Aro~mm oi
Arch Toxicol (1984) 56:50-54
Intoxication following the inhalation of hydrogen fluoride
J. Bmmml, H. St6~, and A. Zober~
4. Medizinische glinik des Klinikums Nfirnberg und Institut fox Nephrologie1, Pathologisches Institut2, Institut for Arbeits- und So-Aalmedizin3,
der Universitlit Erlangen-Nfimberg, D-8500 Nfurnberg 80, Federal Republic of Germany
Abslmet. The prognosis for fluoride inhalation is poor,
owing to the extreme toxicity of the substance and lack of
satisfactory treatment. In the case of massive inhalation, the
slow, progressive destruction of the bronchial mucosa and lung
tissue will be lethal. Irrespective of the dose, a transient
restriction in renal function or acute renal failure will occur.
The transient increase in transaminase seems to be caused by
several factors.
Our cases show that the evaluation of fluoride levels in
biological material is difficult, as dietary intake, e.g., in
drinking water, may complicate acute or chronic occupational
exposure.
Key words: Hydrogen fluoride - Inhalation - Intoxication -
Environmental - Dietary exposure
Intre~efion
Occupational fluoride exixnure may occur through inhalation
in a number of technical processes, for example in the
alnmininm industry, where cryolite is used in the smelting
process, in the glass industry, with its use of hydrofluoric acid
as a corrosive, and finally in the chemical basic material
industry, with the processing of'fluorine-centalning miner-
als.
In accordance with the regulations on harmful work
substances in the Federal Republic of Germany, from the
preventative medicine point of view, medical examinations are
required, following method number G 34 (occupational med-
ical check-up) of the employment accident insurance fund,
wherever exposure to fluorine or other inorganic fluorine-con-
tainirlg substances has occurred.
In 1983, the industrial threshold limit value (MAK) for
fluorides was 2.5tug/tu 3, and for elementary fluorine
0.2 mg/tu3. Also in 1983, a biological threshold limit value
(BAT) was fixed for hydrogen fluoride and its inorganic
compounds, relating to the renal excretion of fluorides. Before
the work-shift, this should be 4 tug fluoride/g creatinlue, and
after the shift 7 tug fluoride/crea .finlne.
According to the accident insurance law of the Federal
Republic of Germany, diseases caused by fluorine or its
compounds are to be reported and compensation can be
Offprint requests to: J. Braun, Institut fOr Nephrologie der Universitlit
Erlangen-Niirnberg, Kontumazgarten 14-18, D-8500 Nilrnberg 80,
Federal Republic of Germany
ToMcology
9 Springer-Verlag 1984
claimed under clause number 1308 of the decree of occupa-
tional diseases. Between 1980 and 1982, 48 cases were reported
and in five cases compensation was paid.
Two case reports on accidental fluoride poisoning from the
fluorspar processing industry are presented in this paper.
Case reports
History
After repair work on a pump in the hydrofluoric acid
production section, mixed acid (70-80% suiphuric acid, about
10% .hydrofluoric acid) at about 150~ C explosively escaped
from a leaking flange. Four workers were splashed with mixed
acid and surrounded by the resulting fumes. As the repair work
was already finilhed, the workers had taken off their protective
clothing and protecting masks. One worker was only hit by a
few drops and was able to get out of the way quickly. He was
treated for minor acid burns and did not require admission to
hospital. One patient died within a few hours of the accident.
His death was completely unexpected. X-ray examinations and
laboratory tests gave no clues as to the cause of his death. An
autopsy was not carried out. Two workers were admitted to
hospital.
Clinical cours~
Case I. H. E., 49 years old. On admission to hospital, the
patient was drowsy, he had superficial burns all over his face,
on his neck and his eyes, his throat and the upper respiratory
tract caused by the fumes, and severe acid burns of about 10 •
27 a n on his lower legs (about 8% of his body surface) caused
by the liquid mixed acid.
To prevent lung oedetua the patient was given tuanuitol,
furosemide, theophylline and methylprednisolone, and genta-
tuycln as prophylaxis against infection. Calcium giuconate 10%
was injected under the skin of his face, neck and both his lower
legs. His eyes were treated with hydrofluoric acid burn jelly
after having been washed several times.
