UKPID MONOGRAPH
NICKEL CARBONYL
SM Bradberry BSc MB MRCP
ST Beer BSc
JA Vale MD FRCP FRCPE FRCPG FFOM
National Poisons Information Service
(Birmingham Centre),
West Midlands Poisons Unit,
City Hospital NHS Trust,
Dudley Road,
Birmingham
B18 7QH
This monograph has been produced by staff of a National Poisons
Information Service Centre in the United Kingdom. The work was
commissioned and funded by the UK Departments of Health, and was
designed as a source of detailed information for use by poisons
information centres.
Peer review group: Directors of the UK National Poisons Information
Service.
NICKEL CARBONYL
Toxbase summary
Type of product
An intermediate in nickel refining and used as a catalyst in the
petroleum, plastic and rubber industries.
Toxicity
Vapourised nickel carbonyl is highly toxic; inhalation may be fatal.
Features
Topical
- Nickel carbonyl is a potential skin irritant but
transcutaneous absorption is poor.
Inhalation
Minor inhalation:
- Dry sore throat, cough, dizziness and headache.
Substantial inhalation:
- Sore throat, cough, chest tightness and dyspnoea occur
within minutes, often associated with dizziness, nausea,
headache and muscle cramps.
- A chemical pneumonitis may develop in severe cases,
sometimes after a latent period of a few days. Anorexia,
abdominal pain, jaundice and diarrhoea are also reported and
rarely myocarditis, delirium, convulsions or coma. Death
may occur due to pulmonary haemorrhage, pulmonary or
cerebral oedema or toxic myocarditis.
- Investigations may show increased hepatic transaminase
activities and a neutrophil leukocytosis. There may be
diffuse opacifications and/or a pleural effusion on chest x-
ray in those with symptoms or signs of pneumonitis. ECG
changes include ventricular ectopic beats in mild poisoning
or ST and T wave changes and QT interval prolongation
(suggesting a toxic myocarditis) in more severe cases.
- Chronic low-level occupational nickel carbonyl inhalation
may cause an obstructive airways defect. EEG abnormalities
and reduced monoamine oxidase activities are also reported.
Management
Topical
1. Remove from exposure and treat symptomatically.
Inhalation
1. Remove from exposure.
2. Patients who are asymptomatic following minimal exposure are not
at risk of developing a delayed pneumonitis and can be released
if clinical assessment is normal.
3. Administer supplemental oxygen by face mask.
4. Intravenous hydrocortisone may be beneficial for severe pulmonary
complications but this is not confirmed.
5. Collect urine for nickel concentration estimation.
6. Perform a chest X-ray, ECG, biochemical profile and blood count.
7. Chelation therapy with oral (or intravenous in severely ill
patients) diethyldithiocarbamate (DDC), if available, or oral
disulfiram should be considered in symptomatic cases.
8. Although the urine nickel concentration in the first eight hours
after exposure correlates with poisoning severity, these results
are unlikely to be available acutely and treatment must be guided
by symptoms. Discuss with NPIS.
9. Alcohol should be avoided for at least 48 hours following
treatment with DDC or disulfiram.
References
Jones CC.
Nickel carbonyl poisoning. Report of a fatal case.
Arch Environ Health 1973; 26: 245-8.
Kurta DL, Dean BS, Krenzelok EP.
Acute nickel carbonyl poisoning.
Am J Emerg Med 1993; 11: 64-6.
Shi Z.
Acute nickel carbonyl poisoning: a report of 179 cases.
Br J Ind Med 1986; 43: 422-4.
Shi Z.
Long-term effects of exposure to low concentrations of nickel carbonyl
on workers' health. In: Nieboer E, Nriagu JO, eds. Nickel and human
health - current perspectives. Vol 25.
New York: John Wiley & Sons, Inc, 1992; 273-9.
Shi Z, Lata A, Yuhua H.
A study of serum monoamine oxidase (MAO) activity and the EEG in
nickel carbonyl workers.
Br J Ind Med 1986; 43: 425-6.
Sunderman Sr FW.
Use of sodium diethyldithiocarbamate in the treatment of nickel
carbonyl poisoning.
