Research - Chemical and Biological Hazards

SUMMARY

Infectious disease remains a serious
problem in U.S. agriculture in two distinct
populations:

o Migrant farm workers experiencing
human-host illnesses, often episodic and
exacerbated by substandard living and
employment conditions.

o All other farm workers experiencing
sporadic, isolated illness that is most fre-
quently zoonotic, vector-borne, or environ-
mentally acquired in nature.

REFERENCES

Both populations may present risk of ex-
posure to the non-farm population through
personal contact, indirect exposure (enviro-
nment or vector), or contamination of food
produce. Obvious innovations and tech-
nologies exist to improve disease recog-
nition, management, and control for both
groups specifically, and non-farm in-
dividuals generally. The broad and varied
scope of this problem is presented,
including areas that should be targeted for
additional research or enhanced program
support.0

1. American Public Health Association, Control of Communicable Diseases in Man. Benensen AS ed, 15th
Ed; 1990.

2. Amer Vet Med Association, Zoonoses Updates (published compilation), JAKU4. Amer Vet Med Ass'n,
Shaumburg IL; 199Q.

3. Currier RW. Iowa Department of Public Health, Des Moines IA; March 1991.
4. Roberto RR. Personal communication. California Department of Health Services, Berkeley CA; April
  1991.

5. Armstrong CW. Personal communication. Virginia Department of Health, Richmond VA; April 1991.

6. Ciesielski SD, Seed JR, Esposito DH, and Hunter N. The epidemiology of tuberculosis among North
Carolina migrant farm workers. JAMA 265: 17151719; April 3, 1991.

7. Centers for Disease Control. A strategic plan for the elimination of tuberculosis in the United States.
MMWR. 1989; 38: S-3.

8. Centers for Disease Control. Tuberculosis among foreign-born persons entering the United States:
recommendations of the Advisory Committee for Elimination of Tuberculosis. M.. 1990; 39(No.
RR18).

9. Davis JP. Personal communication. Wisconsin Division of Health, Madison WI. March 1991.

10. Proctor M. Unpublished investigation. Wisconsin Division of Health, Madison WI. 1990.
11. Proctor M. Internal agency report. Wisconsin Division of Health, Madison WI. 1990.
12. Centers for Disease Control: Poliomyelitis Surveillance Summary 1979, Issued April 1981.
13. Hutchins R. Personal communication. Tennessee Department of Health, Nashville TN. April 1991.

226                                Papers and Proceedings


Infectious Diseases, May 1, 1991

14. Stevens GA. Testimony prepared for the Occupational Safety and Health Administration on Proposed
Field Sanitation Standards. Dehnarva Rural Ministries. July 1984.

15. Federal Register, 29 CFR Field Sanitation; Final Rule Vol52, No 84, p 16049-16096. May 1, 1987.

16. McChesney TC. Personal communication. Arkansas Department of Health, Little Rock AR. April
  1991.

17. Centers for Disease Control. Summary of notifiable diseases, United States, 1989 . MMKQ. 1989 ; 38 (
54 ) .

18. Potter ME, Kaufman AF, Blake PA, and Feldman RA. Unpasteurized milk: The hazards of a health
fetish. JAMA. 252~1048-2052. Ott 1984.

19. Currier RW. Raw milk and human gastroenteric disease: problems resulting from sale of legalized raw
milk. J of Pub Health Policy 2~226-234, Sept 1981.

20. Blazer MD, Sazie E, Williams LP. The influence of immunity on raw milk-associated Campylobacter
infection. JAMA. 257: 43-46. Jan 1987 .

21. Vogt RL, et al. Liig environmental and human strains of Listeria monocytogenes with isoenzyme and
ribosomal RNA typing. Eur J EpidemiolO392-299O:p 229-230. June 1990.

22. Shirely LA. Personal communication. North Dakota Department of Health. April 1991.

23. St Louis ME, Morse DL, Potter ME, et al. The emergence of grade A eggs as a major source of
Salmonella enteritidis infections. JAMA. 259: 2103-2107. 1988.

24. Gunn R4 and Markakis G. Sahnonellosis associated with homemade ice cream. JAMA 240:1885-1886.
  1978.

25. Currier RW, Rapp WF, Juranek DD. A community outbreak of trichinosis in Nebraska: report of an
epidemiologic investigation. Nebraska Medical Journal. Jan-Feb, 1982.

26. Centers for Disease Control. Trichinella spirilis infection - United States, 1990. MMKR. 1991; 40 : 57-60.

27. Williams LP. Personal communication. Oregon Department of Health, Portland OR. April 1991.

28. Staff Epidemiologist. Personal communication. Utah Department of Health, Salt Lake City UT. April
  1991.

29. Marx J. Unpublished data. Marshfield Clinic, Marshfield WI. April 1991.

30. California Morbidity. Mosquito-transmitted malaria in California: 1988-1989. Part 2 of 2. Nr 52, Jan 5,
1990. (Pub1 by Calii Department of Health Services.)

31. California Morbidity. Arboviral disease surveillance - California, 1989. Nr 21/22. June 1, 1990.

32. Fuortes L. Unpublished data. College of Medicine, Univ of Iowa, Iowa City IA. April 1991.

33. Wood C. Unpublished data. Kansas Department of Health and Environment, Topeka KS. April 1991.
34. Currier RW. Farm injury surveillance (SPRAINS Program) - unpublished data. Iowa Department of
Public Health, Des Moines lA. Feb 1991.

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Research - Chemical and Biological Hazards

35. Thoen CO. Zoonoses Update: Tuberculosis. JAKV.4 (Pub1 collection of Zoonoses Updates.) 132-135.
  1990.

36. Currier RW. Zoonoses Update: Bruceiiosis. JAK'v&4 (Pub1 collection of Zoonoses Updates.) p 25-27.
  1990.

37. Music S. Personal communication. Wyoming Department of Health, Cheyenne WY. March 1991.

38. Sasaki DM. Personal communication. Hawaii Department of Health, Honolulu HI. April 1991.

39. Williams LP. Personal communication. Oregon Department of Health, Portland OR. April 1991.

40. Durfee PT, Pullen MM, Currier RW and Parker RL. Human psittacosis associated with commercial

processing of turkeys. JAK'U 167: 804-808. Nov 1, 1975.

41. Doll J. Personal communication. Arizona Department of Health, Phoenix, AZ, April 1991.

42. Smith KA. Personal communication. Ohio Department of Health, Columbus, OH, April 1991.

43. Iowa Department of Public Health. Bovine rabies in Iowa. Iowa Disease Bulletin. Feb 1991.

44. Centers for Disease Control. Rabies surveillance - 1988. Issued Aug 1989.

45. Martin RJ. Personal communication. Illinois Department of Health, Springfield, IL, April 1991.

46. Baer G. Personal communication. Centers for Disease Control, Atlanta, GA., 1990.

47. Currier RW. Unpublished data. Iowa Department of Public Health, Des Moines LA. 1990. 48. Sewell
CM. Personal communication. New Mexico Health and Environment Department, Sante Fe NM.
March 1991.

228

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Surgeon General's Conference on Agricultural Safety and Health
FARM&FE 2000 . A National Coalition for local Action
Convened by the National Institute ftr Occupational Safety and Health
April 30 - May 3, 7991, Des Moines, Iowa

AN OVERViEW OF POTENTIAL HEALTH HAZARDS AMONG FARMERS
           FROM USE OF PESTICIDES

By Aaron Blair, Ph.D.
Occupational Studies Section
National Cancer Institute

Beginning in the mid-1940's, pesticides
have become an increasingly important
weapon in the attempt to control
troublesome agricultural pests. Conse-
quently, agriculture has become a major
consumer of pesticides and now accounts
for about 65 percent of the total domestic
use.' Pesticide use varies by the crops and
livestock raised, but a majority of farmers
report application of some.

In a 1982 survey, approximately 75 percent
of the farmers with crops and 70 percent
with livestock used pesticides.' With 2
million farmers, 6 million additional farm
family members, and nearly 3 million hired
farm workers, there is a large number of
persons with potential contact with pes-
ticides through agricultural use.3

Use of pesticides has been an integral
component of the agricultural revolution,
which over the past 50 years has greatly
increased yields. Losses that would occur
without the use of pesticides are difficult
to estimate, but they could be sizable."

