Toxicology and Industrial Health

000(00) 1–9
Toxicological aspects of cadmium ª The Author(s) 2010
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and occupational health activities DOI: 10.1177/0748233710386404
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to prevent workplace exposure in
Japan: A narrative review

Kan Usuda1, Koichi Kono1, Keiko Ohnishi1,

Shin Nakayama1, Yumiko Sugiura1, Yasuhiro Kitamura1,
Akihiro Kurita1, Yuko Tsuda1, Motoshi Kimura1 and
Yasuhisa Yoshida1,2

Abstract
Chemicals are an essential part of modern manufacture processes. Their use must be managed with great
attention in occupational settings to avoid serious detrimental effects to the health of employees. For
example, cadmium compounds are indispensable for the production of nickel-cadmium rechargeable batteries
or as chemical stabilizer in plastics. It is an exceptionally toxic heavy metal and personnel exposed to cadmium
in the workplace meet with potential health risks that can lead to the development of kidney, skeletal and
respiratory disorders. In consequence, proactive and systematical development of occupational hygiene and
health activities are necessary to reduce chemical exposure to cadmium in the workplace. This review
describes the known facts of cadmium toxicity, the biological effects of cadmium exposure, possible regulation
measures to prevent occupational cadmium exposure in three industrial health management systems and dis-
cusses future cooperation programs in these systems, proactive safety activities and occupational safety and
health management strategies.

Keywords
Cadmium, exposure, metallothionein, OSHMS, working environment measures

Introduction of occupational Cd exposure was released in

Chemicals have been used since the dawn of
civilization to make our daily lives more convenient.
At present, they are essential to expand economic and
industrial activities.
Cadmium (Cd) was isolated from calamine (zinc
carbonate, ZnCO3) in 1817 by the German chemist
Friedrich Stromeyer. Its name was derived from the
Latin cadmia and the Greek kadmeia (kadmeı́a), the
ancient names for calamine (Senning, 2007). Soon
after Friedrich discovered Cd, its sulfide (CdS)
found widespread industrial use as artist’s paint
pigment and leather tanning agent in the second half
of the 19th century. By the mid-1900s, Cd electro-
plating became popular in metallurgy due to its
excellent corrosion resistance.
In spite of its indisputable industrial utility, Cd is
better known as a toxic heavy metal. The first report
Belgium in 1858. It describes lethal inhalation of
toxic cadmium carbonate (CdCO3) dust by silver
polishing workers (Bernard, 2008). Later, the
world’s worst case of Cd poisoning occurred in the
1950s in the prefecture of Toyama, Japan. In this
region, Cd-laden run-off water flowing from the
1
Department of Hygiene and Public Health, Division of
Preventive and Social Medicine, Osaka Medical College,
Takatsuki-city, Osaka, Japan
2
Kansai Technical Center for Occupational Medicine, Osaka-city,
Osaka, Japan
Corresponding author:
Kan Usuda, Department of Hygiene and Public Health, Division of
Preventive and Social Medicine, Osaka Medical College,
Takatsuki-city, Osaka 569-8686, Japan
Email: hyg032@art.osaka-med.ac.jp

