Caballero B. (ed.) Encyclopaedia of Food Science, Food Technology and Nutrition. Ten-Volume Set

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Krebs Cycle See Tricarboxylic Acid Cycle; Oxidative Phosphorylation

Krill See Shellfish: Characteristics of Crustacea; Commercially Important Crustacea; Characteristics of

Molluscs; Commercially Important Molluscs; Contamination and Spoilage of Molluscs and Crustaceans;

Aquaculture of Commercially Important Molluscs and Crustaceans

KWASHIORKOR

C Leitzmann, Justus-Liebig University, Giessen,

Germany

Background

0001 Kwashiorkor is a nutritional disease, common in

rural areas of developing countries, and it primarily

affects children in the second year of life. This typical

disease of the weaning period is associated with a diet

based on starchy, low-protein staple foods, such as

cassava, sweet potatoes, and bananas.

0002 The term ‘kwashiorkor’ was used in the Gold

Coast area of West Africa (present-day Ghana) and

describes the ‘disease of the weaned child when the

next baby is born.’ Cecily Williams introduced this

term into modern medicine in 1933.

0003 The realization of the close interactions between

protein and energy deficiencies led to the introduction

of the term ‘protein-energy malnutrition’ (PEM),

which describes a range of clinical disorders in which

marasmus and kwashiorkor are the two poles. Be-

tween these, there are many forms, with different

clinical features, depending on the varying combin-

ation of deficiencies of protein, energy, and other

nutrients, together with associated infections.

Etiology, Clinical Features, and

Physiological Effects

Etiology

0004 Although dietary protein deficiency plays an import-

ant role in the causation of kwashiorkor, this alone

does not explain the etiology. Kwashiorkor is a com-

plex multifactorial condition in which geographic,

climatic, educational, infective, psychological, cul-

tural, agronomical, nutritional, and other factors,

frequently in combination, are involved. Kwashior-

kor can be considered as the end point of a combin-

ation of these adverse factors, in which the body is not

able to adapt to these changed conditions, and the

characteristic clinical features develop. (See Protein:

Deficiency.)

Clinical Features

0005The clinical picture can vary, depending on the degree

of protein deficiency, accompanied vitamin or

mineral deficiencies, age of onset and duration of

deficiency, genetic and other factors. Figure 1 shows

the typical signs of kwashiorkor.

0006Edema Edema is the cardinal sign of kwashiorkor

and must be distinguished from the edema caused by

other diseases such as hookworm infestation or beri-

beri. Edema causes tissue to swell and may be distrib-

uted over the whole body, but it usually appears first

in the dorsum of the feet and lower legs. Later, it can

also be detected in other parts of the body, including

hands, forearms, back, upper extremities, and, in

severe cases, in the face, especially the cheeks and

around the eyes. Together with increased locally

deposited fat in obese variants of kwashiorkor, the

edema of the face results in the so-called ‘moon-face.’

The edema fluid generally represents 5–20% of the

body weight. Ascites and other effusions into serous

cavities are a late manifestation of edema and may be

attributable to the presence of an infection.

0007Hair changes Kwashiorkor can be accompanied by

striking dyspigmentation and changes in the texture

of the hair, which can vary greatly from one part of

the world to another. Thus, in African children, the

dyspigmentation causes a change from black to red,

blonde or light brown. In South American children,

the ‘flag sign,’ an appearance of alternating streaks of

3432 KWASHIORKOR

dyspigmented and normal black hair, prevails. The

dyspigmented areas reflects periods when the child’s

nutrition was low in protein, 1–3 months before the

color change appears. Nonnutritional environmental

and genetic aspects that can also cause dyspigmenta-

tion should be excluded. Changes in the texture of the

hair can be seen in African children. Curly hair be-

comes sparse and straight, and the bulbs of the hair

roots are reduced in diameter, as a result of which, the

hair is easily pluckable.

0008 Dermatosis Dermatoses are characterized by areas

of desquamation, ulceration and of both hypo- and

hyperpigmentation of the skin. The lesions usually

affect the lower limbs, buttocks, and perineum,

but may be found anywhere on the body. Whereas

the desquamated parts of the skin look as if there

has been a burn and resemble ‘crazy paving’ thehy-

perpigmented areas resemble ‘flaky paint.’ Often

dermatoses are complicated by associated skin

infections.

0009 Fatty liver In many, but not all, cases of kwashior-

kor, the liver is considerably enlarged and can

be palpated. The enlargement occurs mainly because

of an infiltration with fat, especially triglycerides.

