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Renate D. Kimbrough
Chest 1974;65;65S-67S
DOI 10.1378/chest.65.4_Supplement.65S
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Paraquat is a general weed killer of the bipyridyl in rats was 80 mg paraquat/kg body weight in males
family of herbicides (1, 1’-dimethyl 4,4’ bipyri- and 90 mg/kg in females, while the acute oral LD,, in
dylium). Paraquat is available either as the dichloride or male rats was 100 mg/kg and in females 110 mg/kg.2
dimethyl sulfate salt, both compounds are water soluble. These findings indicate that there does not seem to be a
In the United States the following formulations are great difference between the oral and dermal toxicity in
available: Orthoparaquat, a 29.1 percent solution, Ortho rats.
dualparaquat, a 42 percent solution, and Ortho Spot, McDonagh and Martin’ reported four cases of
weed and grass killer, a 0.44 percent solution. Paraquat paraquat poisoning in children. One of the patients, a
was developed in the 1950’s, and came onto the market three-year-old boy, was admitted to the hospital with
in Creat Britain in 1962. It was registered for use in the superficial burns on his right thigh and hands 24 hours
United States in 1964. Registration also permits aerial after he had spilled a 20 percent paraquat concentrate
spraying of diluted formulations. (Cramoxone) on his clothes. He had also been seen
According to a recent editorial in Lancet,1 the total playing near a pool of the liquid. About six to eight hours
number of human deaths known to the manufacturer after admission an erythematous rash appeared on his
from paraquat poisoning is now 124 worldwide. In ad- thigh and hands. The rash developed into a large first
dition, 60 persons who have recovered from paraquat degree burn. No lesions were seen in his mouth. In spite
poisoning are also known. The fatal dose in adults is of the fact that the child did not appear to have ingested
thought to be about 15 ml of a 20 percent solution, or a any paraquat, it was present in his urine. This case
“mouthful” as it is described in most case histories. illustrates that paraquat is also absorbed through human
Formulations which contain 5 percent of paraquat if skin.
accidentally swallowed are usually not fatal. Fatal As pointed out earlier, paraquat is registered in cer-
poisoning in almost all cases has been due to ingestion of tain instances for spraying by airplane in the United
the material. The initial symptoms of poisoning consist of States. Fortunately, the particle size is large enough so
burning of the mouth and throat, followed by nausea that direct inhalation does not seem to present a problem
and vomiting. After a latent period of up to several days, unless high pressure spray or air blast equipment is used.
increasing respiratory distress develops, a transient effect According to Cage4 the “no-effect” level for a “respira-
is also observed on kidney, liver and heart function and ble” paraquat aerosol in the rat is about 0.1 mg/M’ for
transient neurologic signs are seen, but death is usually repeated six-hour exposures, which would suggest that
the result of a progressive fibrosis and epithelial prolifera- 0.1 mg/M’ would not be excessive for occupational
tion that occurs in the lungs. exposure. The threshold limit value for paraquat in
Dermal exposure to the paraquat concentrate may workroom air in the United States set by the American
result in severe skin irritation. Diluted spray solutions Conference of Covernment Industrial Hygienists is 0.5
may produce slight to moderate irritation. Paraquat is mg/M’ at present.
absorbed through the skin. In toxicity studies conducted Patients have on occasion had nose bleeds due to a
in our laboratory we found that the acute dermal LD,0 local effect of paraquat on the nasal mucosa. If paraquat
is splashed into the eye, particularly the paraquat con-
* From the Environmental Protection Agency, Chamblee, Ca.
centrate, severe eye injuries have occurred,’ and in
CHEST 65: 4, APRIL, 1974 SUPPLEMENT 16TH ASPEN LUNG CONFERENCE 655
4
t’
.- -‘
FIGURE 1. Section of lung of rat given 160 mg/kg paraquat FIGURE 3. Section of lung from rat receiving 40 mg/kg parR-
by stomach tube. Rat died six days later. Alveoli contain quat, killed eight weeks later. Note pigment staining with
edema fluid, inflammatory cells and macrophages (PAS stain, Perl stain within macrophages (Per! stain X 500).