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2 Toxicology and Industrial Health 000(00)
Kamioka zinc mine was used to irrigate crops. An
outbreak of Cd food poisoning known as ‘Itai-Itai
disease’ occurred among the inhabitants who
absorbed massive amounts of Cd from their daily
diets, resulting in severe pain in their bones and
joints and propensity to bone breaking (Kazantzis,
2004; Kobayashi et al., 2009).
Occupational Cd exposure may occur in industrial
facilities that release Cd into the air. Today, most
cases of occupational Cd exposure and intoxication
are among workers breathing Cd-contaminated work-
place air in the nickel-cadmium (Ni-Cd) rechargeable
battery industry (Järup et al., 1998), and in those
exposed to the plastic chemical stabilizer used for
polyvinyl chloride (PVC; Chan et al., 1982), both pri-
mary markets for Cd.
In Japan, Cd and its compounds are classified as
Class II chemical substances by the Ordinance on
Prevention of Hazards due to Specified Chemical
Substances. To comply with this regulation, various
occupational hygiene and health activities are imple-
mented by Japanese manufacturing facilities.
Cadmium toxicokinetics
Inhaled Cd deposits in the alveoli and from them can
be absorbed into the blood stream. It has been calcu-
lated that the respiratory absorption of Cd from fumes
is approximately 40% (Klimisch, 1993). In blood, Cd
is transported into the erythrocytes (Nguyen and
Chien, 1989) or bound to large-molecular-weight pro-
teins of albumin (Trisak et al., 1990).
From this point, it is taken up by the liver inducing
the synthesis of metallothionein (MT; Nordberg et al.,
2007), a cysteine-rich, low-molecular-weight (MW)
protein which has a high affinity for divalent heavy
metal ions such as Cd as a response to mitigate their
toxicity by forming non-toxic Cd-MT complexes
(Klaassen and Liu, 1997; Klaassen et al.,1999).
The corresponding low MW Cd-MT complex
formed in the liver is slowly released back into the
blood stream reaching the kidney where it is filtered
through the glomeruli and taken up by the renal
proximal tubule cells by pinocytosis. Within renal
tubular cells, the Cd-MT complex degrades and
releases free Cd, which recombines with MT newly
synthesized by the tubular cells (Nordberg et al.,
1971). Once the MT binding sites are saturated, it
is no longer able to remove all the free Cd in the
tubular cells, which may result in damage to the kid-
ney tubules, Figure 1 (Goyer et al., 1989).
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The damaged tubule is no longer able to sequester
Cd, and therefore increased levels of Cd are observed
in the urine. Thus, the majority of Cd is found in the
liver and kidney, where it has an average biological
half-life of 1730 years that can last the entire life
of the exposed individuals. Its excretion via urine is
very slow and may take approximately the same
amount of time (Goyer, 1997; Nordberg 1992).
Metabolic effect of cadmium
Cd is below zinc in Group 12 of the periodic table.
This makes Cd to share some of zinc’s properties, thus
interfering with its absorption, replacing it in tissues
and compete with it for enzyme binding sites.
Zinc-dependent enzymes can continue to function
to a certain extent when bound to Cd instead of zinc,
but the enzymatic activity is substantially reduced and
will eventually result in zinc deficiency symptoms
(Brzóska and Moniuszko-Jakoniuk, 2001).
In blood, MT binds more strongly to Cd than to
Zinc (Figure 2). Such preferential binding for Cd is
the main reason for zinc deficiency. Once a Cd-MT
complex is formed, its binding sites do not release
Cd as readily as they do zinc, thus no longer able to
transport the necessary amounts of zinc into tissues
(Sato and Nagai, 1989).
Target organs, laboratory and
clinical finding of cadmium exposure
Acute Cd poisoning from inhalation of particulate
matter, either as fumes of very small particle size
or as dust, may resemble the flu-like symptoms of
metal fume fever (Fuortes et al., 1991; Johnson and
Kilburn, 1983).
Long-term Cd exposure has been reported to cause
adverse respiratory effects such as emphysema, dys-
pnea and inflammation of the nose, pharynx and lar-
ynx. Chronic Cd inhalation causes a yellow fringe
that appears gradually in the teeth, sometimes referred
to as a ‘cadmium ring’ (Friberg et al., 1974).
Although initially harmless, the Cd-MT complex
is a low-MW nephrotoxic that undergoes filtration
by the glomeruli and damages the proximal tubules.
The complex is subsequently degraded, Cd is
released and accumulates in the renal cortex (Goyer,
1996; Johnson and Foulkes, 1980; Nordberg and
Nordberg, 1975). Long-term occupational Cd expo-
sure may show increased proteinuria, in particular
Usuda et al. 3

Figure 1. Filtration of cadmium-metallothionein (Cd-MT) complex through the kidney glomeruli and reabsorption of free
Cd2þ in proximal convoluted tubules (PCT) and its induced nephrotoxicity.

b2-microglobulin (b2-MG), as initial sign of

nephropathy (Stewart and Hughes, 1981).
Cd retained in the kidney cortex inhibits 1,25-
dihydroxycalciferol disturbing the calcium and
phosphorus balance, probably by altering vitamin D
metabolism (Nordberg et al., 2007), resulting in calcium
deficiency, osteoporosis, osteomalacia and pseudo-
fractures (Aoshima and Kasuya, 1991; Aoshima et al.,
1993).
The toxicity of Cd is directly related to the
solubility of its salts, which makes Cd2þ ions readily
available. The highly soluble fluoride and nitrate are
reported to be among the most toxic of the Cd com-
pounds (Adachi et al., 2007; Dote et al., 2008; Dote
et al., 2007). The LD50 values for different Cd com-
pounds administered to mice by intragastric adminis-
tration are shown in Table 1 (Friberg et al., 1992).
Cd has been demonstrated to be carcinogenic for Figure 2. Cadmium has a higher binding affinity to
various organs (Huff et al., 2007; Joseph, 2009; metallothionein than zinc at its binding sites.

