Review Article

Chemical hazards and safety management in

pharmaceutical industry
O. G. Bhusnure1*, R. B. Dongare1, S. B. Gholve1, P. S. Giram2

ABSTRACT

Chemical hazards are a major occupational health and safety (OHS) issue in Pharma industry. Management of chemical
hazards requires the combined efforts of OHS specialists, including generalist OHS professionals, occupational hygienists,
and occupational health practitioners. This paper is about industrial chemicals, the manner in which their toxicity is assessed
and the use of such assessments in regulatory decision-making. It begins with general points concerning toxicological data
availability and hazard identification, then moves on to risk assessment and occupational exposure limits, and finally looks
briefly at three specific toxicological issues, asthma, chronic toxic encephalopathy, and ‘‘low toxicity’’ dust effects on the
lung, where the science is far from resolved after brief consideration of the historical context of chemical reactivity and
toxicity issues, acute and chronic exposure, chemical hazard classification systems, and the identification, risk assessment,
and control of chemical hazards. Preventing exposure to toxic chemicals is a primary concern at hazardous waste sites. Most
sites contain a variety of chemical substances in gaseous, liquid, or solid form. These substances can enter the unprotected
body by inhalation, skin absorption, ingestion, or through a puncture wound (injection). Emphasis is placed on the importance
of working with a range of OHS specialists to ensure a range of skills is directed at preventing fatality, injury, disease, and ill
health arising from this complex area of OHS.

KEY WORDS: Dangerous goods, Globally harmonized system, Hazardous chemical, Hazardous substance, Occupational
exposure standard, Occupational hygiene

INTRODUCTION effect on the human and environmental condition.

A chemical hazard is a type of occupational hazard
Chemicals are used to make virtually every man-made caused by exposure to chemicals in the workplace.
product and play an important role in the everyday life Exposure to chemicals in the workplace can cause
of people around the world. The chemical industry is acute or long-term detrimental health effects.
the third largest industrial sector in the world. It is also There are many types of hazardous chemicals,
a major economic force. Worldwide, it employs some including neurotoxins, immune agents, dermatologic
10 million people and generates billions of euros in agents, carcinogens, reproductive toxins, systemic
shareholder value and tax revenue for governments. toxins, asthma genes, pneumoconiotic agents, and
The pharmaceutical industry has been described as sensitizers.[1,2]
dynamic and growing, in terms of sales, number of
employees, and gross domestic product (GDP). It is an Little is known about the health risks of working in the
industry in which companies, government regulators pharmaceutical industry. On the surface, the industry
and researchers focus on the “safety” of the products looks clean. The production of medicinals demands a
and their effects on end users and the environment. carefully maintained and sterile working environment
and the white lab coats worn by workers add to the
Chemical hazards produce by chemical synthesis or
illusion of safety. The appearances are deceptive,
manufacturing, processing, transportation and that
though producing drugs and other medicinals may
involve exposure to toxic industrial chemicals.
Access this article online And while the finished products may be lifesaving
medications for sick people, they can be dangerous
Website: [Link] ISSN: 0974-6943
to healthy workers who are inhaling or absorbing
1
Department of Quality Assurance, Channabasweshwar Pharmacy College, Latur, Maharashtra, India, 2Department of
Pharmacology, Channabasweshwar Pharmacy College, Latur, Maharashtra, India, 3Department of Quality Assurance,
Channabasweshwar Pharmacy College, Latur, Maharashtra, India

*Corresponding author: Dr. O. G. Bhusnure., Department of Quality Assurance, Channabasweshwar Pharmacy College,
Kava Road, Latur - 413 512, Latur, Phone: +91-9765360611. Tel.: 02382-241611. E-mail: omprakashbhusnure@[Link]

Received on: 12-09-2017; Revised on: 18-10-2017; Accepted on: 20-11-2017

Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018 357

 O. G. Bhusnure, et al.

them during the production process. Hazard is a term Class B [Figure 1]

associated with a substance that is likelihood to cause • Flammable gases.
an injury in a given environment or situation. Industrial • Flammable and combustible liquids.
hazard may be defined as any condition produced by • Flammable solid.
industries that may cause injury or death to personnel • Flammable aerosols.
or loss of product or property. Safety in simple terms • Reactive flammable material.
means freedom from the occurrence of risk or injury
or loss. Industrial safety refers to the protection of Class C
workers from the danger of industrial accidents. • Oxidizing materials - oxidizer and organic peroxide.
• Oxidizer: Chlorates, nitric oxide, peroxides,
These paper aim is that how to reduces the chemical
permanganates, perchlorates, nitrites, nitrates, and
hazards that management, responsibility precaution,
easily oxidize metal powder.
safety guideline, how to identified hazards and
• Organic peroxide: Tetra hydro furan, diethyl ether,
how to protect from hazards, specific guideline
dioxane, and methyl isobutyl ether.
regulation, responsibility, and lagout tagout chain.
In pharmaceutical industry safety system in India Class D
that principle responsibility also challenges for risk
• Poisonous and infectious materials.
assessment and safety hazards.
e.g.: Cyanides, tea salts, and asbestos.
OBJECTIVES OF INDUSTRIAL Class E
SAFETY • Corrosive materials.
e.g.: Inorganic acids and bases, hydrogen fluoride.
• Understand the harmful effects of industrial hazards.
• Define the relationship between hazard and risk. Class F
• Explore the routes of exposure to industrial hazards.
• Dangerous reactive materials.
• Shed lights on type of toxicity by industrial hazards.
e.g.: Ethylene dioxide, organic azides, Na, Li, Ca.
• Know the most toxic environmental hazardous
substances. • Pyrophosphoric materials.
• Industrial safety is needed to check all the possible e.g.: White phosphorous, diethyl aluminum chloride,
chances of accidents for preventing loss of life and and lithium.[3,4]
permanent disability of any industrial employee,
any damage to machine and material as it leads to Carcinogens
the loss to the whole establishment. The identification of carcinogenic agents was based
• It is needed to eliminate accidents causing work on the IARC classification and corresponding IARC
stoppage and production loss. monographs.[5,6] Only agents belonging to Group 1
• It is needed to prevent accidents in industry by were considered, i.e., agents for which there is
reducing any hazard to minimum. sufficient evidence of carcinogenicity in humans, and
• It is needed to reduce workman’s compensation, therefore, a causal relationship between agent and
insurance rate and all the cost of accidents. increased incidence of malignant neoplasms has been
• It is required to educate all members regarding the established. The estimates of the number of specific
safety principles to avoid accidents in industry. exposures of a worker were taken from the database
• It is needed to achieve better morale of the industrial carcinogens exposure.[7].These estimates correspond
employees. to the exposure period 1990–1993 across 55 industrial
• It is required to have better human relations within sectors for the EU-15 countries.[7,8]
the industry.
• It is needed to increase production means to a higher Sensitizing and Reprotoxic Substances
standard of living.
The identification of sensitizing substances was
based on the list of compounds published in 2013
TYPES OF HAZARDS by the German Commission for the Investigation
Chemical hazards are toxic, corrosive, irritant, of Health Hazards of Chemical Compounds
carcinogenic, flammable, and mutagenic [Table 1]. (MAK-Commission)[9,10] Sensitizing substances,

