OSHA Hazard Information Bulletins
Dimethylformamide and Testicular Cancer.
 OSHA Safety and Health Information Bulletins - Table of Contents
- Information Date: 19880217
- Record Type: Hazard Information Bulletin
- Subject: Dimethylformamide and Testicular Cancer.
February 17, 1988
| MEMORANDUM FOR: |
REGIONAL ADMINISTRATORS |
| THRU: |
LEO CAREY
Director
Office of Field Programs |
| FROM: |
EDWARD BAIER
Director
Directorate of Technical Support |
| SUBJECT: |
Health Hazard Information Bulletin:
Dimethylformamide and Testicular Cancer |
Information sent to the Occupational Safety and Health
Administration from the Almalgamated Clothing and Textile Workers Union
(ACTWU) indicated that germinal cell testicular cancer has now been
identified in leather tanning and aircraft workers exposed to
dimethylformamide (DMF).
Incidence of germ cell tumors has been reported among aircraft
repairmen in the Journal of Urology as well as leather tanners in the Lancet.
Potential Worker exposure may occur through skin absorption and/or
inhalation. CSHO's should be on the look-out for possible DMF exposures
involving aircraft repair and leather tanning as well as other operations
where DMF may be used.
Attached are the following (2) references:
1. Ducatman, A.M., Conwill, D.E., and Crawl, J., Germ Cell
Tumors of the Testicle Among Aircraft Repairmen, The Journal of Urology, Vol.
136, October 86, p.p. 834-836.
2. Levin, S.M., et. al., Testicular Cancer in Leather Tanners
Exposed to Dimethylformamide, The Lancet, No. 8568, Vol. II, November 14,
1987, p. 1154.
Attachments
GERM CELL TUMORS OF THE TESTICLE AMONG AIRCRAFT REPAIRMEN
Alan M. Ducatman, David E. Conwill* and James Crawl From the
Departments of Occupational Health and Preventive Medicine, Navy
Environmental Health Center, Norfolk, Virginia
ABSTRACT
A cluster of testicular germ cell tumors occurred among 3 of 153
white men who worked in a shop engaged in repair of exterior surfaces and
electrical components of the airframes of F4 Phantom Jet aircraft.
Evaluation of an occupationally identical shop at a second F4 rework facility
at which there had been no previous reports of excess neoplasms revealed 4
additional men with a history of testicular germ cell tumors (p less than
0.01, Poison, compared to the expected number of cases based on national
incidence rates). Our investigation raises but does not prove a hypothesis
of association between subsequent development of testicular germ cell cancer
and history of extensive exposure to a mixture containing dimethylformamide,
which had been used in F4 repair work at these facilities in the 1960s and
1970s. This represents the first report of 2 corresponding mini-epidemics of
testicular tumors among workers in occupationally identical industrial
settings.
A report of several men with testicular germ cell tumors at a
Navy aircraft exterior surface repair workplace triggered an onsite health
hazard evaluation. This investigation led, in turn, to surveys of 2
additional airframe repair shops at different geographic locations -1 at
which the same type of aircraft (F4 Phantom Jets) was repaired and 1 at which
such repair had never been done. At neither of the latter 2 facilities had
any questions of excess neoplasms been raised.
The average annual age-adjusted incidence of testicular germ
cell tumors in the United States is approximately 5 in 100,000 white men of
working age (20 to 64 years), with a peak incidence of about 10 in 100,000
white men 20 to 29 years old. (1) Of concern, the incidence among young men
in the United States and other developed countries has been suggested to have
been increasing for the last few decades. (1,2)
Risk factors for testicular germ cell tumors include
cryptorchidism, testicular atrophy, other urogenital developmental
abnormalities, family history of urogenital abnormalities, and history of
inguinal hernia, mumps orchitis and, possibly, prenatal diethylstilbestrol
exposure. (2-5) Black men appear far less likely to have testicular germ
cell tumors than white men. (1,2) Other hypothesized risk factors include
maternal hyperemesis gravidarum, prenatal ionizing radiation exposure, rural
residence, exposure to pesticides or unrefined petroleum products, testicular
trauma and elevated testicular temperature that might result from wearing
jockey-type undershorts, or traumatic and heat-generating activities, such as
bicycle or horseback riding. (6-10)
Only 2 time-and-space clusters of testicular germ cell tumors
have been reported previously in the medical literature: 1 among students
and graduates of a podiatry school and the other among a group of 52
neighbors in a small town. (11,12) Neither cluster had an evident etiology.