This is the result of a decreased synthesis of

b-lipoproteins, the specific transport agents for

triglycerides. The fat accumulates in small droplets

within the cells, first in the periphery of the lobules,

and then spreads to the center of the lobules. In

general, the liver functions are not altered. Severe

liver failure is unusual, and cirrhosis only occurs in

combination with any hepatic toxin, including afla-

toxins. With recovery, the fatty liver is completely

reversible. (See Liver: Nutritional Management of

Liver and Biliary Disorders.)

0010Muscle wasting The muscles are often wasted, and

the child regresses in their physical development. The

infant becomes weak and is unable either to stand and

walk or to hold up their head when lifted from a lying

to a sitting position. In many cases, it is difficult to

recognize the muscle dystrophy because of edema,

which often conceals the wasting, but in the upper

arms, where there is less edema, a reduction in

circumference is evident.

0011Subcutaneous fat, which reflects the child’s energy

intake in the form of starchy food, and psycho-

motor changes are additional features. The child

appears apathetic and miserable, with intermittent

crying, and is often anorexic. In many cases, some

degree of anemia is present and may be aggravated

by malaria, hookworm infestation, or other para-

sites. Diarrhea is another common finding in

kwashiorkor.

Physiological Effects

0012Kwashiorkor leads to changes in the organs and

systems of the body and results in altered physio-

logical functions.

0013Cardiovascular system Atrophy of the heart (which

leads to reduced cardiac output), circulatory insuffi-

ciency (associated with prolonged circulation time)

and bradycardia have been described. As a result,

the extremities of kwashiorkor patients are cold and

pale, and the pulse rate is low or even impalpable.

Cardiac failure has been postulated as a possible

cause of death in these children.

0014Endocrine organs and hormones The functions

of the endocrine glands are not reduced in kwashi-

orkor. Secretion of human growth hormone from

the pituitary appears to be normal or may be in-

creased. Thyroid-stimulating hormone is also ele-

vated. Owing to the prolonged half-life of cortisol,

the plasma levels are elevated, with a catabolic

effect on nutrients. Thyroid function seems to be

normal, but reduced plasma concentrations of thy-

roxine-binding proteins and a reduced total plasma

concentration of thyroxine have been observed. In

Underweight, Dermatosis

Hair changes

Misery

Edema

Fatty

liver

Moon face

Thin muscles

Fat present

fig0001 Figure 1 Clinical signs in kwashiorkor. (From Jelliffe DB and

Jelliffe EF (1989) Community Nutritional Assessment with Special

Reference to Less Technically Developed Countries, pp. 273–292.

Oxford: Oxford University Press. modified.)

KWASHIORKOR 3433

general, insulin secretion after oral glucose ingestion

is impaired. (See Hormones: Thyroid Hormones.)

0015 Digestive organs Protein depletion probably plays a

predominant role in the pathogenesis of the mucosal

changes. Cells of the intestinal mucosa and pancreas

are atrophic. The mucous membranes of mouth and

tongue are also affected. The synthesis and activity of

digestive enzymes are reduced. Most affected are

the disaccharidases, lactase, sucrase, and maltase. A

reduced absorptive area together with diminished

enzyme activities leads to impaired utilization of nu-

trients. In addition, lactose intolerance is particularly

common.

0016 Kidneys There is no specific structural or functional

abnormality, but in a state of dehydration, the glom-

erular filtration rate is reduced. The impaired ability

to concentrate urine may be attributable to accom-

panying electrolyte deficiencies, particularly to potas-

sium. (See Renal Function and Disorders: Kidney:

Structure and Function.)

0017 Immunological system The immune system is still

developing in the first 2 years of life and is very

sensitive to nutrient deficiencies in early childhood.

In kwashiorkor, the lymphoid tissue, primarily the

thymus, is atrophic, and the immune response to

infectious agents, particularly the cell-mediated

immune response, is diminished. Thus, the child be-

comes more susceptible to infections such as measles

or gastroenteritis. These infections themselves ex-

haust the nutrient stores.

Biochemical and Metabolic Disorders

0018 There is a profound change in the body composition

with the onset of kwashiorkor. Total body water in-

creases from 60% to about 80% of the total body-

weight and may be comparable with that of a

newborn infant. The high water content is mainly

attributable to the reduced body fat stores and to

muscle wasting.

0019 The mineral content also changes. In particular,

potassium decreases as a result of losses from diar-

rheal stools. Other minerals, such as sodium, calcium,

phosphorus, and magnesium, are also diminished.

individual minerals.

0020 Total body protein is severely reduced by up

to about 60% of the expected value in a normal

child. This reduction is accompanied by a change of

collagen protein from 27% in healthy children to

about 40% of total body protein in children

with PEM. Thus, the noncollagen protein is severely

affected.