According to workplace hazardous materials Table 1: Chemical and that exposure limit
information, chemical hazards are classified as.[3,4] Chemical Exposure limit
Ethyl alcohol 1000 ppm
Class A acetone 1000 ppm
• Compressed gas. Methylene chloride 125 ppm
Isopropyl alcohol 400 ppm
• Dissolved gas or liquefied gas.

358 Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018

 O. G. Bhusnure, et al.

Table 2: Pictograms used in chemical hazards

Picture

Indicating words E O F, F+
Name of the symbol Explosive Oxidizing Highly flammable or extremely flammable
Picture

Indicating words T, T+ Xn, Xi B

Name of the symbol Toxic or very toxic Harmful or irritant Harmful or irritant
Picture

Indicating words B N R
Name of the symbol Biohazards Dangerous for the Radioactive
environment

i.e., substances capable of inducing an immunological Substances toxic to reproduction refer to substances
response to an otherwise innocuous antigen,[11] are causing either impaired fertility (“RF”) or subsequent
classified either as “Sa,” “Sh,” or “SP.” The label “Sh” developmental effects in the progeny.[16]
designates substances that can cause allergic or irritant
reactions of the skin and the mucosa close to the skin Chemical exposures are generally divided into two
(skin sensitizing) such as irritant contact dermatitis, categories: Acute and chronic. Symptoms resulting
allergic contact dermatitis, protein contact dermatitis, from acute exposures usually occur during or shortly
and contact urticaria.[12,13] The label “Sa” designates after exposure to a sufficiently high concentration of a
substances causing airway sensitization. contaminant.[17] The number of exposures for a given
contaminant, the symptoms of an acute exposure may
These involve allergic reactions such as bronchial be completely different from those resulting from
asthma or rhinoconjunctivitis, and other effects chronic exposure.[18]
associated with systemic reactions (anaphylaxis).
The label “SP” designates substances causing photo For either chronic or acute exposure, the toxic effect
contact sensitization, i.e., an allergic reaction of the may be temporary and reversible or may be permanent
skin due to the interaction of the substance with (disability or death). Some chemicals may cause
ultraviolet radiation.[14] In general, the classification obvious symptoms such as burning, coughing, nausea,
of a substance as sensitizing is based on either tearing eyes, or rashes. Other chemicals may cause
sufficient empirical evidence of allergenic and/or health.
irritant effects or in cases where the allergenic effect
can be considered probable on the basis of appropriate EFFECTS OF CHEMICALS
empirical evidence.[15] EXPOSURE ON HUMAN BODY
Mutagenic • Skin burn,
According to Annex 6 of the council directive 67/548/ • Ache,
ECC mutagenic substances refer to substances • Anthrax,
giving rise to an enhanced occurrence of genetic • Ulcer in hand, nose, etc.
mutations that may be transmitted to the offspring, • Cancer,
i.e., permanent changes in the amount of the genetic • Irritation on windpipe,
material resulting in a change of the phenotypic • Many chemicals can cause severe burns, if they
characteristics of the organism and its offspring. come in contact with living tissue,

Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018 359

 O. G. Bhusnure, et al.

• Living tissue may be destroyed by following

chemical reactions:
o Dehydration by strong dehydrating agents,
o Digestion by strong acids and bases,
o Oxidation by strong oxidizing agent.[19]

Chemical Hazards Can Enter and Harm the Body

by Four Main Routes
• Absorption through the skin;
• Inhalation;
• Injection; and
• Ingestion.[20]

DIFFERENT WAYS OF CHEMICAL Figure 1: Gas state chemicals will be inhaled or liquid state
chemicals can be absorbed by the skin
HAZARDS CAUSE HARM
• Catching fire.
• Explosive or reactive.
• Corrosive.
• Irritant.
• Causing chronic organ damage over time.
• Causing an allergic reaction.
• Causing genetic or reproductive harm.[20]

The effects of exposure not only depend on the

chemical, its concentration, route of entry, and duration
of exposure, but may also be influenced by personal
factors such as the individual’s smoking habits, alcohol
consumption, medication use, nutrition, age, and sex.