He had no dyspuoea. In the chest X-ray examination both
pulmonary fields were non-pathological. The kidney and liver
parameters shown in Table I were pathological.
On the 2rid day after the accident, anuria followed after a
short ofigur/c phase. The patient therefore required a Scribner
shunt, and intermittent haemodialysis was started. At the same
time he was given high-caloric parenteral nutrition (glucose
40%, amino acid solution) and electrolyte balancing was done.
 51

In the following days, the development of a massive the purulent sputum. In the bronchoscopy a band-shaped
purulent tracheobronchitis Was observed. The blood count fibrinous coat was seen, as well as mucus in the overall
showed a leucocytosis (25,000/ml) with marked left shift. bronchial system and purulent secretion from all segmental
Proteus mirabilis and staphylococcus aureus could be found in bronchi (see autopsy finding in Fig. 2). This production of
mucus required endobronchial suctioning several times a
1. Pathological laboratory values (H.E.) 24 h after the accident day.
(normal values in brackets) Two weeks after the accident, diffuse haemorrhages
occurred acutely in the nasopharynx and in the right stem
Creetlnlne 2.9 mg/dl (0.8-1.1 ms/dl) bronchus. This developed into an atelectasis of the right lung
Urea 110 m~dl (-40 ms/m) after obstruction. The clots had to be removed by bronchos-
SGOT 520 U/I (-18 U/I) copy. Thereafter the right lung opened again. Plasmatic
so~ 222 u/l ( - 2 2 u/t)
coagulation (factors I - X I I I ) was non-pathological, and the
LDH 1.131 U/l (-180 U/l)
thrombocyte number normal.
In the following days, however, the thrombocyte level
Tal~ ~-.Pathological test values (B .H.) shortly after the accident and decreased and multiple uncontrollable haemorrhages occurred
24 h after the accident (normal values in brackets) over the whole respiratory tract. A pneumonic infiltrate
developed in the right lower field. Serologic and culture tests
Leucocytes 22,200/mm3 ( 10,003/mms) Shortly after proved the existence of cand/da a/b/cans. Because of the
Calcium 6.6 mval/l (4 mval/l) the accident increasing respiratory insufficiency, intubation and artificial
Crevtlnlne 1.3 ms/ca (0.8-1.1 mg/dl) respiration became necessary. Despite daily transfusions of
SGOT 63 U/I (18 U/I) 24 h after warm blood, there was repeated bleeding into the tra-
SGPT 44 U/I (22 U/I) the accident cheo-bronchial system, which finally caused death due to
LDH 397 U/l (180 U/l) respiratory insufficiency about 4 weeks after the accident.
Creatlnln~ 1.4 mg/dl (0.8-1.1 mg/dl)

Case2. D. H., 38years old. The patient was not splashed with
Table 3. Fluoride concentrafiohs in the biolosical material (normal liquid mixed acid, arid only inhaled the fumes for a short
values in brackets)
period. When he was admitted to hospital he presented only a
Case 1 5 days before Shortly after patchy flush on his face, neck, throat, and the extensor sides of
the accident the accident both his lower legs. Primary treatment was the same as
described in case 1.
Urine (ms/l) 1.8 (-1.0) -
The patient reacted and was oriented. Above the lung a
Serum (ns/ml) - 67 (-16) low-grade spasticity could be heard, with medium to coarse
Bone (ttg/8WW) Sternum 2,347 bubbling rale. The laboratory tests produced the pathological
after autopsy Thoracic vertebra 2,407
lilac crest 2,038 (up to 400) findings shown in Table 2.
Femoral head 2,252 Despite a daily fluid intake of 3 1and a forced diuresis with
fitresemide, the retention values increased to 1.8mg/dl
Perenchymal omani Kidney 0.47 (-0.8) creetinlne and 100 mg/dl urea. In the following days the kidney
(tq~gWW) Liver 0.57 (-o.7)
and liver parameters returned to normal. Four days after the
after autopsy Lung 0.81 (-0.4)
accident pharynx, larynx, and subgiottls were still slightly
Case 2 1 year after the accident reddened and showed individual erosions. No ulcerations
Serum (ng/ml) 42 (-16) developed on the under-injected skin areas.