0021As a result of diets high in carbohydrates, children

with kwashiorkor may still have subcutaneous and

other fat stores.

General Metabolism

0022Protein metabolism In kwashiorkor, protein is

adequately digested, and nitrogen retention is much

more efficient, as can be seen in a fall of urinary

nitrogen output. Whether or not total protein turn-

over is influenced by the level of protein intake,

protein synthesis decreases in individual tissues such

as muscle and skin, because they act as buffers in

the adjustment of protein metabolism. (See Protein:

Digestion and Absorption of Protein and Nitrogen

Balance.)

0023The pattern of plasma amino acids shows charac-

teristic changes. The concentration of essential amino

acids, especially the branched-chain amino acids, is

decreased. The plasma concentration of albumin is

also decreased, since the rate of synthesis is very

sensitive to reduced protein intake and falls immedi-

ately at the onset of dietary protein deficiency. The

concentration of g-globulins is usually normal and

may even be elevated in the presence of infection.

Other plasma proteins, such as transferrin and

retinol-binding protein, are lowered and this explains

the frequency of accompanying anemia and kerato-

malacia in kwashiorkor. Reduced concentrations

of some plasma enzymes, including cholinesterase,

alkaline phosphatase, amylase, and lipase, have also

been reported.

0024Lipid metabolism As a result of decreased ability of

the liver cells to synthesize lipoproteins, levels of

plasma triglyceride and plasma cholesterol are low.

Owing to increased lipolysis in the fatty tissue, the

concentration of free fatty acids in the plasma tends

to be high. (See Fatty Acids: Metabolism.)

0025Carbohydrate metabolism Hypoglycemia and glu-

cose intolerance are frequent occurrences. Glucose

intolerance is probably attributable to an impaired

insulin release or a peripheral insensitivity to insulin

and could predispose to diabetes in later life. (See

Carbohydrates: Digestion, Absorption, and Metabol-

ism; Glucose: Maintenance of Blood Glucose Level.)

Effect on Growth and Mental

Development

Growth Failure

0026Compared with adults, young children need high

nutrient supplies for rapid growth. Thus, growth

failure can be understood as an early adaptation to

3434 KWASHIORKOR

reduced dietary energy and protein intake. In con-

trast to mild forms of malnutrition, where stunted

growth is characteristic, growth retardation in

kwashiorkor is of less importance. In kwashiorkor,

the restricted intake of nutrients together with acute

infections, such as measles or gastroenteritis, leads

to diminished body weight. Affected children have

between 60 and 80% of the expected weight for

their age. A decreased weight: height ratio, lowered

mid-arm circumference and diminished skinfold

thickness are also characteristic signs. (See Growth

and Development.)

Mental Development

0027 It is rather difficult to assess the effects of malnutri-

tion in early childhood on brain and mental develop-

ment because malnutrition frequently occurs in an

unfavorable psychological environment, such as de-

privation of parental and social care, with less mental

stimulation of the children. Consequently, it becomes

difficult to separate these effects from those of mal-

nutrition or other factors.

0028 The development of the human brain occurs

mainly between midgestation and the second year of

life. In this time, there is a rapid increase in the total

cell number, which continues past the first year of

postnatal life. The myelination also starts to increase

before birth and continues until the second year of

life. In this period, the brain development is vulner-

able to nutrient deficiencies, which are demonstrated

by a reduced number of brain cells in cerebrum,

cerebellum, and brain stem, and reductions of total

lipid, cholesterol, and phospholipid content. A

smaller head circumference, reflecting reduced brain

growth, has also been observed in undernourished

children.

0029 Although a correlation between anatomical

changes of the brain and intellectual development

is uncertain, many observations in developing coun-

tries have shown correlations between intelligence

scores and malnutrition in the first 2 years of life. It

seems that acute malnutrition such as kwashiorkor

exerts less of an influence on intelligence than chronic

malnutrition. The results are somewhat different, and

the duration and time of malnutrition, as well as the

psychological environment of the children, must also

be considered.

Drug Metabolism

0030 Malnutrition is frequently accompanied by infections

and other complications, necessitating treatment

with drugs such as antibiotics. Present knowledge

about drug metabolism in undernourished organisms

is limited. In kwashiorkor, the binding capacity for

drugs such as salicylates, which are carried in the

circulation bound to plasma proteins, is lowered,

owing to decreased plasma albumin concentrations.

Higher concentrations of free forms of the drug may

be toxic. The ability of the liver to detoxicate drugs

by oxidizing them may be impaired and can result in

a prolonged half-life of the drug. For these reasons,

all drugs should be used with caution.

