This report contains the collective views of an international group of
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    policy of the United Nations Environment Programme, the International
    Labour Organisation, or the World Health Organization.

    Published under the joint sponsorship of
    the United Nations Environment Programme,
    the International Labour Organisation,
    and the World Health Organization

    World Health Orgnization
    Geneva, 1986

         The International Programme on Chemical Safety (IPCS) is a
    joint venture of the United Nations Environment Programme, the
    International Labour Organisation, and the World Health
    Organization. The main objective of the IPCS is to carry out and
    disseminate evaluations of the effects of chemicals on human health
    and the quality of the environment. Supporting activities include
    the development of epidemiological, experimental laboratory, and
    risk-assessment methods that could produce internationally
    comparable results, and the development of manpower in the field of
    toxicology. Other activities carried out by the IPCS include the
    development of know-how for coping with chemical accidents,
    coordination of laboratory testing and epidemiological studies, and
    promotion of research on the mechanisms of the biological action of

        ISBN 92 4 154267 5 

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     2.1. Identity
     2.2. Physical and chemical properties
     2.3. Analytical methods



     4.1. Environmental levels
          4.1.1. Air
          4.1.2. Water
          4.1.3. Soil
          4.1.4. Food
          4.1.5. Other products
          4.1.6. Terrestrial and aquatic organisms
     4.2. General population exposure
     4.3. Occupational exposure



     6.1. Aquatic organisms
     6.2. Terrestrial organisms
     6.3. Microorganisms
     6.4. Bioaccumulation


     7.1. Single exposure
          7.1.1. Toxicity
          7.1.2. Skin Irritation
          7.1.3. Eye irritation
     7.2. Short-term exposures
     7.3. Long-term exposures
     7.4. Effects on reproduction
     7.5. Mutagenicity
     7.6. Carcinogenicity



     9.1. Evaluation of health risks for man
     9.2. Evaluation of effects on the environment
     9.3. Conclusions







Dr L. Albert, Environmental Pollution Programme, National Institute 
   of Biological Resource Research, Xalapa, Mexico  (Vice-

Dr E. Astolfi, Faculty of Medicine of Buenos Aires, Buenos Aires, 

Dr I. Desi, Department of Environmental Hygienic Toxicology, 
   National Institute of Hygiene, Budapest, Hungary  (Vice-

Dr R. Drew, Department of Clinical Pharmacology, Flinders
   University of South Australia, Bedford Park, South

Dr Y. Hayashi, Pathology Division, National Institute of
   Hygienic Sciences, Tokyo, Japanb

Dr S.K. Kashyap, National Institute of Occupational Health,
   Ahmedabad, Indiaa

Dr R. Kimbrough, Center for Environmental Health, Centers for
   Disease Control, Atlanta, Georgia, USA  (Rapporteur)b

Dr A.N. Mohammed, University of Calabar, Calabar, Nigeriaa

Mr Y.T. Mosuro, Federal Ministry of Health, Food, and Drug
   Administration and Laboratory Services, Oshodi, Nigeriab

Dr Y. Osman, Occupational Health Department, Ministry of
   Health, Khartoum, Sudanb

Dr O.E. Paynter, Office of Pesticide Programs, US Environmental 
   Protection Agency, Washington DC, USAa

Dr W.O. Phoon, Department of Social Medicine and Public
   Health, Faculty of Medicine, University of Singapore,
   Singapore  (Chairman)a

Dr L. Rosival, Centre of Hygiene, Research, Institute of 
   Preventive Medicine, Bratislava, Czechoslovakia  (Chairman)b

Dr Sakdiprayoon Deema, Ministry of Agriculture and Cooperatives, 
   Bangkok, Thailandb

Dr F.W. van der Kreek, Ministry of Welfare, Health, and
   Culture, Leidschendam, Netherlandsb

Dr D. Wassermann, Department of Occupational Health, The
   Hebrew University, Hadassah Medical School, Jerusalem,

Dr Xue Shou Zheng, School of Public Health, Shanghai Medical
   University, Shanghai, Chinab

 Representatives of Other Organizations

Dr A. Berlin, Health and Safety Directorate, Commission of the
   European Communities, Luxembourgb

Dr V.E.F. Solman, International Union for Conservation of
   Nature and Natural Resources (IUCN), Ottawa, Ontario,


Dr H. Kaufmann, International Group of National Associations
   of Agrochemical Manufacturers (GIFAP), Brussels, Belgiuma

Dr A.A. van Kolfschoten, International Group of National
   Associations of Agrochemical Manufacturers (GIFAP),
   Brussels, Belgiumb


Dr S. Dobson, Institute of Terrestrial Ecology, Monks Wood
   Experimental Station, Huntingdon, United Kingdom 
    (Temporary Advisor)a,b

Dr M. Gilbert, International Register for Potentially Toxic
   Chemicals, United Nations Environment Programme, Geneva,

Dr K.W. Jager, Division of Environmental Health, International
   Programme on Chemical Safety, World Health Organization,
   Geneva, Switzerland  (Secretary)a,b

Dr A. Pelfrene, Vector Biology and Control, Insecticides
   Development and Safe Use, World Health Organization,
   Geneva, Switzerlandb

Dr T. Vermeire, National Institute for Public Health and
   Environmental Hygiene, Bilthoven, Netherlands  (Temporary

Dr D.C. Villeneuve, Health Protection Branch, Department of
   National Health and Welfare, Tunney's Pasture, Ottawa,
   Ontario, Canada  (Temporary Advisor) (Rapporteur)a

Mr J.D. Wilbourn, International Agency for Research on Cancer,
   Lyons, Francea

a    Present at first Task Group meeting.
b    Present at second Task Group meeting.


     Every effort has been made to present information in the 
criteria documents as accurately as possible without unduly 
delaying their publication.  In the interest of all users of the 
environmental health criteria documents, readers are kindly 
requested to communicate any errors that may have occurred to the 
Manager of the International Programme on Chemical Safety, World 
Health Organization, Geneva, Switzerland, in order that they may be 
included in corrigenda, which will appear in subsequent volumes. 