Fill. L Extensive uecrmes after acid burning

with a mixture of sulpheric and hydrofluoric
acid
52
One year after the accident the patient still complained of
hoarseness, recurrent fits of cou~hing and pain in the
nasopharynx. During this lime, he suffered several nose bleeds
flora both sides. Fibrinous, partly granulating deposits on the
cylindrically thickened vocal cords were found during ENT
examination.
An analysis of the lung function did not show any essential
ventilation or distribution impairment. The blood gas analysis
values were normal.
Pathological.anatomicalfindings
Exterior inspection at post-mortem examination (H.E.)
showed extensive patchy skin necroses in all layers on the
flexor sides of both legs.
Interior inspection showed massive changes in the whole
tracheo-bronchiai system, with a severe ulcerating necrotised
laryngitis and patchy, haemorrhagically infiltrated pseudo-
membraneous coating. These severe changes intensified
towards the caudal end of the trachea and in the bronchi. The
left stem bronchus was obstructed by blood clots and viscous
mucus shortly below the bifurcation on to the lung hilus. Apart
fxom parenchymal necrosis and secondary bleeding, the lungs
showed severe bronchobronchiolitis with confluent broncho-
pneumonia.
Numerous greater and smaller bronchi were obstructed
with blood and mucus. On top of these changes, sepsis with
pyuemia and mycotic superinfection had developed. The
EIlI. 2. Severely ulcerated and necrotised tracheobronch/fis with
pseudomembraneous coa~a8 and obstruction of the left maln stem
bronchus (autopsy finding)
bacteriological tests showedproteus mirabilis, eacherichia coil,
and cand/da albicans in lungs and spleen.
Histological findings showed extreme destruction with
circumscribed alveolar parenchyma necrosis in the lung, as
well as a thickened oedema and coating of the still preserved
aivenli with hyaline membranes. Numerous alveolar septa
were fibrously widened to various degrees.
Examination of the bone system revealed normally built
spongy trabeculae. There were no hints of a manifest or
incipient esteoscierosis.
The renipnncture cylinders taken immediately after the
patient's death showed acute tubular damage with dissemi-
nated necroses of the tubular epithelium, and secondary
involvement of the interstitium. The pathological-anatomical
finding in the kidney tissue corresponds to the one in acute
renal failure, irrespective of its cause (we owe the histological
kidney findings to Prof. Dr. Thoenes, MainT.).
Toxicologicalfindings
In both cases, examination of the fluoride content in the
biological material with an ionselective electrode was carried
out. The results are listed in Table 3.
DillCIISl~n
Hydrofluoric acid, which is the main toxic agent in the cases
presented here, penetrates the skin, destroys deeper tissue
layers and may cause inhibition of vital enzymes and dangerous
disturbances in metabolism, e.g., calcium or carbohydrate
balance, bychemical binding of the fluoride ion to calcium or
magnesium ions.
Long-term high fluoride uptake may cause a disturbance of
mineral metabolism, which in turn leads to severe bone
d~m~ge, in most cases in the form of osteosclerosis (bone
fluorosis). In rare cases osteoporosis was observed after
chronic fluoride exposure.
The main clinical picture of acute fluoride poisoning after
gaseous exposure is massive local skin and mucusa irritation, as
seen in our two cases. As mentioned above, absorption may
also lead to systemic effects on internal organs. The deceased
patient (H. E.), however, did not die of specific metabolic
fluoride affects, but of the consequences of severe acid burns to
the respiratory tract after inhaling the mixed acid.
These findings correspond to the results of animal
experiments by Reichelt and Eggert (1979). According to these
findln~, there is no haemorrhagic lung oedema after inhaling
hydrogen fluoride but complete destruction of the lung
S ~ .
In the second case (D. H.) with only mlnlmsd inhalation,
the mucosa changes were not very marked so that vital function
was not significantly impaired. The toxicity of the hydrofluoric
acid fumes, however, becomes evident even in this case, in the
consequences of the mucosal irritation in the upper respiratory
tract, which still exist 1 year after the accident.