Diagnosis, Treatment, and Prevention

Diagnosis

0031The diagnosis of kwashiorkor includes the above-

mentioned clinical features and anthropometric

measurements, such as weight between 60 and

80% of the standard, reduced mid-arm circumfer-

ence, and triceps skin-fold thickness. A decreased

serum albumin concentration below 35 g l

1

repre-

sents the probability of protein deficiency. Other

plasma proteins, such as retinol-binding protein,

have been used in diagnosis, because they react

more sensitively to protein deficiency. (See Nutri-

tional Assessment: Anthropometry and Clinical

Examination.)

Treatment

0032Children with severe kwashiorkor require treatment

in hospital. Table 1 shows the major points of

treatment. Since the main causes of death are dehy-

dration and other complications, such as electrolyte

disturbances, hypoglycemia, and various infections,

the treatment has to start with fluid replacement

and treatment of the various complications. After

initial resuscitation, refeeding should be started

with one- to two-hourly oral or nasogastric feeds of

an electrolyte solution. On the second day, a three-

hourly milk feed with added sugar (or any similar

preparation) should be given. The amount of 90 ml

per kilogram of body weight per day can be in-

creased in the following few days. At the same

time, the feeding frequency can be reduced to every

4 h. Once the child’s appetite has improved, local

staple food should be added to the meals to provide

an extra source of energy, which can meet the

need for catch-up growth.

0033Severely undernourished children are also likely to

be deprived of vitamins (particularly vitamin A, D,

folic acid, and some B-group vitamins) and trace

minerals; supplements of these nutrients are needed.

Refer to individual vitamins.

0034After the acute phase of illness, the children

need several weeks of special feeding and some super-

vision until recovery is complete. For this period of

KWASHIORKOR 3435

treatment, nutrition rehabilitation units, where

recovery of children is combined with nutrition

education for the mothers, are most suitable. Mothers

are taught the use of local foods, cooking, feeding

practice, and preparation of weaning diets that are

more suitable for the children. Moreover, mothers

receive instructions for dealing with simple illnesses

such as diarrhea. This may help to prevent children

who are cured from going back to the conditions

that precipitated the malnutrition.

Prevention

0035 In view of its multifactorial causation, the prevention

of kwashiorkor cannot be achieved through medical

or nutritional means alone. Political, economical, and

agricultural measures are also necessary. From the

nutritional point of view, the management of weaning

is most important. Mothers need educational services

in order to understand the special dietary needs of the

child at weaning. They should be educated to prepare

weaning diets with higher protein and energy con-

tents. (See Infants: Weaning.)

0036 Owing to lack of time, children are fed only once or

twice a day with bulky foods, frequently late at night,

when they are too tired to eat. Thus, it is impossible

for children to receive their nutrient needs; it is neces-

sary to feed children at least four times a day.

Prognosis

0037 The prognosis of severe kwashiorkor depends on the

particular living conditions, including hygiene, which

can lead to severe infections, on complications such as

cardiac failure, and on the facilities available to treat

the sick child. In addition, the conditions to which the

child must return after treatment are very important.

Prognosis is often unfavorable, with mortality rates

between 10 and 25% for severe kwashiorkor cases.

(See Malnutrition: The Problem of Malnutrition;

Marasmus.)

See also: Carbohydrates: Digestion, Absorption, and

Metabolism; Fatty Acids: Metabolism; Glucose:

Maintenance of Blood Glucose Level; Growth and

Development; Hormones: Thyroid Hormones; Infants:

Weaning; Liver: Nutritional Management of Liver and

Biliary Disorders; Malnutrition: The Problem of

Malnutrition; Malnutrition in Developed Countries;

Marasmus; Nutritional Assessment: Anthropometry

and Clinical Examination; Protein: Digestion and

Absorption of Protein and Nitrogen Balance; Deficiency;

Renal Function and Disorders: Kidney: Structure and

Function

Further Reading

Albrecht R and Pe

lissier MA (1995) About the oxidative

stress status in children with kwashiorkor. Food Chem-

istry and Toxicology 33: 1081–1083.

Elmadfa I and Leitzmann C (1998) Erna¨ hrung des

Menschen, 3rd edn. Stuttgart: Verlag Ulmer.