                           *    *    *

     A detailed data profile and a legal file can be obtained from 
the International Register of Potentially Toxic Chemicals, Palais 
des Nations, 1211 Geneva 10, Switzerland (Telephone no. 988400 - 


     A WHO Task Group on Environmental Health Criteria for 
Organochlorine Pesticides other than DDT (Endosulfan, Quintozene, 
Tecnazene, Tetradifon) was held at the Health Protection Branch, 
Department of National Health and Welfare Ottawa from 28 May - 1 
June, 1984.  The meeting was opened by Dr E. Somers, Director-
General, Environmental Health Directorate, and Dr K.W. Jager 
welcomed the participants on behalf of the three co-sponsoring 
organizations of the IPCS (UNEP/ILO/WHO).  The Task Group reviewed 
and revised the draft criteria document and concluded that the data 
available were so sparse that no proper evaluation could be made of 
the potential hazard of tetradifon for the general population, 
exposed workers, or the environment.  The Task Group recommended 
that a preliminary hazard assessment should be circulated to all 
IPCS and IRPTC national focal points with a request for further 

     A second WHO Task Group was convened in Geneva 9-13 December 
1985 to review and revise an amended draft and to make an 
evaluation of the risks of tetradifon on human health and the 

     The initial drafts of the tetradifon document were prepared by 
DR D.C. VILLENEUVE of Canada and DR S. DOBSON of the United 

     The proprietary data mentioned in this document were made 
available to the Central Unit by Duphar BV for use at the Task 

     The present draft was prepared by the IPCS Secretariat, 
updating the preliminary hazard assessment with new information 
received in more than 50 replies. 

     Selected sections from the Health and Safety Guide on 
Tetradifon, published by the World Health Organization, are 
included as an Annex. 

     The efforts of all who helped in the preparation and 
finalization of the document are gratefully acknowledged. 

                        *   *   *

     Partial financial support for the publication of this criteria 
document was kindly provided by the United States Department of 
Health and Human Services, through a contract from the National 
Institute of Environmental Health Sciences, Research Triangle Park, 
North Carolina, USA - a WHO Collaborating Centre for Environmental 
Health Effects.  The United Kingdom Department of Health and Social 
Security generously supported the costs of printing. 


     Technical tetradifon (1,2,4-trichloro-5-(4-chlorophenyl)-
sulfonyl benzene) is a white crystalline solid that is more than 
94% pure.  It is used in formulation as an acaricide. The method of 
choice for its determination is gas-liquid chromatography with 
electron capture detection. 

     Tetradifon is persistent and only slightly mobile in soils.  
The compound degrades more rapidly with increasingly aerobic 
conditions.  Both the parent compound and its initial degradation 
product in soil, adsorb on soil particles and resist leaching. 

     The short-term toxicity of tetradifon is low for birds, 
moderate for fish, and moderate to high for aquatic crustacea. It 
is relatively non-toxic for bees.  Long-term studies are not 
available for these organisms.  Tetradifon does not bioaccumulate 
significantly in fish, which metabolize and eliminate the compound 
rapidly.  No adverse effects on terrestrial plants have been 
reported and tetradifon did not have any effects on cultures of an 
aquatic unicellular alga  (Chlorella pyrenoidova). 

     Exposure of the general population is mainly through food, 
but, with recommended application rates, residues in food are 
virtually absent.  Occupational exposure levels for workers 
spraying crops at recommended use levels have been estimated to be 
far below toxic levels, based on oral and dermal LD50s for rats. 

     In the rat, most (70%) of a single, orally-administered dose 
of tetradifon was excreted via the bile in the faeces within 48 h.  
Part of the remainder was distributed in all organs and tissues.  
The results of one study suggest that tetradifon and its 
metabolites are rapidly excreted from the body.  On continued 
dosing in beef cattle, tetradifon was detected in adipose tissue.  
It is not known whether tetradifon is excreted in milk. 

     The oral LD50 for technical tetradifon in the rat ranges from 
5000 to 14 700 mg/kg body weight.  Tetradifon has been classified 
in the category of technical products that are unlikely to present 
acute hazards if used as recommended.  The formulated product may 
be more toxic, depending on the other components of the 
formulation.  The toxicity may also vary with the purity of the 
product.  In the past, both chlorinated dibenzodioxins and 2,4,5-T 
have been identified in samples of tetradifon.  It has been shown 
that, with regular strict quality control procedures, levels of 
these contaminants are below the limits of detection. 

     In a 90-day study on rats, 50 mg/kg tetradifon in the diet was 
a no-observed-adverse-effect level.  At higher dose levels, 
induction of microsomal liver enzymes occurred, with increased 
liver weight and increased endoplasmic reticulum. At 200 mg/kg 
diet, histological changes were noted in the thyroid.  In a 2-year 
study on rats, induction of microsomal enzymes and increased liver 
weight were noted at a dietary level of 1200 mg/kg. 

     No effects on reproduction were found in a 2-generation 
reproduction study on rats administered tetradifon at 0, 40, 200, 
or 1000 mg/kg diet.  In a 90-day study on the F2b generation, the 
only effects of dietary tetradifon were a lower body weight gain 
and an increased dose-related incidence of dilated renal pelvis. 

     In a 1-year study on dogs, enlarged livers were seen at 
dietary concentrations of 5000 mg technical tetradifon/kg. Small 
infarct-like spots in the outer cortical layer of the kidneys were 
reported at a dietary level of 5000 mg/kg and in one of 4  dogs 
administered 1000 mg/kg diet.  Serum-alkaline phosphatase values 
were slightly elevated at 5000 mg/kg diet. The no-observed-adverse-
effect level in this study was suggested to be in the range of 500 
- 1000 mg/kg diet, which is roughly equivalent to a daily intake of 
12.5 - 25 mg/kg body weight. 

     Tetradifon was negative in short-term  in vitro tests for 

     Negative results were obtained in a screening test for 
carcinogenicity in mice, but the test was considered to be 
inadequate for the evaluation of the carcinogenicity of this 

     No adverse health effects from exposure to tetradifon have 
been reported in man. 

     Although the information available for this evaluation of 
tetradifon is incomplete and not always up to present-day 
standards, there are no indications, at present, that the normal 
recommended use of tested tetradifon products as an acaricide 
causes any health or safety hazards for the general population, 
exposed workers, or the environment. 