Ann Clin Lab Sci 1990; 20: 12-21.
Substance name
Nickel carbonyl
Origin of substance
Nickel carbonyl is produced by passing carbon monoxide over
finely divided nickel. (CSDS, 1991)
Synonyms
Tetracarbonyl nickel (CSDS, 1991)
Nickel tetracarbonyl (DOSE, 1994)
Chemical group
A compound of nickel, a transition metal (d block) element.
Reference numbers
CAS 13463-39-3 (DOSE, 1994)
RTECS QR6300000 (RTECS, 1996)
UN 1259 (DOSE, 1994)
HAZCHEM CODE NIF
Physico-chemical properties
Chemical structure
Nickel carbonyl, Ni(CO)4 (DOSE, 1994)
Molecular weight
170.75 (DOSE, 1994)
Physical state at room temperature
Liquid (CSDS, 1991)
Colour
The liquid is colourless, the solid is white.
(CSDS, 1991)
Odour
Musty, sooty odour. (HSDB, 1996)
Viscosity
0.212 cP at 25°C (HSDB, 1996)
pH
NIF
Solubility
Sparingly soluble in water: 0.18 g/L at 9.8°C.
(MERCK, 1989; HSDB,1996)
Soluble in alcohol, benzene, chloroform, acetone and carbon
tetrachloride. (DOSE, 1994)
Autoignition temperature
<93°C (vapour) (HSDB, 1996)
Chemical interactions
Nickel carbonyl reacts violently with dinitrogen tetroxide, and
may explode when mixed with bromine, or a butane-oxygen mixture.
A shock-sensitive explosive is formed following reaction with
tetrachloropropadiene. (CSDS, 1991)
Major products of combustion
NIF
Explosive limits
Vapour explodes in air or oxygen at 20°C, partial pressure 15°mm,
liquid explodes at 60°C. (HSDB, 1996)
Flammability
Flammable - burns with yellow flame. In direct sunlight, both
the liquid and gas will flash. (HSDB, 1996)
Boiling point
43°C (CSDS, 1991)
Density
1.32 at 17°C (liquid) (CSDS, 1991)
Vapour pressure
53329 Pa at 25.8°C (CSDS, 1991)
Relative vapour density
5.95 at 50°C (gas) (HSDB, 1996)
Flash Point
<-20°C (closed cup) (CSDS, 1991)
Reactivity
On exposure to atmospheric oxygen, a deposit is produced on
nickel carbonyl which may ignite. Mixtures with air or oxygen at
low partial and total pressures explode after an induction
period.
The vapour forms an explosive mixture with air. It is highly
flammable and may explode if heated to 60°C or above.
(CSDS, 1991)
Uses
Nickel carbonyl is an intermediate in the Mond process of nickel
refining.
It is used in organic synthesis, the manufacture of catalysts and
nickel vapour plating. (CSDS, 1991; DOSE, 1994)
Hazard/risk classification
Index no. 028-001-00-1
Risk phrases
F; R11, Carc. Cat. 3; R40, Repr. Cat. 2; R61, T+; R26 - Highly
flammable. Possible risk of irreversible effects. May cause
harm to the unborn child. Very toxic by inhalation.
Safety phrases
S53-45 - Avoid exposure - obtain special instruction before use.
In case of accident or if you feel unwell, seek medical advice
immediately (show label where possible).
EEC no. 236-669-2 (CHIP2, 1994)
INTRODUCTION
Gaseous nickel carbonyl is formed in the Mond process of nickel
purification by the reaction of elemental nickel with carbon monoxide.
Most exposures are occupational via inhalation. The gas can be
condensed into a liquid which boils at 43°C.
MECHANISM OF TOXICITY
In vitro studies demonstrate that nickel causes crosslinking of
amino acids to DNA, alters gene expression, induces gene mutations and
the formation of reactive oxygen species (Costa et al, 1994a and b;
Haugen et al, 1994; Huang et al, 1994; Shi et al, 1994). Nickel also
suppresses NK cell activity and interferon production (Shen and Zhang,
1994).