Despite efforts to tailor the toxicologic
properties of pesticides to specific pests,
the fundamental similarity of all organisms
at the subcellular level raises concerns
about potential pesticide exposure of a
large segment of the population.

Although we should not lose sight of the
benefits pesticides provide, the purpose of

this review is to evaluate the potential for,
and evidence of, adverse health outcomes
from pesticide exposure in humans. Acute
effects have been well established, and the
major focus of this presentation will be on
chronic effects.

ACUTE EFFECTS

Effects from acute exposure to pesticides
are well established, but statistics on injury
and death from acute exposures are in-
complete for the United States as a whole.
Some results indicate that the number of
fatalities fell between the 1950's and the
1970's? Based on extrapolation from a
survey of a small number of hospitals,
EPA estimated that there were fewer than
3,000 annual admissions to hospitals for
pesticide poisoning.'

In California, however, where physicians
are required by law to report suspected
pesticide poisonings to the Department of
Food and Agriculture, approximately 2,000
poisonings have been reported annually in
recent years.' About 50 percent of these
were from occupational exposures.

More effective reporting systems are
needed before the magnitude of adverse
health conditions from acute exposures can
be well monitored. Assessments in agricul-
ture should include migrant workers, farm
laborers, and dependents of farmers, as
well as farm operators.

Surgeon General's Conference on Agricultural Safety and Health - 1991                229


Research - Chemical and Biological Hazards

CHRONIC EFFECTS

Of growing concern are chronic health
outcomes that do not occur immediately
after exposure, including carcinogenic,
developmental, immunological, reproduc-
tive, and neurological effects.&' The
lengthy interval between exposure and
chronic effects makes risk assessment for
these outcomes more difficult to evaluate
than acute effects.

As testing procedures have improved,
concern has increased over long-term
health effects from pesticides. Today sig-
nificant efforts are devoted toward ex-
perimental and epidemiologic evaluation
of pesticides. The quantity and quality of
the data available, however, vary by
disease outcome.

Establishment of a formal testing program
by the National Cancer Institute (NCI) in
1968 and continued by the National
Toxicology Program (NTP) in 1978 gave
carcinogenicity screening of chemicals, of
which pesticides were an important con-
cern, an early start. This experimental
effort stimulated epidemiologic inves-
tigation of pesticides and cancer.

The availability of cancer registries also
enhanced opportunities for cancer research
by providing a readily available source of
well-diagnosed cases. Registries for other
chronic disease endpoints are only begin-
ning to be established. Since we lack some
of these resources, the occurrence of non-
malignant chronic disease from pesticide
exposure has not been evaluated as
thoroughly.

CARCINOGENIC EFFECTS

Some 47 pesticides have been evaluated in
the NCI-NTP bioassay program (Table I)."

Information from other sources is
available, but is not considered here
because study protocols sometimes deviate
from the preferred model and because the
purpose of this paper is to provide an
indication of hazards presented by pes-
ticides and not to provide a comprehensive
review of all available data.

In the NCI-NTP assays, six pesticides, or
13 percent(chlordecone, dichlorvos,
aminotrizole, sulfallate,
dibromochloropropane (DBCP), and EDB)
were positive in both sexes in mice and
rats. Another 10 (21 percent) were
positive in both sexes of one species
(chlordane, chlorobenzilate, dieldrin, hep-
tachlor, tetrachlorvinphos, toxaphene,
nitrofen, captan, chlorthalonil, and
dichloropropene). Five (11 percent) were
positive in one sex of at least one species
(aldrin, dicofol, piperonyl sulphoxide,
chloramben, and trifluralin). For 19 (40
percent) there was no evidence of car-
cinogenicity in any sex/species group and
seven (15 percent) provided inadequate or
equivocal evidence for carcinogenicity.

Several of the pesticides positive in bioas-
says are no longer on the market, or their
use is severely restricted, but others are
widely used. The 16 chemicals positive in
both sexes in at least one species include
organochlorine and organophosphate in-
secticides, herbicides, fungicides, and
fumigants, suggesting that no chemical
class of pesticides can be considered
problem free.

Pesticides are selected for testing for
various reasons, including suspicion of
carcinogenicity. With 45 percent of the
pesticides tested showing some evidence of
carcinogenicity, the concern about chronic
human exposure would seem well founded.

230                                   Papers and Proceedings


An Overview of Potential Health Hazards among Farmers from Use of Pesticides, May 1, 1991

Table 1. Results of Carcinogenicity Testing of Pesticides from the National Toxicology Program of
Bioassays in Mice and Rats (modified from reference 10).

INSECTICIDES

Aldicarb
Aldrin
Azinphosmethyl
Chlordane
Chlordecone
Chlorobenzilate
Coumaphos
Diazinon
Dichlorvos
Dicofol
Dieldren
Dimethoate
Dioxathion
Endosulphan
Endrin
Fenthion
Heptachlor
Lindane
Malathion
Maloxon
Methoxychlor
Methyl parathion
Mexacarbate
Parathion
Phosphamidon
Photodieldrin
Piperonyl butoxide
Piperonyl sulphoxide
Tetrachlorvinphos
Toxaphene

MICE

I!!!
v

+

+

+

+

t

t

+

I

E

t

t

+

t

t

t

RATS

I!!!
?

E
E

L

t

I

HERBICIDES

Aminotriazole
Chlorambene
Fluometuron
Monuron
Nitrofen
Sulfallate
Trifluralin

FUNGICIDES

Anilazine
Captan
Chlorthalonil
Fenaminosulf
0-Phenylpheno-I
Pentachloro-
nitrobenzene
Triphenyltin-OH

M
7

t
:

+

+

t

FUMIGANTS

DBCP                t
Dichloropropene     I
EDB                 t

E = Equivocal
I = inadequate evidence
M = Male
F = Female

MICE

t

t

+

RATS

M
.

t

:

t

t

t

t

t

Pesticides may exert their carcinogenic
effects through several mechanisms,
including mutation, inhibition of gap-
junctional cellular communication,

in vivo and in vitro tests, the nine chemicals
were found to, be active in most assays.
These included organophosphate insec-
ticides (acephate, demeton, mono-

pcroxisome proliferation, and other
promotional activities." In an evaluation   crotophos, and trichlorfon), phthalimide
of genetic damage from 65 pesticides in 14  fungicides (captan and folpet), and thio-

Surgeon General's Conference on Agricultural Safety and Health - 1991

231


Research - Chemical and Biological Hazards

carbamate herbicides (diallate, sulfallate,
and triallate).`*

Another group of 26 chemicals were
positive in some tests, but were generally
less active than the nine chemicals above.
Pesticides in this group included phenoxy
herbicides (2,4-D and 2,4-DB); organo-
phosphate insecticides (azinphos-methyl,
crotoxyphos, disulfoton, and methyl
parathion); ethylenebisdithiocarbamate
fungicides (manzeb, maneb, mancozeb, and
zineb); and pyrethroid insecticides (allet-
hrin, chrysanthemic acid, and ethyl chysan-
themate). Thirty pesticides gave no
evidence of genetic toxicity.

Some pesticides may influence the car-
cinogenic process in an epigenetic manner.
For example, inhibition of intercellular
communication can disrupt development or
promote cancer."

Broad occupational surveys from around
the world have noted rather consistent
excesses of leukemia, non-Hodgkin's
lymphoma, multiple myeloma, soft-tissue
sarcoma, and cancers of the brain, skin,
lip, stomach, and prostate among
farmers.

A number of pesticides have been shown
to inhibit gap junction intercellular com-
munication including DDT, dieldrin, chlor-
dane, heptachlor, Kepone, mirex, and
endrin.14 Several of these pesticides have
been shown to have a promotional effect
on liver carcinogenesis in the rat.l'

Peroxisome proliferation and the resultant
increased generation of hydrogen peroxide
represent another possible non-genotoxic
carcinogenic mechanism. Phenoxy acid

herbicides appear to be peroxisome
proliferators in several rodent species."
Much of the epidemiologic data available
on the carcinogenicity of pesticides comes
from studies of persons employed in
agriculture.