2.1.  Identity

Chemical structure:


Molecular formula:    C12H6C14O2S

CAS chemical name:    1,2,4-trichloro-5-[(4-chlorophenyl)-
Synonyms:             4-chlorophenyl-2,4,5-trichlorophenyl sulfone, 
                      2,4,4',5-tetrachlorodiphenyl sulfone 

Common trade names:   Akaritox, Aredion, Duphar 23737, ENT 23737, 
                      FMC 5488, Mition, NIA 5488, Polacaritox, 
                      Roztoczol, Roztozol, Tedion V18, 
                      Tetradichlone (a complete list of trade names 
                      is available from IRPTC) 

CAS registry number:  116-29-0

2.2.  Physical and Chemical Properties

     Some physical and chemical properties of tetradifon are given 
in Table 1.  The solubility of tetradifon in different organic 
solvents at room temperature varies from 10 g/litre (in kerosene 
and methanol) to 255 g/litre (in chloroform) (Van Rossum et al., 

     Tetradifon is manufactured by a Friedel-Craft's reaction 
between 2,4,5-trichlorophenylsulfonyl chloride and 
monochlorobenzene in the presence of anhydrous aluminium chloride 
or ferric chloride (Van Rossum et al., 1978), or by Sandmeyer 
diazotization (Windholz et al., 1983).  The technical product is 
more than 94% pure, but since production processes may vary, the 
type and quality of impurities present may differ in commercial 
products from different companies.  In addition, the limits of 
detection for different chlorinated dibenzodioxins, in commercial 
products vary.  In a study by Woolson et. al. (1972), the limit of 
detection for chlorinated dibenzodioxins was equal to or less than 
0.5 mg/kg.  The di-, tri-, tetra-, and hexachlorinated 
dibenzodioxins were not separated from each other;  the authors 
stated that higher chlorinated dibenzodioxins were found in some 
samples of tetradifon, but no specific information was given. 

Table 1.  Some physical and chemical properties 
of tetradifona
Physical state                 crystalline solid                           
Colour                         slightly yellow                             
Relative molecular mass        356.04                                      
Melting point                  148 - 149 C                                
Vapour pressure (20 C)        0.32 x 10-10 kPa                            
Octanol/water partition        4.61                                        
Solubility in water (10 C)    0.05 %                                      
                    (20 C)    0.08 %                                      
                    (50 C)    0.34 %                                      
a   From: Van Rossum et al. (1978) and Duphar 
    BV, personal communication (1982).

     Impurities including 2-chlorophenyl-2,4,5-trichlorophenyl 
sulfone up to a maximum level of 5 g/kg and 2,4,5-trichloro-
phenoxyacetic acid (2,4,5-T) have been reported by Matano et al. 
(1971) and trace amounts of highly-chlorinated dibenzodioxins, but 
not 2,3,7,8-TCDD by Woolson et al. (1972).  It has been shown that 
regular strict quality control procedures maintain the total sum of 
all isomeric tetrachlorodibenzofurans in technical tetradifon at 
less than 10 g/kg (detection limit) (Duphar BV, 1985).  
Furthermore, analysis of concentrated mother liquids revealed that 
the concentrations of 2,3,7,8-tetrachlorodibenzofuran, the sum of 
all isomeric tetrachlorodibenzo- p -dioxins, and 2,3,7,8-tetra-
chlorodibenzo- p -dioxin were all lower than 1 g/kg, and that 
2,4,5-tri-chlorophenoxyacetic acid (2,4,5-T) was not present as an 
impurity (Duphar BV, 1985). 

     Tetradifon is resistant to hydrolysis by acid and alkali and 
is non-corrosive (Worthing, 1979).  Particle size has a strong 
influence on its biological effectiveness in that small particles 
show a better rain resistance than larger ones (Maas, 1979).  In 
1954, tetradifon was introduced in the Netherlands as a non-
systemic acaricide, which was toxic for the eggs (ovicide) and all 
non-adult stages of a wide range of phytophagous mites.  It is 
used, particularly in mixtures, in horticulture, including domestic 
greenhouses, mainly on top-fruit, vegetables, ornamentals, hops, 
cotton, and sugarcane, and forestry. 

     Tetradifon remained stable to ultraviolet radiation (UVR) for 
12 h at 50 - 60 C (Duphar BV, 1985). 

2.3.  Analytical Methods

     Several methods have been used for the extraction of 
tetradifon residues from different tissues.  Burke & Mills (1963) 

introduced a method involving microcoulometric gas-liquid 
chromatography (GLC).  Mitchell (1976) used GLC with electron 
capture detection to study the tetradifon contents of apple and 
cucumber samples.  According to Van Rossum et al. (1978), the 
recovery of tetradifon from crop samples using the GLC method was 
85 - 100%.  They also reported that tetradifon could be extracted 
from soil samples with ether and then detected directly by GLC with 
electron capture detection.  The limit of detection in soil samples 
was 0.02 mg/kg. 

     Analytical methods are based on total organic chlorine, column 
chromatography, and UV spectrophotometric detection (Zweig & 
Sherma, 1972; Suzuki et al., 1973, 1974; Burke, 1976; Bontoyan, 
1979).  Zweig & Sherma (1972) mentioned a recovery of 95 - 102% 
from vegetables.  Gas chromatography is recommended by CIPAC 
(Henriet et al., 1983) for the analysis of formulations and 
technical material. 


     Tetradifon is manufactured in the Netherlands and in Italy and 
formulated in several countries.  The uses of tetradifon in 
selected countries are shown in Table 2. 

Table 2. The uses of tetradifon in selected countriesa
Country         Quantity    Year     Uses
Colombia        2786 kg     1982     agricultural acaricide
                2073 kg     1981     recommended in the growth  
                2343 kg     1980     of cotton, fruits, and 
                                     other products

Mexico          1000 kg     1981     on strawberries, tomatoes,
                                     grapes, cucumber, apples,
                                     and citrus fruits

Sweden          400 kg      1981     agricultural and 
                                     horticultural use

Thailand        42 100 kg   1984
                14 600 kg   1983
                14 175 kg   1982     acaricide
                12 237 kg   1981     acaricide
                1620 kg     1980     acaricide
                216 kg      1979     acaricide
                1000 kg     1978     acaricide
                208 kg      1977     acaricide
                272 kg      1976     acaricide

United Kingdom  320 kg/year 1975-79  acaricide

USA                         1983     used prior to 1983; 
                                     registration voluntarily 
                                     cancelled in 1983 by 
a  Information received from national contact points of 
   IRPTC (1984).

     Responses to a questionnaire received from 49 countries around 
the world indicated the continuing registration and use of 
tetradifon in 37 countries.  Nine developing countries stated that 
tetradifon was not used, and 3 countries (China, the Federal 
Republic of Germany, and the USA) stated that registration of 
tetradifon had been discontinued for reasons other than its 
toxicity.  Thirteen of these countries taken together used 
approximately 200 tonnes of tetradifon per year during the years 
1982-84 (information received from national contact points of the 
IPCS and IRPTC, 1985). 


