Commentary
The Role of Pesticides in Skin Disease
P esticides are toxic chemicals used against insects,
fungi, viruses, weeds, and rodents. They are ex-
tensively used in all parts of the world and are eco-
nomically important in agriculture. Undoubtedly, much
increase in farm productivity has been achieved since
World War II through the use of synthetic insecticides.
It also is known that billions of dollars have been saved
due to the use of herbicides in agriculture instead of
hiring expensive farm labor, especially in advanced
countries.
The transition from natural to synthetic insecticides
occurred after World War II. These chemicals can be
classified as: (1) chlorinated hydrocarbons, (2) organic
phosphates, (3) phenoxyalkanoic acids, and (4) car-
bamates. They are used in farming, forestry, and gar-
dening.
Many reports have been published about the toxic
nature of chemical pesticides. They produce several
skin diseases in humans in three related stages: (1) oc-
cupational exposure to the intermediate chemicals
from manufacture in the factory, (2) contact by spray
operators to end products in agricultural fields, and (3)
contact by consumer groups to the contaminated
products. Systemic toxicity occurs after skin absorp-
tion, inhalation, or ingestion. Despite many studies,
the accurate incidence of different kinds of skin dis-
eases associated with pesticides still remains unclear.
Thestructuresof various chemicals that can cause skin
diseases are shown in Figure 1.
Contact Dermatitis from Herbicides and Insecticides
Contact dermatitis to pesticides has occurred mainly
in farmers and workers who were negligent in carrying
out protective measures. In 1966, Spencer^ first re
ported herbicide dermatitis from contact to Randox
(Monstanto Agricultural Products Co., St. Louis, MO)
(2-chlorO'N,N-dial!yi acetamide) in three farmers. He
Address for correspondence; Wei-Min Li, M.D., Department of
Dermatology, Veterans General Hospital-Taichung, Taiv*/an, Republic
of China.
295
WEI-MIN LI, M.D.
from (he Department of Dermatology, Veterans General
Hospital, Taichung, Taiwan, Republic of China
suggested that both primary irritant and epidermal
sensitization accounted for the clinical findings. The
characteristic change was violaceous erythema asso-
ciated with edema on covered areas where repeated
contact had occurred.
Since 1966, little has been written about the sensi-
tizing potentials of the herbicides. In 1977, Iden and
Schroeter^ patch tested 22 patients and found that al-
lergic contact dermatitis to Ramrod (Monstanto Agri-
cultural Products Co., St. Louis, MO) (Propachlor; 2-
chloro-N-isoprophyl-acetanilide) and Lasso (Monstanto
Agricultural Products Co., St. Louis, MO) (Alchlor; 2-
chloro-2', 6'-diethyl-N-[methoxymethyl] acetanilide)
existed, but they failed to draw any conclusions about
its incidence.
Natural pyrethrum and its synthetic counterpart are
common insecticides used in many home aerosol
bombs and may cause dermatitis on parts of the body
exposed to the spray. Natural pyrethrum is a moder-
ately potent allergic sensitizer and was the cause of
occupational dermatitis as recorded in 1921 by
McCord and Kilkee.^ Cutaneous reactions to chlori-
nated hydrocarbon insecticides, such as DDT (dichlo-
rodiphenyl-trichloroethane) and lindane (benzene
hexachloride), rarely have occurred.
Chloracne from Manufacture of Herbicides
Several outbreaks of chloracne have been reported
during the manufacture of herbicides 2,4,5 T (2 4,5-
trichlorophenoxy-acetic acid), 2,4,-D (2,4-dichloro-
phenol), and PCP (pentachlorophenol). After vigorous
studies, the intermediate chemical 2,3,7,8-tetrachlo-
rodibenzop-dloxin (TCDD) was found to be the ac-
negenic compound.
In 1977, Taylor et al.'* reported 41 workers devel-
oping chloracne as a result of exposure to TCAB (3,4,3'
296 INTERNATIONAL JOURNAL OF DERMATOLOGY )une 1986 Vol. 25

Herbicides 4'-tetrachloroazoxybenzene), an extraneous interme-

diate formed during the manufacture of a new herbi-
CHj CHCH cide. Toxicity occurred possibly by direct skin contact,
inhalation, or ingestion.
Clinically, chloracne consist of straw-colored cysts,
comedones, pustules, and abscesses. In addition, hy-
perpigmentation also may occur. The predilection sites
are the cheeks, ears, postauricular regions, genitalia,
chest, and back.

Cutaneous Porphyria from Fungicides

and Herbicides

An outbreak of porphyria cutanea tarda in Turkey

was reported by Schmid in I960.'' The syndrome con-
sisted of blistering and epidermolysis of skin on the
exposed areas. Photosensitivity, hypertrichosis, and
dark or red urine occurred in these patients. The etiol-
ogy of this peculiar syndrome was soon identified by
Cihad Cam.^ He noted that all patients had consumed
2,4D
wheat treated with the fungicide hexachlorobenzene.
2,4,5, - T
In 1964, Bleiberg et al.^ discovered acquired por-
phyria in workers engaged in the manufacture of 2,4-
D and 2,4,5-T. These patients also developed chlor-
acne. A highly volatile chlorinated phenolic ether, an
intermediate chemical, appeared to be the cause.