In case 1, acute renal failure occurred already on the 2nd
day after the accident. Various pathological factors may be
responsible, such as a toxic fluoride concentration, toxic
pmduets from the corroded tissue, comparable to the toxins
after thermal burns, and volume and electrolyte shifts into the
corroded tissues. In the second case with only short exposure,
only short-term impairment of renal function occurred, with a
temporary increase of the values for renal function. Surpris-
ingiy, both patients showed a cleax increase in serum

I ~ . $ . Fibrinous w/alerting of the alveolar septa and hyaline membrane in ~ e alveoH (EVG 360x)
transami--~es'which quickly returned to normal. As fluoride is
not a specifically hepatotoxic substance, this finding can be
explgined either by muscle necroses after the corrosion and the
extensive injections or as a consequence of temporary liver
damage caused by toxic metabolic products from the necrotic
tissue.
In the case of the deceased patient (H. E.) we have
available a urine fluor level obtained 5 days before the accident
in a routine test during a medical check-up (we thank Dr. von
Chnssy, Bayerisehes Landesinstitut for Arbeitsmedizin,
Munich). This value was 1.8 mg fluoride/1 urine, well above the
normal mean value of 0.5 mg fluoride/l urine, but also clearly
below the biological threshold limit value (BAT). Shortly after
the accident, the serum fluoride content was measured as 67
ng/ml; this surpasses the mean serum value of 16 ng/ml (Zober
et al. 1980) usually found in Germany by about four times. This
value first seemed quite plausible and compatible with the
acute accidental fluoride exposure, but surprisingly, clearly
increased bone fluoride concentrations were found postmor-
tem in the range of 2,000 P4g/gwet weight. The normal values
for fluoride in bone are, depending on age, between 10 and
270 P4g fluoride/g wet weight (Schellmann and Zober 1975).
This represents, in relation to the patient's age, a 10-fold
increase.
With the pharmacokinetics of fluoride, about 50% of the
amount taken up exogenously is stored in bone. The fluoride
concentration found in this case, therefore, can only be
ascribed to long-term chronic exposure. The urine fluoride
level found in the occupational medical check-up, however,
does not hint at a high occupational exposure. Therefore, some
53
research into the ~patient's environment was carried out. One
of theauthors (A. Z.) was able to prove that the drinking
water concentration in H. E.'s residential area was 1.8 mg
fluoride/I ch~eto geological conditions. This means that he had
taken up fluoride over many years with his food, which
expl-~-~the urine fluoride concentration before the accident
and the clearly increased fluoride concentrations in bone, but,
in all probability, the fluoride inhalation and the absorption
during the accident are responsible for the fluoride content in
the lung of at least double the normal value. The serum level of
67 ng fluoride/ml is at least partly the result of the acute
resorptive toxic effect.
In two cases of hydrofluoric acid intoxication which were
described in 1964 and are comparable to these cases with
respect to the accident mech-niMm, serum flUOride levels
30-40 times the normal values of 3 - 4 Itg/ml were determined
(Greendyke and Hodge 1964). It has to be kept in mind,
though, that the titration method of that time was clearly a less
specific and less sensitive analytical method.
It seems jnstified to judge the fluoride level of 67 ng/ml as
also being due to the acute exposure when compared to the
serum fluoride levels in the second case 1 year after the
accident. The second patient, D. H., who lives in the same
area as H . E . , had 42 ng fluoride/ml serum. This 2.5-fold
increase over the standard is probably due to the increased
intake of fluoride with the drinking water.
In summary, it can be stated that in the evaluation of
fluoride concentrations fx~3m biological material, environ-
mental dietary exposure has to be taken into consideration as
well as occupational exposure.
54
References
Grecndykc RM, Hoclgc HC (1964) Acc/dcnml death due to hydro-
fluofic acid. J Forensic So/9:383-390
Reichelt H, Eggert H (1979) Die |nhAh,fivc Fhlorwassclstoff-lntoxi-
kafion. Dt. Gesundh.-Wesen 34:572-574
Schellmann B, Zober A (1975) Normal values of fluoride from a
defined region of the human iliac crest. Int Arch Occup Environ
Hlth 35:233-244
Zober A, Carls H, Schaller K-H (1980) Fluorid. In: S9
zur P r ~ gesundheitssch&d]icher Arbeitmtoffe der deutschen
F o m ~ u n p p m e J m c h ~ - Arbe~tssruppe "Analyti~che Chemic"
(ed), Verlag Chemie, Weinheim (Analy~che Methoden Band 2,
pl-9)
Re~ived November 18, 1983/Accepted July 24, 1984