     Only limited information is available on tetradifon as an 
environmental pollutant.  Its water solubility is low, and a study 
by Yaron et al. (1974) showed that there was only restricted 
leaching from soil by rain. 

4.1.  Environmental Levels

4.1.1.  Air

     No data are available on tetradifon levels in air.

4.1.2.  Water

     No data are available on tetradifon levels in water.

4.1.3.  Soil

     Only minute amounts of tetradifon were found in the deep 
layers of soil from an irrigated potato field sprayed at a rate of 
10 kg/ha.  Tetradifon persisted throughout the irrigation season.  
Transport of tetradifon into the soil was not affected by the 
amount of water applied (Yaron et al., 1974). 

     In a degradation experiment, sandy loam soil was incubated 
aerobically for 106 weeks.  Approximately 70% of the added 
tetradifon was recovered unchanged and 20% was recovered as 
extractable metabolites (Borst et al., 1983).  Four metabolite 
fractions were identified.  One chlorine atom appeared to be 
substituted by more polar groups (-SOCH3, -SO2CH3, -SO3H, -SCH3) 
(Borst et al., 1983; Willems et al., 1983).  In a water/sandy loam 
hydro-soil system, tetradifon had a half-life of 36 weeks.  Almost 
all of the tetradifon was retained in the soil phase.  Under more 
aerobic conditions, degradation was more rapid, 31% of the added 
tetradifon being recovered after 32 weeks (Willems & Nimmo, 1981).  
The movement of tetradifon and partially degraded tetradifon in 
overlying loam soil was also investigated.  The results showed that 
neither tetradifon nor its degradation products are leachable 
compounds (Willems & Smit, 1982). 

4.1.4.  Food

     In a study on the fate of insecticides in an irrigated field, 
Yaron et al. (1974) found a tetradifon concentration of 250 mg/kg 
(wet weight) in the peel of potato tubers.  This was due to the 
direct contact of the pesticide with the tuber.  No tetradifon was 
found in the tuber pulp or in the leaves of the potato plant; the 
amounts of pesticide applied in this study were much greater (2 
applications of 10 kg pesticide/ha soil) than those normally used. 

     Radioactive tetradifon in a solution prepared from either a 
wettable powder (WP) or a miscible oil (MO) was sprayed on 2 apple 
trees.  Changes in radioactivity in and on the leaves were followed 
for 4 months.  Externally, the greater part of the activity was 
lost from the leaves within the first few days.  Uptake into the 

leaves reached a maximum in approximately 1 day equalling 8% of 
initial activity with the WP and 30% with the MO.  More than a 
month after spraying, intact tetradifon could still be found on and 
in the leaves. The level in the ripe apples was less than 0.2 mg/kg 
(Halberstadt, 1958). 

     Cassil & Fullmer (1958) sprayed fruit-bearing apple, pear, 
peach, lemon, and orange trees with either 500 or 1500 g of 25% 
tedion wettable powder per 455 litres of water, 32 days before 
harvest.  Pears and peaches were sprayed at 0.56 litre/m2, oranges 
and lemons at 1.16 litres/m2, and apples were sprayed manually to 
runoff.  Maximum residue levels on the surface of the fruits 
sprayed at 500 and 1500 g varied from 1.5 to 3.6 and from 3.4 to 
7.0 mg/kg, respectively. Tetradifon residues diminished largely as 
a result of fruit growth and not through decomposition. 

     In a second study, Cassil & Fullmer (1958) followed tetradifon 
residue levels on similarly-sprayed oranges for 100 days.  As in 
the first study, they concluded that tetradifon is very stable when 
exposed to weathering at high summer temperatures. 

     For many years, the US Food and Drug Administration has 
examined more than 10 000 food samples yearly using methods with 
which it is possible to determine residues of tetradifon. Residues 
have been found infrequently and have been limited primarily to 
fresh fruits.  From 1964 to 1969, 1607 fruit samples were examined 
and tetradifon residues ranging from trace to 2 mg/kg were found in 
only 2.05% of the fruits; from 1970 to 1976, 1201 fruit samples 
were examined and similar tetradifon residues were found in only 
1.42% of the samples. On the basis of the total number of fruit 
samples examined, the average residue of tetradifon in fruits was 
0.007 mg/kg for 1964-69 and 0.004 mg/kg for 1970-76.  The only 
other foods in which tetradifon residues were found during these 
years were one sample of cereal by-products, one sample of fish, 
and one sample of leafy vegetables.  Findings have been less 
frequent in recent years and have primarily been found in produce 
imported from Mexico (US FDA, personal communication, 1984). 

     In New Zealand, apples from 32 growers were checked for 
tetradifon residues.  The maximum level found was 0.7 mg/kg 
(average 0.11 mg/kg) (Department of Health, Wellington, personal 
communication, 1984). 

     No studies are available from other countries.

4.1.5.  Other products

     When tetradifon was sprayed on a tea plantation at 0.5 g/litre 
and 750 - 1000 litres/ha, initial deposits on leaves were in the 
range of 12.6 - 13.6 mg/kg.  After 10 days, residues were < 5 
mg/kg (Rajukkannu et al., 1981).  No other studies were available 
for review. 

4.1.6.  Terrestrial and aquatic organisms

     In pregnant beef cattle fed apple pomace containing about 0.07 
- 0.53 mg tetradifon/kg and 0.53 - 8.33 mg total DDT/kg, for 160 
days, tetradifon accumulated in depot fat at a rate similar to 
those of DDT and DDD, but only 29% as fast as DDE. On day 160, the 
concentrations in the extracted fat were 0.16 mg tetradifon/kg  and 
2.56 mg total DDT/kg (Rumsey et al., 1977).  The depletion of these 
two compounds following cessation of exposure was not investigated.  
Thus, this study does not give any information on the persistence 
of tetradifon in cattle. 

     Tetradifon was not detected (detection level: 0.05 mg/kg) in 
the tissues of 750 fish samples collected from 11 major lakes and 
rivers in Alberta, Canada (Chovelon et al., 1984). 

4.2.  General Population Exposure

     In a market-monitoring programme conducted in California and 
Arizona, during 1967, the maximum tetradifon residue found on 
citrus fruits (whole fruit) was 0.3 mg/kg (Gunther, 1969). The 
results of market-basket studies in the USA during 1966-67, which 
included both domestic and imported food, showed that tetradifon 
was virtually absent (USDA, 1968).  In a market-basket study in 
Spain in 1971-72, tetradifon was not detected in 97% of fruit 
samples and in 87% of vegetable samples (Carrasco et al., 1976). 