Broad occupational surveys from around
the world have noted rather consistent
excesses of leukemia, non-Hodgkin's lym-
phoma, multiple myeloma, soft-tissue sar-
coma, and cancers of the brain, skin, lip,
stomach, and prostate among farmers."-"
These excesses occur against a background
of lower overall mortality, particularly for
heart disease and other cancers including
lung, colon, bladder, kidney, esophagus,
and liver. This pattern of low mortality
from most causes of death, but excesses for
a few cancers, suggests a role for work-
related factors.

The low prevalence of smoking among
farmers is probably related to their more
favorable rates for heart disease and can-
cers of the lung, esophagus, and bladder.15
High levels of physical fitness may
contribute to their lower rates of colon
cancer and heart disease."

Case-control and other studies provide
further evidence that farmers are at higher
risk for selected cancers than the general
population. In a recent survey of the
literature," excesses among farmers were
seen in 12 of 13 studies of leukemia, 12 of
15 studies of Hodgkin's disease, 14 of 19
studies of multiple myeloma, 18 of 29
studies of nqn-Hodgkin's lymphoma, three
of three studies of lip cancer, three of
three studies of skin cancer, five of seven
studies of brain cancer, three of five
studies of soft-tissue sarcoma, six of six
studies of stomach cancer, and two of
three studies of prostate cancer.

232                                  Papers and Proceedings


The excesses for specific cancers among   Although farmers come into contact with a
farmers may have broad public health    variety of potentially hazardous substances,
implications, since several of the high-rate  pesticides have received the most attention
tumors appear to be increasing in the    in epidemiologic studies, possibly because
general population of many developed   several pesticides are carcinogenic in
countries.le Of special interest are the    bi0assays.l' Early epidemiologic inves-
rising rates for multiple myeloma, non-   tigations evaluated cancer risks associated
Hodgkin's lymphoma, melanoma, and    with pesticide exposure in general.
cancer of the brain.           The International Agency for Research on
In England and Wales" and the United   Cancer (IARC) in a recent deliberation
State?, prostate cancer has also been    concluded that exposures occurring during
increasing. Changes in diagnosis and    the application of insecticides were
reporting may account for some of the   probably carcinogenic in man." Cohort
increase for these tumors."*"       studies of applicators and manufacturers of
The rising rates for non-Hodgkin's lym-    insecticides have tended to show excesses
phoma, multiple myeloma, and leukemia in  of cancers of the lung and the lymphatic
agricultural areas of the central United   and hematopoietic system, although some
States, however, is a further indication of  investigations show deficits.lO~ll
the possible involvement of agricultural
exposures. Excesses of cancer of the brain  In these studies it was not possible to
and lymphatic and hematopoietic system   determine the specific chemicals accoun-
have also been observed in rural farm   ting for these excesses, but most subjects
populations in Quebec."2         were employed during a time when or-
                 ganochlorine insecticides were the
Risks were correlated with pesticide usage  chemicals used predominately. Although
and were observed among women, as well  many epidemiologic studies have evaluated
as men, raising the possibility of effects   cancer risks among farmers and other
from nonoccupational exposure. The    pesticide-exposed workers," only recently
specific agricultural factors that might    have there been attempts to assess risks
account for the cancers excessive among   from exposure to specific pesticides."
farmers have not been definitively iden-
tified, but a number of etiologic clues exist.  Among those studies that have, soft-tissue
                 sarcoma, Hodgkin's disease, non-Hodgkin's
Exposures of interest include pesticides,   lymphoma, leukemia, and lung cancer have
fertilizers, fuels and engine exhausts, or-   been associated with DDT;42"`28 non-
ganic and inorganic dusts, solvents,     Hodgkin's lymphoma with organophos-
ultraviolet light, and zoonotic viruses.3   phates;25 soft-tissue sarcoma with a variety
Many, perhaps even most, of the members  of animal insecticide?; leukemia with
of the general population may also have   crotoxyphos, dichlorvos, famphur, pyreth-
contact with some of these substances.   rins, methoxychlor, and nicotine%; and non-
Studies of farmers may, therefore, provide  Hodgkin's lymphoma'5*29-33 and soft-tissue
explanations for the rising incidence of cer-  sarcoma34'38 with phenoxyacid herbicides. A
tain cancers among the general population.  potential problem for other cancers is
                 suggested by an important study of workers
                 engaged in the production of 2,4,5-

An Overview of Potential Health Hazards among Farmers from Use of Pesticides, May 1, 1991

Surgeon General's Conference on Agricultural Safety and Health - 1991               233


Research - Chemical and Biological Hazards

Table II. Pesticide Effects on the Immune System (modified from reference 39).

Pesticide       Species Summarv of Effects

t ORQANOPHOSPHATES

Methylparathion . . . . . Rabbit  Thymus atrophy and reduced DTH response.
              Mouse  Decreased host resistance to infection Salmonella typimurium.
Parathion . . . . . . . . . . . . Mouse  Altered colony forming activities of bone marrow stem cells.
Malathion . . . . . . . . . . . Mouse  Suppression of CTL response in vitro.

b ORQANOCHLORINES

DDT . , . . . . , . . , . . , , , . , Rabbit  Thymus atrophy and reduced DTH response.
Mirex . . . . . . . . . . . . . . . _ Chicken Decreased IgG levels.
Hexachlorgbenzene . . Mouse  increased sensitivity to endotoxin and malaria challenge.
              Rat   Increased humoral immune responses to tetanus toxoid and delayed-
               type hypersensitivity to ovalbumin.
Dieldrin  . . . . . . . . . . . . . Mouse  Decreased AFC response and increased susceptibility to viral infection.
Chlordane . . . . . . . . . . . Mouse  Decreased contact hypersensitivity after in utero exposure.
              Mouse  Suppression of AFC responses and T-cell activity in a MLC reaction
               following in vitro exposure.

p CHLOROPHENOXY COMPOUNDS

Pentachlorophenol . . . Mouse  Decreased host resistance to virus-induced tumor metastases.
2,4-D . I.. . . . . , . . , , . . . Mouse  Enhanced T- and B-cell responses following dermal application.

t CARBAMATES

Carbofuran . . . . . . . . . . Rabbit Reduced DTH response.
           Mouse Decreased host resistance to Salmonella tvphimurium infection.
Aldicarb . . . . . . . . . . . . . Mouse  Decreased AFC response to sheep erythrocytes.
              Human  Increased response to Candida antigen, increased number of lym-
              phocytes expressing CD8 markers and decreased CD4 + /CD8 + cell
               ratio.
             Mouse  No alterations in AFC response, B- or T-lymphocyte mitogenesis, host
               resistance to influenza virus infection, CTL response or percentages of
               T-cells, T-cell subpopulations or B-cells.
  DTH = delayed-type hypersensitivity.
  CTL = cytotoxic T lymphocytes.
  AFC = antibody-forming cells.
  MLC = mixed lymphocyte culture.

trichlorophenol and derivative herbicides,   those employed for less than one year.
products contaminated with 2,3,7,&tetra-
chlorodibenzo-p-dioxin.3' In this report, 20  Risks were elevated for soft-tissue sar-
years after first exposure, a significant 50   comas and cancers of the esophagus, stom-
percent excess of total cancer occurred    ach, intestines, larynx, lung, and prostate.
among workers employed for more than   In the 20-year latency category, lung can-
one year while no excess occurred among   cer increased with duration of exposure

234                                   Papers and Proceedings


with standardized mortality ratios (SMRs)
of 96, 126, 146, and 156 for duration of
exposure categories of C 1 year, 1 to < 5
years, 5 to < 15 years, and 15 or more
years, respectively.