TOXICOKINETICS
Absorption
Nickel carbonyl can be absorbed by inhalation and ingestion, the
former being more important occupationally. Significant percutaneous
absorption does not occur. Vapourised nickel carbonyl is the most
readily absorbed form of inhaled nickel.
Distribution and excretion
Following nickel carbonyl inhalation, nickel is transported in the
blood bound principally to albumin. High concentrations are found
in the kidneys, liver, lungs and brain. Nickel is excreted primarily
in the urine with a half-life following acute inhalation of up to 50
hours although some absorbed nickel is retained in body stores and
excreted over several months (IPCS, 1991; Sunderman, 1992b).
Nickel crosses the placenta and is passed to the child in maternal
milk (Fairhurst and Illing, 1987; IPCS, 1991).
CLINICAL FEATURES: ACUTE EXPOSURE
Inhalation
Pulmonary toxicity
The clinical features observed following acute nickel carbonyl
exposure have been classified as immediate and delayed although such a
distinction may not be clear (Sunderman and Kincaid, 1954).
Individuals who are moderately poisoned typically will develop a dry
sore throat, cough, chest tightness and dyspnoea within minutes often
associated with dizziness, nausea, headache, and muscle cramps
(Vuopala et al, 1970; Shi, 1986).
In more severe cases a chemical pneumonitis may develop sometimes
after a latent period of a few days (Brandes, 1934). These patients
may exhibit features of generalised systemic upset (muscle pains,
fatigue) in addition to gastrointestinal and neurological symptoms
(see below) (Sunderman and Kincaid, 1954; Jones, 1973; Sunderman,
1989). Haemoptysis has also been described (Shi, 1986).
Clinical signs include hyperaemia of the conjunctivae and throat,
cyanosis, tachycardia and tachypnoea with wheeze and crackles on
auscultation of the lung fields (Shi, 1986). There may be diffuse
opacifications and/or a pleural effusion on chest x-ray (Shi, 1986).
Death may occur in cases with severe pulmonary manifestations
(Anonymous, 1903; Brandes, 1934; Sunderman and Kincaid, 1954; Jones,
1973) with post-mortem evidence of pulmonary nickel deposition,
pulmonary consolidation or haemorrhage, pleural thickening, a
fibrinoid alveolar infiltrate and/or pulmonary or cerebral oedema
(Brandes, 1934; Sunderman and Kincaid, 1954; Jones, 1973).
Gastrointestinal toxicity
The respiratory effects of mild nickel carbonyl exposure are
associated frequently with nausea (Vuopala et al, 1970; Shi, 1986).
More substantial exposures cause anorexia, vomiting, abdominal pain
and diarrhoea which usually accompany development of a chemical
pneumonitis (Vuopala et al, 1970; Shi, 1986).
Neurotoxicity
Dizziness and headache are very common following mild or moderate
nickel carbonyl exposure (Anonymous, 1903; Shi, 1986). In more severe
cases there may be dysphoria, somnolence, blurred vision (Shi, 1986)
and rarely delirium, convulsions (Sunderman and Kincaid, 1954;
Sunderman, 1989) or coma (Brandes, 1934). Exaggerated limb reflexes
have also been reported (Brandes, 1934). Nickel particles have been
identified in the brain of fatal cases (Brandes, 1934).
Hepatotoxicity
Patients with nickel carbonyl poisoning may have transiently raised
hepatic transaminase activities (Shi, 1986), hepatic tenderness
(Vuopala et al, 1970) and/or hepatomegaly (Brandes, 1934). Jaundice
has been reported in more severely poisoned patients (Sunderman and
Kincaid, 1954).
Haemotoxicity
A leukocytosis is common in moderate to severe acute nickel carbonyl
poisoning (Sunderman and Kincaid, 1954; Shi, 1986).
Cardiotoxicity
Electrocardiographic changes have been reported following acute nickel
carbonyl exposure and vary from a sinus tachycardia or ventricular
ectopic beats in mild cases (Shi, 1986) to ST and T wave changes and
QT interval prolongation (suggesting a toxic myocarditis), in those
more significantly exposed (Shi, 1986). Post mortem findings from
early nickel carbonyl fatalities described "fatty" (Anonymous, 1903)
and dilated (Anonymous, 1903; Brandes, 1934) heart chambers.