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4 Toxicology and Industrial Health 000(00)

Table 1. LD50 values for cadmium compounds in mice by intragastric administration

LD50 (confidence LD50 for cadmium ion
Compound Molecular formula interval; mg/kg b.w.) alone (mg/kg b.w.)
Cadmium sulfate CdSO4 88 (70100) 47
Cadmium nitrate Cd(NO3)2 100 (80120) 48
Cadmium iodide CdI2 170 (140190) 51
Cadmium chloride CdCl2 90 (80110) 57
Cadmium oxide CdO 70 (40110) 63
Cadmium carbonate CdCO3 310 (220400) 200
Cadmium (element) Cd 890 (6401200) 890
Cadmium sulfide CdS 1200 (11001200) 910

Waalkes, 2003). The International Agency for
Research on Cancer (IARC) classifies Cd and certain
of its compounds as Group 1 (carcinogenic to humans;
IARC, 2008). There is ample evidence in the recent
published literature that strongly suggests Cd causes
lung cancer (Hertz-Picciotto and Hu, 1994; Nordberg,
2006; Oberdörster et al., 1994; Verougstraete et al.,
2003), breast cancer (Antila et al., 1996; McElroy
et al., 2006; Zang et al., 2009), renal cancer (Il’yasova
and Schwartz, 2005), prostate cancer (Goyer et al.,
2004; Lee et al., 2009; Sahmoun et al., 2005;
Verougstraete et al., 2003), pancreatic cancer
(Schwartz and Reis, 2000) and bladder cancer (Kellen
et al., 2007).
Regulation of occupational
cadmium exposure
Three industrial health management strategies
The major sources of occupational exposure to Cd
are metalworking, producing, processing and han-
dling of Cd powders (Ando et al., 1996; Davison
et al., 1988; Fuortes et al., 1991). Thus, occupational
Cd exposure occurs mainly by inhalation of particu-
late matters in fumes or dust present in contaminated
air. These particles are odorless, invisible and non-
irritating at low concentrations.
Other routes of Cd exposure include dermal contact
and ingestion, but these routes are rare and can be
negligible in recent occupational settings. The three
industrial health management strategies in use to
manage occupational health activities are working
environment control (engineering control), work
practice control (administrative control) and health
care, Table 2 (Koshi, 1996).
Substitution
Due to the poisonous nature of Cd, its industrial use
has been increasingly restricted by environmental
rules. Cd recycling is recommended by environmental
agencies to limit the release of this toxicant into the
environment.
Substitution is the most desirable control
measure. By replacing Cd with other nonhazardous
chemicals exposure can be brought to a minimum.
Since the 1990s, lithium ion and nickel-metal
hydride (NiMH) batteries have successfully
replaced Ni-Cd batteries (Rydh and Svärd, 2003).
The European Union has already banned the sale
of consumer Ni-Cd batteries (The Commission of
the European communities, 2005; UNDP Chemi-
cals Branch 2008).
There are many other examples in which Cd is
been replaced in commercial applications: zinc or
aluminum coatings can be used instead of Cd in
corrosion prevention applications. Non-toxic azo pig-
ments are used as a replacement in pigments. Cerium
sulfide is used for plastic pigmentation. Calcium,
zinc, magnesium and barium compounds are used as
substitutes for Cd-containing stabilizers.
The prevention of occupational and environmental
Cd exposure is still a major concern in developed
nations, but because of its unique and matchless traits,
Cd is still an indispensable metal for several industries
(GIA, 2008).
Working environment measurement
In present-day Japan, employers who assign employ-
ees to work with Cd indoors must provide an unpol-
luted and safe workplace environment. Japanese
industrial safety and health law requires working
environment measurement (WEM) of airborne Cd
by certified engineers once at regular intervals of
6 months or less. The WEM protocol gives the
methodology for analysis as well as guidelines for
the location of sampling points and collection of
samples (Koshi, 1996).

