WORLD HEALTH ORGANIZATION FOOD AND AGRICULTURE
ORGANIZATION
ORGANISATION MONDIALE DE LA SANTE ORGANISATION POUR L'ALIMENTATION
ET L'AGRICULTURE
WHO/VBC/DS/87.73
ORIGINAL: ENGLISH
Distr.: LIMITED
DATA SHEETS ON PESTICIDES No. 73
ZIRAM
It must be noted that the issue of a Data Sheet for a
particular pesticide does not imply endorsement of the pesticide by
WHO or FAO for any particular use, or exclude its use for other
purposes not stated. While the information provided is believed to
be accurate according to data available at the time when the sheet
was compiled, neither WHO nor FAO are responsible for any errors or
omissions, or any consequences therefrom.
The issue of this document does Ce document ne constitue pas une
not constitute formal publication. Il ne doit faire
publication. It should not be l'objet d'aucun compte rendu ou
reviewed, abstracted or quoted résumé ni d'aucune citation sans
without the agreement of the l'autorisation de l'Organisation
Food and Agriculture des Nations Unies pour
Organization of the United l'Alimentation et l'Agriculture
Nations or of the World Health ou de l'Organisation Mondiale de
Organization. la Santé.
CLASSIFICATION:
Primary Use: Fungicide
Secondary Use: Animal repellent
Chemical Group: Dithiocarbamate
1.0 GENERAL INFORMATION
1.1 COMMON NAME
Ziram (ISO, BSI and JMAF; exception West Germany)
1.1.1 Identity:
IUPAC: Zinc dimethyldithiocarbamate
CAS: (T-4)-bis (dimethyldithiocarbamate) zinc
CAS Reg. No.: 137-30-4
Molecular formula: C6H12N2S4Zn
Molecular weight: 305.8
Structural formula:
1.1.2 Synonyms
AaprotectR; AavolexR; AaziraR; Accelerator LR; Aceto
ZDEDR; Aceto ZDMDR; Alcoba ZMR; CarbazincR; Corona
CorozateR; CorozateR; CumanR; CymateR; Drupina 90R; Eptac
1R; ENT 988; Fulcasin (Fuklasin)R; FungostopR; Hermat ZDMR;
HexazirR; Karbam WhiteR; MethasanR; MethazateR;
Methylzimate; Methylzineb; Methylziram; Mexene (apezene)R; Miblam
(capilban)R; MolurameR; MycronilR; NCI-C50442; Pomarsol Z
forteR; ProdaramR; RhodiacidR; Soxinal (Soxinol) PzR;
Tricarbamix Z; TriscabolR; TsimatR; Tsiram; USAF P-2; Vancid
MZ-96R; VulcacureR; Vulkacite (Vulkacit)LR; Weisstaub; Z
75R; Zarlate; ZC (Z-C) sprayR; ZerlateR; ZimateR;
ZincmateR; ZinkcarbamateR; Zirame; ZiramvisR; ZirasanR;
ZirbeckR; Zirex; ZirideR; ZirthaneR; ZitoxR.
1.2 SYNOPSIS
Ziram is a dithiocarbamate fungicide with some insect repellent
properties. It is a metabolic poison of low acute toxicity to
mammals: it may cause skin irritation. It is listed in WHO Hazard
Class III. Ziram is toxic to zinc sensitive plants. It has also been
used extensively in the rubber industry as a promoter of
vulcanization.
1.3 SELECTED PROPERTIES
1.3.1 Physical characteristics
Ziram is a colourless odourless powder which melts at 250°C,
the technical product melts at 240-244°C. It is corrosive to copper
and iron.
1.3.2 Solubility
In water, 65 mg/l at 25°C; it is slightly soluble in ethanol
and diethyl ether, moderately soluble in acetone, and soluble in
dilute alkali, chloroform and carbon disulphide.
1.3.3 Stability
Ziram is stable under normal conditions but decomposes in acid
media. It does not accumulate in soil.
1.3.4 Vapour pressure
Negligible at room temperature.
1.4 AGRICULTURE, HORTICULTURE AND FORESTRY
1.4.1 Common formulations
These include a wettable powder, 300-960 g a.i./kg; a repellent
paste; 370 g a.i./kg with sticker; dusts, 35-75 g a.i./kg; and a
flowable formulation, 479 g a.i./l.
