Occupational Lead Poisoning and Carbon Monoxide Toxicity: Hygiene & Toxicology 11

This article discusses the occupational exposure limits, toxico-kinetics, and toxico-dynamics of lead and carbon monoxide toxicity in the Hygiene & Toxicology 11 course. It covers the sources of exposure, distribution, and excretion of lead and carbon monoxide, as well as the symptoms and effects of lead and carbon monoxide poisoning. The article also includes the Long-term PEL for lead and carbon monoxide in Singapore.

Hygiene & Toxicology 11
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LEAD
Occupational Lead Poisoning
Several jobs are associated with lead poisoning as shown below:
i. Smelting or casting lead.
This entails the production of lead fume through secondary or primary smelting, in addition
to lead foundries, and other operation such as recycling of scrap metal. Other synonym for
this task is lead production which comprises of melting, pouring or refining lead. Smelting of
lead produces lead fumes and dust that are inhaled directly through the respiratory system
thus exposing the worker to lead related complications Balali-Mood et al. (1).
ii. Removing of lead coatings
This includes thermal stripping or sanding of old paints through scraping, abrasive blasting,
welding or torch burning. Lead exposure risk can also be encountered in occupations such as
destruction of old structures, maintenance of steel bridge, painting of petroleum tanks,
destruction of highway and railroad bridges and underground storage tanks, and commercial
and institutional remodelling. The removal of lead coatings exposes the worker to lead
poisoning through contact of the paint chips with the skin, exposure of lead dust to the skin,
hair and respiratory system Lin et al. (2).
iii. Heating, spraying lead products or machining
This poses risk of exposure to lead poisoning through the production of lead fume or dust
generated by heating, machining or spraying lead products. The specific tasks in this category
include repairing of the radiator or battery, welding, grinding lead alloys. Repair and
extraction of water lines or cast iron soil pipes. Splicing and resplicing of electrical cables,
molten lead spraying, firing ammunition, and removal and renovation of stained glass
window Grover et al. (3).
iv. Production of lead products
The manufacture of lead products include tasks such as the manufacture of lead-acid battery
and glaze; making of lead-glazed pottery, manufacture of crystal glass, production of lead
joints, cables, pewter, stained or leaded glass, paint and ink, leaded plastics. Mixing and

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weighing of lead powders, manufacture of ammunition and electric appliances such as
ceramic coated capacitors and resistors Meyer et al. (4).
Occupational Exposure Limits applicable in Singapore
The Singapore Statutes Online (5) Permissible exposure level of lead under the first schedule
is as follows:
Long-term PEL
Lead, inorganic dusts and fumes, as Pb – 0.15 mg/m3b
Lead arsenate - 0.15 mg/m3b
Lead chromate as Pb -0.05 mg/m3b
and as Cr – 0.012 mg/m3b
Toxico-Kinetics of Lead
Lead enters into the body from the environment in different forms through inhalation, eating
and drinking, and through the skin. The absorption of lead is reliant on a number of factors
such as the physical form of lead, absorbed particle size, the transit time of the GI, and the
well-being status of the person. More importantly, there is an inverse proportion between the
particle size of lead and its absorption. Smaller particles are easily ingested.
 Lead absorption through inhalation
Most of the lead used today enters the body through inhalation (breathing). When lead is
scattered in the air in the form of dust or mist, it is easily inhaled and absorbed through the
lungs and the upper respiratory tract. The leading source of occupational lead absorption is
through inhalation of airborne lead Meyer et al. (6). The amount of lead absorption through
inhalation is dependent on the size of the lead particle, the volume of the patients respiratory,
the amount of deposition, and the mucociliary clearance of the inhaled lead.
 Lead absorption through eating and drinking
Lead absorption through ingestion occurs when one handles lead containing items such as
make-ups and then goes ahead and consumes food without proper hand washing. Once it gets
through the mouth and swallowed, lead is absorbed through the digestive system causing
various gastrointestinal tract complications Laidlaw et al. (7).