An important exposure route of concern at a hazardous

waste site is inhalation. The lungs are extremely Figure 2: Effective safety cycle
vulnerable to chemical agents. Even substances that
do not directly affect the lungs may pass through lung Although ingestion should be the least significant
tissue into the bloodstream, where they are transported route of exposure at a site, it is important to be aware
to other vulnerable areas of the body. Some toxic of how this type of exposure can occur. Deliberate
chemicals present in the atmosphere may not be detected
ingestion of chemicals is unlikely, however, personal
by human senses, i.e., they may be colorless, odorless,
habits such as chewing gum or tobacco, drinking,
and their toxic effects may not produce any immediate
eating, smoking cigarettes, and applying cosmetics on
symptoms. Respiratory protection is, therefore,
site may provide a route of entry for chemicals.[20]
extremely important if 2-3 there is a possibility that
the work-site atmosphere may contain such hazardous The last primary route of chemical exposure is
substances. Chemicals can also enter the respiratory
injection, whereby chemicals are introduced into
tract through punctured eardrums. Direct contact of
the body through puncture wounds (for example, by
the skin and eyes by hazardous substances is another
stepping or tripping and failing onto contaminated
important route of exposure. Some chemicals directly
sharp objects). Wearing safety shoes, avoiding physical
injure the skin. Some pass through the skin into the
bloodstream where they are transported to vulnerable hazards, and taking common-sense precautions are
organs. Skin absorption is enhanced by abrasions, cuts, important protective measures against injection.[20]
heat, and moisture. The eye is particularly vulnerable
because airborne chemicals can dissolve in its moist CHEMICALS HAZARDOUS
surface and be carried to the rest of the body through the REGULATION
bloodstream (capillaries are very close to the surface
of the eye). Wearing protective equipment, not using Under the WHS regulations, a hazardous chemical
contact lenses in contaminated atmospheres (since they is any substance, mixture or article that satisfies the
may trap chemicals against the eye surface), keeping criteria of one or more globally harmonized system of
hands away from the face, and minimize contact with classification and labeling of chemicals (GHS) hazard
liquid and solid chemicals can help protect against skin classes, including a classification in Schedule 6 of the
and eye contact. WHS regulations.

360 Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018

 O. G. Bhusnure, et al.

Most substances and mixtures that are dangerous goods Carcinogens

under the ADG Code are hazardous chemicals, except • Coal tar, creosote oil, anthracene oil, paraffin oils,
those that have only radioactive hazards (Class 7 and chromium,
dangerous goods), infectious substances (division 6.2), • Nickel, cobalt, etc.,
and most Class 9 (miscellaneous) dangerous goods. • Hazards may arise when impure or contaminated
chemicals are used.
A comparison of dangerous goods classifications under
the ADG code with those under the GHS is provided Sources of hazards in pharma
in Appendix B. To manage risk under the WHS • Handling and storage of huge quantity hazardous
Regulations, a duty holder must: chemicals.
• Identify reasonably foreseeable hazards that could • Transferring, loading and unloading of solvents and
give rise to the risk. chemicals to reaction vessels.
• Eliminate the risk so far as is reasonably practicable. • Human errors while handling hazardous chemicals.
• If it is not reasonably practicable to eliminate the • Emission of hazardous air pollutants from reaction
risk - minimize the risk so far as is reasonably vessels due to overloading or under designed
practicable by implementing control measures in reaction vessels.
accordance with the hierarchy of risk control. • Volatile organic compounds (VOCs) releases from
• Maintain the implemented control measure so that uncontained (or not connected to scrubbers).
it remains effective. • Reaction vessels and most common VOCs include
• Review, and if necessary revise all risk control methanol, dichloromethane, toluene, ethylene
measures so as to maintain, so far as is reasonably glycol, N, ndimethylformamide, and acetonitrile.
practicable, a work environment that is without risks • Leaks of effluents from wastewater treatment plants or
to health and safety.[20] from effluent collection sumps from process area.[20,21]
Adverse Effect The hazards of organic synthesis
Health hazards Organic chemical synthesis presents industrial hazards
These are properties of a chemical that have the of three main types. First, the active agents used to
potential to cause adverse health effects. Exposure attack and modify the structure of organic compounds
usually occurs through inhalation, skin contact, or are, by their very nature, exceptionally able to attack
ingestion. Adverse health effects can be acute (short- and modify the organic compounds of the human body,
term) or chronic (long-term). Typical acute health thus producing highly poisonous effects. Second, the
effects include headaches, nausea or vomiting, and intermediate compounds in most organic syntheses are
skin corrosion, while chronic health effects include often characterized by the readiness with which they
asthma, dermatitis, nerve damage, or cancer.[20,21] enter into chemical combination with other organic
matter; they are active. This often confers toxic properties
Physicochemical hazards of great variety on them. Third, the final products, though
These are physical or chemical properties of the they are medicines designed to be introduced into the
substance, mixture or article that pose risks to human body, may nevertheless produce severe poisoning
workers other than health risks, as they do not occur under conditions of industrial exposure.[22]
as a consequence of the biological interaction of the
chemical with people. They arise through inappropriate Sulfonating Agents
handling or use and can often result in injury to people The sulfonating agents, chlorosulfonic acid (HOSO2CI)
and/or damage to property as a result of the intrinsic is extensively used in the manufacture of p-acetylamino
physical hazard. Examples of physicochemical benzene sulfonyl chloride. The fumes of the acid
hazards include flammable, corrosive, explosive, itself are highly irritating, and in many sulfonation
chemically reactive, and oxidizing chemical.[20,21] reactions, HCI gas and SO2 are given off. It is often not
economically feasible to trap these irritant by-products
Source of chemical hazards in a small synthesis, and they are often vented into the
Air born toxics outside air. This is a bad practice, which will cause a
• Irritants, large amount of bronchitis and conjunctivitis under
• Ipecac, podophyllum, etc. adverse wind and weather conditions. Scrubbing towers
• Asphyxiants, of simple and cheap design, or very high stacks, are
• Carbon dioxide, monoxide, methane, ethane, and usually required to eliminate the nuisance.[22]
hydrogen cyanide,
Final Products of Synthesis
• Hydrogen sulfide, helium, nitrogen, etc.,
• Narcotics/anesthetics, Mepacrine and acriflavine
• Acetone, ether, chloroform, methyl ethyl ketone, Among the final products of organic synthesis,
etc. mepacrine itself deserves mention as an especially

Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018 361

 O. G. Bhusnure, et al.

Figure 3: Lockout tagout chain for safety management

troublesome primary irritant and sensitizer. Rather though weaker, irritant properties; workers bottling
extensive compressing and grinding, thrice repeated, tablets of this dye often suffer from a conjunctivitis
are necessary to prepare the material in the form of considerable severity if they transfer the material
of tablets; dust control during these operations is to their eyes by injudicious rubbing with dust-stained
mandatory, but extremely difficult, because of the hands.[22]
structure of the machines involved. In a study made
at the Abbott Laboratories (Watrous, 1944), exposure Nicotinic acid
to the dust at levels between 035 and 4–2 µg/l was Nicotinic acid and its salts have a peculiar effect on the
sufficient to cause conjunctivitis in more than half of skin of certain workers who handle these chemicals
the workmen, and dermatitis, rhinitis, and stomatitis in bulk: This consists of a diffuse erythema on the
in about a third. Similar symptoms have recently exposed parts of the skin, usually not accompanied
been described by Barlow et al. (1946). Acriflavine by itching, and resembling sunburn in appearance. It
another dye of the acridine series, possesses similar, is usually transient, disappearing in from 12 to 24 h,

362 Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018

 O. G. Bhusnure, et al.

Figure 4: Hazards elimination and control

Figure 5: Elements and safety model of chemical hazards

though sometimes it assumes a popular character on from systemic absorption of the powdered drug by
the 2nd day and lasts several days.[22] inhalation. In a series of four cases showing industrial
dermatitis from exposure to penicillin, Friedlaender
Powdered penicillin et al. (1946) found the patients to be sensitive to pure
Dry powdered penicillin has proved to be a potent crystalline penicillin rather than to any particular
sensitizer and skin irritant in all the American factories impurity in the commercial product.[22]
where it is handled. It may produce follicular erythema,
diffuse; popular rashes on the exposed parts of the Local anesthetics
body, or, in some cases, severe generalized urticaria The local anesthetics, procaine, butyl (butacaine
which persists for days or weeks after exposure ceases. sulfate), and butesin (n-butyl aminobenzoate), form
In the latter cases, it seems probable that a generalized a group of substances more or less prone to cause
sensitivity has been created by the previous contact sensitization and dermatitis on prolonged contact with
with the substance, and that the urticaria results the skin. The tendency for procaine to sensitize the skin

Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018 363

 O. G. Bhusnure, et al.

of dentists and others who frequently spilled solutions Chloroform and ethylene dichloride
on their hands were recognized many years ago and Chloroform and ethylene dichloride (1,2-dichloroethane)
was one of the factors which made prepared solutions are occasionally used to extract alkaloids and other fat-
in cartridges so popular with dentists. Women engaged soluble principles. Both solvents are liver poisons, and
in filling cartridges with sterile solutions of procaine men working with them under ordinary conditions may
are subject to a characteristic occupational dermatitis develop certain vague symptoms which are referable
caused by excess solution overflowing from the tubes to the gastrointestinal tract and which suggest very
and running down their arms.[22] slight liver damage. These consist of anorexia, a heavy
feeling in the epigastrium, and fatigue. At this time the
Neoarsphehamine
urine may give a positive test for urobilinogen, and in
Neoarsphenamine, sensitization of the skin in those my experience, this is an indication for transferring
who pack it in ampoules. In such cases, the minute the workman temporarily to other employment. By-
amount of dust which settles on the skin during the products may accumulate relatively high concentrations
process may cause popular rashes on the exposed skin in parts of the plant and cause unexpected effects.
areas. In one such case, the skin was so sensitive to
contact with the drug that a patch test made with a few In pharmaceutical industry, most of the dermatitis can
milligrams of the powder exhibited vesiculation within be attributed to synthetic drugs, especially acridine
12 h. Such marked reactions, however, are rare; patch and phenothiazines.
tests are usually negative, but many mild dermatoses
of this kind subside when contact with the drug ceases CHEMICAL SAFETY GUIDELINES
and recur when it is resumed. Neoarsphenamine
may also act as a primary irritant if it is allowed to Always follow these guidelines when working with
accumulate under the nails of those handling it.[22] chemicals [Table 2 and Figure 2]:
• Assume that any unfamiliar chemical is hazardous
2-methyl-1, 4-naphthoquinone and treat it as such.
-2-methyl-1, 4-naphthoquinone, a synthetic form of • Know all the hazards of the chemicals with
Vitamin K, has the property of sensitizing the skin which you work. For example, perchloric acid is
and producing dermatitis. Workers who handle this a corrosive, an oxidizer, and a reactive. Benzene
chemical present a dark-brown staining of the skin, and is an irritant that is also flammable, toxic, and
may later show popular or eczematoid dermatitis.[22] carcinogenic.
• Never underestimate the potential hazard of any
Sulfonechloramides chemical or combination of chemicals. Consider
At least two sulfonechloramides which are used any mixture or reaction product to be at least as
as antiseptics or disinfectants have rather unusual hazardous as - if not more hazardous than - its most
properties as local irritants and sensitizers. hazardous component.
• Never use any substance that is not properly labeled. It
When these chemicals contaminate the working
may not be what you think it is date all chemicals when
environment in the form of dust, they may produce
they are received and again when they are opened.
dermatitis, rhinitis, conjunctivitis, and bronchitis in
their capacity as primary irritants.[22] Follow all chemical safety instructions, such as those
listed in material safety data sheets or on chemical
Solvents
container labels, and precisely.
Methyl alcohol is not commonly used. Ethyl alcohol • Minimize your exposure to any chemical, regardless
offers medical hazards only to the extent to which it is of its hazard rating, and avoid repeated exposure.
denatured with more toxic materials. • Use personal protective equipment (PPE), as
appropriate for that chemical.
Benzene
• Use the buddy system when working with hazardous
Benzene itself is, unfortunately, such an excellent solvent chemicals. Do not work in the laboratory alone.[23]
for many active principles, as well as for numerous
important synthetic chemicals, that it constitutes a major
HEALTH AND SAFETY
problem in the pharmaceutical industry. This is not the
place to describe or discuss the well-known facts about MANAGEMENT DUTIES IN
acute and chronic benzene poisoning, except to affirm RELATION TO HAZARDOUS
from my own experience that these well-established CHEMICALS
facts are still completely unknown or disregarded in
more backward works, and that they cry out for more Under the WHS act, a person conducting a business
popular diffusion among workmen and foremen, even or undertaking has the primary duty to ensure, so far
in the most progressive organizations.[22] as is reasonably practicable, that the health and safety