1.4.2 Pests controlled
It may be used as a repellent against Japanese beetles and
cucumber beetles and as a fungicide in the control of several plant
diseases. Aquatic snails may also be controlled effectively
1.4.3 Use pattern
Ziram is used on almonds, apples, apricots, bananas, beans,
beets, blueberries, broccoli, brussel sprouts, cabbage, caneberries,
cauliflower, carrots, cantaloupes, celery, cherries, collards,
cranberries, cucumbers, melons, nectarines, onions, peaches, pears,
pecans, peppers, pumpkins, radishes, squash, spinach, strawberries,
tomatoes, turnips, watermelons and ornamentals. It may be applied at
3-16 kg/ha up to the day of harvest on some crops. It is compatible
with common fungicides and pesticides except those containing copper
or mercury. If plants are difficult to wet, a sticker may be added
to the formulation.
1.4.4 Unintended effects
Ziram is non-phytotoxic except to zinc sensitive crops such as
tobacco and cucurbits at high application rates. It is not known to
be repellent to beneficial insects.
1.5 PUBLIC HEALTH PROGRAMMES
There are no recommended uses.
1.6 HOUSEHOLD USE
There are no recommended uses.
2.0 TOXICOLOGY AND RISKS
2.1 TOXICOLOGY - MAMMALS
2.1.1 Absorption route
Ziram is slowly absorbed from the gastrointestinal tract;
through the intact skin; and by inhalation of spray mist and dusts.
2.1.2 Mode of action
Ziram and other dithiocarbamates are metabolic poisons. Their
acute toxic effects are similar to those of carbon disulfide which
has led to the suggestion that this metabolite, common to all
dithiocarbamates, is the cause of their effects. This is supported
by the observation that most dithiocarbamates of very low acute
toxicity are excreted unmetabolized in the feces following oral
dosing. The exact mode of action is unknown. However, microsomal
injury and cytochrome P-450 injury accompanied by increased heme-
oxygenase activity is a common occurrence with these compounds.
Monoamine oxidase Inhibition, abnormal Vitamin B6 and tryptophane
metabolism and cellular loss of zinc and copper have been implicated
in studies of the biochemical effect. Ziram is not a potent
initiator of thyroid dysfunction among dithiocarbamates and the
effects have not been shown to be dose dependent. The metabolically
generated sulfur inhibits some intracellular enzyme systems.
2.1.3 Excretion products
Although the metabolism and excretion of ziram has not been
extensively studied, insight can be gained from pooled information
from other dithiocarbamate studies. Initial degradation probably
occurs in the gastrointestinal tract where the parent compound is
reduced to the carbamic acid residue which is rapidly absorbed and
metabolized by hepatic enzymes. A portion of the acid may be
excreted, unchanged, as a glucuronide. Further metabolism of the
acid releases CS2 and dimethylamine. A high proportion of the parent
compound may be metabolized to carbon disulfide and the small
portion recovered in blood or in expired air represents only that
portion of the dose not involved in tissue reactions.
Dimethyldithiocarbamate may also be degraded to
dimethylthiocarbamate, sulfate and formaldehyde following
methylation and oxidation reactions in body tissues in general.
Dimethylthiocarbamic acid is excreted as a glucuronide.
2.1.4 Toxicity, single dose
Dermal LD50: No information.
Oral LD50:
Rat (F) 1400 mg/kg b.w.
Mouse 480 mg/kg b.w.
Rabbit 400 mg/kg b.w.
I.P. LD50:
Rat (M,F) 23 mg/kg b.w.
Mouse 73 mg/kg b.w.
I.V. LD50:
Mouse 18 mg/kg b.w.
2.1.5 Toxicity, repeated dose
No mortality or growth retardation in weanling rats followed
oral daily doses of 100 mg/kg b.w. for one month. Normal thyroid
tissues were found in rats ingesting diets containing 0.25% of ziram
for one month.
2.1.6 Dietary studies
Short term: Rats survived dietary levels of 5000 and 2500
mg/kg diet for a month but growth was retarded and there was slight
anaemia. Growth retardation at 500 mg/kg diet was slight.