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Usuda et al.
Table 2. Purpose and contents of three industrial health management system
Working environment control
(engineering control)
Administrative control
Criteria levels by JMHLW
Purpose of the management Emission control, generation
control, isolation, removal
Substitution, chemical form
and condition
Production process,
facilities, devices
Management contents Remote control, FA, sealing up
Local exhaust ventilation,
general ventilation
Working environment
measurement
Abbreviations: JMHLW: Japanese Ministry of Health, Labor and Welfare, OSHA: Occupational Safety and Health Administration,
ACGIH: American Conference of Governmental Industrial Hygienists, TWA: 8-hour time-weighted average, OSHA PEL: permissible
exposure limits established by occupational safety and health administration, ACGIH TLV: threshold limit value established by the
American conference of governmental industrial hygienists, BEI: biological exposure index, FA: factory automation, PPE: personal
protective equipment.
The Japanese Ministry of Health, Labor and
Welfare (JMHLW) requires that the WEM results
confirm that the level of airborne Cd in the workplace
does not exceed 0.05 mg/m3. Depending on the
condition of the environment, a rating that goes from
first- to third-grade is assigned. For second- and third-
grade locations, the engineering controls need to be
revised to ensure improvement of the environmental
working conditions.
Engineering control requires review and repair of
seals, general ventilation systems, exhaust ducts and
use of push-pull ventilation to curb Cd pollution in the
working environment. These measures are suitable for
other toxic chemicals as well (Matsumoto et al., 2003).
Medical examination
Japanese companies must conduct periodic medical
examinations of their Cd workers. The screening and
surveillance guidelines for occupational Cd expo-
sure set by the Occupational Safety and Health
Administration (OSHA) require testing of Cd in
urine (CdU), blood (CdB) and b2-MG in urine
(McDiarmid et al., 1996).
As OSHA standards are internationally recognized,
periodic monitoring of these indicators is also followed
in Japanese occupational settings as markers of renal
tubular damage, biological monitoring of CdU, CdB
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5
Work practice control
(administrative control) Health care
OSHA PEL-TWA,
ACGIH TLV-TWA, OEL BEI
Invasion restraint Disease prevention
Work posture, position, Medical examination
method
PPE, education, training Personnel changes
Written safety policies, Health guidance
rules
Supervision, schedules Suspension
Reducing the duration, Treatment
frequency of exposure
and b2-MG is an important tool for assessment of the
internal Cd exposure level and as early indicators of
Cd toxic effects (Kawasaki et al., 2004).
When these markers suggest exposure to Cd, the
company and its resident physician need to put in
place administrative controls to minimize the time
an individual worker is exposed to Cd by restricting
his or her access to Cd-contaminated areas, reducing
the 8-hour time-weighted average (TWA) exposure
levels or temporarily removing the worker from work.
Permissible exposure limits such as those estab-
lished by OSHA (OSHA PEL-TWA; OSHA, 2004)
or threshold limit values established by the American
Conference of Governmental Industrial Hygienists
(ACGIH TLV-TWA; ACGIH, 2009) are accepted
industrial hygiene guidelines to set suitable adminis-
trative controls. As shown in Table 3, OSHA
PEL-TWA sets 0.005 mg/m3 for Cd dust or fume.
OSHA has recognized that some processes in certain
industries may be unable to achieve the 0.005 mg/m3
limit through engineering and work practices. These
industries must follow separate engineering control
air limits (SECAL) of either 0.015 or 0.05 mg/m3
(OSHA, 2004). ACGIH TLV-TWA recommends air-
borne exposure limit of 0.01 mg/m3 for elemental Cd
and 0.002 mg/m3 for Cd compounds (respirable
fraction; ACGIH, 2009). In Japan, the Japan Society
for Occupational Health (JSOH) recommended
6 Toxicology and Industrial Health 000(00)
Table 3. Recommended or mandatory occupational
exposure limits (OELs)
Agency OELs (mg/m3) Comment
OSHA PEL-TWA 0.005 Cd dust or fume
OSHA SECAL 0.015–0.05
ACGIH TLV-TWA 0.01 Total Cd
0.002 Respirable fraction
JSOH OEL-TWA 0.05
