortions, and symptoms of masculinity.

Antibiotics

Antibiotics are chemical substances capable of destroying micro-organisms such as bacteria and viruses that cause infection in animals and humans. The principal ones are: erythromycin, the penicillins, the tetracyclines, streptomycin, and clindanycin.

The effects of occupational exposure to antibiotics can include

Allergic reactions: Itching and redness of the eyes, runny nose, skin rashes, asthma, and occasionally shock due to an allergic reaction (anaphylaxis).

Vitamin deficiency: Workers with repeated exposure to antibiotics experience a change in the number and type of bacteria which are normally present in the intestines which break down and absorb vitamins in the intestines.

Fungal infections: Daily exposure to antibiotic dust can lead to fungal infections of the skin and nails. Additionally, women workers may develop vaginal yeast infections following exposure to antibiotics.

Toxic effects: Exposure to certain antibiotics may lead to development of some of the toxic side effects that occur when that drug is given as medicine.

Other effects: Older female workers have been incorrectly told that flushing may be due to hormonal changes rather than the antibiotic drugs they are inadvertently taking in. Headaches and stuffy nose are other common complaints. Allergic heart disorders, bronchial asthma, poisoning, and allergic disorders of the liver have also been reported. Some experts are concerned that prolonged contact with antibiotics may cause cancer, although there have been no studies confirming this suspicion. Described below are common adverse reactions to some specific antibiotics.

Information on working with drugs must be interpreted with caution because … Workers can be exposed to more than one drug at a time and the effects of multiple exposures are not known. The effects of short exposures to a variety of drugs may be very different from the effects of longer exposures to only one or two drugs. The routes of absorption are different. The respiratory system and skin are the main routes of entry for pharma products in the workplace. The gastrointestinal tract and other internal routes are the normal routes of entry for pharma drugs in patients. Practically no research has been conducted on the relationship between external dose, internal dose, and effects.

Penicillin

Because of the highly allergenic nature of the penicillins and their extensive use, many people have become allergic to them. The most serious reaction is shock. This type of acute reaction usually occurs minutes after exposure. Symptoms are tightness in the chest, asthmatic breathing, dizziness, swelling of the lips, tongue, or face, edema of the lungs, heart failure and in some cases, death. Other reactions are hives, ‘black hairy tongue,’ fungus infection, and rectal itch.

Tetracycline

Modification of the bacteria of the intestines and other organs has been reported following occupational exposure to tetracycline (as well as to streptomycin and penicillin). In workers exposed to tetracycline and to streptomycin, modification of the bacteria led to a drop in the body’s vitamin content, especially of the B vitamins. Another problem associated with occupational exposure to tetracycline is drug resistance. Workers may develop infections that are resistant to treatment with tetracycline.

Drugs for heart disease

Nitroglycerin, commonly used in dynamite, is also the basis of several medicines for heart patients — isosorbide dinitrate, pentaerythritol tetranitrate, and mannitol hexanitrate. Nitrates act on the blood vessels of the body and their effects are felt in several ways. Almost everyone exposed to nitro dust experiences a severe pounding headache which is caused by the relaxation of the blood vessels within the skull. Headaches may be accompanied by a rapid heart beat and a flushed face.

Nitrates dilate the blood vessels and make blood pressure fall. As a result, dizziness and even fainting may occur. Other more serious effects are heart pain, heart attacks, and sudden death following ‘withdrawal’ from exposure.

Suggestions for controlling exposures Use a respirator with a high-efficiency (HEPA) filter. All respirators should be checked to make sure they fit well enough to really protect you. Wear gloves that will protect your skin from contact. Wear long sleeves to keep the drug from getting on your arms. Wash your hands whenever you leave your work area. Noise: Exposure to noise can be alleviated by acoustic enclosures of high-noise sections of packaging lines. Also, programmed job rotation for the personnel working on manufacturing and packaging lines may be useful in reducing monotony and limiting exposure to noise. Mechanical hazards: Appropriate devices doing away with, or guarding against, possible “hand traps” should be installed.

Tranquilisers

Both chlordiazepoxide and meprobamate are prescribed as sedatives. Both are habituating and additive. In combination with alcohol, they may cause a person to lose consciousness and in high doses, can lead to coma and death. Workers producing tranquilisers are at risk of these adverse effects and have found that they pass out over a beer after work. There is a real danger of accidents, both in the plant and on the way home, when workers become drowsy as a result of exposure to tranquilisers and barbiturates.

Antidepressants

Tricyclic antidepressants like amitriptyline, nortriptyline, and imipramine can cause irregular heartbeat (cardiac arrhythmias), posing a particular problem for production workers with heart conditions.

Standards for exposure prevention

There are no OSHA standards regulating exposure to pharma. The lack of knowledge about workplace effects of pharma products explains why there are no Threshold Limit Values (TLVs) for pharmacologically active substances (except for acetylsalicylic acid — a value of 5 mg/m3, 1979). Now and then threshold limits are recommended for pharma products by research workers, mostly in the former USSR. The almost complete absence of official data shows that it is necessary to reduce exposures to the lowest possible levels.

Studies

Some researchers have concluded that it is difficult to evaluate causes of morbidity in pharma workers because manufacturing processes and additives differ between factories and exposures are to multiple chemicals.

Mortality: A 1988 study of 826 pharma workers found increased death risk from cancer and suicide. Men had elevated rates of cancers of the colon, central nervous system, and kidney; women had elevated rates of breast cancer.

Morbidity: Many workers develop allergic reactions to medicinals that involve bronchial sensitivity, asthma, and difficulty in breathing. It is difficult to evaluate morbidity in pharma workers because of the wide diversity of chemicals used in the manufacturing process.

Asbestosis: The respiratory disease found most often among OCAW members working at pharma plants is asbestosis, a disease which often leads to increased mortality. The threat of asbestos-induced disease is potentially present at all pharma plants built before the ’70s. Maintenance workers are especially at risk.

Reproductive effects: One study of women found an increase in spontaneous abortion increasing with exposure to methylene chloride, benzene, estrogens, and toluene. Twelve of the 24 female production workers had intermenstrual bleeding. Exposure to solvents and methylene chloride in particular may have harmful effects on pregnancy.