Convulsions occurred in dogs fed ziram at a rate of 25 mg/kg
b.w./day and some died after five to nine months. Symptomatology,
haematology, urinalysis, organ weights and histology were normal in
dogs fed 5.0 or 0.5 mg/kg b.w./day for one year.
Ziram administered in the diet of female rats at 2.5 mg/kg b.w.
for nine months resulted in decreased antibody formation, phagocytic
activity and complement activity. Lymphatic blastogenic centres in
spleen were also reduced.
Long term: Rats were fed ziram 0, 25, 250 or 2500 mg/kg of
diet for two years. Rats fed 2500 mg/kg suffered retarded growth and
rats fed 250 mg/kg developed atrophic testes
2.1.7 Carcinogenicity
The limited data available does not permit adequate assessment
of the carcinogenic potential of ziram. In the feeding study above,
11 tumours were found in treated rats, three malignant tumours of
pituitary and two thyroid adenomas at highest dose, seven tumours
were found in controls.
In rats, liver and subcutaneous tumours were induced by twice
weekly gavage administration at 70 mg/kg b.w. for 22 months, and to
a lesser extent following a subcutaneous implant of 15 mg/kg b.w.
observed over two months. A low survival rate was a complicating
factor in these studies. In a two year dietary study, 600 mg/kg diet
induced an increase in thyroid C-cell carcinoma in male rats only.
It is possible that a maximum tolerated dose was not achieved in the
dietary study.
In a study on mice, oral administration of ziram from seven
days to 78 weeks of age first by gavage (4.6 mg/kg b.w.) then at 15
mg/kg of diet from weaning age, induced no increase in tumours.
Similarly no oncogenic potential was observed in mice over a six
month period following daily oral administration of 75 mg/kg b.w.
for 20 weeks, nor during 78 weeks of observation following a single
subcutaneous injection of approximately 46 mg/kg b.w. at weaning.
Furthermore, an increased incidence of alveolar/bronchiolar adenomas
was observed only in female mice fed 1200 mg/kg diet. This study was
complicated by an intercurrent Sendai virus infection.
Ziram can react with nitrite under mildly acid conditions to
form N-nitrosodimethylamine, which is carcinogenic in several animal
species.
Mutagenicity: Ziram was mutagenically active in base-
substitution sensitive S. typhimurium strains TA 1535, TA 100, TA
1534 and TA 1530 but not TA 1537, TA 1538, TA 98, G46, TA 151 and TA
1512. No increase in the number of recessive lethals in Dropsophila
melanogaster (929 chromosomes) was obtained with ziram. No
significant increase in gene conversion occurred in S. cerevisiae
although metabolic activation systems were not used. An increased
number of chromosome aberrations in metaphases of bone marrow cells
were found in mice treated with 100 mg/kg b.w. orally. Approximately
six times higher frequency of chromosome and chromatid aberrations
were observed in metaphases of culture peripheral lymphocytes from
workers handling ziram.
Reproduction: Some female rats receiving ziram at 50 mg/kg
b.w./day for two months or more became sterile; some foetuses that
were conceived were resorbed and some that were born had abnormal
tails. Male fertility was not affected.
Teratogenicity: See section above.
Irritation and sensitization: Ziram was found to be a primary
skin irritant with a threshold limit value of 10% concentration in a
24 hour occluded patch test in guinea pigs and, it was also shown to
have mild to moderate contact hypersensitivity potency in a guinea
pig maximization test.
Neurotoxicity: No information available.
Metabolism: Ziram has been shown to be an inhibitor of many
enzymes. It is inhibitory to the oxidation of succinate, alpha-
ketoglutarate, glutamate and isocitrate as well as on oxidative
phosphorylation by isolated liver mitochondria. It also inhibits
aldehyde dehydrogenase and dopamine-oxidase. It induces the
accumulation of acetaldehyde in the blood stream following ethanol
treatment.
2.1.8 Modification of toxicity
No available information.
2.2 TOXICOLOGY - MAN
2.2.1 Absorption
Ziram is poorly absorbed from the gastrointestinal tract or
through the intact skin. It may be absorbed from the respiratory
tract.
2.2.2 Dangerous doses
There is no information regarding doses leading to illness. The
probable oral lethal dose for humans is 50 to 500 mg/kg b.w.