364 Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018

 O. G. Bhusnure, et al.

of workers and other persons are not put at risk from Resuscitation
work carried out as part of the conduct of the business Resuscitation means restoration of life of one who
or undertaking. This includes ensuring the safe use, is apparently dead (collapsed or shocked). Further
handling and storage of substances. supportive care should be provided as with any other
medical emergency.
The WHS regulations include specific duties for
a person conducting a business or undertaking to Decontamination
manage the risks to health and safety associated with
using, handling, generating, and storing hazardous A victim whose skin or clothing has been contaminated
chemicals at a workplace. requires immediate removal of garments and shoes.
Then, vigorous showering with soap and water, including
The duties include: attention to the fingernails and scalp is advised.[26]
• Correct labeling of containers and
• Pipework, using warning placards and Symptomatic Treatment
• Outer warning placards and displaying of safety Acute overexposure may result in a variety of signs
signs.[24] and symptoms that require general supportive
medical management regardless of the specific agent.
HAZARDOUS CHEMICALS Examples include the control of convulsive seizures
GENERATED OR bronchospasm.[26]

MANUFACTURED IN THE TLV CONCEPT

WORKPLACE
• American Council of Government Industrial Hygienists
Some processes will produce hazardous chemicals as has established Threshold Limit Values (TLV).
by-products or waste. These hazards may not be easily • TLV-time-weighted average time-weighted average
identified when generated at the workplace, for example, concentration for a normal 8-h working day and a
hydrogen sulfide in a sewer or diesel exhaust fume from 40-h working week, to which nearly all workers
truck engines. Information on by-products may be may be repeatedly exposed day after day, without
available from a SDS, but not always. Use of welding adverse effect.[27]
rods may liberate toxic fumes and vapors, grinding • TLV-short-term exposure limit.
metals release toxic metal dust or fumes, off-gassing of
solvent vapors from glues used to manufacture timber It is defined as a 15-min, time-weighted average which
products such as Medium Density Fibre, and dusts should not be exceeded at any time during a working day,
released from machining timbers are hazardous to health even if the 8-h time-weighted average is within the TLV.
or can present a dust explosion risk.[24]
The workers should not be exposed to the substances
Preventive Measures more than these limits.
• Solvents used in extraction, purification of synthetic
drugs and chemical analysis should be handled with TLVs are only guidelines and are not intended as absolute
care. boundaries between safe and dangerous concentrations.
• Flammable and explosive chemicals should be kept
Every occupational health professional should have a
at a proper distance.
copy of the current TLVs. [28,29]
• Tolerance levels for toxic chemicals set by federal
regulation have to be followed.
• Suitable label to the chemicals for proper handling. SAFETY AND HEALTH GOALS
• Personal protective cloth. • Provide workers with a safe work environment.
• Application of cream before the commencement of • Conduct routine/regular workplace inspections.
work. • Provide PPE.
• Use of goggles.[25]
• Develop and implement safe work procedures and
rules.
MANAGEMENT OF • Provide on-going safety training.
OVEREXPOSURE TO CHEMICALS • Enforce safety rules and appropriate discipline.
• Provide on-going property conservation practices.[30]
Removal from Exposure
• Prompt removal of the person from the exposure SAFETY MEASURES
site is the first step.
• Air respirators and lifelines are a mandatory first • Before starting work with a chemical a “chemical
aid [Figure 3]. hazard pocket guide” should be consulted for

Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018 365

 O. G. Bhusnure, et al.

necessary information about the chemical. It will Control of Chemical Hazards

give the type of reaction the chemical may produce, Priorities for control action [Figure 4]
its inflammability, carcinogenicity, prevention, and
Elimination
treatment procedures, etc.
• No eating, drinking, or smoking where chemicals The most effective and reliable controls are those that
are used. result in the elimination of the hazardous chemical.
• Skin should be covered with protective clothing.
• Clothing should be removed immediately it gets Substitution
wet or contaminated with a chemical. Substitution of a hazardous chemical for a less
• Eyes or skins should be washed with plenty of water hazardous one is the next control of choice; however,
after an accident. care must be taken to ensure that the substituted
• Face mask may be used in toxic dust or gases. chemical does not introduce new hazards. Substitution
• Workers working in antibiotic-related products must be also may involve using the chemical in a less hazardous
changed routinely so that an individual is not exposed form or process (e.g., use of the chemical in a pellet
to a certain antibiotic for a long period of time. form rather than a dust).
• Whenever a dust allergy or respiratory problem
precipitates, the worker should immediately be Isolation
removed from the workplace and put under proper Isolation of the chemical in time or space from those
health care. potentially exposed can be an effective means of
• In case of inflammable gas or solvent leakage, the control (e.g., locating people in a protected control
exhaust fans should be started, and all the source room, installing a buffer area around a chemical
of fire should be extinguished.[31] reactor, using the material when people are not in the
vicinity).
ROLE OF CONTROLLING
Engineering controls
HAZARDS
Engineering controls typically reduce exposure at
The next three sections (a planner’s Guide, A the source (e.g., by enclosing the process in vessels
Supervisor’s Guide, and A Worker’s Guide) or pipes, or by local exhaust ventilation). Prevention
of uncontrolled releases is important; this may be
Provide detailed information on the roles and achieved using strategies such as quantity reduction
responsibilities in developing and implementing and segregation.
effective chemical management, based on the phase in
which each person fits (i.e., planning, implementation, Administrative controls
or execution). Each section serves as a standalone In general, administrative controls will be required to
guide for each phase.[32] supplement higher-level controls.
Use the following descriptions to select the section Administrative controls may include maintenance of
that best applies to your role in the process: equipment and training of workers and their managers
in the operation of the equipment. Preventative
A planner’s guide (blue) is for those persons (planners)
maintenance is important in preventing uncontrolled
responsible for planning and initially designing the
releases. Work procedures may need to be developed
chemical management process. Planning roles include
to ensure that engineering controls function as
but are not limited to prime contractor, owner, owner’s
designed; this includes any safe-handling procedures
representative, licensee, operator, and supplier.
and special storage instructions.[33]
A supervisor’s guide (red) is for those persons
Personal protective equipment
(implementers/supervisors) responsible for organizing
workers and ensuring that the chemical management Any residual risk may require workers to wear PPE
process gets done. to reduce exposure to chemicals absorbed through
respiration or skin or eye contact.
Implementation roles include but are not limited to
supplier, supervisor, and site supervisor. Specialist knowledge may be required to ensure
selection of the correct type of PPE for a specific
A worker’s guide (green) is for those persons chemical.
(executers/workers) who physically manage the
chemicals on the job site and therefore are directly or Selection of gloves for protection against chemicals
indirectly exposed to the chemicals. absorbed through the skin requires reference to chemical
resistance charts or databases and consideration of the
Execution roles include but are not limited to potential for chemical permeation, penetration, and
supervisor, worker, and driver. [32] degradation of the PPE. In some situations, chemically

366 Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018

 O. G. Bhusnure, et al.

resistant safety footwear is required. Inappropriate or Precautionary statements are separated into five
poorly maintained PPE itself can act as a source of categories:
chemical exposure (e.g. contaminated gloves can be a • Prevention statements refer to precautions to be
source of ongoing exposure through persistent permeation taken to prevent an accident or exposure.
or occlusion of the chemical inside the gloves). • Response statements refer to instructions in case of
an accident.
While it would be expected that the risk associated • Storage statements refer to instructions for safe
with tasks such as decanting of chemicals would be storage of the chemical.
controlled through the enclosure or other engineering • Disposal statements refer to appropriate disposal
controls, some chemical handling tasks may require instructions.
eye protection. Depending on the task, this may be • General statements for use as appropriate.[35]
safety goggles or full face protection.

There is a wide range of PPE for respiratory protection. INDUSTRIAL SAFETY SYSTEM
While Australian standards provide information on The Industrial Safety System and Type
appropriate selection of respirators, the interpretation
Industrial automation has minimized the human
of these standard and the selection of the appropriate
respiratory protection require specialist Knowledge. interaction with the machines but has not completely
Fitting, maintenance and user training are important eliminated it. Industrial safety systems are introduced to
for all types of PPE, but especially for respiratory protect the human who works in hazardous plants. Some
protection.[34] examples of these are oil and gas, chemical, and nuclear
plants. The industrial safety systems not only protect the
humans but also protect the environment and the plant
IDENTIFYING CHEMICAL
itself from the chemical reactions [Figure 5].
HAZARDS
Process Control System
Chemical Label
These systems do not control any process but in fact,
Current labeling requirements in Australia vary
come into play when it is not possible to control
according to the intended use of the material and is
a process through normal means. They are rather
based on the classification of chemicals in accordance
installed as a protective measure and are quickly
with the requirements of the Australian Code for the
becoming the need of every working environment.[36]
Transport of Dangerous Goods by Road and Rail
(NTC, 2011) and/or the Standard for the Uniform They are installed for the monitoring of the
Scheduling of Drugs and Poisons (TGA, 2007). 10. manufacturing environment, and they control the
Introduction of the GHS, along with the national manufacturing process electronically. A laser diode
model work. is used for the detection of liquid or gas present in
the environment. If the gas or liquid is detected, then
The manufacturer or importer is responsible for
their particular frequency signature is converted to a
ensuring that any chemical or chemical product is
digital signal and the processor identifies the signal
classified and labeled according to current regulatory
received.[36]
requirements. From the perspective of the OHS
professional and the workplace user of the chemical, Safety Shutdown System
the important label components under the GHS
are signal words, hazard statements, precautionary These systems are particularly helpful in the state of
statements, and pictograms.[35] emergency as they automatically shutdown a system
to a safe state whenever they sense a danger. They can
Signal words are used to indicate the relative level be connected to the fire and gas systems to achieve
of severity of a hazard. The GHS uses “danger” and securer working environment.[36]
“warning” as signal words. “Danger” is used for a
more severe or significant hazard, while “warning” is Fire and Gas Systems
used for the less severe hazards. These systems are highly sensitive and intelligent.
They sense the inflammable gas, material, or liquid
Hazard statements describe the nature of a hazard, spill at an early stage. They also detect the fire within
including the degree of hazard, where appropriate. the working environment and give audible and visual
A unique hazard statement is assigned to each hazard signals of the threat detected. These systems can be
class and category.[35] activated automatically or manually.
Precautionary Statements There are other systems such as pressure safety valves
Precautionary statements are assigned to each hazard and emergency shutdown systems that are widely
class and category. used in the manufacturing industry.

Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018 367

 O. G. Bhusnure, et al.

The “Laboratory Standard,” 29 CFR 1910.1450, • Know the current legal requirements concerning
requires a Chemical Hygiene Program and designated regulated substances.
Chemical Hygiene Officer. The basic tenets of safe • Determine the required levels of PPE and equipment.
laboratory work will be found in your local Chemical • Ensure that facilities and training for the use of any
Hygiene Program.[36] material being ordered are adequate.[36]

General safety Guidelines and Rules Laboratory Workers

• Never work alone in the laboratory. • Plan and conduct each operation in accord with the
• Never mouth pipette. facility’s chemical hygiene procedures, including the
• Wear safety glasses or goggles at all times in the use of PPE and engineering controls, as appropriate.
laboratory. • Develop good personal chemical hygiene habits.
• Practice personal hygiene rules (e.g., wash hands • Report all accidents and potential chemical
before leaving the laboratory). exposures immediately.[36]
• No eating or drinking in the laboratory.
• Use PPE - do not wear laboratory coats outside the Basic Principles of Safety Management
laboratory area - wear closed toe, sturdy shoes. • No employee should risk injury or death to do a job.
• Practice good housekeeping techniques - keep • Safety can and should be managed.
walkways clear - label and date all containers.[36] • Accident prevention leads to more efficient and
profitable operations and improves the quality of
ROLES AND RESPONSIBILITIES life for employees.
• Each employee has a right and responsibility to
IN IMPLEMENTING THE help in the ongoing safety improvement process.
LABORATORY STANDARD Encourage your employees to help identify and
resolve safety concerns as they arise.[36]
The following are the National Research Council’s
recommendations concerning the responsibilities
of various individuals for chemical hygiene in PROCESS SAFETY MANAGEMENT
laboratories. (PSM) IN INDIA
Chief Executive Officer Current Trends in PSM in India
• Bears ultimate responsibility for chemical hygiene As per KPMG (2003), the Indian Chemical
within the facility. Industry contributes to 6.7% of India’s GDP, with
• Provides continuing support for institutional revenues of USD 28 billion. As per Indian Chemical
chemical hygiene.[36] Manufacturer’s Organization (website, 2004), the
industry has the following credits to its name:
Chemical Hygiene Officer
The Indian fertilizer industry is the fourth largest in the
• Develops and implements appropriate chemical
World. It is the largest manufacturer of pesticides in
hygiene policies and practices.
Asia, second only to Japan the Indian pharmaceutical
• Monitors procurement, use, and disposal of
industry is the largest in the developing world.
chemicals used in the lab.
The large-scale players in the industry have been
• Ensures that appropriate audits are maintained.
proactively adopting management systems for
• Helps project directors develop precautions and process safety, occupational health, and environment.
adequate facilities. Although the PSM system is not mandated by Indian
• Knows the current legal requirements concerning law, a number of chemical industries in India are
regulated substances. voluntarily adopting the PSM system developed by
• Seeks ways to improve the chemical hygiene OSHA. USA PSM is increasingly being woven into
program.[36] business strategy, during the project conceptualization
stage itself. While the large-scale players are
Laboratory Supervisors
systematically adopting best practices in PSM, the
• Laboratory supervisors have overall responsibility fragmented medium and small-scale manufacturing
for chemical hygiene in the laboratory. sector are yet to systematically adopt PSM.[37]
• Ensure that laboratory workers know and follow
the chemical hygiene rules. CHALLENGES
• Ensure that protective equipment is available and
in working order. • Enhancing ratification and implementation of
• Ensure that appropriate training has been provided. existing regulations.
• Provide regular, formal chemical hygiene, and • Expanding risk assessments and controls.
housekeeping inspections, including routine • Improving management capacity and raising
inspections of emergency equipment. awareness.