Premalignant and Neoplastic Skin Lesions from

Manufacture of the Herbicide Paraquat

In 1979, Howard^ reported several cases of paraquat-

formulation workers suffering from irritant dermatitis,
nail damage, and epistaxes as a result of direct contact
of the skin and mucous membranes to the chemicals
Insecticides during manufacturing. Chronic skin disease was not
detected at that time. Nail damage in spray operators
CCIs
from contact to paraquat also was emphasized by
Hearn and Keir in 1971 .^ They described a white band
across the nails of these patients after contact either
to the concentrated or diluted solution, possibly re-
sulting in loss of the whole nail.
Cases of premalignant and neoplastic skin lesions
DDT Lindane associated with occupational exposure during the
manufacture of 4,4'-bipyridyl were reported by Bowra
Fungicides
et al. in 1982.^ In the manufacturing process, 4,4'-bi-
pyridyl was quaternized with methylchloride or di-
methyl sulfate to form the end product, paraquat. In
their studies, skin lesions were identified in 20 workers.
Six cases proved to have squamous cell carcinoma by
histopathologic studies; however, details of cutaneous
lesions have not been described.
We have studied 15 Chinese patients who had
Hexachlorobenzene worked in bipyridyl manufacturing factories for periods
FIG. 1. Structures of various cbemicals that can cause skin dis- ranging from 1 to 12 years in Taichung, central Tai-
eases. wan.'" Multiple hyperpigmented macules, several mil-
No. 5 PESTICIDES IN SKIN DISEASE
limeters to centimeters in diameter were noted on the
exposed areas such as the face, neck, and dorsal as-
pects of hands and forearms in all 15 patients. Six cases
showed multiple erythematous hyperkeratotic papules
or plaques, mostly located on the irregular pigmented
macules of the neck, dorsum of hands, and on the
forearm. Histologically, a total of nine specimens from
those of the keratotic lesions of three patients revealed
Bowen's disease. So far, none ofthe lesions has shown
any squamous cell carcinoma.
Service times of the three patients who developed
Bowen's disease were 6, 9, and 10 years, respectively.
It apparently took a long induction period for the pre-
malignant lesions to occur. Since the first paraquat fac-
tory in Taiwan was established in 1969, there has not
been an adequate induction period for the neoplastic
lesions to occur." This may explain why, so far, we
have not seen squamous cell carcinoma in our series.
The pigmented spots seen on most workers took less
time to appear.
Bowra et al. thought that the skin lesions were prob-
ably associated with "magnesium process" and sug-
gested that "tarry" by-products from the manufacture
of 4,4'-bipyridyl may be the cause.** All paraquat fac-
tories in Taiwan, however, use only the high-temper-
ature sodium process to synthesize bipyridine."
We have observed that the cases with pigmented
spots, keratosis, and premalignant lesions arose in per-
sons who mainly worked in the bipyridyl crystallization
and centrifugation processes. It is known that, in the
sodium process, only 35% of the pyridine consumed
was converted to 4,4'-bipyridyl, and substantial quan-
tities of bipyridyl isomers, polypyridyls, and tarry by-
products were produced.
The tars formed by the sodium process were chem-
ically different from those formed by the magnesium
process. Workers were exposed to the above-stated
chemicals during crystallization and centrifugation.
There was no history of exposure to other known skin
carcinogens, such as arsenic. We speculate that our
cases are involved in the sodium process and could
be due to bipyridyl, bipyridyl isomers, or any inter-
mediate chemicals.
In view of its occurrence on exposed areas and its
long induction period, photocarcinogenic factors may
play a role in the pathogenesis of the lesions. Distinct
clinical signs and the clustering of similar cases in one
factory should alert the dermatologist to suspect this
297
occupational disease. Further chemical analysis and
animal experiments may aid in discovering the caus-
ative agent.
Conclusions
Early reports have stated many concerns about the
role of pesticides in occupational dermatitis.'"^ As time
elapsed, more severe dermatoses, such as chloracne
and cutaneous neoplasms have been discovered,
especially after the wide synthesis of organic pesticides
in factories. Since most of the causes were intermediate
chemicals and workers were mostly Involved, pesti-
cides are important in industrial dermatology. Unfor-
tunately, the skin lesions have been unresponsive to
treatment. In this situation, prevention is even more
important than treatment. Industrial hygiene programs
should be stressed. Protective measures can be un-
dertaken in two ways: factory chemical engineers
should improve production techniques and use closed-
system facilities for the manufacture of chemicals;
workers must protect themselves by wearing protective
clothing, masks, gloves, and by taking showers im-
mediately after work. It is hoped that these measures
will minimize the incidence of pesticides in skin dis-
eases.
References
1. Spencer MC. Herbicide dermatitis. |AMA. 1966;198:1b9-170.
2. Iden DL, Schroeter A l . Allergic contact dermatitis to herbicides.
Arch Dermdtol. 1977;113;98.3.
^. McCord CP, KilkeeCH. Pyrethrum dermatitis. |AMA. 1921;77:
448-449.
4. Taylor |S, Wuthrich RC, Lloyd KM. et al. Chloracne from man-
ufacture of a new herbicide. Arch Dermatol. 1977;t t3:616-
619.
5. Schmid R. Cutaneous porphyria in Turkey. N EngI I Med.
196G;2f>3:397-398.
6. Bleiberg I. Wallen M, Brodkin R, et al. Industrially acquired por-
phyria. Arch Dermatol. 1964;89;793-797.
7. Howard |K. A clinical survey of paraquat formulation workers.
Br) Ind Med. 1979;36:220-223.
8. Hearn CED, Keir W. Nail damage in spray operators exposed
to paraquat. Br I Ind Med. 1971;28:399-403.
9. Bowra GT, Dufficld DP, Osborn A), et al. Premalignant and neo-
pl,istic skin lesions associated with occupational exposure lo
"tarry" byproducts during manufacture of 4,4'bipyridyl. Br)
Ind Med. 1982,39:76-81.
10. Li WM. Premalignant skin lesions associated with occupational
exposure during the manufacture of herbicide paraquat. Derm
Sinica. 1984;2:l-8.
11. Wang ID, Li WM, Hu EC, et al. Epidemiologic study of paraquat
manufa( turers in Taiwan, (in preparation).