Immunologic evaluations of pesticide ex-
posure in humans are in their infancy.
Effects observed in animals are not always
seen in human studies.40 For example,
altered numbers of T-cells and a decreased
ratio of CD4/CD8 T-cells were found in

IMMUNOLOGIC EFFECTS        women exposed to aldicarb-contaminated
                   drinking water." In investigations of al-
Pesticides have immune effects that are of  dicarb in mice, one noted an inverse dose-
interest in their own right, but they may   related suppression of antibody response,44
also be an important mechanism in car-   while the another study did not.45
cinogenesis. A critical role for suppression
of immune responsiveness by pesticides has
been demonstrated for infectious disease    A critical role for suppression of im-
and maybe for other diseases.39        mune responsiveness by pesticides has
                            been demonstrated for infectious disease

Pesticides have displayed a variety of ef-
fects on the immune system (Table II),     and maybe for other diseases.
including suppression of cytotoxic T lym-
phocyte (CTL) response by malathion,
thymus atrophy and delayed-type hypersen-  There is also the possibility of a linkage
sitivity (DTH) response by methyl-     between immunologic effects from pest-
parathion and DDT, decreased antibody-   icide exposure and cancer. It is well
forming cells (AFC) responses from     documented that patients with naturally
dieldrin and chlordane, enhanced T-and B-  occurring or medically induced immuno-
cell responses by 2,4-D, and reduced DTH  deficiencies experience striking excesses of
and host resistance by carbofuran. As with  non-Hodgkin's lymphoma.46M
carcinogenicity, immunologic effects are
observed from pesticides in various     In addition, excesses of leukemia and
chemical classes (organochlorines, or-    stomach cancer have been observed among
ganophosphates, carbamates, and phenoxy-  persons with primary immunodeficiency
acids). In vitro studies of human leukocyte  syndromes, while increases of soft-tissue
functions have also shown inhibition of    sarcoma, melanoma of the skin, and
blastogenic stimulation".          squamous carcinomas of the skin and lip
                   have been observed in renal transplant

Lymphocyte PHA stimulation was reduced  patients.""" The fact that several of the
10 percent by carbamates, 11 to 18 percent  tumors excessive among farmers (e.g., non-
by organophosphates, and 11 to 17 percent  Hodgkin's lymphoma, leukemia, skin, lip,
by organochlorines. Contact dermatitis   and stomach) also occur among im-
and allergic chemical dermatitis are well-   munodepressed patients could be a coin-
recognized health effects from pesticide   cidence, but it may suggest that effects on
exposure and can occur from exposure to  the immune system play a role in farming-
various insecticides, fungicides, and       related cancers.
fumigants.4uz

Epidemiologic investigations of alterations
of the immune system are difficult because

An Overview of Potential Health Hazards among Farmers from Use of Pesticides, May 1, 1991

SUrQeon General's Conference on Agricultural Safety and Health - 1991                235


Research - Chemical and Biological Hazards

of large interindividual variability and the
confounding effects from infections, drug
use and other factors that influence im-
mune responses. Alterations in immune
responses may also be short lived.

Monitoring of the immune system over an
extended period may be necessary to
determine the relevance of any alterations
to subsequent disease risk. Consequently,
it may be necessary to rely primarily upon
experimental investigations in the near
future. Thomas, et aE.,"O note two impor-
tant criteria in extrapolating experimental
results to humans.

b First, the pharmacologic pattern for the
pesticide should be the same in humans as
in the animal model. This is difficult to
achieve because information on absorption,
distribution, biotransformation and excre-
tion for the chemical of interest is rarely
available in both humans and the animal
model.

b Second, the human end point of interest
must be appropriate for the species
selected.

NEUROTOXIC EFFECTS

The nervous system of the pest is the tar-
get for many pesticides, so the fact that
there are acute neurotoxic effects in
humans is not surprising. Anecdotal case
reports and epidemiologic studies also
suggest that some neurologic symptoms
may persist for years.`l

Chronic effects observed include tremors,
anorexia, anemia, muscular weakness,
hyperexcitability, EEG pattern changes,
insomnia, irritability, convulsions,
headache, dizziness, and depression.
These occur from various insecticide class-

es including organochlorines, organo-
phosphates, and carbamates.S1

Many of the above symptoms developed
among workers with prolonged exposure to
Kepone (chlordecone) in the Hopewell
incident.s2 The symptoms gradually disap-
peared over an 18-month period, but symp-
toms persisted after several years in seven
of the 23 most severely affected patients.n

Less information is available concerning
neurotoxic effects from herbicide exposure.
Neuromuscular rigidity has been observed
in rats after phenoxyacid exposure (2,4-D
and MCPA)SIV 55 and peripheral nerve con-
duction velocities were slowed among
workers engaged in the manufacture of
2,4-D and 2,4,5-T.=

Other nervous system conditions may be
associated with pesticide exposure. A case
report of Guillain-Barre syndrome noted
recent skin exposure to the cotton de-
foliant, merphosn

An association with spraying of pesticides
was reported in a case-control study of
idiopathic Parkinson's disease.JB Risk of
Parkinson's disease was also associated
with longer duration farming and exposure
to pesticides in a study in Hong Kong.s

In another case-control study, however, it
was associated with a rural residence and
drinking well water, but not with use of
pesticides."0 The subjective end points
noted in most human studies of neurologic
conditions make epidemiologic investiga-
tions difficult.

Evaluation of these end points is generally
not possible in animals. Closing the gap
between the two approaches is critical for
a thorough evaluation of neurotoxic effects
of chronic pesticide exposure.

236                                   Papers and Proceedings


REPRODUCTIVE EFFECTS

Mattison et al. classify reproductive
toxicants as direct-acting or indirect-
acting.6l Direct-acting toxicants may

increased estrone metabolisms by liver
microsomal enzymes by lindane, reduced
egg production by organophosphates, and
reduced fertility by carbamates.

resemble a biologically important molecule  CONCLUSIONS
and function as agonists or antagonists in
the reproductive process.         Experimental and epidemiologic inves-
                   tigations indicate that pesticides can cause
They may also have direct effects because  a variety of adverse effects including car-
of their chemical reactivity. Most     cinogenicity, immunotoxicity, neurotoxicity,
chemically-reactive substances are      and reproductive
cytotoxic, carcinogenic, or mutagenic.    toxicity. From this brief review several
                    points stand out.
Indirect-acting reproductive toxicants
include chemicals that must be meta-    b First, the carcinogenicity of pesticides
bolized to produce effects, those that inter-  has been more thoroughly evaluated than
fere with critical enzyme systems, or those  other toxic effects and approximately 45
that enhance or suppress secretion or    percent of the chemicals tested had an
clearance of critical control chemicals.    effect in at least one sex of one species in
Some chemicals may act both directly and  NCI-NTP bioassays. If this experience is
indirectly. For example, activities for or-   relevant to other end points, the potential
ganochlorine insecticides are suspected to  for any type of adverse outcome from
act directly through estrogen receptors and  pesticide exposure could be considerable.
indirectly through prohormone hepatic
induction.                b Second, the specific pesticides that are
                  positive in the various toxicologic tests do
Reproductive effects of specific pesticides  not appear to be restricted to a few
have recently been reviewed by Mattison et  chemical classes. Effects are noted from
al., 1990."' Adverse outcomes in experi-   insecticides (organochlorines, or-
mental and/or epidemiologic investigations  ganophosphates, carbamates, and pyreth-
have been reported for DBCP, chlorde-   rins), herbicides, and fungicides.
cone, ethylene dibromide, and carbaryl in