CLINICAL FEATURES: CHRONIC EXPOSURE
Inhalation
Chronic exposure to low concentrations of nickel carbonyl may result
in an obstructive airways defect (low FEV1 and PEFR) (Shi, 1992; Shi,
1994). Pulmonary eosinophilia (Loeffler's syndrome) due to a type III
hypersensitivity reaction to nickel has been described (Sunderman and
Sunderman, 1961).
EEG abnormalities and reduced monoamine oxidase activity are also
reported in those subject to repeated occupational exposure (Shi et
al, 1986).
MANAGEMENT
Inhalation
Patients who are completely asymptomatic following suspected nickel
carbonyl inhalation are not at risk of developing delayed sequelae and
can be discharged if clinical assessment is normal. Symptomatic
patients require a full assessment including collecting urine for
nickel concentration estimation, checking a biochemical profile and
blood count and performing a chest x-ray and ECG.
Acute severe nickel carbonyl inhalation requires prompt supportive
treatment. Intravenous hydrocortisone may be beneficial in the
management of severe pulmonary complications but its value has not
been confirmed in controlled clinical trials. The role of chelation
therapy is discussed below.
Antidotes
Calcium EDTA
Parenteral calcium disodium EDTA did not protect mice or rabbits
against the lethal effects of nickel carbonyl (West and Sunderman,
1958b).
There are no human data.
Diethyldithiocarbamate and disulfiram
Diethyldithiocarbamate (DDC) has been advocated in the treatment of
acute nickel carbonyl poisoning (Sunderman, 1992a; Kurta et al, 1993).
DDC forms a chelate with Ni2+ such that 2(DDC) + Ni2+ ---- nickel
bis(DDC) which is renally excreted. DDC is not available as a
pharmaceutical preparation in many countries although disulfiram
(Antabuse), which is metabolised to DDC (two molecules of DDC from
each of disulfiram) has been employed.
All rats exposed to lethal concentrations of nickel carbonyl vapour
survived if treated immediately with 50 or 100 mg/kg parenteral DDC
(West and Sunderman, 1958a). A similar degree of protection was
observed when DDC was administered at eight hours, but this benefit
was at least partially lost at 24 hours. In the same study immediate
oral administration of the antidote offered some protection against
nickel carbonyl poisoning but was less effective than parenteral DDC,
especially at higher nickel carbonyl concentrations (West and
Sunderman, 1958a).
Baselt and Hanson (1982) compared the effect of oral disulfiram, DDC
and d-penicillamine in the treatment of rats acutely exposed to nickel
carbonyl vapour (1.4 mg/L) for 15 minutes. Disulfiram was not an
effective antidote in these circumstances and although d-penicillamine
protected against death at a nickel carbonyl concentration of 1.4
mg/L, only DDC was effective following exposure to a nickel carbonyl
concentration of 1.7 mg/L (Baselt and Hanson, 1982).
Well documented clinical studies involving DDC in nickel carbonyl
poisoning are scarce. Sunderman and Sunderman (1958) reported the
first clinical case of acute nickel carbonyl poisoning treated
effectively with oral DDC. A 25 year-old male was accidentally
sprayed with nickel carbonyl and immediately developed dizziness,
nausea, tachypnoea, cyanosis and chest pain (Sunderman and Sunderman,
1958). He was administered 95 per cent oxygen, 2 g oral DDC and 2 g
oral sodium bicarbonate within minutes, then 1 g oral DDC twice daily
for ten days. The urine nickel concentration on the day of exposure
was 2000 µg/L (normal <30 µg/L). He made a full recovery. This and
other individual case reports involving the use of DDC and disulfiram
in nickel carbonyl poisoning are summarised in Table 1.