Hansen JDL, Buchanan N and Pettifor JM (1982)

Protein energy malnutrition (PEM). In: McLaren DS

and Burman D (eds) Textbook of Paediatric Nutrition,

tbl0001 Table 1 Synopsis of the major points of treatment of severe PEM

Object of treatment Treatment

Complications

Dehydration Plasma 20 ml kg

1

in hypovolemia. Half-strength Darrow’s solution at 50–100 ml kg

1

over 6 h followed

by 100–150 ml per kilogram per day for maintenance

Electrolyte disturbance Potassium: 6 mmol per kilogram per day

Calcium: 3 g per day

Magnesium: 2–3 mmol per kilogram per day

Hypoglycemia Dextrose, 50%, 1 ml kg

1

iv stat. and then 10% dextrose solution iv as maintenance

Infection Antibiotics covering both Gram-negative and Gram-positive organisms, e.g., penicillin 25 000–50 000

units per kilogram per day in four divided doses, iv, im, or orally, and kanamycin 5–15 mg per

kilogram per day in two to three divided doses, im

Dietary deficiencies Initially frequent small feeds, e.g., half-strength Darrow’s solution in a dose of 90 ml per kilogram per

day in eight divided feeds for 24 h, then full strength milk (90 ml per kilogram per day) increasing to

150 ml per kilogram per day over 2–3 days

Cereals and other foods are added once improvement occurs

Vitamin A: 33 000 mg im on admission and then 5000 mg orally per day

Vitamin K: 5 mg iv or im on admission

Vitamin D: 10 mg per day

Ferrous sulfate: 5 mg per kilogram per day once improvement in general condition has occurred

Folic acid: 5 mg per day for 10 days

iv, intravenous; im, intramuscular.

Source: From Hansen JDL et al. (1982).

3436 KWASHIORKOR

2nd edn, pp. 114–142. Edinburgh: Churchill Living-

stone.

Jackson AA (1990) The aetiology of kwashiorkor. In:

Harrison GA and Waterlow JC (eds) Diet and Disease

in Traditional Societies, pp. 76–113. Cambridge: Cam-

bridge University Press.

Jelliffe DB and Jelliffe EF (1989) Community Nutritional

Assessment with Special Reference to Less Technically

Developed Countries, pp. 273–292. Oxford: Oxford

University Press.

King FS and Burgess A (1993) Nutrition for Developing

Countries, 2nd edn. Oxford: Oxford University Press.

McLaren DS (1982) Protein energy malnutrition (PEM).

In: McLaren DS and Burmann D (eds) Textbook of

Paediatric Nutrition, 2nd edn, pp. 103–113. Edinburgh:

Churchill Livingstone.

Passmore R and Eastwood MA (1986) Human Nutrition

and Dietetics, 8th edn, pp. 279–291, 516–545. Edin-

burgh: Churchill Livingstone.

Poskitt EME (1988) Practical Paediatric Nutrition,

pp. 96–113. Stoneham, MA: Butterworth.

Suskind RM and Lewinter-Suskind L (1990) The Malnour-

ished Child, Nestle

Nutrition Workshop Series 19. New

York: Raven Press.

Waterlow JC (1992) Protein Energy Malnutrition, 2nd edn.

London: Edward Arnold.

KWASHIORKOR 3437

Labeling (Labelling) See Food Labeling (Labelling): Applications

LABORATORY MANAGEMENT

Contents

Chemical Safety

Microbiological Safety

Chemical Safety

G Collier, University of Hull, Hull, UK

This article is reproduced from Encyclopaedia of Food Science,

Background

0001 There are several obvious prerequisites for safe

working. These include well-designed buildings,

equipment suited to the intended purposes, and

carefully planned operating systems that are clearly

defined and effectively administered. Moreover,

the choice and use of buildings, equipment and

systems of work should be strongly influenced by

a clear, progressive, and well-publicized safety

policy. In addition to defining aims and objectives,

the policy statement should specify the persons

to whom particular safety responsibilities are

delegated; the extent of those responsibilities; the

arrangements for advice and instruction on safety

matters; and the procedures for reporting defects

and making complaints.

0002 It is widely recognized that the same principles that

have been adopted within many organizations with

respect to total quality management (TQM) are

equally applicable to the management of health and

safety. Organizations that have applied this approach

to their health and safety management systems, often

as part of a TQM philosophy, generally achieve high

standards of health and safety performance.

0003The TQM approach seeks to promote continuous

improvement in all aspects of an organization’s activ-

ities. In health and safety terms, the ultimate goal is a

harm-free environment. Such an objective is clearly

desirable, even in financial terms. Since the staff of

any organization is invariably its most valuable asset,

ill health and accidents have appreciable financial and

operational consequences. An effective system for

managing health and safety will reduce what is

known, in quality terms, as the cost of nonconfor-

mance.

0004The following paragraphs highlight certain aspects

of chemical safety that are of particular relevance.