males and DDT, chlordecone, lindane, or-  b Third, adverse outcomes have been
~~~a~~sosphates, and carbamates among   noted in epidemiologic, as well as ex-

       .                perimental investigations, indicating that
                        humans are also at risk.

Effects among males have included disrup-
tion of spermatogenesis by DBCP, reduced  RECOMMENDATIONS
sperm motility and viability by chlorde-
cone, abnormal sperm morphology and    1. Given the evidence for adverse health
sterility by ethylene dibromide, and sperm  outcomes from pesticides, enhanced efforts
abnormalities by carbaryl. In animals,    are needed to control exposures in agricul-
studies have noted reduced egg shell thick-  ture and elsewhere.
nesses from DDT, reduced egg production
and number of offspring from chlordecone,

An Overview of Potential Health Hazards among Farmers from Use of Pesticides, May 1, 1991

Surgeon General's Conference on AgriClJkUral Safety and Health - 1991               237


Research - Chemical and Biological Hazards

2. More thorough evaluations (experime-
ntal and epidemiologic) are needed to
more fully characterize the potential ad-
verse effects that may occur from pesticide
exposures.

3. Epidemiologic investigations must focus
on exposures to specific pesticides. This
will require detailed exposure assessment
procedures to characterize the type and
intensity of exposures.

4. Studies of farm populations should
receive a high priority given the
widespread use of pesticides in agriculture
and the potential for exposure among

farmers and farmer laborers, and their
dependents.

Retrospective designs can be used to ad-
dress specific questions, but prospective
studies should also be initiated. Prospec-
tive investigations provide the opportunity
to obtain information on exposure as it
occurs, which would eliminate the potential
for response bias and would minimize
exposure misclassification. Once exposures
are well characterized, prospective designs
can also be used to evaluate a number of
adverse health outcomes, a highly efficient
approach in these times of funding
limitations.0

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An Overview of Potential Health Hazards among Farmers from Use of Pesticides, May 1, 1991

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21. Doll R, Peto R. The causes of cancer: Quantitative estimates of avoidable risks of cancer in the United
States today. JNCI 66: 1191-1308, 1981.

22. IARC (International Agency for Research on Cancer): IARC Monographs on the Evaluation of the
Carcinogenic Risk of Chemicals to Humans. Occupational Exposure in Insecticide Application and Some
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23. Axelson 0. Pesticides and cancer risks in agriculture. Med oncol Tumor Pharmacother 4: 207-217, 1987.

24. Zahm SH, Blair A, Holmes FF, Boysen CD, Robe1 RJ. A case-referent study of soft-tissue sarcoma and
Hodgkin's disease - farming and insecticide use. Stand J Work Environ Health 14: 224-230, 1988.

25. Zahm SH, Weisenburger DD, Babbitt PA, Saal RC, Vaught JB, Cantor KP, Blair A. A case-control
study of non-Hodkgin's lymphoma and the herbicide &4-dichlorophenoxyacetic acid (2,4-D) in eastern
Nebraska. Epidemiology 1:349-356, 1990.

26. Brown LM, Blair A, Gibson R, Everett GD, Cantor KP, Schuman LM, Burmeister LF, Van Lier SF,
Dick F. Pesticide exposures and other agricultural risk factors for leukemia among men in Iowa and
Minnesota. Cancer Res 50: 6585-6591, 1990.

27. Woods JS, Polissar L, Severson RK, Heuser LS, Rulander BG. Soft tissue sarcoma and non-Hodgkin's
lymphoma in relation to phenoxyherbicide and chlorinated phenol exposure in western Washington. JNCI
78: 899-910, 1987.

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Research - Chemical and Biological Hazards

28. Flodin U, Frederiksson M, Persson B, Axelson 0. Chronic lymphatic leukemia and engine exhausts, fresh
wood, and DDT: A case-referent study. Br J Ind Med 45: 33-38, 1988.

29. Hoar SK, Blair A, Holmes FF, Boysen CD, Robe1 RJ, Hoover RN, Fraumeni JF Jr. Agricultural
herbicide use and risk of lymphoma and soft-tissue sarcoma. JAMA 256: 1141-1147, 1986.

30. Hardell L, E&son M, Lenner P, Lungren E. Malignant lymphoma and exposure to chemicals,
especially organic solvents, chlorophenols, and phenoxy acids: A case-control study. Br J Cancer 43:
169--176,1981.

31. Persson B, Dahlander A, Fredriksson M, Brage HN, Ohlson CG, Axelson 0. Malignant lymphoma and
occupational exposures. Br J Ind Med 46: 516-520, 1989.

32. Wigle DT, Semenciw RM, Wilkins K, Riedel D, Ritter L, Morrison HI, Mao Y. Mortality study of
Canadian male farm operators: Non-Hodgkin's lymphoma mortality and agricultural practices in
Saskatchewan. JNCI 82: 575-582, 1990 .

33. Bond GG, Wetterstroem NH, Roush GJ, McLaren EA, Lipps TE, Cook RR. Cause-specific mortality
among employees engaged in the manufacture, formulation, or packaging of 2,4dichlorophenoxyacetic
acid and related salts. Br J Ind Med 45: 98-105, 1988.

34. Hardell L, Sandstrom A. Case-control study: soft-tissue sarcoma and exposure to phenoxyacetic acids
and chlorophenols. Br J Cancer 39: 711-717, 1979.

35. Eriksson M, Hardell L, Berg NO, Moller T, Axelson 0. Soft tissue sarcomas and exposure to chemical
substances: A case referent study. Br J Ittd Med 38: 27-33, 1981.

36. Vineis P, Terracini B, Ciccone G, Cignetti A, Colombo E, Bonna A, Maffi L, Pisa R, Ricci P, Zanini E,
Comba P. Phenoxy herbicides and soft-tissue sarcomas in female rice weeders: A population-based case-
referent study. Stand J Work Environment Health 13: 9-17, 1986.

37. Lynge E. A follow-up study of cancer incidence among workers in manufacture of phenoxy herbicides in
Denmark. Br J Cancer 52: 259-270, 1985.

38. Fingerhut MA, Halperin WE, Marlow DA, Piacitelli LA, Honchar PA, Sweeney MH, Greife AL, Dill
PA, Steenland R, Suruda AJ. Cancer mortality in workers exposed to 2,3,7,8tetrachlorodibenz-p-dioxin.
N Engi J Med 324: 212-218, 1991.

39. Thomas PT, Busse WW, Kerkvliet NI, Luster MI, Munson AE, Murray M, Roberts D, Robinson M,
Silkworth J, Sjoblad R, Smialowicz R. Immunologic effects. In: The Effects of Pesticides on Human
Health. (Eds.) Baker SR, Wilkinson CF. Adv Modern Environ Toxic01 Vol XVIII. Princeton Sci Pub1
Co, Inc. Princeton, NJ: 261-295, 1990.

40. Thomas PT, Faith RE. Adult and prenatal toxicity induced by halogenated aromatic hydrocarbons. In:
Immunotoxicology and Immunophatmacofogy. (Eds.) Dean J, Luster M, Munson A, and Amos H.
Raven Press, New York, NY, 1985.

41. Lee TP, Moscati R, Park BH. Effects of pesticides on human leukocyte functions. Res Cotnm Ghan
Palhol Pharmacol23:597-609, 1979.

42. Sullivan JB Jr. Immunological alterations and chemical exposure. Clinical Tox 27: 311-343, 1989.

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An Overview of Potential Health Hazards among Farmers from Use of Pesticides, May 1, 1991

43. Fiore M, Ander CHA, Hong R, Golubjatnikov R, Seiser JE, Nordstrom D, Han&an L, Belluck D.
Chronic exposure to aldicarb-contaminated groundwater and human immune function. Environ Res 41:
633-645, 1986.

44. Olson LJ, Erickson BJ, Hinsdill RD, Wyman JA, Porter WI', Binning LK, Bidgood RC, Nordheim EV.
Aldicarb immunomodulation in mice: An inverse dose-response to parts per billion levels in drinking
water. Arch Environ Confam Toxkoi 16: 433-439, 1987.

45. Thomas PT, Ratajczak HV, Eisenberg WC, Furedi-Machacek M, Ketels KV, Barbera PW. Evaluation of
host resistance and immunity in mice exposed to the carbamate pesticide aldicarb. Fundam Appr Toxicol
9: 82-89, 1987.

46. Hoover R, Fraumeni JF Jr. Risk of cancer in renal transplant recipients. Lancet 2: 55-57, 1973.

47. Filipovich AH, Spector BD, Kersey J. Immunodeficiency in humans as a risk factor in the development
of malignancy. Prev Med 9: 252-259, 1980.

48. Blohme I, Brynger H. Malignant disease in renal transplant patients. Transplanfarion 39: 23-25, 1985.

49. Penn I. Immunosuppression and skin cancer. Clin Plast Surg 7: 361, 1980.

50. Kinlen L, Doll R, Peto J. The incidence of tumors in human transplant recipients. Transplant Proc 15:
1039-1042, 1983.

51. Ecobichon DJ, Davies JE, Doull J, Ehrich M, Joy R. McHillan D, MacPhail R, Reiter LW, Slikker W
Jr, and Tilson H. Neurotoxic effects of pesticides. In: The Ejfecti OfPesticides on Human Health. (Eds.)
Baker SR, Wilkinson CF. Adv Modern Environ Toxic01 Vol XVIII. Princeton Sci Pub1 Co, Inc.
Princeton, NJ: 131-199, 1990.

52. Taylor JR, Selhorst JB, Houff SA, Martinez AJ. Chlordecone intoxication in man. I. Chemical
observations. Neurology 28: 626-630, 1978.

53. Taylor JR. Neurological manifestations in humans exposed to chlordecone: Follow-up results.
Neurotoxicology 6: 231-236, 1985.

54. Squib RE, T&on HA, Mitchell CL. Neurobehavioral assessment of 2,4-dichlorophenoxyacetic acid (2,4-