     In the USA in the years 1975-76, tetradifon was not detected 
in foods including unfortified infant and toddler total diet 
samples from 10 cities in the USA sampled between August 1975 and 
July 1976 (Johnson et al., 1981a,b).  Furthermore, there have been 
no findings of tetradifon in FDA total diet ("market basket") 
studies from 1976 to the present time (US FDA, personal 
communication, 1984). 

     While most measurements in food were negative, no information 
was available on the use patterns in the countries where the food 
was monitored. 

4.3.  Occupational Exposure

     Following the analyses of dermal exposure pads or hand rinses 
and of respirator pads, an estimate of the levels of dermal and 
respiratory exposure that sprayers would potentially incur was made 
by Wolfe et al. (1967, 1972).  The values derived were 36.4 mg/h 
for dermal exposure and 0.07 mg/h for inhalation (Durham & Wolfe, 
1962; Wolfe et al., 1967).  No information on the risks of combined 
dermal and inhalation exposure is available for formulators or 
workers manufacturing the product. 


     In a preliminary study, a few rats were fed 10 mg 35S-
tetradifon/rat per day for 10 days and then examined.  The highest 
percentages of radioactivity during the 10 days were found in the 
faeces and urine, followed by fat, gastrointestinal tissue, liver, 
and muscles (Halberstadt, 1958). One rat was given 10 mg 35S-
tetradifon suspended in peanut oil/water, by stomach tube, and 
killed 48 h later.  Seventy-one percent of the dose was eliminated 
with the faeces, 4% with urine, and 7% was recovered from the 
gastrointestinal tract.  The remaining 18% was present in very 
small quantities in all organs and tissues.  Only 20 - 40% of the 
activity in organs was associated with unchanged tetradifon 
(Halberstadt, 1958).  The Task Group realized that results from 
single animals are difficult to interpret, however, no other data 
were available. 

     In another study (De Lange et al., 1975), rats received a 
single oral dose of approximately 1 mg labelled tetradifon. The 
elimination of radioactivity in urine and faeces was measured in 6 
rats, for 96 h.  Collection of urine and faeces was continued for 
168 h in 3 more rats.  The elimination of radioactivity in these 
rats was low in urine (2 - 4%) and high in faeces.  Total 
recoveries were about 75% of the dose after 96 h and 87% after 168 
h; the carcass contained about 11% at 96 h.  When the bile duct was 
ligated in 3 rats, excretion via the urine increased and was equal 
to about two-thirds of the dose.  By cannulating the bile duct in 3 
rats, the biliary excretion of 1 mg tetradifon was determined to be 
30 - 60% of the dose.  This means that up to two-thirds of the dose 
was absorbed. 

     The distribution of tetradifon in intact rats was studied (De 
Lange et al., 1975).  The radioactivity in the fatty tissues was 
found to exceed the plasma level by a factor of 50 at 96 h; the 
level in the lung was about 15 times higher than the plasma level.  
The continuing excretion of radioactive material after 96 h 
suggests depletion of these depots. 

     Unchanged tetradifon was not detected in any of the urine and 
bile samples.  The chromatographic determination of metabolite 
patterns in urine suggested that the principal metabolites could be 
chlorinated benzenesulfonic acids. However, another pattern seems 
to be present in the bile. 


6.1.  Aquatic Organisms

     The LC50s for tetradifon in 2 species of crustacea and 3
species of fish are summarized in Table 3.  The compound is 
moderately toxic for fish, and moderately to highly toxic for 
crustacea.  The guppy  (Lebistes reticulatus) showed signs of 
intoxication when exposed to tetradifon at 1 mg/litre for 5 h but 
recovered completely after being transferred to untreated water 
(Adlung, 1957).  Guppies, 3-4 weeks old, did not show any signs of 
intoxication when exposed to suspensions containing 2 mg technical 
tetradifon/litre for 96 h (Gijswijt, 1984a). 

     Waterfleas  (Daphnia magna) were exposed to water suspensions 
of tetradifon of 0.2 or 2.0 mg/litre for 48 h (both concentrations 
exceed the water solubility of tetradifon).  No toxic effects were 
observed (Gijswijt, 1984b). 

6.2.  Terrestrial Organisms

     Sherman & Sanchez (1968) did not find any toxic effects on 
plant growth or gross leaf pathology, when tetradifon was sprayed 
on papaya plants, once a week for 3 weeks, at a concentration of 
1.97 g/litre. 

     Tetradifon is relatively non-toxic for birds.  Hill et al. 
(1975) studied its toxicity for 4 species: bobwhite quail, ring-
necked pheasant, mallard (all at 10 days of age), and 12-day-old 
Japanese quail.  Tetradifon was included in food at concentrations 
of up to 5000 mg/kg and fed to the birds for 5 days.  The mortality 
rate was estimated at 8 days.  Bobwhite quail showed a 10% 
mortality rate at 5000 mg tetradifon/kg diet, but no deaths 
occurred in any other species.  The LC50 for birds is therefore 
greater than 5000 mg/kg diet.  No long-term studies on birds were 
available for review.  Beran (1970) reported an oral LD50 for bees 
of 1600 g/bee and an LD50 of 160 g/bee for tetradifon when 
applied topically.  This second LD50, expressed as a surface 
deposit, was stated to be equivalent to an application rate of 25 
kg tetradifon active ingredient/ha.  Tetradifon, at aqueous 
concentrations of 0.2 - 1.6%, applied externally to bees was not 
toxic over a 24-h period (Roger, 1968).  A topical LD50 of > 1250 
g/bee was reported by Lippold (1960).  Roger (1968) fed Tedion V18 
emulsifiable concentrate in honey syrup to honey bees and reported 
an oral LD50 of 176 g/bee (of the formulation).  Meller (1959) 
reported the oral LD50 of tetradifon for bees to be between 50 and 
100 g/bee.  No contact activity of tetradifon was detected.  A 
field trial with a spray concentration of up to 4 g/litre did not 
produce any effects in honey bees.  Tetradifon was classified by 
Anderson & Atkins (1968) as "relatively non-toxic" for bees (LD50 
greater than 11 g/bee).  A higher toxicity of tetradifon for bees, 
with an oral LD100 over 12 h of 1.01 g/bee, several orders of 
magnitude below other reported values was reported in a series of 
studies by Arzone & Vidano (1974) and Vidano & Arzone (1975).  No 
explanation for this discrepancy is given. 