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 Lead absorption through the skin
Lead absorption through the skin is limited with less than one percent cases being reported.
Lead dust or particles can enter via the skin if it is broken. An example of lead that can go
through the skin is inorganic lead Ritchey et al. (8).
Distribution of lead
Most of the lead that is absorbed through inhalation or ingestion gets directly into the blood
stream. Once lead is in the blood stream, it is circulated throughout the body and stored in
different body tissues and organs Jones et al. (9). Some of the lead that is not stored is rapidly
sieved and out of the body and excreted. The absorbed lead which is not eliminated from the
body is exchanged mainly through three elements: blood, mineralizing tissues (bone and
teeth), and soft tissue (brain, spleen, muscles, heart, liver and kidneys).
 Blood
Lead enters the blood compartment immediately after absorption. Lead in the blood is mainly
located within the red blood cells (RBCs). Only a little portion of the total lead burden is
carried by the blood, nevertheless, it serves as the first recipient of absorbed lead and spreads
it throughout the body, making it reach other body tissues or for elimination as waster
products Khan et al. (10).
 Soft tissue
The movement of lead in and out of the tissues is rapid, and it is distributed to various organs
and tissues through the blood. Studies conducted on animals show that the liver, lungs and
kidneys have the highest concentrations of soft-tissue lead straightaway after severe
exposure. The brain is also a compartment of distribution. The study by Ragan et al. (11)
prevention of lead poisoning in children indicated that adults retain less amounts of lead in
soft tissue that children. The approximate half-life of lead in soft tissues is 40 days, and
selective brain build-up may take place in the hippocampus.
 Mineralizing tissue
A greater amount of lead absorbed and retained in the human body ends up being deposited
in the bones. Over 90% of the total lead body burden is contained in the bones and teeth of
adults, whereas, 75% is contained in children. There is also irregular distribution of lead in

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mineralizing tissues, with most of the concentrations occurring in bone regions especially
those undergoing the most active calcification during exposure Gangoso et al. (12).
 Excretion
Most of the lead absorbed into the body is eliminated through renal clearance or through
biliary clearance in the excrete. The quantity of lead eliminated and the time of excretion is
determined by various factors. Colossal decline in ones BLL may require more months or
even years, despite of the total elimination of the sources of exposure. It has been
approximated that half-life of lead elimination in adults is 30 days, while in children it can go
up to ten months Rastogi (13).
Toxico-dynamics of Lead
The toxicity of lead is notably as a result of its ability to mimic Calcium and substitute it in
most of the primary cellular processes that rely on calcium Busse (14). Lead penetrates the
cell membrane if different ways. Lead movement through the erythrocyte membrane is
facilitated by the anion exchanger in a singular direction and via the Ca-ATPase pump in the
opposite direction. Lead penetrates the cell membranes in other tissues through voltage-
dependent or other forms of calcium channels. After lead has permeated the cytoplasm, it
progresses its disparaging mimicking action by inhabiting the calcium binding sites on most
of the proteins that are calcium-dependent. Lead binds to calmodulin which is a type of
protein found in the synaptic terminal and operates as a sensor of free calcium accumulation
and as an intermediary of neurotransmitter secretion. Additionally, it modifies the role of the
protein kinace C enzyme, a fundamentally universal protein significant in most of the
physiological functions. The triggered kinase also impacts the expression of the Immediate
Early Response Genes. Lead can also trigger gene expression through a mechanism triggered
by protein Kinase C and it is suggested that this impact may be associated with modifications
in synaptic functioning.
Through the capacity of lead to mimic calcium, lead is deposited in the bones and becomes a
complete component of the bone, especially in cases of inadequate intake of calcium.
Different psychological states of stress (such as breastfeeding, pregnancy, and diseases) can
mobilise the deposited lead and is transported back to the blood stream, and also as a result of
high intake of calcium in the diet. The stable condition of the lead in bones slows done
recovery from lead poisoning, even when the toxic lead has entirely been removed (14).