Abbreviations: OEL: occupational exposure limit, TWA: 8-hour
time-weighted average, OSHA PEL: permissible exposure limits
established by Occupational Safety and Health Administration,
ACGIH TLV: threshold limit value established by the American
Conference of Governmental Industrial Hygienists, SECAL:
separate engineering control air limit to be achieved in specified
processes and workplaces those are not possible to achieve
PEL through engineering and work practices alone, JSOH: Japan
Society for Occupational Health.
occupational exposure limit (OEL) of 0.05 mg/m3 for
TWA (JSOH OEL-TWA; The Japan Society for
Occupational Health, 2007).
Personal protective equipment
When engineering or administrative controls fail to
provide complete Cd elimination, personal protective
equipment (PPE) becomes the last line of defense.
Respirator masks, gloves and goggles are popular
PPEs worn by employees. The respirator mask
removes the Cd contaminants from air or supplies the
wearer with an alternate source of clean breathing air,
reducing the risk of Cd or other chemical exposure
(Que Hee and Lawrence, 1983; Smith et al., 1980;
Spear et al., 2000). It should be noted that PPE is not
a substitute for engineering or administrative controls,
and workers should not rely on these devices alone to
prevent exposure.
Proactive safety activities and the
occupational safety and health
management system
The three industrial health management strategies aim
to technical control of occupational hygiene and
health while proactive safety activities seek risk
reduction and to limit lost workdays.
Proactive safety activities such as zero-accident
(Figure 3), KY (‘kiken yochi,’ which translates as
foresee danger or predict risky activity), HHK (‘hiyari
hatto kigakari’ translating as be alert, be tense, be
worried) and workplace safety inspection by occupa-
tional physicians have been enthusiastically
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Figure 3. The zero-accident flag shows a symbol repre-
senting workers upholding the number zero.
implemented in Japanese workplaces as ‘3K’ jobs
(‘kitanai, kiken and kitsui’ meaning dirty, dangerous
and hard) to avoid or prevent on-the-job accidents
(Hino Motors Ltd, 2007; Kyowa Hakko Kogyo Co
Ltd, 2005; Sumitomo Metal Industries Ltd, 2006).
Both the industrial strategies and the proactive
safety activities are bottom-up efforts to ensure that
the workplace complies with all legal requirements.
The concept behind these activities is a regulation-
based program with perception-based activity highly
dependent on on-site actions. As a consequence,
bottom-up regulation-based efforts have several weak
points such as the lack of clear index of decision prior-
ity for regulation, overemphasis of actual situation and
insufficient objective evaluation. Recently, the impor-
tance of top-down effort by an executive decision
maker and an effective balance between bottom-up and
top-down strategies in occupational health activities is
gaining recognition.
The occupational safety and health management
system (OSHMS) is an innovative top-down,
risk-based approach designed to encourage staff to
minimize risks. The Japan industrial safety and
health association (JISHA) developed the JISHA
OSHMS standards according to the guidelines set
by the JMHW and the International Labor Organiza-
tion (ILO).
The JISHA OSHMS registration service is avail-
able since 2003 and has been an important factor to
shift from bottom-up regulation-based approach to
top-down risk-based approach (Hino Motors Ltd,
2007; Kyowa Hakko Kogyo Co Ltd, 2005; Sumitomo
Chemical Co Ltd, 2008; Sumitomo Metal Industries
Ltd, 2006). As shown in Figure 4, key factors of
OSHMS include policy statement by the company’s
chief executive officer (CEO), workers’ participation,
Usuda et al.
Figure 4. Continuous improvement of working
environment and health by the Plan-Do-Check-Act cycle
of the occupational safety and health management system.
risk assessment, documentation of procedures,
records and operation objectives and planning in line
with the Plan/Do/Check/Act (PDCA) cycle toward
continuous risk reducing and improvement (Hitachi
Chemical Co Ltd, 2008).
The reason for recommendation of OSHMS is that
Japan’s ‘baby boom’ generation born in 1947 to 1949
developed new occupational safety, hygiene and
health procedures during the period of high economic