Repeated: No available information.
2.2.3 Observations on occupationally exposed workers
Several collective farm workers who used a 70% formulation of
ziram to treat seed experienced irritation of the skin, nose, throat
and eyes, gastritis, and a slight reduction in haemoglobin.
Less severe irritation of the skin and upper respiratory tract
was encountered in a factory where the air concentration of ziram
was 0.77-3.7 mg/m3.
Possible inhibition of cholinesterase and changes in the
bioelectric activity of the muscles during voluntary motion were
reported in workers. Abnormal chromosomes or chromatids were
reported in 5.9% of cultured lymphocytes of workers with three to
five years exposure to ziram.
2.2.4 Observations on exposure of the general population
No available information.
2.2.5 Observations on volunteers
No available information.
2.2.6 Reported mishaps
The ingestion of 0.51 of ziram solution of unknown
concentration was fatal within a few hours. Findings included focal
necrosis of the mucosa of the small intestine, congestion and
microscopic edema of many organs, haemorrhages, focal atelectases,
acute emphysema and desquamation of alveolar and bronchial
epithelium.
2.3 TOXICITY TO NON-MAMMALIAN SPECIES
2.3.1 Fish
No information available.
2.3.2 Birds
LD50 Wild Bird 100 mg/kg b.w.
Ziram has been shown to have an adverse effect on body weight,
to retard testicular development, and to induce degeneration in
seminiferous epithelium of mature fowl.
2.3.3 Other species
No information available.
3.0 FOR REGULATORY AUTHORITIES - RECOMMENDATIONS ON REGULATION OF
COMPOUND
3.1 RECOMMENDED RESTRICTIONS ON AVAILABILITY
(For definition of categories, see the Introduction to Data Sheets)
All liquid formulations over 70%, category 3
All other liquid formulations, category 4
All solid formulations over 28%, category 4
All other solid formulations, category 5
3.2 TRANSPORTATION AND STORAGE
Formulations in categories 3 and 4: Should be transported or
stored in clearly labelled rigid and leakproof containers and away
from containers of food and drink. Storage should be under lock and
key and secure from access by unauthorized persons and children.
Formulations in category 5: Should be transported or stored
in clearly labelled, leakproof containers out of reach of children
away from food and drink.
3.3 HANDLING
Formulations in categories 3 and 4: Protective clothing (see
part 4) should be provided for those handling concentrates. Adequate
washing facilities should be available close at hand. Eating,
drinking and smoking should be prohibited during handling and before
washing after handling. Adequate ventilation must be maintained.
Formulations in category 5: No special facilities other than
those for handling of any chemical need be required. Adequate
ventilation must be maintained.
3.4 DISPOSAL AND/OR DECONTAMINATION OF CONTAINER
If not decontaminated, container must either be burned or
crushed and buried below topsoil. Care must be taken to avoid
subsequent contamination of water sources. Container may be
decontaminated (for method see paragraph 4.3). Decontaminated
containers should not be used for food, feed or drinking water.
3.5 SELECTION, TRAINING AND MEDICAL SUPERVISION OF WORKERS
Formulations in categories 3 and 4: Pre-employment medical
examination for workers is desirable. Workers suffering from activ
hepatic, renal or skin disease should be excluded from contact.
Training of workers in techniques to avoid contact and the need for
strict abstention from alcohol use prior to and after ziram use is
essential.
Formulations in categories 5: Warning of workers to minimize
contact and about the dangers of alcohol use prior to and after
ziram use is essential.
3.6 ADDITIONAL REGULATIONS RECOMMENDED IF DISTRIBUTED BY AIRCRAFT
All formulations: Pilots and loaders should have special
training in application methods. Flagmen if used, should wear a
broad brimmed hat, a facial mask and coveralls, and be located well
away from the dropping zone.
3.7 LABELLING
Formulations in categories 3 and 4, Minimum cautionary
statement:
"WARNING - POISON"
(skull and cross bones insignia)
Ziram is a dithiocarbamate; a metabolic poison of slight acute
toxicity and possible long term toxic effects. It is a primary skin
irritant; avoid contact with skin and eyes. Inhalation of dust or
spray, or swallowing the compound may be dangerous. Wear protective
gloves and clean protective clothing when handling this material.