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As a result of the continuous presence of lead in the blood, all tissues are essentially
damaged, especially the kidneys and the immune system. The harm caused to the nervous
system due to lead poisoning is the most dangerous one. Lead poisoning in adults causes
peripheral neuropathy, mainly featured by demyelination of the nerve fibres. Extreme
exposure to high levels of lead leads to encephalopathy characteristic of insomnia, vertigo,
migraine, convulsions, and even death. Reduces levels of lead triggers increased lead-induced
neuropathy, which predominantly impacts the growing brain and aggravates difficulties in
behaviour and cognitive impairment. Studies in epidemiology have indicated a significant
relation between levels of lead in the blood and bones and poor outcomes in psychometric
tests Rosin (15). A comparable association has also been evidenced in behavioural studies
experimented on animals which had been exposed to lead immediately after birth (12). The
process of learning is premised on the establishment and remodelling of synapses, and the
toxicity of the metal on this process indicates that lead categorically damages the synaptic
function. Nigg (16) shows that the rate of lead uptake on the blood-brain 2 into the brain
occurs at a very high speed. The damaging effects of mental retardation and cognitive deficit
caused by lead on the brain is attributed to its alteration of three primary neurotransmission
systems namely glutamatergic, the dopaminergic, and cholinergic systems.
CARBON MONOXIDE (CO)
Sources of Exposure
 Exposure to harmful levels of CO include:
 The use of poorly maintained or heating appliance that is unvented.
 Buildings or houses on fire
 Heating the home using a gas stove, oven or grill
 In appropriately vented natural gas appliances such as stoves or water heaters
 Driving vehicles in enclosed spaces such as garages
 Proximity to engine exhaust outlets
 Using a camp stove, heater, or light with in a tent
 Blocked heating exhaust vents or clogged chimneys
 Running gas powered machines or generators indoors without enough air circulation
 Industrial employees working at pulp mills, steel foundries, and the production of
formaldehyde Weaver (17).

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Co is formed as a by-product of consuming organic compounds. Insufficient oxygen inhibits
the complete conversion of CO to carbon dioxide which is not poisonous. Hence, the reason
why exposure cases of CO takes place in private residences where the combustion of organic
compounds occurs in poorly ventilated spaces with reduced amount of oxygen (17). When
inhaled, toxic CO impairs the delivery of oxygen and utilization at the cellular level. Low
levels of oxygen in the blood will impair all organs especially the brain and heart which have
the highest demand for oxygen. The characteristic affinity of CO to reversibly bind
haemoglobin makes it work very fast, and as a result major body organs will lack enough
blood supply causing relative functional anaemia with onset symptoms such as nausea,
headaches, and fatigue (17).
Occupational Exposure Limits applicable in Singapore
Long-term PEL (5)
Carbon monoxide – 25 ppma and 29mg/m3b
Toxico-kinetics of Carbon Monoxide
CO gains entrance into the body through inhalation (mouth and nose) and to the lungs then
readily absorbed into the blood unchanged and then distributed throughout the whole body.
The movement of carbon monoxide to the Hb-binding site is achieved through two
procedural phases: transfer of CO in the gas phase, between alveoli and the airway opening,
and the movement in the dissolved step, across the interface of air-blood. The mechanisms of
movement in the gas phase include physical action of the respiratory system and the cellular
diffusion within the alveoli. On the other hand, the mechanism of the liquid phase involves
the diffusion of carbon monoxide across the obstruction in alveolar-capillary, red blood cell
(17).
The transportation of CO up to the Hb-binding sites involves its movement across the alveoli-
capillary membrane, through the plasma via diffusion, permeation across the membrane of
the red blood cells (RBC), and ultimately the stroma of RBC before the commencement of
the reaction between CO and Hb. The Fick’s firs law of diffusion is a fitting example of a
physicochemical law that governs the movement of molecules across the blood phase and
membrane. The interchange and gas balance between air and blood takes place very fast. This
movement is hastened by a partial pressure differential of CO across this membrane. For
instance, an intake of air comprising of elevated CO levels through inhalation will quickly