D) in rats. Neurobehav. Toxicoi Teratol5: 331-335, 1983.

55. Elo H, Ylitalo P. Distribution of 2-methyl-4 chlorophenoxyacetic acid and 2,4-dichlorophenoxyacetic acid
in male rats: Evidence for the involvement of the central nervous system in their toxicity. Toxicol Appl
Phamacol51: 439-446, 1979.

56. Singer R, Moses M, Valciukas J, Lilis R, Selikoff IJ. Nerve conduction velocity studies of workers
employed in the manufacture of phenoxy herbicides. Environ Res 29: 297-311, 1982.

57. Fisher JR. Guillain-Barr& syndrome following organophosphate poisoning. JAMA 238: 1950-1951, 1977.

58. Golbe LI, Farrell TM, Davis PH. Follow-up study of early lie protective and risk factors in Parkinson's
disease. Movement Disorders 5: 66-70, 1990.

59. Ho SC, Woo J, Lee CM. Epidemiologic study of Parkinson's disease in Hong Kong. Neurology 39: 1314-
1318, 1989.

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Research - Chemical and Biological Hazards

60. KoIIer W, Vetere-Overfield B, Gray C, Alexander C, Chin T, DolezaI J, Hassanein R, Tanner C.
Environmental risk factors in Parkinson's disease. Neurology 40: 1218-1221, 1990.

61. Mattison DR, BogumiI RJ, Chapin R, Hatch M, Hendricks A, JarreII J, LaBarbera A, Schrader SM,
Selevan S. Reproductive effects of pesticides. In: The Effects of Pesticides on Human Health7 (Eds.)
Baker SR, Wilkihson CF. Adv Modern Environ Toxic01 Vol XVIII. Princeton Sci Pub1 Co, Inc.
Princeton, NJ: 1297-1389, 1990.

62. Godon D, Lajoie P, Thouez J, Nadeau D. Pesticides et cancers en milieu ruraI agricole au Quebec:
Interpretation geographique. Sot Sci Med 29: 819-833, 1989.

242

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Surgeon General's Confemnce on Agricultuml Safety and Health
FM&&FE 2000 . A National Coalition for Local Action
Convened by the National Institute f0f Occupational Safety and Health
April 30 - May 3, 7991, Des Moines, Iowa

GASES, VAPORS, LIQUIDS, AND DRUGS

  By WZliam Popendorf, Ph.D., C.I.H.
Institute of Agricultural Medicine, University of Iowa

INTRODUCTION

A wide range of gaseous and liquid
hazards exists in agriculture (Table I).l*'
Virtually all of the gaseous hazards from
which we can anticipate health effects exist
in one form or another in general industry.

While we know of their existence in
agriculture, only a few of these hazards
have been surveyed in farm settings. We
do not know how frequently (on the aver-
age) farmers are exposed to individual
agents. We do not know the range of con-
centrations of such exposures. We do not
know the extent of the health effects ex-
cept for the occasional severe case report
or fatality.

And if we really did know these para-
meters, we face yet another challenge; how
to translate them into "agricultural

hygiene," the industrial hygiene paradigm
of "anticipation, recognition, evaluation,
and control" learned in general industry
over the past 50 years., As we begin to
apply this paradigm, another challenge is
to understand the limitations of rote
transfer-ml of this paradigm from general
industry to agriculture without also
understanding its nature and its culture.

This presentation will begin with a review
of some of these agents, their sources on
the farm, and some of the limitations of
the traditional hierarchy of controlling
these hazards either at their source, along
the pathway of the exposure route, or at
the receiver (in this case the farmer or
farm worker). A discussion of health ef-
fects will be minimized except for agents
that are by-and-large unique to agriculture.

Table I. Typical Toxic Agricultural Liquids, Gases, and Vapors.

Ammonia  ............................. from urine, urea, and anhydrous
Carbon dioxide ...................... animal respiration and combustion
Carbon monoxide ................... combustion sources
Hydrogen sulfide .................... manure gas
Nitrogen dioxide ..................... from fresh silage
Oxygen Depletion ................... asphyxiation in confined spaces
Pesticides ............................. primarily dermal absorption hazards except fumigants
Welding ............................... fumes and gases
Fuel storage .......................... leaks and fires
Fuel and waste oil ................... skin cancers and dermatitis
Ltquified Propane [LPI gas ........ fires
Liquified anhydrous ammonia ..... dermal injury

Surgeon General's Conference on Agricultural Safety and Health - 1991               243


Research - Chemical and Blologlcal Hazards

DEFINITIONS

I feel obliged to define a few terms and
concepts ingrained into industrial hygiene
folklore. The first (Figure 1) is the para-
digm of anticipation, recognition, evalua-
tion, and control. Historically, this process
began with the recognition of adverse
health effects existent within a working
population.

Anticipation Is the prospective application of
dose-response knowledge generated either
in the laboratory or in other industries.

Recognition requires the commitment of
farmers, interested farm groups, and
governmental agencies to survey both the
farming environment and the health status of
farmers.

Evaluation must develop new ways to
interpret surveillance data from the farm set-
ting for the agricultural population.

Control includes not only "hazard com-
munication" but also modified sources and
interruptions in the pathways of exposure
before the farmer, with or without personal
protection, is dosed.

1

Figure 1. The Agricultural Hygiene Paradigm.

Today, we can anticipate (and hopefully
avoid) adverse health effects based on
toxicology or prior experiences in other
work settings. To evaluate the degree of
risk, we have developed a system of "per-
formance based" exposure limits guidelines
(guidelines called Threshold Limit Values
[TLVs] and their regulatory equivalents
called Permissible Exposure Limits
[PELs]), the goal of which is to prevent

244

adverse health effects by keeping expo-
sures and doses to acceptable low levels
without specifying the method or "work
practices" to achieve those levels.

The second is a concept that adverse
health effects are the culmination of an
often-complex chain of events beginning
with the agent emanating into the working
environment from a sometimes nebulous
source and traveling through a physical
pathway to create either an airborne,
dermal, or even oral dose; the dose is
generally dependant upon the duration of
exposure and the degree of personal pro-
tection being used by the worker; the
agent may act at the site of contact or be
absorbed into the body and be transported
to some biological target organ where it
acts toxicologically to create a clinically
identifiable effect.

Over the years, a hierarchy of control
options has been inculcated into the
profession whereby controlling the source
is the preferred option, controlling the
pathway between the source and worker is
the second option, and controlling the re-
ceiver is the third and least preferred op-
tion. Hygienists believe that respirators or
other forms of personal protective equip-
ment are not a quick cure-all, contrary to
popular belief. And even when they are
recommended, good practice dictates (and
OSHA now requires) that the respirator
should be selected based on the measured
level of exposure.

GASES AND VAPORS

The following history of silo gas is
representative of the fragmented progres-
sion of anticipation, recognition, evalua-
tion, and control of a potentially common
agricultural health hazard.

Papers and Proceedings


Gases, Vapors, Liquids, and Drugs, May 1, 1991

Occupational hazards associated with silo
gas were first reported in 1914 via case
studies of four fatalities of farmers working
in and among their freshly filled silos.
Their deaths were attributed to carbon
dioxide (CO,).

It was not until the 1950's (30 to 40 years
later) that investigations revealed the
presence and importance of nitrogen
dioxide (N01).46 The major portion of
toxic NO, appears to be produced from
organic nitrates, aggravated by the addition
of heavy nitrate fertilizer and/or drought
conditions.6

The process of NO, production begins
within hours of ensilage, peaks in three to
seven days, but may last for up to two
weeks. Levels of NO, as high as 200 ppm
have been reported seven days after fill-
ing;" this is well over its current TLV of 3
ppm (with a 5 ppm STEL).

Our broad understanding of the magnitude
and frequency of this hazard is limited by a
lack of systematic environmental surveil-
lance and poor reporting of farm injuries
and fatalities. Our understanding of its
overall impact on the health of farmers is
further limited by the difficulty in diag-
nosing nonfatal cases of the disease due to
the multiple and usually latent phases of
its clinical manifestations.`l' Thus, the
severe and fatal cases of silo fillers' disease