Bathe immediately after work. Ensure that containers are closed and
stored under lock and key. Empty containers must be disposed of in
such a way as to prevent all possibility of accidental contact with
them. Keep the material out of reach of children and well away from
foodstuffs, animal feed and their containers. Maintain adequate
ventilation during use. In case of contact, immediately remove
contaminated clothing and wash the skin thoroughly with soap and
water; for eyes, flush with water for 15 minutes. If poisoning
occurs, call a physician. Avoid alcohol use for at least 10 days
after exposure. There is no specific antidote, treatment must be
systematic.
Formulations in category 5 - Minimum cautionary statement -
This formulation contains ziram, it is poisonous if swallowed. Keep
the material out of reach of children and well away from food
stuffs, animal feed and food containers. Maintain adequate
ventilation during use. Avoid alcohol use prior to and after ziram
use.
3.8 RESIDUES IN FOOD
Maximum residue levels: Maximum residue levels have been
recommended by the Joint FAO/WHO Meeting on Pesticide Residues.
4.0 PREVENTION OF POISONING IN MAN AND EMERGENCY AID
4.1 PRECAUTIONS IN USE
4.1.1 General
Ziram is a dithiocarbamate of slight acute toxicity and
possible long term toxic effects. In addition to its inherent
toxicity it induces an alcohol intolerance similar to that of
Antabuse(disulfiram), a related dithiocarbamate. It is slowly
absorbed by the oral and dermal routes and by inhalation of spray
mist or dust. A primary irritant, avoid contact to skin and eyes,
spills must be washed immediately from the skin and eyes. Adequate
ventilation is essential.
4.1.2 Manufacture and formulation
Formulation should not be attempted without advice from the
manufacture of the technical product. Although volatility is low,
vapour and dusts should be controlled preferably by mechanical
means. Protective equipment for the skin and respiratory protection
are essential; adequate ventilation is also essential.
4.1.3 Mixers and applicators
When opening the container and when mixing, care should be
taken to avoid contact with the mouth and eyes. Maintain adequate
ventilation during handling; coveralls and gloves should be worn.
Mixing if not mechanical, should always be carried out with a paddle
of appropriate length. The applicator should avoid working in spray
mists and avoid contact with mouth. Splashes must be washed
immediately from the skin or eyes with large quantities of water.
Before eating, drinking or smoking, hands and other exposed skin
should be washed.
4.1.4 Other associated workers (including flagmen in aerial
operations)
Persons exposed to ziram and associated with its application
should observe the precautions described in 4.1.3 under "Mixers and
applicators".
4.1.5 Other populations likely to be affected
With correct application and appropriate warnings of use the
general public is unlikely to be exposed to hazardous amounts of
ziram. Warnings of use are essential; there are reports of contact
skin irritation in sensitised persons following exposure after
correct horticultural applications and after continuous use of
vulcanized rubber or plastic products contaminated with ziram during
their manufacture
4.2 ENTRY OF PERSONS INTO TREATED AREAS
Unprotected persons should be kept out of treated areas until
the spray solution is dry.
4.3 DECONTAMINATION OF SPILLAGE AND CONTAINERS
Residues in containers should be dissolved in a combustible
solvent (alcohol, benzene, etc.) and burned in a furnace. The empty
containers may be decontaminated by rinsing two or three times with
a combustible solvent, the rinse burned. An additional rinse should
be carried out with the 15% calcium hypochlorite solution which
should remain in a container overnight, and be poured into a deep
pit with abundant water. Impermeable gauntlets should be worn during
this work and a soakage pit should be provided for the rinsings.
Decontaminated containers should only be used for marking road
works, etc. Spillage of ziram and its formulations should be removed
by washing with 15% calcium hypochlorite solution and then rinsing
with large quantities of water. Drain into a deep pit or sewer with
abundant water.
4.4 EMERGENCY AID
4.4.1 Early symptoms of poisoning
Early symptoms may include dizziness, confusion, drowsiness,
lethargy, ataxia, headaches, or coma; nausea, vomiting, diarrhoea
and stomach pains; muscle weakness and ascending paralysis;
respiratory paralysis. Skin rash and eye irritation may occur as a
result of direct contact.