growth before reaching the mandatory retirement age
starting in 2007 (Sato, 2005). It is expected that their
accumulated knowledge and skills for industrial
health management is not successfully passed on to
the next generation and that this generational alterna-
tion may cause potential deterioration and confusion
of occupational safety, hygiene and health.
Thus, an effective industrial health management
system such as OSHMS that does not depend only on
personal factors will provide the necessary workplace
health safety standards for official and unofficial (dis-
patched worker, contract labor and part-time labor)
employees. Cooperation with other proactive activities
will be essential for continuously updating OSHMS
and for expanding the scope of risk assessment.
Funding
Part of this work was supported by The Occupational
Health Investigation Project of the Occupational Health
Promotion Foundation, Japan.
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7
References
Adachi K, Dote T, Dote E, Mitsui G, and Kono K (2007)
Strong acute toxicity, severe hepatic damage, renal
injury and abnormal serum electrolytes after intravenous
administration of cadmium fluoride in rats. Journal of
Occupational Health 49: 235–241.
Ando Y, Shibata E, Tsuchiyama F, and Sakai S (1996) Ele-
vated urinary cadmium concentrations in a patient with
acute cadmium pneumonitis. Scandinavian Journal of
Work Environment and Health 22: 150–153.
Antila E, Mussalo-Rauhamaa H, Kantola M, Atroshi F, and
Westermarck T (1996) Association of cadmium with
human breast cancer. Science of the Total Environment
186: 251–256.
AoshimaK, Kasuya M (1991) Preliminary study on serum
levels of 1,25-dihydroxyvitamin D and 25-hydroxy-
vitamin D in cadmium-induced renal tubular dysfunction.
Toxicology Letters 57: 91–99.
Aoshima K, Katoh T, Teranishi H, Horiguchi H, and
Kasuya M (1993) Abnormalities of calcium, phosphor-
ous and vitamin D metabolism with proximal renal tub-
ular dysfunction in subjects environmentally exposed to
cadmium (in Japanese). Nippon Eiseigaku Zasshi 47:
1009–1020.
Bernard A (2008) Cadmium & its adverse effects on
human health. Indian Journal of Medical Research
128: 557–564.
Brzóska MM, Moniuszko-Jakoniuk J (2001) Interactions
between cadmium and zinc in the organism. Food and
Chemical Toxicology 39: 967–980.
Chan OY, Tan KT, Kwok SF, and Chio LF (1982) Study on
workers exposed to cadmium in alkaline storage battery
manufacturing and PVC compounding. Annals of the
Academy of Medicine Singapore 11: 122–129.
Davison AG, Fayers PM, Taylor AJ, et al. (1988) Cadmium
fume inhalation and emphysema. Lancet 331: 663–667.
Dote T, Adachi K, Yamadori E, et al. (2008) Abnormalities
in cadmium fluoride kinetics in serum, bile, and urine
after single intravenous administration of toxic doses
to rats. Journal of Occupational Health 50: 339–347.
Dote E, Dote T, Shimizu H, Shimbo Y, Fujihara M, and
Kono K (2007) Acute lethal toxicity, hyperkalemia
associated with renal injury and hepatic damage after
intravenous administration of cadmium nitrate in rats.
Journal of Occupational Health 49: 17–24.
Friberg L, Elinder CG, and Kjellstrom T (1992) Cadmium.
In: World Health Organization (WHO) (ed.) Environ-
mental Health Criteria 134, Geneva: WHO.
Friberg L, Piscator M, Nordberg GF, and Kjellstrom T
(1974) Cadmium in the Environment. 2nd ed. Cleveland:
CRC Press.
8 Toxicology and Industrial Health 000(00)
Fuortes L, Leo A, Ellerbeck PG, and Friell LA (1991)
Acute respiratory fatality associated with exposure to
sheet metal and cadmium fumes. Journal of Toxicology
and Clinical Toxicology 29: 279–283.
Global Industry Analysts Inc. (GIA) (2008) Cadmium- A
Global Strategic Business Report. Global Cadmium Market
to Exceed 19.3 Thousand Tons by 2012. California: GIA.
Goyer RA (1996) Toxic effects of metals: arsenic. In:
Klaassen CD (ed.) Casarett and Doull’s Toxicology:
The Basic Science of Poisons. 5th ed. New York:
McGraw-Hill, 696–698.
Goyer RA (1997) Toxic and essential metal interactions.
Annual Review of Nutrition 17: 37–50.
Goyer RA, Liu J, and Waalkes MP (2004) Cadmium and
cancer of prostate and testis. Biometals 17, 555-558.
Goyer RA, Miller CR, Zhu SY, and Victery W (1989) Non-
metallothionein-bound cadmium in the pathogenesis of
cadmium nephrotoxicity in the rat. Toxicology and
Applied Pharmacology 101: 232–244.
Hertz-Picciotto I, Hu SW (1994) Contribution of cadmium