Table 1. Case reports of DDC and disulfiram in nickel carbonyl
poisoning
Max urine Treatment Outcome Study
[Ni] µg/L
2000 2g oral DDC daily from Survived Sunderman
day 1 - 11 & Sunderman,
1958
535 4 g oral DDC on day 2 Died (day 4) Jones, 1973
1720 0.75 - 2.25 g oral Survived Kurta et al,
disulfiram daily days 1993
1, 2, 9-11
1.2 - 2.8 g oral DDC
daily days 2 - 8
The patient described by Jones (1973) presented the day following
exposure to nickel carbonyl, had a maximum urine nickel concentration
of 535 µg/L 24 hours post exposure, received 4 g oral DDC on day two
and died from respiratory complications on day four. Another patient
with severe nickel carbonyl poisoning survived despite the development
of a chemical pneumonitis requiring 60 per cent oxygen and continuous
positive airways pressure (CPAP) ventilation for four days (Kurta et
al, 1993). The maximum urine nickel concentration was 1720 µg/L and
the patient received 0.75 - 2.25 g oral disulfiram daily on days one,
two and 9-11 with 1.2 - 2.8 g oral DDC daily on days two to eight.
Sunderman (1990) reported that more than 375 persons exposed to nickel
carbonyl vapour over 30 years had been treated successfully with DDC.
No deaths occurred in those who received "adequate" doses of DDC
within four days of exposure. However data for only 23 of these cases
have been published (Sunderman and Sunderman, 1958; Sunderman, 1979;
Sunderman, 1990; Table 2).
Although the details of these cases are scarce and the data are
uncontrolled, it is noteworthy that 75-100 per cent recovered. Only
three of the four nickel carbonyl poisoned patients described by
Sunderman (1979) received treatment; the fourth (untreated) patient
died.
There is experimental evidence that disulfiram and DDC promote the
accumulation of bivalent nickel ions in the brain (Jasim and Tjälve,
1984; Belliveau et al, 1985; Tjälve and Borg-Neczak, 1994; Nielsen and
Andersen, 1994) and this may limit the use of these agents as nickel
antidotes (Tjälve and Borg-Neczak, 1994).
Antidotes: Conclusions and recommendations
1. Well documented clinical studies using DDC (or disulfiram) in
nickel carbonyl poisoning are scarce.
2. Sunderman (1992a) has recommended a treatment protocol for DDC in
acute nickel carbonyl poisoning (Table 3), variations of which
are advocated widely (Poisindex, 1996). This is based on urine
nickel concentrations in the first eight hours following exposure
and makes no allowance for urine volume. These treatment doses
have no firm scientific rationale and, moreover, the analytical
results are unlikely to be available in the necessary time
course. However, it is reasonable to consider treatment with DDC
(where available) in life-threatening nickel carbonyl poisoning.
3. Disulfiram is a therapeutic alternative but clinical experience
with this antidote is very limited. Although theoretically the
dose of disulfiram required should be approximately half that of
DDC (Poisindex, 1996) this is not borne out in animal studies in
which disulfiram is less effective than DDC and higher doses are
required.
MEDICAL SURVEILLANCE
Prior to employment involving nickel carbonyl exposure special
consideration should be given to those with a history of respiratory
disease.
Monitoring of nickel concentrations in 'spot' samples of blood and
urine is not indicated routinely as these concentrations do not
reflect the total body nickel burden in those exposed to nickel
carbonyl. Furthermore, urine nickel concentrations vary considerably
and should be interpreted as groups of 24 hour samples rather than
individual urine specimens (Sunderman et al, 1986; Nickel Producers
Environmental Research Association and the Nickel Development
Institute, 1994).
Table 2. Case series of DDC in nickel carbonyl poisoning
Mean ± SD DDC treatment
max urine Day started Daily Duration %
n= [Ni] µg/L mean ± SD dose g days Recovery Study
6 935 ± 610 5.7 ± 3.9 1 - 2 ? 100 Sunderman &
Sunderman, 1958
4 450 - 580 2.0 ± 0 ? ? 75 Sunderman, 1979
("Range") (n = 3)
13 638 ± 656 ? 2 "2 - 14" 100 Sunderman, 1990
"average"
Table 3. DDC in nickel carbonyl poisoning: Sunderman's treatment protocol (Sunderman, 1992a)
-> Mild exposure (initial 8 h urine nickel concentration < 100µg/L)
Oral DDC 1.0 g (0.2 g every 2 min for 5 doses)
-> Moderate or severe exposure (initial 8 h urine nickel concentration > 100µg/L)*
First day: Oral DDC 1.0 g 0 h
0.8 g 4 h
0.6 g 8 h
0.4 g 16 h
Thereafter: Oral DDC 0.4 g tds (until urine nickel concentration
normal)
-> Consider parenteral DDC (25 mg/kg) if urine nickel concentration >500 µg/L
* In very severe poisoning (initial 8 h urine nickel concentration >500 µg/L) an initial
intravenous DDC dose of 25 mg/kg (dissolved in phosphate buffer) is suggested.