Table 3.  Toxicity of tetradifon for aquatic organisms
Organism              Age/      Grade      Temp  pH   Parameter   Concentration   Reference
                      weight               (C)                   (g/litre)
Scud                  2 months  technical  23.8  7.1  24-h LC50   370 (280-500)   Sanders (1969)
 (Gammarus lacustris) 2 months  technical  23.8  7.1  48-h LC50   140 (100-200)   Sanders (1969)
                      2 months  technical  23.8  7.1  96-h LC50   110 (80-150)    Sanders (1969)
                                           21         96-h LC50   111 (82-150)    Johnson & Finley (1980)
 (Gammarus fasciatus)

Rainbow trout         1.1 g     technical  12         96-h LC50   1200            Johnson & Finley (1980)
 (Salmo gairdneri)                                                 (949-1600)

Rainbow trout                                         96 h LCO    10              Sterner et al. (1978)
 (Salmo gairdneri)

Channel catfish       0.3 g     technical  18         96-h LC50   2100            Johnson & Finley (1980)
 (Ictalurus punctatus)                                             (1150-3830)

Bluegill              0.8 g     technical  24         96-h LC50   880 (664-1166)  Johnson & Finley (1980)
 (Lepomis macrochirus)           
     Addition of tetradifon to insecticides increases their 
toxicity for bees (synergism) (Johansen, 1983). 

     In studies on other insects, Lippold (1960) reported LD50
values for topically applied tetradifon (acetone solution) as > 
9000 g/insect for the Mexican bean beetle  (Epilachna varivertis); 
> 4300 g/insect for the milkweed bug  (Oncopeltus fasciatus), and 
> 6900 g/insect for plum curculio  (Conotrachelus nenuphar). 

6.3.  Microorganisms

     The growth of cultures of the fresh water green alga  Chlorella 
 pyrenoidova in a suspension of tetradifon at 2 mg/litre for 96 h 
did not differ significantly from that of controls (Gijswijt, 

6.4.  Bioaccumulation

     In a study to examine uptake and loss of tetradifon, guppies 
 (Lebistes reticulatus) were exposed to water containing 15 g 14C-
labelled tetradifon/litre, for 14 days, and then transferred to 
clean water for a further 7 days. Fish were sampled at regular 
intervals throughout the study and whole body extracts 
(acetonitrile and methanol under reflux) were made.  Tetradifon was 
determined in these extracts using high-performance liquid 
chromatography (HPLC). Maximum tetradifon residues were found on 
the third day and represented a bioconcentration factor of 200 
times the water concentration.  The residues declined over the 
remainder of the study, in spite of continued exposure to 
tetradifon.  The decline was rapid and stabilized at between 15 and 
45X water concentrations between days 7 and 14.  Seventeen, 21, and 
28 days after transfer to clear water, tetradifon could not be 
detected in fish extracts.  The results are explained by rapid 
metabolism and excretion of tetradifon after an initial lag period 
(Willems & de Winter, 1985).  These results confirm that tetradifon 
does not bioaccumulate significantly in fish. 


7.1.  Single Exposure

7.1.1.  Toxicity

     Data on the acute toxicity of tetradifon in experimental 
animals are summarized in Table 4. 

Table 4.  Acute toxicity of tetradifon
Animal   Route            LD50 (mg/kg     Reference
                          body weight)
rat      oral             5000 - 14 700   Bordas (1968); Jones
                                          et al. (1968)

rat      oral             566a            Ben-Dyke et al. (1970)

dog      oral             2000            Hendriksen (1956)

rabbit   dermal           > 10 000        Ben-Dyke et al. (1970);
                                          US NIOSH (1977)

mouse    intraperitoneal  75              Ishida & Shirakawa

mouse    subcutaneous     1953 (TDLo)b    Bionetics (1973)
a  Tedion V18 emulsifiable concentrate, containing 8% tetradifon
   (weight/volume) was tested.  LD50 only in part related to 
b  TDLo = lowest toxic dose.

     Ishikawa et al. (1978) examined the effects of tetradifon on 
plasma-alpha-lipoprotein cholesterol in male Sprague Dawley rats 
following an intraperitoneal injection of 40 mg/kg body weight.  No 
effects were observed with regard to alpha-lipoprotein cholesterol, 
plasma-triglycerides, and weight gain.  Treatment with tetradifon 
resulted in slightly elevated levels of total plasma-cholesterol, 7 
days after treatment, with a return to threshold levels by day 21. 

7.1.2.  Skin irritation

     A total of 0.5 g technical tetradifon was applied to the back 
of the rabbit under an occlusive dressing.  No skin irritation was 
noted (Koopman 1985a).  However, the tetradifon formulation Tedion 
EC-8 was slightly irritating to rabbit skin (0.5 ml of the 
concentrate, which contains 80 g/litre in xylene) (Koopman 1985b). 

7.1.3.  Eye irritation

     Application of 100 mg technical tetradifon in the rabbit's eye 
produced slight irritation (Koopman, (1985c); Tedion EC-8 was 
moderately irritating at a dose of 0.1 ml of the concentrate 
containing 80 g tetradifon/litre in xylene (Koopman 1985d). 

7.2.  Short-Term Exposures

     Street et al. (1971) reported tetradifon to be fairly 
effective in rats in reducing dieldrin storage and hexobarbital 
sleeping time, and increasing the oxidative metabolism of  O -
ethyl- O -( p -nitrophenyl)-phenylphosphonothioate (EPN).  The 
compound was added to the diet at a concentration of 50 mg/kg and, 
depending on the enzymatic test, exposures ranged from 10 to 15 

     When tetradifon was tested in rats (7 days at 200 mg/kg body 
weight) and fish (7 days at 2 mg/litre water), no clinical changes 
were seen.  The main biochemical alterations were increased values 
for some enzymes (Zamfir et al., 1972). 

     A good correlation was found between no-observed-adverse-
effect levels based on the induction of liver microsomal enzymes in 
male rats and no-observed-adverse-effect levels based on 
histopathological changes, for 13 organochlorine pesticides.  
Tetradifon was one of the least active substances in this series.  
The lowest dose level that induced an effect was 50 mg/kg diet for 
2 weeks (Den Tonkelaar & Van Esch 1974). 