in cigarettes to lung cancer: an evaluation of risk assess-
ment methodologies. Archives of Environmental Health
49: 297–302.
Hino Motors Ltd (2007) CSR Report 2007 To make the
world a better place to live by helping people and goods
get where they need to go -safely and economically-
while focusing on sustainable development. Tokyo:
Hino Motors, Ltd.
Hitachi Chemical Co Ltd (2008) Sustainability Report
2008. Tokyo: Hitachi Chemical Co Ltd.
Huff J, Lunn RM, Waalkes MP, Tomatis L, and Infante PF
(2007) Cadmium-induced cancers in animals and in
humans. International Journal of Occupational and
Environmental Health 13: 202–212.
Il’yasova D, Schwartz GG (2005) Cadmium and renal cancer.
Toxicology and Applied Pharmacology 207: 179–186.
International Agency for Research on Cancer (IARC)
2008: Monograph: Overall evaluations of carcinogeni-
city to humans. Lyon: IARC.
Järup L, Bellander T, Hogstedt C, and Spång G (1998)
Mortality and cancer incidence in Swedish battery
workers exposed to cadmium and nickel. Occupational
and Environmental Medicine 55: 755–759.
Johnson DR, Foulkes EC (1980) On the proposed role of
metallothionein in the transport of cadmium. Environ-
mental Research 21: 3460–3465.
Johnson JS, Kilburn KH (1983) Cadmium induced metal
fume fever: results of inhalation challenge. American
Journal of Industrial Medicine 4: 533–540.
Joseph P (2009) Mechanisms of cadmium carcinogenesis.
Toxicology and Applied Pharmacology 238: 272–279.
Downloaded from tih.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 26, 2015
Kawasaki T, Kono K, Dote T, Usuda K, Shimizu H, and
Dote E (2004) Markers of cadmium exposure in workers
in a cadmium pigment factory after changes in the
exposure conditions. Toxicology and Industrial Health
20: 51–56.
Kazantzis G (2004) Cadmium, osteoporosis and calcium
metabolism. Biometals 17: 493–498.
Kellen E, Zeegers MP, Hond ED, and Buntinx F (2007)
Blood cadmium may be associated with bladder carci-
nogenesis: the Belgian case-control study on bladder
cancer. Cancer Detection and Prevention 31: 77–82.
Klaassen CD, Liu J (1997) Role of metallothionein in
cadmium-induced hepatotoxicity and nephrotoxicity.
Drug Metabolism Reviews 29: 79–102.
Klaassen CD, Liu J, and Choudhuri S (1999) Metallothio-
nein: an intracellular protein to protect against cadmium
toxicity. Annual Review of Pharmacology and Toxicology
39: 267–294.
Klimisch HJ (1993) Lung deposition, lung clearance and
renal accumulation of inhaled cadmium chloride and
cadmium sulphide in rats. Toxicology 84: 103–124.
Kobayashi E, Suwazono Y, Dochi M, Honda R, Kido T,
and Nakagawa H (2009) Influence of consumption of
cadmium-polluted rice or Jinzu River water on occur-
rence of renal tubular dysfunction and/or Itai-itai disease.
Biological Trace Element Research 127: 257–268.
Koshi S (1996) A basic framework of working environment
control for occupational health in Japan. Industrial
Health 34: 149–165.
Kyowa Hakko Kogyo Co Ltd (2005) Kyowa Hakko Group
Sustainability Report 2005. Tokyo: Kyowa Hakko
Kogyo Co Ltd.
Lee JD, Wu SM, Lu LY, et al (2009) Cadmium concentra-
tion and metallothionein expression in prostate cancer
and benign prostatic hyperplasia of humans. Journal of
Formosan Medical Association 108: 554–559.
Matsumoto N, Yokota K, Johyama Y, and Takakura T
(2003) The working environment control of anhydride
hardeners from an epoxy resin system (In Japanese).
Sangyo Eiseigaku Zasshi 45: 133–138.
McDiarmid MA, Freeman CS, Grossman EA, and Martonik
J (1996) Biological monitoring results for cadmium
exposed workers. American Industrial Hygiene Associa-
tion Journal 57: 1019–1023.
McElroy JA, Shafer MM, Trentham-Dietz A, Hampton JM,
and Newcomb PA (2006) Cadmium exposure and breast
cancer risk. Journal of National Cancer Institute 98:
869–873.
Nguyen QH, Chien PK (1989) Cadmium uptake kinetics in
human erythrocytes. Biological Trace Element Research
22: 119–129.
Usuda et al.
Nordberg GF (1992) Application of the ‘critical effect’
and ‘critical concentration’ concept to human risk
assessment for cadmium. IARC Scientific Publications
118: 3–14.
Nordberg GF (2006) Lung cancer and exposure to environ-
mental cadmium. Lancet Oncology 7: 99–101.
Nordberg GF, Nogawa K, Nordberg M, and Friberg LT
(2007) Cadmium. In: Gunnar F, Nordberg GF, Fowler
BA, Nordberg M, and Friberg LT (eds) Handbook on