Following acute nickel carbonyl exposure the urine nickel
concentration in an initial eight hour urine collection is a useful
guide to the severity of poisoning although this analysis is not
widely available; a concentration greater than 500 µg/L indicates
substantial intoxication (Sunderman, 1992a).
OCCUPATIONAL DATA
Occupational exposure standard
Short-term exposure limit (15-minute reference period) 0.24 mg/m3
(Health and Safety Executive, 1995).
OTHER TOXICOLOGICAL DATA
Carcinogenicity
Epidemiological studies have shown a significant increase in deaths
from carcinoma of the lung and nasal sinuses among nickel refinery
workers (Morgan, 1958; Roberts et al, 1992; Anderson, 1992; Morgan and
Usher, 1994). The excess risk of death continues for several years
after leaving employment (Muir et al, 1994).
The exact aetiological agent is unknown. Although animal data suggest
nickel carbonyl may be carcinogenic there is insufficient human
evidence to confirm this (IARC, 1990).
In a study of respiratory tract cancer among nickel refinery workers,
Morgan (1958) proposed that nickel-containing dusts, copper sulphate
or arsenic-contaminated sulphuric acid were more likely causative
agents than nickel carbonyl.
Fortunately, measures to improve industrial hygiene have greatly
reduced the occupational hazard of nickel carbonyl exposure (Doll et
al, 1977) but respiratory tract malignancies among employees in the
nickel industry remain notifiable diseases in the UK (Seaton et al,
1994).
Reprotoxicity
Occupational exposure of fertile women to nickel carbonyl is avoided
in some industries although there are no conclusive human data
regarding its reprotoxicity (Reprotox, 1996).
Genotoxicity
NIF
Fish toxicity
NIF
EC Directive on Drinking Water Quality 80/778/EEC
Nickel: Maximum admissible concentration 50 µg/L (DOSE, 1994).
AUTHORS
SM Bradberry BSc MB MRCP
ST Beer BSc
JA Vale MD FRCP FRCPE FRCPG FFOM
National Poisons Information Service (Birmingham Centre),
West Midlands Poisons Unit,
City Hospital NHS Trust,
Dudley Road,
Birmingham
B18 7QH
UK
This monograph was produced by the staff of the Birmingham Centre of
the National Poisons Information Service in the United Kingdom. The
work was commissioned and funded by the UK Departments of Health, and
was designed as a source of detailed information for use by poisons
information centres.
Date of last revision
7/10/96
REFERENCES
Andersen A.
Recent follow-up of nickel refinery workers in Norway and respiratory
cancer. In: Nieboer E, Nriagu JO, eds. Nickel and human health -
current perspectives. Vol 25.
New York: John Wiley & Sons, Inc., 1992; 621-7.
Anonymous.
Nickel carbonyl poisoning.
Lancet 1903: 1; 268-9.
Baselt RC, Hanson VW.
Efficacy of orally-administered chelating agents for nickel carbonyl
toxicity in rats.
Res Commun Chem Pathol Pharmacol 1982; 38: 113-24.
Belliveau JF, O'Leary GP, Cadwell L, Sunderman FW.
Effect of diethyldithiocarbamate on nickel concentrations in tissues
of NiCl2-treated rats.
Ann Clin Lab Sci 1985; 15: 349-50.
Brandes WW.
Nickel carbonyl poisoning.
JAMA 1934; 102: 1204-6.
CHIP2/Chemicals (Hazard Information and Packaging for Supply)
Regulations 1994.
Health and Safety Commission.
Sudbury: Health and Safety Executive, 1994.
Costa M, Zhuang Z, Huang X, Cosentino S, Klein CB, Salnikow K.