The Control of Substances Hazardous to

Health (COSHH)

0005Against a background of increasing awareness of

a need to provide a general legal foundation for

good occupational hygiene practices, the European

Commission adopted a Framework Directive (80/

1107/EEC) on the protection of workers against

chemical, physical and biological hazards. In the

UK, this led to the Control of Substances Hazardous

to Health (COSHH) Regulations, which may be

considered to represent best current practice.

0006Under these Regulations, no employer may carry

out any work that is liable to expose employees to any

substance hazardous to health unless he or she has

made a suitable and sufficient assessment of the risks

created by that work to the health of those employees,

and of the steps that need to be taken to prevent or

control exposure. The Regulations are wide-ranging,

not least in their definitions of substances hazardous

to health.

0007 In practice, there is no single simple way of defin-

ing what is, or is not, a hazardous substance. The

hazard is the potential of the substance to cause

harm to health. Whether that potential is realized,

i.e., whether, in other words, there is a risk or danger

to health, will depend upon a number of factors:

the amount of substance used; its physical state;

the likelihood of exposure and the method of entry

into the body. All these circumstances need to

be taken into account. The hazard, or potential

for harm, arises from the intrinsic properties of

the substance and, depending upon what those

properties are, there may be hazard of a high or

low order.

0008 The COSHH Regulations define several categories

of hazardous substance as follows:

0009 Substances that have been formally designated as

very toxic, toxic, harmful, corrosive, or irritant.

0010 Substances to which an occupational exposure

standard (OES) or maximum exposure limit

(MEL) has been assigned. An OES is the concen-

tration of an airborne substance, averaged over a

reference period, at which, according to current

knowledge, there is no evidence that it is likely

to be injurious to personnel if they are exposed

by inhalation, day after day, to that concentration.

A MEL, however, is a strictly applied limit. It is the

maximum concentration, averaged over a refer-

ence period, to which personnel may be legally

exposed under any circumstances. Furthermore,

employers have a duty to ensure that exposure is

kept as far below the MEL as is reasonably prac-

ticable. So far, MELs have been assigned only to

substances that have been generally perceived to

present a high level of hazard, including a number

of carcinogens, mutagens, and teratogens.

0011 Biological agents.

0012 Dust, of any kind, in substantial concentrations

(see below).

0013 Other substances with similar hazards to those in

the previous categories.

0014 The risk assessment that is required must be under-

taken by a competent person. It involves consideration

of all the types of substances to which an employee

is likely to be exposed and the effects that such sub-

stances can have on the body. The nature and extent of

exposure must also be assessed, taking due account

of reasonably foreseeable deterioration in, or failure

of, control measures. Although inhalation is the main

route of entry into the body, some substances may be

readily absorbed through the skin, and this needs to be

taken into account when designing control measures.

0015There is a firm requirement to ensure that exposure

is prevented wherever reasonably practicable. Only

where this is not reasonably practicable (i.e., when it

cannot be achieved without completely disproportion-

ate expense or trouble) is adequate control an accept-

able alternative. Nevertheless, the opportunities for

prevention of exposure are often limited, requiring

either elimination of the use of the substance al-

together or substitution by a less hazardous material.

0016In most circumstances, effective control is the only

practicable option, and this is mainly achieved by

enclosure, total or partial, and local exhaust ventila-

tion. The use of personal protective equipment is only

acceptable in a minority of situations where adequate

control cannot be achieved by other means.

0017As soon as control measures are introduced, a

system of regular maintenance, examination, and

testing must be instituted, and the results must be

recorded, together with details of any repairs or

other remedial work. Defects must be promptly

reported by employees, and remedial action must be

taken as soon as possible.

0018Once effective and well-maintained control meas-

ures are in place, that is by no means the end of the

matter. The TQM approach requires constant feed-

back to improve performance, and three further lines

of action are appropriate.

0019Where it is necessary to ensure the maintenance of

adequate control, a procedure for monitoring for

hazardous substances is required. The use of certain

specified substances renders this mandatory. Usually,

monitoring is not just a matter of atmospheric sam-

pling but requires repeated or continuous measure-

ments in an individual’s breathing zone.

0020Health surveillance may also be called for in certain

circumstances, and the results, like those of monitor-

ing exercises, must be recorded. When an individual

leaves an employer’s service, their health surveillance

record should be passed to their new employer.

0021Above all, there is a requirement to provide

continual information, instruction, and training to

employees. Success in meeting this requirement is

clearly crucial to the success of all other measures.

In this connection, one of the notable developments

of the last few years has been the ever more stringent

requirement for the inclusion of chemical hazard

information on labels and packaging.