the Toxicology of Metals 3rd ed. Amsterdam, The
Netherlands: Elsevier, 445–486.
Nordberg GF, Piscator M, and Lind B (1971) Distribution
of cadmium among protein fractions of mouse liver.
Acta Pharmacologica et Toxicologica 29: 456–470.
Nordberg M, Nordberg GF (1975) Distribution of
metallothione in bound cadmium and cadmium chloride
in mice: preliminary studies. Environmental Health
Perspectives 12: 103–108.
Oberdörster G, Cherian MG, and Baggs RB (1994) Impor-
tance of species differences in experimental pulmonary
carcinogenicity of inhaled cadmium for extrapolation to
humans. Toxicology Letters 72: 339–343.
Que Hee SS, Lawrence P (1983) Inhalation exposure of
lead in brass foundry workers: the evaluation of the
effectiveness of a powered air-purifying respirator and
engineering controls. American Industrial Hygiene
Association Journal 44: 746–751.
Rydh CJ, Svärd B (2003) Impact on global metal flows
arising from the use of portable rechargeable batteries.
Science of the Total Environment 302: 167–184.
Sahmoun AE, Case LD, Jackson SA, and Schwartz GG
(2005) Cadmium and prostate cancer: a critical epide-
miologic analysis. Cancer Investigation 23: 256–263.
Sato M (2005) Two so-called 2007 problems have become
hot topics of discussion recently in Japan. In: Watanabe
T (eds) The Yomiuri Shimbun Michio Sato Column,
29 July 05. Tokyo: The Yomiuri Shimbun.
Sato M, Nagai Y (1989) Effect of zinc deficiency on the
accumulation of metallothionein and cadmium in the rat
liver and kidney. Archives of Environmental Contami-
nation and Toxicology 18: 587–593.
Schwartz GG, Reis IM (2000) Is cadmium a cause of
human pancreatic cancer? Cancer Epidemiology
Biomarkers and Prevention 9: 139–145.
Senning A (2007) Elsevier’s Dictionary of Chemoetymol-
ogy: The Whies and Whences of Chemical Nomencla-
ture and Terminology. Amsterdam: Elsevier Science.
Smith TJ, Ferrell WC, Varner MO, Putnam RD (1980)
Inhalation exposure of cadmium workers: effects of
Downloaded from tih.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 26, 2015
9
respirator usage. American Industrial Hygiene Association
Journal 41: 624–629.
Spear TM, DuMond J, Lloyd C, and Vincent JH (2000) An
effective protection factor study of respirators used by
primary lead smelter workers. Applied Occupational
and Environmental Hygiene 15: 235–244.
Stewart M, Hughes EG (1981) Urinary beta 2 microglobu-
lin in the biological monitoring of cadmium workers.
British Journal of Industrial Medicine 38: 170–174.
Sumitomo Chemical Co Ltd (2008) CSR Report 2008 Data
Book. Tokyo: Sumitomo Chemical Co Ltd.
Sumitomo Metal Industries Ltd (2006) Annual Report 2006
Year Ended March 31, 2006. Osaka: Sumitomo Metal
Industries Ltd.
The American Conference of Governmental Industrial
Hygienists (ACGIH) (2009) 2009 TLVs and BEIs.
ACGIH: Cincinnati.
The Commission of the European Communities (2005)
Commission decision. Amending for the purposes of
adapting to the technical progress the annex to directive
2002/95/EC of the European parliament and of the coun-
cil on the restriction of the use of certain hazardous sub-
stances (RoHS) in electrical and electronic equipment
(EEE). Official Journal of the European Union L 280,
18–19.
The Japan Society for Occupational Health (2007) Recom-
mendation of occupational exposure limits (2008-2009).
Journal of Occupational Health 50: 426–443.
Trisak ST, Doumgdee P, and Rode BM (1990) Binding of
zinc and cadmium to human serum albumin. Interna-
tional Journal of Biochemistry 22: 977–981.
United Nations Environmental Programe (UNDP) Chemicals
branch (2008) Division of technology, industry and eco-
nomics (DTIE) Draft final review of scientific information
on cadmium -Version of November 2008 Lead and cad-
mium activities UNEP Chemicals. Geneva: UNDP.
US Department of Labor Occupational Safety and Health
Administration (OSHA) (2004) Cadmium. Washington,
DC: OSHA publications office.
Verougstraete V, Lison D, and Hotz P (2003) Cadmium,
lung and prostate cancer: a systematic review of recent
epidemiological data. Journal of Toxicology and Envi-
ronmental Health B Critical Review 6: 227–255.
Waalkes MP (2003) Cadmium carcinogenesis. Mutation
Research 533: 107–120.
Zang Y, Odwin-Dacosta S, and Yager JD (2009) Effects of
cadmium on estrogen receptor mediated signaling and
estrogen induced DNA synthesis in T47D human breast
cancer cells. Toxicology Letters 184: 134–138.