     Verschuuren et al. (1973) conducted a study on rats in which 5 
structurally-related acaricides were compared.  Groups of 10 male 
and 10 female rats were fed these substances in the diet at 0, 50, 
200, 1000, or 3000 mg/kg for 90 days.  In the case of tetradifon, a 
dietary level of 50 mg/kg was a no-observed-adverse-effect level. 
There was no growth retardation at any level.  Histological changes 
in the thyroid were noted at 200 mg/kg diet; liver weight was 
increased at 1000 mg/kg with the appearance of SER whorls, 
consisting of smooth endoplasmic reticulum. 

     Niepolomski et al. (1972) administered doses of 0, 30, 90, 
270, 810, or 2430 mg tetradifon/kg body weight, by gavage, to 
groups of 10 male and 10 female Wistar rats, for 90 days. Only the 
30 mg/kg level did not produce any effects.  From 90 mg/kg onwards, 
dose-related pathomorphological changes in liver, kidney, and lung 
and impairment of lipid metabolism were seen. 

     Technical tetradifon was administered to groups of 4 dogs at 
dietary levels of 0, 500, 1000, and 5000 mg/kg, for 1 year (Keller, 
1959).  No effects of tetradifon treatment were seen on behaviour, 
general health, and haematological and most biochemical parameters.  
Serum-alkaline phosphatase values were slightly elevated at 5000 
mg/kg diet.  Gross autopsy at the end of the study revealed 
enlarged livers at 5000 mg/kg diet and small grey infarct-like 
spots in the outer cortical layer of the kidneys in one dog at the 
dietary level 1000 mg/kg and 2 dogs at the 5000 mg/kg dietary 
level.  The gross findings were not described at the microscopic 
level. Histopathology did not reveal any compound-related changes. 
The no-observed-adverse-effect level was suggested to be in the 
range of 500 - 1000 mg/kg feed. 

7.3.  Long-Term Exposures

     Two 2-year studies were conducted with tetradifon as long ago 
as  1955 (Duphar BV, 1960).  Both chemically pure and commercial 
grade tetradifon were tested in groups of 15 male and 15 female 
rats at concentrations of 0, 30, 100, 300, 1200, 5000, or 20 000 
mg/kg in the diet.  No dose-related changes were found in body 
weight, haemoglobin, white blood cell and red blood cell 
concentrations, or differential blood count. 

     Pathology and histological examination of liver, kidney, 
spleen, heart, lung, stomach, small intestine, colon, thyroid, 
adrenal, testis/ovary, and bone marrow after 24 months did not show 
any dose-related effects at levels of 300 mg/kg or less in either 
groups.  At 1200 mg/kg upwards, degenerative changes developed in 
the liver and kidney in both groups. 

     In the studies available for review, the numbers of animals 
used, the tests, and the reports were limited compared with 
present-day standards.  However, review of these studies suggests a 
no-observed-adverse-effect level for short-term and long-term 
exposure of rats of between 2.5 and 15 mg/kg body weight. 

7.4.  Effects on Reproduction

     A 2-generation reproduction study with tetradifon (98.4% pure) 
was carried out on Charles River Sprague Dawley rats (25 per sex 
per group) at dose levels 0, 40, 200, or 1000 mg/kg diet.  The 
parents in both generations were fed the appropriate diets for at 
least 9 weeks and then subjected to 2 subsequent matings.  No 
differences attributable to tetradifon administration were noted in 
parental body weight, food or water consumption data, survival 
rates, pregnancy rates, implantation efficiencies, or parturition 
indices.  The first F1 generation offspring were killed and 
examined at weaning.  One-fifth of the second F1 litters was 
evaluated for teratogenic effects after Caesarian section, one 
fifth was born naturally and examined 3 weeks postnatally, and 
three-fifths of the litters were used to produce the F2 litters.  
The first F2 litters were killed and examined at weaning.  Half of 
the second set of F2 litters (F2a) were delivered by Caesarian 
section and used for teratological evaluation.  The other half of 
the second set of F2 litters (F2b) was evaluated after 3 months of 
postnatal treatment at dietary levels of 40, 200, and 1000 mg 
tetradifon/kg, after weaning.  Evaluation of the survival indices, 
sex ratios, and body weights of the fetuses taken by Caesarian 
section, and the offspring examined at 3 weeks postnatally, did not 
reveal any compound-related differences between the control and 
treated groups.  In the F2b litters examined 3 months postnatally, 
body weight gains were lower than control values in all treated 
groups; there was no correlation with dose. However, in the same 
set of litters, there was a dose-dependent increase in the 
incidence of dilated renal pelvis (7.8%, 11.9%, and 26.7%, 
respectively, in 37.5, 42.9, and 87.5% of the litters) compared 
with the control value (6.6% in 40.0% of the litters).  The 
difference was statistically significant only at the highest dose.  

These phenomena were not seen in the offspring examined at weaning.  
Moreover, in the F1 offspring evaluated at weaning, dilated renal 
pelvis was seen in 10.8% of the control pups and 19.4% of the low-
dose group but not in the middle- and high-dose groups.  The 
significance of the findings is not clear. 

7.5.  Mutagenicity

     Tetradifon was not among the compounds that responded 
positively in tests using two strains of  Bacillus subtilis, two 
strains of  Escherichia coli, and four strains of  Salmonella 
 typhimurium. However, it must be noted that no metabolic 
activation was attempted with tetradifon and also that  Salmonella 
TA 98 and TA 100, two of the most sensitive strains, were not 
included in the early studies of this group (Shirasu et al., 1976).  
The same group (Moriya et al., 1983) reported negative results for 
tetradifon in a bacterial reversion assay with  S. typhimurium TA 
100, TA 98, TA 1535, TA 1537, TA 1538 and  E. coli WP2 hcm. 

     Tetradifon was weakly positive in a sister chromatid exchange 
assay in human lymphocyte cultures at a 10-4 molar concentration, 
but inactive at 10-5 or 10-6 molar concentration (Sobti et al., 

     Cultures of human lymphocytes treated with tetradifon did not 
show any significant increase in the proportion of metaphase 
figures containing chromosome abberrations, compared with the 
concurrent solvent controls.  Thus, tetradifon did not show any 
evidence of mutagenic potential in this  in vitro cytogenetic assay 
(Allen, 1985). 