No industrial cluster has been identified previously and no cluster of
testicular germ cell tumors has been investigated by further sampling of
similarly employed populations elsewhere.
MATERIALS AND METHODS
Preliminary evaluation of the reported cluster of cases at
facility A and inquiries about the occurrence of other types of tumors were
done before our investigation by personnel from the Naval Hospital serving
the facility. Populations at 2 additional facilities, designated facilities
B and C, with no initial reports of any excess cancer then were surveyed to
identify potential cases. Facility B was selected for comparison because it
is the only Navy facility other than facility A at which exterior airframe
repair on F4 Phantom Jet aircraft has been done. In contrast, major airframe
structural repair of F4 Phantom Jet aircraft has been done at facility C.
Interviews with workers (including all identified cases), supervisors and
medical personnel at the facilities covered medical and occupational
histories, possible independent risk factors, and potential workplace and
life-style exposures. Present and historical worksite practices at all
facilities were investigated with site visits and reviews of industrial
hygiene data.
A case was defined as any employee working at an airframe repair
facility at least 3 years before the onset of signs or symptoms leading to a
documented histopathological diagnosis of testicular germ cell cancer.
Three
years were chosen as the shortest reasonable latency for a hypothesized
environmental cancer, as in other reports. (11) Medical records and
histopathological documentation were reviewed for all cases. Questionnaire
and interview attempts also were made to identify any historical cases in
retired or deceased workers. Denominator/employee census data during the
years of interest were provided by management at the facilities. Of
particular interest in the analysis are denominator data concerning white
male workers because all cases identified were among these groups and because
black subjects appear far less likely to have germ cell tumors of the testes.
(1,2)
RESULTS
Tables 1 to 3 reveal case findings for the facilities surveyed.
At facility A, 3 of 153 white men employed in the F4 airframe repair shop
were confirmed to have had testicular germ cell tumors from 1981 to 1983.
All 3 men met our case definition. Only 1 other man with a confirmed history
of testicular germ cell tumor was found from the remainder of the entire
facility (a total of 3,200 employees, with 2,450 white men of working age).
This individual, a 46 year-old sheet metal, worker, had noticed symptoms of
embryonal carcinoma within 1 year of his (Missing pages
835-836.)
THE LANCET TESTICULAR CANCER IN LEATHER TANNERS EXPOSED TO DIMETHYLFORMAMIDE
Sir, - We describe here three cases of testicular malignancy in
leather tanner workers who did essentially the same job in the same plant
during the same period. Testicular cancer is the most common malignancy
among white men aged 15-44.(1) Age-adjusted mortality in the United States
has not varied in the past 40 years, but the incidence in whites has almost
doubled.(2) These three men worked as swabbers on the spray lines in the
leather finishing process and, after latency periods of 8, 13, and 14 years,
testicular cancers developed with common histological features.
Dimethylformamide (DMF) may have been responsible.
Case 1.- At 32 years of age this man developed a painful,
nodular swelling of the right testis in May, 1982, 13 years after his first
exposure as a swabber. He underwent testicular biopsy and orchiectomy, and
histological analysis revealed an embryonal cell carcinoma. Retroperitoneal
dissection revealed evidence of metastatic disease, histologically identical
with the testicular tumor, in two of thirteen excised lymph-nodes. There
have been no signs of further metastatic disease. This man worked as a
swabber at three other tanneries from 1969 to 1975, before his employment at
the plant from 1975 to 1979. His job entailed spreading liquid dyes onto
leather hides on a conveyer belt. The dyes were applied by three spray guns
about 60 cm "upstream" of the swabbers and about 45 cm above the belt.
The
hides passed under an exhaust hood before reaching the swabbers, who used
felt-bottomed paddles to spread the dyes over the leather. The men had to
lean over the hide, with their faces close to the leather. They wore no
gloves and contamination of skin and clothing by liquid dye was virtually
continuous. During spray-line operations at the plant in question, a fine
mist was present in the air, accompanied by a strong, solvent-like odor which
was said to be detectable up to 200 meters from the tannery. General
ventilation was provided only by windows; these were usually kept open,
except in winter. This man had not had mumps and he had no history of
testicular abnormalities at birth, inguinal hernia, or unusual testicular
trauma. His mother denied having received X-ray examinations or taking
diethylstilboestrol (DES) during pregnancy.