that are reported probably represent the
tip of the proverbial iceberg.

A few systematic surveys have recently
been made of chronic gaseous hazards in
modern semi-enclosed animal production
buildings. Mulhausen" found that air
quality in poultry barns frequently ex-
ceeded exposure limits of 25 ppm for am-
monia (NH,) during fall and winter and

sometimes even exceeded its S'I'EL of 35
ppm; H,S was undetected. Donham

et al." l3 surveyed similar swine barns and
found 50 percent exceeded the TLC for
ammonia; many of these buildings also ex-
ceeded the TLC for CO, H,S, and CO
(from un-vented space heaters).

Source: urine (urea)-wet floors, slats,
    gutters, etc.

Anticipated Health Hazards:

Irritating to eyes, nose,
trachea (wet body parts) . . . . . . . . . . IO-15 ppm

TLV = recommended exposure
limit (for gas) . . . . . . . . . . . . . . . . . . . . . . 25 ppm

Absorbed into an aerosol may provoke
bronchitis, asthma, or other
pulmonary effects . . . . . . . . . . . . . . . . , ~20 ppm

Figure 2. Ammonia (NH,).

At these concentrations, ammonia by itself
would only be a strong irritant to the eyes,
nose, and throat. However, in both poultry
and swine farm settings, it may be impor-
tant to consider the simultaneous presence
of both ammonia and organic dust aerosols
at levels often in excess of 5 mg/m3. The
hypothesis here is that the pulmonary
damage caused by ammonia could be con-
siderably greater if the gas were adsorbed
onto a respirable-sized aerosol (Figure 2).

In addition to hydrogen sulfide, mercap-
tans and organic acids (such as methyl and
ethyl-mercaptan, carbonyl-sulfide, skatole,
and propionic, butyric, and valeric acids)
have been identified in the gases
emanating from the anaerobic decay of
manure typically stored in a pit under most

Surgeon General's Conference on Agricultural Safety and Health - 1991               245


Research - Chemical and Biological Hazards

hog and some dairy barns.14dU It should be
acknowledged that under normal barn
conditions, hydrogen sulfide is not at levels
of great health concern (Figure ,).I2 I3

Source: anaerobic manure digestion

Anticipated Health Hazards:

Threshold of odor detection . . . . . . 0.1-0.2 ppm
Offensive odor . . , . . . . . . . . . . . . . . . . . . 3-5 ppm
TLV = recommended exposure
limit , , . . . , . . . , , . . . . . . . . . . . . . . . . . . 10 ppm
Olfactory paralysis
(cannot be smelled) . . . . . . . . . . .25-100 ppm
Serious eye injury (gas eye) . . . . .50-100 ppm
Bronchitis (dry cough) . . . . . . . . . loo-150 ppm
Pneumonitis and pulmonary
edema . , . . , , . . . . . . . . . . . . . . . . 200500 ppm
Rapid respiratory arrest (death) . . > 1000 ppm

Figure 3. Hydrogen Sulfide (H,S).

However, when the manure is agitated
prior to pump-out to be returned to the
fields as fertilizer, it is rapidly released
into the air above the frothing liquid.lsW19
During agitation, the author has measured
levels of H,S as high as 300 ppm at pig
breathing height and 1500 ppm in the pit
(Figure 4).

o Methyl-mercaptan  o Propionic acid
o Ethyl-mercaptan   o Butyric acid
o Carbonyl-sulfide   o Valerie acid
o Skatole

Figure 4. Mercaptans and Organic Acids As-
sociated with Hydrogen Sulfide from Manure.

Manure gas deaths often involve multiple
victims during futile rescue attempts.17,20
As was the case with silo gas, manure gas
deaths even as recently as 1989 are

sometimes m&diagnosed as asphyxiation
from methane.M

Control of agricultural respiratory hazards
should rely first on reduction at the source,
second on ventilation or some other
physical barrier to its movement, and third
on personal protection. Control of the
source of most of the above agents will
require further research before the process
of gas generation is sufficiently understood
to be reduced or avoided.

High rates of ventilation of farm shops or
animal confinement building is often
resisted by operators who prefer to
conserve heat in cold winter climates, and
if too much ventilation were installed
without consideration of make-up air re-
quirements, high levels of CO could be
drawn back down heater exhaust vents
(Figure 5).

Source: improperly adjusted heaters or no
    make-up air

Anticipated Health Hazards:

TLV = recommended exposure
limit . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 50 ppm
Induces spontaneous abortions
in swine . . . . . . . . . . . . . . . . . . . . 100-l 50 ppm
Asphyxiation dependent upon duration
of exposure . . . . . . . . (2-3 hours at 500 ppm)
            cl5 mins >2000 ppm

Figure 5. Carbon Monoxide (CO).

As in any other industry, the use of
respirators should be considered a temp-
orary and supplemental protection. In agri-
culture there are no trained persons avail-
able to assist in the selection, fit, or main-
tenance of respirators. Thus, when pur-
chased at all, respirators are selected

246

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without knowledge of measured
levels of exposure and often
without even the benefit of an
adequate "work practices"
evaluation as shall be discussed
below.

Table II. Major Groups of Field-Use Agricultural Pesticides.

INSECTICIDES

LIQUIDS

Pesticides are formulated as
solids (such as granules and
wettable powders), liquids, and
gases and vapors (mostly
fumigants). Pesticides can
present a hazard to applica-
tors,21-P to harvesters re-entering
a sprayed field, 24* 25 and to rural
residents via air, water, and
even food contamination.s28

Organophospates . . . . . . . . . . . . . . . Counter, Parathion, Guthion,
                Lorsban, Rabon
Carbamate . . . . . . . . .._........ . . ..Temik, Furidan, Lannate, Sevin
Organochlorines . . . . . . . . . . . . . . , . , Dieldrin, Lindane, Chlordane
HERBICIDES
Phenoxy-aiiphatic acids . . . . . ...2.4-D. 2,4,5-T, Trioxone
Bipyridyis . . . . . . . . . . . . . . . . . . . . . _ Paraquat, Diquat
Triazines . . . . . . . . . . . . . . . . . . . . . . . . . . Atrasine, Blasex, AAtrex
OTHER/MISCELLANEOUS
Thiocarbamates (fungicides) . Thiram, AAtack, Mabam,
                Maneb, Zineb

Arsenicals (herbicides) , . . . . . Paris Green, Cacodyiic acid
Acentaniiides (herbicides) . . . . . Alachlor, Lasso, Ramrod
Dicarboximides (fungicides) . . . Difolitan, Captan
Dinitrotoluidine (herbicides) . . . Amex, Prowl, Treflan

Toxicologically, the major field-

use pesticides can be broken down into six
major chemical groups shown in Table II.
Most of these agricultural chemicals
present dermal hazards either from ab-
sorption directly through intact skin and/or
from dermatitis. Some of these insect-
icides are also used indoors, especially in
greenhouses were exposure is often
higher,.

Gases, Vapors, Liquids, and Drugs, May 1, 1991

Common Commercial Names

There are two additional groups of non-
field agricultural chemicals: one is
fumigants (such as phosphine [usually
aluminum phosphide or Phostoxin] or a
volatile organic like carbon disulfide or
ethylene dichloride) used in produce
storage areas, and the other is disinfectants
(such as chlorine, quaternary ammonia
compounds, organic iodides, and cresol-
based compounds) used in indoor animal
production facilities.' Certain of these
chemicals present respiratory hazards par-
ticularly when used in combinations; other
of these liquid chemicals present a risk of
contact or an allergic dermatitis.30

While a review of pesticide toxicities is
being presented separately, they are
presented here because they demonstrate
an approach to anticipation, recognition,
evaluation, and control quite different
from general industry. Some level of an-
ticipation was available from the time of
registration, but much of that interest was
directed toward consumers rather than
users who are exposed at much higher lev-
els.

Given that starting point, it is unfortunate
that the recognition of hazards to users has
often been a protracted process, in some
ways no better than the history of many
chemicals used in general industry. How-
ever, evaluation of exposure, when it final-
ly started to be conducted, was not site nor
user specific but was conducted in re-
sponse to more recent EPA pesticide regis-
tration requirements.

EPA then promulgated what amounts to a
"use practices standard" in the form of

Surgeon General's Conference on Agricultural Safety and Health - 1991               247


Research - Chemical and Biological Hazards

label instructions, which specify the ways
the chemical can be safely and legally
used. The implication is that if all users
follow these instructions, exposure will be
sufficiently low to prevent adverse health
effects. This process contrasts sharply with
general industry where employers are ex-
pected to "assure a workplace free from
recognized hazards."

Controls under these circumstances have
also differed from general industry. It can