Sample Handling

0022Samples of material are presented to the laboratory in

many different forms. When submitted for quality

assurance or other routine testing, the nature of the

3440 LABORATORY MANAGEMENT/Chemical Safety

material may be known in some detail. In all other

circumstances, the material should be treated as

potentially harmful, and appropriate measures

should be adopted to control exposure of personnel.

0023 Samples must be adequately labeled, and labora-

tory workers should always ensure that they have

the maximum amount of relevant information before

handling the material. Many of the comments made in

the following paragraphs in respect of dusts, solvents,

and hazardous reagents are equally applicable to

materials submitted to the laboratory as samples for

examination or other experimental work.

Dusts

0024 Finely powdered materials and dusts can be hazard-

ous to health when present in the environment in

substantial concentrations. That which can be said

to constitute a substantial concentration is, to some

extent, dependent on particle size. This, in turn,

governs the aerodynamic diameter and drag, the

degree of penetration into the respiratory system,

and the region of deposition.

0025 Total inhalable dust (i.e., airborne material that

enters the nose and mouth during breathing) includes

particles up to 50 mm in diameter. The larger particles

are commonly called ‘nuisance dusts,’ and the body

usually expels them by coughing or sneezing. Total

inhalable dust of any kind, present at concentrations

of 10 mg m

3

or greater as an 8-h time-weighted

average, is regarded as hazardous to health.

0026 The term ‘respirable dusts’ is applicable to smaller

particles (of average diameter 7 mm or less), which are

much more harmful because they can penetrate deep

into the respiratory system, reaching the gas-exchange

regions of the lungs.

0027 As a general guide:

0028 particles of diameter > 7 mm will deposit in the

mouth and throat;

0029 particles of diameter 4.7–7 mm will deposit in the

pharynx;

0030 particles of diameter 3.3–4.7 mm will deposit in

the trachea and bronchi;

0031 particles of diameter 1.1–2.1 mm will deposit in the

terminal bronchi;

0032 particles of diameter about 1 mm and less will

deposit in the alveoli.

0033 Respirable dusts include grain dust, which may

be defined as dust arising from the harvesting, drying,

handling, storage, or processing of barley, wheat,

oats, maize, and rye, including contaminants. In

the UK, grain dust has been assigned a MEL

of 10 mg m

3

as an 8-h time-weighted average

respirable dust of any kind, present at concentrations

of 4 mg m

3

or greater as an 8-h time-weighted aver-

age, is regarded as hazardous to health (see COSHH,

1999). Atmospheric concentrations are determined

gravimetrically.

0034Occupational exposure to respirable dusts can

cause asthma and other allergic lung conditions as

well as a variety of recognized dust diseases. Such

dusts should therefore be considered as respiratory

sensitizers, which, when inhaled, can trigger irrevers-

ible allergic reactions in the respiratory system.

Once this has occurred, subsequent exposure, even

to minute amounts, may cause respiratory illness in-

cluding asthma, rhinitis and extrinsic allergic alveoli-

tis. If exposure is allowed to continue, symptoms are

likely to become progressively worse and may result

in chronic disease, which may become so severe as to

threaten life. The earlier a sensitized person is

removed from exposure, the greater the probability

of avoiding serious damage to health.

0035The highest priority should be accorded to preven-

tion of exposure. If this is not reasonably practicable,

then effective control measures, such as partial en-

closure and local exhaust ventilation, must be insti-

tuted. Dust respirators or masks should be used only

for short-term tasks where satisfactory dust control

cannot be achieved by other means.

Solvents and Toxic Reagents

0036Many organic solvents present a fire and explosion

hazard because of their low flash points. The magni-

tude of the hazard is dependent upon the quantity of

the solvent involved and on other physicochemical

properties such as autoignition temperature, explo-

sive limits, vapor density and ability to accumulate

electrostatic charge.

0037Fire or explosion may occur when flammable

vapors are mixed with oxygen or air in proportions

that lie between certain critical values known as the

upper and lower explosive limits (UEL and LEL). For

many common solvents, the LEL is only a few per cent

in air, and good ventilation is essential to prevent the

formation of an explosive atmosphere when signifi-

cant quantities are used. As most organic solvent

vapors are denser than air, low-level ventilation may

be required for larger-scale operations in order to

avoid dangerous accumulation of vapors at floor level.

0038In this connection, it is helpful to have some

appreciation of the percentage loss of a solvent, by

evaporation, when it is used in various laboratory

operations. This may range from a loss of about

1% or less of the liquid for a simple decantation,

to around 20% or more for hot filtration, but the

precise values vary considerably from one solvent to

another. Nevertheless, the larger the volume of vapor

LABORATORY MANAGEMENT/Chemical Safety 3441

liberated, the greater the chance of ignition by a

remote heat source.