368 Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018

 O. G. Bhusnure, et al.

• Minimizing generation of hazardous chemicals and 15. Bundesanstalt Für Arbeitsschutzund Arbeitsmedizin:
wastes. Technische Regelnfür Gefahrstoffe TRGS 905; 2008. Available
from: [Link]
• The adoption of more proactive and precautionary 16. Ferguson KK, O’Neill MS, Meeker JD. Environmental
policies and management approaches is ultimately contaminant exposures and preterm birth: A comprehensive
needed to achieve necessary environmental and review. J Toxicol Environ Health B Crit Rev 2013;16:69-113.
human health protection standards.[38] 17. Windham G, Fenster L. Environmental contaminants and
pregnancy outcomes. Fertil Steril 2008;89 2 Suppl:e111-6.
18. Annual Refresher on Health and Safety for Hazardous Waste
CONCLUSION Sites Investigation Personnel 200. p. 45.
19. Burnett L, Lunn G, Coico R. American Chemical Society, Safety
The concluded that knowing and understanding the in Academic Chemistry Laboratories. 1990. 5th ed. Biosafety:
risk of hazardous facility and hazard release are the Guidelines for Working with Pathogenic and Infectious
Microorganisms. Currents Protocols in Microbiology; 2009
most important segments of an optimal pharmaceutical 13:1A.1.1.-1A.1.14.
safety management. An effective hazard and risk 20. Department of Environmental Health and Safety. 800 West,
assessment allows developing an incident action Cambell Rd, SG No. 10 Appendix No. 6 Managing Risks
plan and implement strategies and tactics. The bulk of Hazardous Chemical in the Workplace Code of Practice
Code-61. 2012. p. 10.
of societal costs, however, are actually being borne 21. ACGIH, Threshold Limit Values for Chemical Substances
by the workers themselves. There is an urgent need and Physical Agents, and Biological Exposure Indices. USA:
of rethinking the production process by taking into ACGIH Worldwide, Cincinnati; 2002.
account the health impact on workers from the very 22. Allanou R, Hansen BJ, van der Bilt Y. Public Availability of
Data on EU High Production Volume Chemicals. Italy: EUR
beginning. 18996, European Chemicals Bureau, Ispr; 2000
23. Industrial Safety Program Under 21 CFR [Link].5Safe
REFERENCES Work Australia. Labelling of Workplace Hazardous
Chemicals: Code of Practice; 2011a. Available from: http://
1. University of Medicine and Dentistry of New Jersey. Annual [Link]/AboutSafeWorkAustralia/
Refresher on Health and Safety for Hazardous Waste Site WhatWeDo/Publications/Pages/labelling-hazardous-
Investigation Personnel. New Brunswick, NJ: University [Link].
of Medicine and Dentistry of New Jersey - School of Public 24. PLC (Programmable Logic Controllers) MANUAL;
Health, Office for Public Health Practice, Centers for Education 2008-2017. p. 12.
and Training; 2001. 25. American Chemical Society. Safety in Academic Chemistry
2. U.S. Food and Drug Administration, Office of Regulatory Laboratories. 5th New York: American Chemical Society; 1990.
Affairs, Division of Field Investigations. (Current Edition). 26. Burnett L, Lunn G, Coico R. Biosafety: Guidelines for working
Investigations Operations Manual or the Website Address. with pathogenic and infectious microorganisms. Curr Protoc
Available from: [Link] Microbiol 2009;13:1A.1.1.-1A.1.14.
[Link]. 27. Indian Chemical Manufacturers Association. KPMG and
3. Subramanyam CV, Setty JT, Suresh S, Devi VK. Pharmaceutical Chemtech Foundation: The Indian Chemical Industry -
Engineering Principals and Practices. 1st ed. New Delhi: M.K New Directions, New Hope; 2003. Available from: [Link]
Jain for Vallabh Prakashan; 2003. p. 480-4. [Link].
4. Sambamurthy K. Pharmaceutical Engineering. New Delhi: 28. [a] Frank A, Massey R. The True Costs of Reach. Copenhagen:
New Age International Publishers; 2003. p. 440-9. Nordic Council of Ministers; 2004. Paul TA, Warner JB.
5. IARC: A Review of Human Carcinogens. Chemical Agents and [b] Green Chemistry: Theory and Practice. Oxford: Oxford
Related Occupations. Vol. 100F. Lyon: IARC; 2012. University Press; 1998. CDC - Chemical Safety - NIOSH
6. IARC: A Review of Human Carcinogens. Arsenic, Metals, Workplace Safety and Health Topic. Available from://www.
Fibres, and Dusts. Vol. 100C. Lyon: IARC; 2012. [Link]. [Last retrieved on 2015 Sep 03].
7. Kauppinen T, Toikkanen J, Pedersen D, Young R, Ahrens W, 29. Chemical Hazards. Ch. 8. Available from: [Link]
Boffetta P, et al. Occupational exposure to carcinogens in the [Link]; [Link]
European Union. Occup Environ Med 2000;57:10-8. glossary_of_terms/glossary_of_terms_h.html. [Last reterived
8. Raison-Peyron N. Occupational dermatitis diagnosis. Rev Fr on 2016 Feb 02.]
Allergol 2006:46 Suppl 1:S45-50. 30. Available from: [Link]
9. Deutsche Forschungsgemeinschaft (DFG). List of MAK and [Link].
BAT Values 2013: Maximum Concentrations and Biological 31. IARC. A Review of Human Carcinogens: Radiation. Vol. 100D.
Tolerance Values at the Workplace. Weinheim: Wiley; 2013. Lyon: IARC; 2012.
10. Schnuch A, Lessmann H, Schulz KH, Becker D, Diepgen T, 32. Haagsma JA, Tariq L, Heederik DJ, Havelaar AH: Infectious
Drexler H, et al. When should a substance be designated as disease risks associated with occupational exposure:
sensitizing for the skin (‘Sh’) or for the airways (‘Sa’) ? Hum A systematic review of theliterature. Occup Environ Med
Exp Toxicol 2002;21:439-44. 2012;69:140-6.
11. Akan G, Lemanske R. Allergic disease. Pathophysiology and 33. CDC Chemical safety NIOSH Workplace Health Topics Page
immunopathology. In: Lieberman P, Anderson JA, editors. No. 12.
Allergic Diseases. Totowa, NJ: Humana Press; 2007. p. 1-14. 34. Available from: [Link] spots.2011/07.
12. Belsito DV. Occupational contact dermatitis: Etiology, 35. Haagsma JA, Tariq L, Heederik DJ, Havelaar AH. Infectious
prevalence, and resultant impairment/disability. J Am Acad disease risks associated with occupational exposure: A
Dermatol 2005;53:303-13. systematic review of the literature. Occup Environ Med
13. Raison-Peyron N. Occupational dermatitis diagnosis. Rev Fr 2012;69:140-6.
Allergol 2006;46 Suppl:S45-50. 36. Available from: [Link]
14. Vocks E, Ring J. Lichtallergien under and 37. CDC. Chemical Safety NIOSH Workplace Health Topics
lichtempfindlichkeitsreaktionen. Z Umweltchem Okotox [Link]. 12.
2002;14:237-44. 38. Available from: [Link]

Journal of Pharmacy Research | Vol 12 • Issue 3 • 2018 369