4.4.2 Treatment before person is seen by a physician, if these
symptoms appear following exposure
The person should stop work immediately, remove all
contaminated clothing, wash the affected skin with soap and water.
Flush contaminated eyes with fresh water for 10-15 minutes. If the
compound was ingested and the victim is alert, induce vomiting if it
has not already occurred. Provide artificial respiration if
required, preferably by mechanical means. Prevent consumption or
other contact with alcohol. Contact a doctor immediately, give
supportive care and remove the patient to hospital as soon as
possible.
5.0 FOR MEDICAL AND LABORATORY PERSONNEL
5.1 MEDICAL DIAGNOSIS AND TREATMENT IN CASES OF POISONING
5.1.1 General information
Ziram is a dithiocarbamate pesticide of slight acute toxicity
and possible long term toxicity. It is used as a protective
fungicide on fruit and vegetable crops and in several manufacturing
processes. It is absorbed from the gastrointestinal tract; by
inhalation of dust or spray mist, and through the intact skin. Ziram
induces alcohol intolerance, similar to that of Antabuse
(disulfiram).
5.1.2 Symptoms and signs
Symptoms of poisoning include nausea, vomiting, abdominal pain,
diarrhoea, anorexia and weight loss; headaches, lethargy, dizziness,
ataxia, confusion, drowsiness and coma; suppression of tendon
reflexes; initial hypotonia progressing to flaccid paralysis
(Landry's syndrome); respiratory paralysis. Severe dermatitis and
eye inflammation can occur after local contamination.
5.1.3 Laboratory
Due to rapid metabolism and excretion, detection of ziram in
blood is generally not possible. Detection of ziram metabolites in
urine may confirm absorption but will not necessarily reflect the
degree of poisoning. Skin testing may be useful in identifying
sensitization to ziram. Treatment should not be deferred pending
laboratory results.
5.1.4 Treatment
There is no specific antidote; provide symptomatic and
supportive treatment. For contact poisoning, remove all contaminated
clothing and wash the affected skin and hair with soap and water;
flush contaminated eyes with fresh water for 10-15 minutes. If ziram
has been ingested, if the patient is alert and if vomiting has not
already occurred, induce vomiting, preferably with Syrup of ipecac.
Continue to observe patient for signs of depression, consciousness
level and/or respiration. If these signs occur, gastric intubation,
aspiration and lavage should be performed immediately. Lavage with
isotonic saline or sodium bicarbonate solution should be followed by
activated charcoal by intubation to limit absorption of any residual
ziram in the gastrointestinal tract. If the irritant properties of
ziram have not already induced a bowel movement, give a mild
cathartic (e.g. magnesium sulfate). Intravenous administration of
glucose and ascorbic acid (0.2 g/min up to one gram total) may be
useful to accelerate the excretion of unreacted absorbed ziram.
Provide artificial respiration if necessary, preferably b
mechanical means. In extreme cases, if the patient is unconscious or
in respiratory distress, oxygen should be provided. The patient
should avoid fats, oils and lipid solvents which might enhance
absorption and prohibit all forms of ethanol consumption for at
least three weeks.
5.1.5 Prognosis
If the acute toxic effect is survived, the chances of complete
recovery are very good.
5.1.6 References of previously reported cases
Buklan, A. I. (1974), Sud-med. Ekspert, 17:51
Chernov, O. V. (1968), Gig. Tr. Prof. Zabol., 12:35-37
Martson, L. V. and Pilinskaya, M. A. (1971), Gig. Sanit.,
36:107-108
5.2 SURVEILLANCE TESTS
There are no readily available techniques to determine the
degree of exposure prior to the appearance of symptoms.
5.3 LABORATORY METHODS
5.3.1 Detection and assay of compound
CIPAC Handbook (1970) Vol. 1; 716
Lowen, W. K. and Pease, H. L. (1964), Anal. Methods Pestic.,
Plant Growth Regul. Food Addit., 3.:69
McLeod, H. A. and McCully, K. A., (1969), J. Ass. Off. Analyt.
Chem., 1226-1240
Supin, G. S. et al. (1973), Khim. Sel Khoz., 11:840-842
Van Hoof, E. and Heyndrickx, A. (1973), Ghent. Rijks-Univ.
Fac. Landbl. Med., 38:911-916