Case 2.- In April, 1984, at the age of 36 this man was admitted
to the hospital with a small, painful nodular growth on the right testis, 14
years after beginning work on the spray line. After radical orchiectomy the
tumour was found to be a combined embryonal cell carcinoma and seminoma.
Excision of retroperitoneal lymph-nodes found no evidence of metastasis, and
he has shown no evidence of disseminated disease since surgery. He was a
working forman on the same spray line at the plant, filling in from about 2
hours a day while the swabbers took breaks, but he supervised the line
throughout the working day. He maintained and cleaned the spray guns every
day and repaired them when they became clogged. He began spray-line work at
the plant in 1970 and has been a supervisor since 1974. He could recall no
testicular injury and had not had mumps. There was not history of maternal
DES use. His mother could not recall whether she had received diagnostic
X-rays during pregnancy.
Case 3.- In March, 1984, at the age of 25 this man had an
occasionally tender lump on his left testicle. A radical left orchiectomy
was performed; the tumour was an embryonal cell carcinoma with foci of
choriocarcinoma. One of six excised nodes was positive for metastasis, and
the clinical course has been marked by metastasis to lungs and mediastinum,
treated with chemotherapy and radiotherapy. He had begun spray-line work at
another plant in 1976, and in 1978 he began employment in the plant where all
three cases worked. He had had his right kidney removed in 1979 after a
motorcycle accident. He denied trauma to the testes. He had had mumps at
age 8, without clinically evident orchitis. His mother denied DES use and
could not recall receiving diagnostic X-rays while pregnant.
The health and safety staff of the Amalgamated Clothing and
Textile Workers Union identified a wide range of dyes and solvents in the
plant and in the other tanneries. All the tanneries used DMF, which became
the focus of concern in light of the report by Ducatman et al (3) in 1986,
who found clusters of embryonal cell carcinoma of the testis in two aircraft
repair facilities among mechanics who had worked extensively with
DMF.
DMF and its metabolite monomethylformamide cause testicular
damage in laboratory animals, (4,5) and workplace exposure to DMF had been
reported to be associated with increased chromosomal aberrations.(6)
Kommineni (7) reported one embryonal cell carcinoma of the testis in nine
mice exposed to DMF.
1983 National Occupational Exposure Survey data suggest that
there are over 100,000 workers in the United States exposed to DMF currently
or in the past decade in the production of paint, fibers, and pharmaceuticals
and as a solvent for pesticides and other materials. The identification of
clusters of testicular cancers of the same cell type in two separate
populations working with DMF in different industrial settings may represent a
sentinel health event.(8) Worker (and consumer) exposure to DMF-containing
materials should be reduced to the extent technically feasible until further
epidemiological and toxicological investigation of its carcinogenic potential
is completed.
STEPHEN M. LEVIN DEAN B. BAKER PHILIP J. LANDRIGAN SUSAN V. MONAGHAN
ivision of Environmental and Occupational Medicine, Department
of community Medicine, Mount Sinai School of Medicine, New York, NY 10029,
USA
ERIC FRUMIN MITCHELL BRAITHWAITE WILLIAM TOWNE
Amalgamated Clothing and Textile Workers Union, New York
1. Young JL, Percey CL, Asire AJ. Surveillance, epidemiology,
and end results: Incidence and mortality data, 1973-1977. Nat Cancer Inst
Manager 1981; no. 57.
2. Schottenfeld D, Warshauer ME, Sherlock S, et al.
The epidemiology of testicular cancer in young adults. Am J Epidemal 1980;
112:232-46.
3. Ducatman AM, Conwill D, Crawl J. Germ cell tumors of the
testicle among aircraft repairmen. J Urol 1986; 136:834-836.
4. Barlow SM, Sullivan FM. Reproductive hazards of industrial
chemicals. London: Academic Press, 1982:346-54.
5. Pham HC, Nguyen X, Azum-Gelade MC. Toxicological study of
formamide and its derivatives N-methyl and N-ethyl. Therapie
1971;26:409-24.
6. Berger H, Haber I, Wunscher G, Bittersohl G.
Epidemiologische Untersuchungen zur Dimethylformamidexposition. Z Gesamte Hyg
1985;31:366-69.
7. Kommineni C. Pathologic studies of aflatoxin fractions and
dimethyl-formamide in MRC rats. Dissertation thesis. Lincoln: University of
Nebraska, 1972.
8. Rutstein DD, Mullan RJ, Frazier TM, et al. Sentinel health
events (occupational): a basis for physician recognition and public health
surveillance. Am J Publ Health 1983;73:1054-62.
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