0039 Ignition may also occur without the obvious pres-

ence of a high-temperature source. Liquids flowing

in pipes can readily generate static electricity, which

may result in a spark. It is therefore advisable to

dispense large volumes via metal pipes that have

been doubly earthed.

0040 Solvents with a low autoignition temperature (e.g.,

carbon disulfide (100



C) and diethyl ether (180



C))

are particularly hazardous. In such cases, the presence

of a hot plate in contact with a vapor/air mixture is

quite capable of causing violent ignition.

0041 Storage of highly flammable liquids must be in

accordance with statutory requirements, which gen-

erally limit the total volume to about 50 l within any

given working area. The capacity of individual bench

bottles must not exceed 500 ml. Many disastrous fires

have resulted from inadvertent spillage, and places in

which substantial volumes of flammable liquids are

used should have clearly defined emergency proced-

ures to ensure rapid evacuation and ventilation of the

affected area.

0042 Certain solvents (alcohols and, especially, ethers)

have a propensity for peroxide formation on storage,

and these may detonate on distillation or on evapor-

ation to low bulk. Such solvents should not be stored

for extended periods, once opened. Bottled ether

waste should have 100 ml of saturated ferrous sulfate

solution added to each 2.5 l before disposal.

0043 Owing to their volatility and the large volumes in

common use, many solvents present significant health

risks in addition to any fire and explosion hazard.

Long-term effects of exposure to high concentrations

may include dermatitis, damage to the central ner-

vous system, the liver, the kidneys or the blood, and

even cancers. Smoking in the vicinity of chlorinated

solvent vapors is particularly hazardous, not because

of any fire hazard but because of toxic breakdown

products that can be produced by pyrolysis.

0044 Many laboratory reagents in common use are also

toxic to some degree and therefore hazardous. The

term ‘toxic’ does not have an absolute quality of the

kind that tends to be assumed in common parlance.

Almost all chemicals can cause harm in certain

circumstances, and, conversely, even highly toxic

chemicals can be used safely if adequate precautions

and control measures are taken. Most toxicological

studies have been undertaken with laboratory

animals, and not every species shows the same degree

or type of response. Extrapolation of data to the

human species is therefore fraught with difficulty.

Nevertheless, toxicological data from studies of

other mammals can normally be taken as a useful

indication of the likely degree of toxic hazard to

human beings, and reference works such as the Regis-

try of Toxic Effects of Chemical Substances (NIOSH)

can be valuable sources of information.

0045In toxicology experiments, increasing doses of the

test substance are administered to laboratory

animals, and the response is observed. The dose

level that results in the death of half of the group of

animals receiving it is known as the LD

value (a

lethal dose for 50%) and is usually expressed as milli-

grams of the substance per kilogram of body weight

of the animal (mg kg

1

). As a rough guide, for oral

ingestion by the rat, substances with LD

values

lying between 200 and 2000 mg kg

1

should be

regarded as harmful, and those with values between

about 25 and 200 mg kg

1

, as toxic. Any substance

with an LD

of less than 25 mg kg

1

should be

treated as very toxic. For substances on which exten-

sive toxicological data already exist (by far the minor-

ity), formal assignments to one of these categories

may already have been made.

0046Consideration of the toxicity levels of the sub-

stances involved, together with the respective amounts

of the substances to be used, will be an important

aspect of the risk assessment for any operation involv-

ing hazardous substances. Such considerations will

influence the conditions under which the operation

is carried out, whether partial containment in a fume

cupboard is necessary, and what degree of personal

protection is required.

0047Many operations are carried out in solution, and in

such cases, the solvent may present a greater hazard

than the reagents. Very often, however, the fact that

the reagent is present in the solution state, together

with a solvent that may greatly facilitate absorption

through the skin, considerably increases the risks

associated with its use.

Waste Disposal

0048All producers of waste, of whatever kind, have a duty

of care to ensure that it is safely disposed of, without

risk to others and, as far as possible, without detri-

ment to the environment. The welter of environmen-

tal protection legislation throughout the developed

world is intended to ensure that this duty is respon-

sibly discharged.

0049Laboratory waste is regarded as especially hazard-

ous and is usually subject to special controls. Until

relatively recently, it was quite common practice to

dispose of all aqueous waste down the drains, but this

is no longer acceptable, as it can have adverse conse-

quences for the public sewers to which most labora-

tory drains are connected. In order to avoid causing

problems with sewage treatment, no effluent outside

the pH range of 5–9 should be discharged into the

3442 LABORATORY MANAGEMENT/Chemical Safety