Molecular mechanisms of nickel carcinogenesis.
Sci Total Environ 1994a; 148: 191-9.
Costa M, Salnikow K, Cosentino S, Klein CB, Huang X, Zhuang Z.
Molecular mechanisms of nickel carcinogenesis.
Environ Health Perspect 1994b; 102: 127-30.
CSDS/Chemical Safety Data Sheets. Vol 4b
Cambridge: Royal Society of Chemistry 1991.
Doll R, Mathews JD, Morgan LG.
Cancers of the lung and nasal sinuses in nickel workers: a
reassessment of the period of risk.
Br J Ind Med 1977; 34: 102-5.
DOSE/Dictionary of substances and their effects. Vol 6.
Cambridge: Royal Society of Chemistry, 1994.
Fairhurst S, Illing HPA.
Toxicity review 19. The toxicity of nickel and its inorganic
compounds.
London: HMSO, 1987.
Haugen A, Maehle L, Mollerup S, Rivedal E, Ryberg D.
Nickel-induced alterations in human renal epithelial cells.
Environ Health Perspect 1994; 102: 117-8.
Health and Safety Executive.
EH40/95. Occupational exposure limits 1995.
Sudbury: Health and Safety Executive, 1995.
Huang X, Zhuang Z, Frenkel K, Klein CB, Costa M.
The role of nickel and nickel-mediated reactive oxygen species in the
mechanism of nickel carcinogenesis.
Environ Health Perspect 1994; 102: 281-4.
HSDB/Hazardous Substances Data Bank.
In: Tomes plus. Environmental Health and Safety Series I. Vol 27.
National Library of Medicine, 1996.
IARC.
Monographs on the evaluation of the carcinogenic risk of chemicals to
humans. 1990; 49: 257-445.
IPCS.
Environmental Health Criteria 108. Nickel.
Geneva: WHO, 1991.
Jasim S, Tjälve H.
Effect of thiuram sulphides on the uptake and distribution of nickel
in pregnant and non-pregnant mice.
Toxicology 1984; 32: 297-313.
Jones CC.
Nickel carbonyl poisoning. Report of a fatal case.
Arch Environ Health 1973; 26: 245-8.
Kurta DL, Dean BS, Krenzelok EP.
Acute nickel carbonyl poisoning.
Am J Emerg Med 1993; 11: 64-6.
MERCK/The Merck Index.
An encyclopedia of chemicals, drugs, and biologicals. 11th ed.
Budavari S, ed.
New Jersey: Merck and Co., Inc., 1989.
Morgan JG.
Some observations on the incidence of respiratory cancer in nickel
workers.
Br J Ind Med 1958; 15: 224-34.
Morgan LG, Usher V.
Health problems associated with nickel refining and use.
Ann Occup Hyg 1994; 38: 189-98.
Muir DCF, Jadon N, Julian JA, Roberts RS.
Cancer of the respiratory tract in nickel sinter plant workers: effect
of removal from sinter plant exposure.
Occup Environ Med 1994; 51: 19-22.
Nickel Producers Environmental Research Association and the Nickel
Development Institute.
Safe use of nickel in the workplace - a guide for health maintenance
of workers exposed to nickel, its compounds and alloys.
North Carolina, 1994.
Nielsen GD, Andersen O.
Effect of tetraethylthiuramdisulphide and diethyl-dithiocarbamate on
nickel toxicokinetics in mice.
Pharmacol Toxicol 1994; 75: 285-93.
Poisindex.
In: Micromedex International Healthcare Series. Vol 87.
Colorado: Micromedex, Inc., 1996.
Reprotox.
In: Tomes plus. Environmental Health and Safety Series I. Vol 27.
Washington DC: Fabro S, Scialli AR. Reproductive Toxicology Center,
Columbia Hospital for Women, 1996.
Roberts RS, Julian JA, Jadon N, Muir DCF.
Cancer mortality in Ontario nickel refinery workers. In: Nieboer E,
Nriagu JO, eds. Nickel and human health - current perspectives. Vol
25.
New York: John Wiley & Sons, Inc, 1992; 629-48.
RTECS/Registry of Toxic Effects of Chemical Substances.