x 50).
nation revealed edema and hemorrhage.
addition, injuries to the fingernails, nail beds and skin Rats dying six days after a single dose of paraquat
have also been reported.6 All of these injuries are pri- showed an inflammatory reaction in the lungs (Fig 1).
marily due to the local corrosive effect of this product. Polymorphonuclear leukocytes, macrophages and edema
Death following paraquat poisoning is usually the fluid were observed in the alveoli. Evidence of the earlier
result of progressive fibrosis and epithial proliferation in hemorrhage was still present. A brown pigment which
the lungs. This effect has been described in human stained positive for iron with Perl’s stain was observed,
beings, rats, guinea pigs, mice and dogs.1 and probably represented hemosiderin. A highly
We2 have studied the effect of paraquat on the lung eosinophiic PAS-positive membrane lining the alveoli
of the Sherman rat. The early effect of paraquat after a was also noted. In rats surviving ten days following a
single oral dose of 150 mg/kg by stomach tube, was single toxic dose of paraquat the lungs showed begin-
pulmonary edema within 48 hours. ning proliferation of fibrous and alveolar cells (Fig 2).
Examination of the affected lungs with the electron- Rats given a single oral dose of 40 mg/kg body weight,
microscope showed swelling and large vacuoles in the killed eight weeks later showed fairly extensive areas of
cytoplasm of the membranous pneumocytes. Dark consolidation. Microscopic examination of these finn
prominent granules were also seen in the cytoplasm and grayish areas revealed extensive fibrosis and a brown
were thought to represent ribosomes. Widening of the pigment positive for iron with Pen’s stain (Fig 3), which
basement membrane with separation of the epithelial was consistent with hemosiderin findings. Slight pro-
cells from the basement membrane was noted. Pulmo- liferation of epithelial cells was also observed.
nary edema and red blood cells were observed in the When rats were fed 500 ppm paraquat daily in their
alveoli.2 A rat which died four days after a single oral diet (20-30 mg/kg body weight) an occasional rat de-
dose of 160 mg/kg of paraquat in water showed firm veloped areas of consolidation. These areas of consoli-
dark lungs on gross inspection, and microscopic exami- dation contained proliferated epithelial cells which were
surrounded by inflammatory cells and fibroblasts. A
prominent amorphous material was also observed in the
66S 16TH ASPEN LUNG CONFERENCE CHEST 65: 4, APRIL, 1974 SUPPLEMENT
DISCUSSION
Dr. Corrin: I think it is important to re-emphasize the suggest that we ban the sale of this material but our
point that you made, and that is the route by which farming friends tell us that this is an extraordinarily
paraquat reaches the lung. I know of no fatal cases of valuable chemical and a ban would put a great burden
paraquat poisoning in which the route to the lung has on them.
been the respiratory tract. All the fatal cases that have Dr. Kimbrough: I think it would be far better if the law
been reported are those in which the paraquat is in- could be changed and the dilute form of paraquat would
gested. In our experimental preparations, the data agree be the only form available on the market. This would
closely with yours in that the epithelium is the major site decrease the number of cases of such fatal poisonings.
of damage. There is some endothelial degeneration but Dr. K. Fisher: I would like to extend Dr. Kimbrough’s
the epithelial damage can proceed to complete necrosis remarks on the role of oxygen in paraquat poisoning. We
with the endothelium being apparently quite normal. have found that paraquat is far more rapidly and uni-
This is particularly interesting when one realizes that formly fatal in animals breathing an atmosphere of oxy-
this toxic substance had reached the alveolar wall via the gen than in those breathing room air. We have also
circulation and not via inhalation. This material is so found that concentrations of paraquat which are bac-
extremely toxic that one might ask what we can do to teriostatic to aerobically grown E coli have no effect on
reduce the hazard of this material. One might initially anaerobic growth of E coli.
CHEST 65: 4, APRIL, 1974 SUPPLEMENT 16TH ASPEN LUNG CONFERENCE 67S