be argued that the registration process is
itself a form of controlling the source,
screening out chemicals deemed too hazar-
dous for agricultural use and restricting
certain others to "licensed users."

In that sense, a form of hazard com-
munication was adopted by agriculture a
little before general industry. However,
the EPA registration and labelling process
has yet to address the machinery control-
ling the pathway of exposure.

When it comes to personal protection,
control has for a long time been mis-
directed at airborne versus the dermal
route of exposure; and those respiratory
controls which are specified, were estab-
lished without a decision logic common to
general industry for over 30 years3'p3'. I am
happy to report that EPA is currently
developing a respirator selection decision
logic at least consistent with a "use prac-
tices standard."

One might ask why a "use practices stan-
dard" versus a "performance standard"
approach used in agriculture. The one
asking the question must not be a farmer.

Even if the administrative and support
structure were in place to conduct on-site
monitoring at each farm or "place of
employment," the activities, working en-

vironments, and chemical exposure levels
in most agricultural settings vary suf-
ficiently by season, day, and even by hour
as to make such measurements moot,
which is not to say that measurements and
even performance standards have no place
in agriculture.

For instance, work in animal production
facilities is amenable to the application of
traditional TLVs, environmental
monitoring, and respirator selection
criteria. "Use practice standards" have
their own limitations; they must account
for many variables, thus often making
them overly restrictive conducive to low
compliance. It remains a challenge for the
future to define the conditions favoring
either form of standard or to determine if
either is even adequate.

The other category of agricultural
chemicals is fertilizers. Anhydrous am-
monia is the most heavily used fertilizer in
production agriculture. Anhydrous am-
monia is hazardous to the skin and
especially to the eyes because it is highly
hygroscopic, highly caustic, and extremely
cold (-280F under pressure).

Almost any eye contact with this chemical
will result in permanent blindness." In-
haling high concentrations of ammonia can
result is severe damage to the upper
respiratory tract, resulting in bronchiectasis
as a possible sequela."

Most of the occupational injuries from
anhydrous ammonia occur because of
faulty couplings, bleeder valves, shutyoff
valves, broken hoses, or plugged applicator
tips. In addition to an established program
of preventive maintenance, a pro-active
hazard communication for both commer-
cial and private applicators is essential to
establish consistent wearing of eye protec-

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Gases, Vapors, Liquids, and Drugs, May 1, 1991

Table III. Skin Conditions of Agricultural Workers (adapted from
reference 2).

Classification of Skin Condition

Irritant contact dermatitis . . . . . . . . . . . . . . . . .

Allergic contact dermatitis . . . . . . ._. . . . .

Photo-contact dermatitis . . . . , . . , . . . . . . . . .

Sun-induced dermatoses .................
Infectious dermatoses .....................
Heat-induced dermatoses ................
Arthropod-induced dermatoses ..........

Aaents (examblesl

ammonia fertilizers
animal feed additiies
vegetable crops and bulb plants
insecticides, herbicides, and
fumigants
herbicides and insecticides
antibiotic feed additives
plants
creosota
feed additive
plants containing furocoumarins
sunlight
cattle, swine, and sheep
moist and hot environments
chiggers, bees, and wasps

tion and ensuring the availability of clean
water to flush eyes and skin in case of
contact.

In addition to their fire hazard and intrin-
sic toxicity, many of the liquids involved in
agriculture can produce dermatitis (Table
III). Compared to other occupational
groups, farmers have a proportionately
higher prevalence of skin diseases.","

Irritant contact dermatitis is perhaps the
most common type of agricultural der-
matoses.3539 Irritant substances are ubi-
quitous and include ammonia fertilizers,
several pesticides, soaps, petroleum
products, and solvents. Avoidance
schemes must include work practices to
eliminate or reduce exposure to the most
irritative substances and/or the use of
personal protection equipment.
Allergic contact dermatitis is typified by
Poison ivy or poison oak reactions. These
are exquisite sensitizers as are certain

herbicides and pes-
ticides? These reactions
are more difficult to
control, because suscep-
tible farmers are ex-
quisitely sensitive to very
small amounts of offen-
ding liquids.

VETERINARY DRUGS

Veterinary drugs are
broadly divided into two
classes of biologicals and
antibiotics (Table IV).
Biologicals are made
from living products to
enhance the immunity of
an animal to a specific
infectious disease or
diseases.

Users of biologicals are at risk of either
accidental inoculation or splashing the
product into the eyes, mucous membrane,
or broken skin. Users at risk include not
only veterinarians and their assistants, but
also farmers, ranchers, and their
employees, except for certain diseases for
which a government-regulated control
program is in effect (e.g., brucellosis,
rabies, pseudorabies).

The most frequent reports of occupational
illnesses associated with biologicals involve
veterinarians, whether splashing brucellosis
strain 19 in their eyes or accidental
inoculating themselves. Symptoms may
include infection, inflammation, severe
localized swelling and pain, and/or an
allergic reaction. The infection mimics the
acute infection seen from acquisition of
the disease directly from either cattle or
swine. Disability may last for days to
weeks in the worst cases."'

Surgeon General's Conference on Agricultural Safety and Health - 1991

249


Research - Chemical and Biological Hazards

Table IV. Veterinary Drugs Potentially
Hazardous to Users.

Biologicals

Brucellosis strain 19
Newcastle disease vaccine
Contagious exthyma (orf) vaccine
Jhone's disease bacterin
Escherichia co/i bacterins
Erysipelas vaccines

Antibiotics

Penicillin
Tetracycline
Sulfamethazine
Erythromycin
Virginiamycin

Other products that have been associated
with occupational illnesses include New-
castle disease vaccine, contagious ecthyma
vaccine, Jhone's disease bacterin, ES-
clzetichia coli bacterins, and erysipelas
vaccines. Newcastle disease and con-
tagious ecthyma (orf) vaccines are live
products used in chickens and sheep,
respectively.

Workers may contaminate their eyes with
Newcastle vaccine as it is being applied
inside poultry buildings via a nebulizer,
resulting in a moderate conjunctivitis with
influenza-like systemic symptoms. Orf vac-
cine can cause the same pox-like lesions at
the site of inoculation as a naturally ac-
quired infection.

Both of these diseases are self-limited and
disability will only last for a few days,
unless the orf lesions are numerous.41342
Injuries induced by the bacterins for
Jhone's and E. Coli, and by most erysipelas

vaccines are limited to the inflammatory
response induced by the adjuvants.

Control of these hazards again resides
largely in "use practice standards," good
animal handling techniques and facilities to
prevent the uncontrolled and untimely
movements of stressed animals." The use
of pneumatic syringes, lock-on needle
hubs, and multiple dose syringes will also
help reduce injuries.

Eye protection is indicated in many instan-
ces. A full-face respirator is recommended
while aerosolizing vaccines such as New-
castle, but the other components of a full
respirator program are rarely instituted.

Antibiotics are products derived or syn-
thesized from living organisms, mainly
mold species of the genus streptowtyces.
Antibiotics are used to treat infectious
diseases therapeutically or to improve the
rate of gain and feed efficiency in cattle,
swine, and poultry.

Again not only veterinarians but also live-
stock producers and feed manufactures
and formulators are exposed to these
agents via aerosols of antibiotic-containing
feeds within livestock buildings or via
aerosols or direct contact while preparing
feeds either on the farm or in feed manu-
facturing plants. The two main occupa-
tional hazards are allergic reactions and
the development of antibiotic-resistant
infections.

The main products used as feed additives
include penicillin, tetracycline, sul-
famethazine, erythromycin, and vir-
giniamycin. These same products plus
many more are used therapeutically. Pen-
icillin is the primary agent that may induce
an allergic reaction manifest in the form of
a skin reaction from direct contact, or

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