In: Tomes plus. Environmental Health and Safety Series I. Vol 27
National Institute for Occupational Safety and Health (NIOSH), 1996.
Seaton A, Agius R, McCloy E, D'Auria D.
Practical Occupational Medicine.
London: Edward Arnold, 1994.
Shen HM, Zhang QF.
Risk assessment of nickel carcinogenicity and occupational lung
cancer.
Environ Health Perspect 1994; 102: 275-82.
Shi X, Dalal N, Kasprzak KS.
Enhanced generation of hydroxyl radical and sulfur trioxide anion
radical from oxidation of sodium sulfite, nickel(II) sulfite, and
nickel subsulfide in the presence of nickel(II) complexes.
Environ Health Perspect 1994; 102: 91-6.
Shi Z.
Acute nickel carbonyl poisoning: a report of 179 cases.
Br J Ind Med 1986; 43: 422-4.
Shi Z.
Long-term effects of exposure to low concentrations of nickel carbonyl
on workers' health. In: Nieboer E, Nriagu JO, eds. Nickel and human
health - current perspectives. Vol 25.
New York: John Wiley & Sons, Inc, 1992; 273-9.
Shi ZC.
Study on lung function and blood gas analysis of nickel carbonyl
workers.
Sci Total Environ 1994; 148: 299-301.
Shi Z, Lata A, Yuhua H.
A study of serum monoamine oxidase (MAO) activity and the EEG in
nickel carbonyl workers.
Br J Ind Med 1986; 43: 425-6.
Sunderman Sr FW.
Efficacy of sodium diethyldithiocarbamate (dithiocarb) in acute nickel
carbonyl poisoning.
Ann Clin Lab Sci 1979; 9: 1-10.
Sunderman FW.
A pilgrimage into the archives of nickel toxicology.
Ann Clin Lab Sci 1989; 19: 1-16.
Sunderman Sr FW.
Use of sodium diethyldithiocarbamate in the treatment of nickel
carbonyl poisoning.
Ann Clin Lab Sci 1990; 20: 12-21.
Sunderman Sr FW.
Use of sodium diethyldithiocarbamate in the treatment of nickel
carbonyl poisoning. In: Nieboer E , Nriagu JO, eds. Nickel and human
heath - current perspectives. Vol 25.
New York: John Wiley & Sons, Inc., 1992a; 281-93.
Sunderman Jr FW.
Toxicokinetics of nickel in humans. In: Nieboer E , Nriagu JO, eds.
Nickel and human heath - current perspectives. Vol 25.
New York: John Wiley & Sons, Inc., 1992b; 69-76.
Sunderman FW, Kincaid JF.
Nickel poisoning - II. Studies on patients suffering from acute
exposure to vapors of nickel carbonyl.
JAMA 1954; 155: 889-94.
Sunderman FW, Sunderman Jr FW.
Nickel poisoning VIII. Dithiocarb: A new therapeutic agent for
persons exposed to nickel carbonyl.
Am J Med Sci 1958; 236: 26-31.
Sunderman FW, Sunderman Jr FW.
Loffler's syndrome associated with nickel sensitivity.
Arch Intern Med 1961; 107: 405-8.
Sunderman FW, Aitio A, Morgan LG, Norseth T.
Biological monitoring of nickel
Toxicol Ind Health 1986; 2: 17-78.
Tjälve H, Borg-Neczak K.
Effects of lipophilic complex formation on the disposition of nickel
in experimental animals.
Sci Total Environ 1994; 148: 217-42.
Vuopala U, Huhti E, Takkunen J, Huikko M.
Nickel carbonyl poisoning.
Ann Clin Res 1970; 2: 214-22.
West B, Sunderman FW.
Nickel poisoning VII. The therapeutic effectiveness of alkyl
dithiocarbamates in experimental animals exposed to nickel carbonyl.
Am J Med Sci 1958a; 236: 15-25.
West B, Sunderman FW.
Nickel poisoning VI. A note concerning the ineffectiveness of
edathamil calcium-disodium (calcium disodium
ethylenediaminetetraacetic acid).
AMA Arch Ind Health 1958b; 18: 480-2.