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increase blood COHb. Through the instant and forceful binding of CO to Hb, CO’s partial
pressure is maintained low, leading to an elevated accumulation variance between blood and
air, and subsequently CO diffusion into blood. Continued breathing in of air free of CO will
increasingly lower the gradient to its reversal point (elevated CO pressure on the blood side
than alveolar air) and then there will be release of CO into alveolar air. Due to the strong
biding of CO to Hb and substantially rapid reaction than CO elimination by ventilation, the
concentration gradient of air-blood is normally higher than the gradient of blood-air, and the
uptake of CO will be an equivalently quicker process than the clearance of CO (17).
The diffusion of CO is reliant on ventilation and the position of the body. In restful supine
position, the diffusion of CO may be substantially higher compared to a restful sitting
position. In both scenarios, the diffusion of CO during exercise is much higher than at rest
Pendergast et al. (18). Diffusion rate of CO will rise with the increase of exercise. The
elevation is as a result of the rise in both the pulmonary capillary blood flow and membrane-
diffusing element Cotes et al. (19). The lung volume does not affect the diffusion of CO
within the mid-range of crucial capacity. Nevertheless, the variation in rates of diffusion
could be momentous in extreme volumes; at full lung capacity, the diffusion is much higher
than normal, whereas at residual volume its level is lower than normal (17).
The rate of elimination of carbon monoxide from a state of equilibrium will take a
monotonically declining, second-order function Goldstein (20). However, the elimination rate
might not be uniform due to transitory exposures to CO, in which the equilibrium state may
not be attained at the end of exposure. In such a scenario of intermittent high exposures of
CO, it is likely that the decrease in COHb could be biphasic, and can best be estimated by a
double exponential function. The opening decline rate or distribution may noticeably be rapid
than the final phase of elimination Motterlini et al. (21). Studies have shown a decreasing
divergence of CO in blood and exhaled air, an indication that the rate of CO elimination from
extravascular pools are slower compared to those shown for blood Daher et al. (22).
However, (21) notes that the total rates of elimination seem to be autonomous of the initial
concentration of COHb.
Toxico-dynamics of Carbon Monoxide
Carbon monoxide is quickly absorbed into the lungs without being altered in anyway. Over
90% of the gas binds to haemoglobin after absorption, and approximately 10% to cytochrome

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C-oxidase and myoglobin. CO dissolved in plasma is below 1% and equally the same amount
is oxidized to carbon monoxide.
Carbon monoxide binds with high affinity to several proteins containing heme. The affinity
of Hb for CO is 250 times higher than for oxygen Hall (23). The oxygen carrying capacity is
reduced due to the competition by CO for binding to Hb, and consequently oxygen
displacement. The binding of CO to Hb leads to equilibration of the R-state (relaxed, high-
affinity quaternary Hb state), increasing oxygen affinity of other sites in the tetramer of Hb,
and further inhibiting the delivery and release of oxygen. The study by Hampson et al. (24)
indicated that there is no direct correlation between clinical severity or clinical improvement
of patients under CO poisoning with the elimination of COHb or with the level of COHb in
the blood. The canine studies conducted by (20) indicate that the CO gas toxicity absorbed
through inhalation is much higher than transfusion of the same accumulation of CO-exposed
erythrocytes. The outcomes of the study points out the toxic impacts of CO outcomes from
the world effect of CO inhibition on the delivery of oxygen alongside on the binding to
cellular proteins containing heme. Furthermore, CO binds to other proteins with heme such
as skeletal muscle and myoglobin in heart.
The transportation of carbon monoxide in the entire body significantly shows the binding of
carbon monoxide to heme proteins, for example myoglobin and Hb. The highest
accumulation of total carbon monoxide ascertained from the tissues acquired from human
autopsies were from the lung, kidney, spleen, and skeletal muscle, alongside noticeable levels
in the adipose tissue and brain. On the other hand, the brain is significantly affected by
carbon monoxide effects due to its rather high demand for oxygen. Increased levels of carbon
monoxide in the skeletal muscle, blood, spleen, and heart is a reflection of the huge presence
of carbon monoxide binding proteins in these tissues. Carbon monoxide while in blood,
quickly spreads into erythrocytes in which it occurs majorly as a complex with Hb (COHb).
When the gas exists in the muscle it majorly occurs as a complex with myoglobin (COMb).
In the case of pregnant woman, the presence of the gas in the maternal system permeates to
the fetal tissues in which it binds to the Hb of the fetal among other heme proteins.
Mitochondrion respiration is inhibited by CO through binding the ferrous heme a3 in the
active part of COX, causing a total shut down of oxidative phosphorylation, just as cynide
and nitric oxide behaves (24). The inhibition of COX slows down oxidative phosphorylation,
causing a decline in the production of ATP in tissues such the heart and brain.

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