7.6.  Carcinogenicity

     Innes et al. (1969) tested many pesticides in a special 
screening test.  Small groups of mice were given tetradifon at 100 
mg/kg body weight by intubation on the 7th - 28th day of age, 
followed by 260 mg/kg diet for approximately 18 months. Tetradifon 
was reported not to produce a significant increase in the incidence 
of tumours.  No further details were given and this study was not 
considered adequate for the evaluation of the carcinogenicity of 
tetradifon.  No other studies were available for review. 


     No adverse health effects on human beings from exposure to 
tetradifon have been reported. 

     In photo-patch tests on 51 patients, Horiuchi & Ando (1978) 
found tetradifon to be one of the least active compounds of 29 
pesticides tested. 


9.1.  Evaluation of Health Risks For Man

     The oral LD50 in rats ranged from 5000 - 14 700 mg/kg body 
weight.  In the WHO Classification of Pesticides by Hazard, 
tetradifon was included in the category of technical products 
unlikely to present acute hazards in normal use (WHO, 1984). The 
formulated product may be more toxic, depending on other components 
of the formulation. 

     In experimental animals, most orally administered tetradifon 
is eliminated rapidly with the faeces. 

     A no-observed-adverse-effect level of 50 mg/kg diet was 
reported in a 90-day study on rats.  At higher dose levels, the 
liver increased in weight, and induction of microsomal liver 
enzymes occurred.  At levels exceeding 200 mg/kg, there was an 
increase in thyroid weight with histological changes. In 2-year 
studies on rats, dietary levels of 1200 mg/kg or more caused 
degenerative changes in the liver and kidneys. 

     No reproductive or teratogenic effects were found in a 2-
generation reproduction study on rats.  However, in a 90-day 
dietary study on the F2b offspring, there was a dose-related 
increased incidence of dilated renal pelvis. 

     In several short-term  in vitro tests adopted to detect somatic 
mutagenicity, tetradifon showed a negative response. No information 
on the mutagenic effects on germ cells is available at present. 

     Adequate carcinogenicity studies are not available.

     The general population is mainly exposed through food, but 
market-basket studies have shown that, at normal application rates 
of tetradifon as an acaricide, residues are virtually absent from 

     Under normal application conditions, it has been estimated 
that occupational exposure levels would be less than 0.01% of the 
dermal toxic dose per hour.  No adverse health effects from 
exposure to tetradifon have been reported in man. 

9.2.  Evaluation of Effects on the Environment

     Tetradifon is not toxic for  Chlorella pyrenoidova. A single 
study reported the absence of toxic effects on papaya plants.  The 
short-term toxicity of the compound is low for birds, moderate for 
fish, and moderate to high for aquatic crustacea.  Tetradifon is 
relatively non-toxic for honey bees and its toxicity for other 
insects is low.  However, it may synergize with insecticides to 
increase their insecticidal potency.  Tetradifon does not 
bioaccumulate significantly in fish.  No long-term toxicity data 
are available and, therefore, more subtle hazards cannot be 

adequately evaluated.  On the basis of the data available, 
tetradifon does not present a short-term threat for the 

9.3.  Conclusions

     Notwithstanding the fact that the information available for 
this evaluation of tetradifon is incomplete and not always up to 
present-day standards, there are no indications, at present, that 
the normal recommended use of tested tetradifon products as an 
acaricide causes any health or safety hazards for the general 
population, exposed workers, or the environment. 


1.   More information is needed on metabolism, on the effects on 
reproduction, and on long-term toxic effects including 

2.   It is advised that the purity of the products registered and 
used be ascertained, since the contamination of the product by some 
chlorinated compounds may increase its toxicity. 


     In the "Guidelines to the Use of the WHO Recommended 
Classification of Pesticides by Hazard" (WHO, 1984), tetradifon is 
classified in the list of technical products unlikely to present an 
acute hazard in normal use. 


ADLUNG, K.G.  (1957)  [The toxicity of insecticides and
acaricides in fish.]  Naturwissenschaften, 44: 471-472 (in

ALLEN, J.A. (1985)  Tetradifon, metaphase, chromosome analysis
 of human lymphocytes cultured in vitro, Weesp, Netherlands,
Duphar BV (Unpublished Proprietary Report No. 56645/78/85).

ANDERSON, L.D. & ATKINS, E.L.  (1968)  Pesticide usage in
relation to bee-keeping.  Ann. Rev. Entomol., 13: 213-238.

ARZONE, A. & VIDANO, C.  (1974)  [Verification of the action
on honey bees of pesticides declared harmless to useful
insects.]  Ann. fac. Sci. Agr. Univ. Stud. Torino, 9: 171-182
(in Italian with English summary).

BEN-DYKE, R., SANDERSON, D.M., & NOAKES, D.N.  (1970)  Acute
toxicity data for pesticides.  World Rev. Pest Control, 7-9:

BERAN, F.  (1970)  [Our present knowledge on the toxicity and
hazard to bees of our pesticides.]  Gesunde Pflanzen, 22 (2):
21-31 (in German).

 carcinogenic, teratogenic, and mutagenic activities of
 selected pesticides and industrial chemicals. II. Teratogenic
 study in mice and rats, Bethesda, Maryland, Bionetics Research
Laboratories (Report No. NCI-DCCP-C6-1973-1-2).

BONTOYAN, W.R.  (1979)  Report on the twenty-second annual
meeting of the Collaborative International Pesticides
Analytical Council (CIPAC)  J. Assoc. Off. Anal. Chem., 62:

BORDAS, S., ed.  (1968)   [Dangerous pesticides,] 6th ed.,
Budapest, Mezogazdasagi Kiado, pp. 1-720 (in Hungarian).

WILLEMS, A.G.M. (1983)   Identification of tetradifon
 degradation products in sandy loam soil, Weesp, Netherlands,
Duphar BV (Unpublished Proprietary Report No. 56630/183/82).

BURKE, J.A.  (1976)  Report on chlorinated pesticides.  J.
 Assoc. Off. Anal. Chem., 59: 338-340.

BURKE, J.A. & HOLSWADE, W.  (1966)  A gas chromatographic
column for pesticide residue analysis: retention times and
response data.  J. Assoc. Off. Agric. Chem., 47: 374-385.

BURKE, J. & MILLS, P.A.  (1963)  Microcoulometric gas
chromatographic determination of thiodan and Tedion in green
vegetables.  J. Assoc. Off. Agric. Chem., 46: 177-182.

Pesticide residues in total diet samples, Spain 1971-72.
 Pestic. Monit. J., 10(1): 18-23.

CASSIL, C.C. & FULLMER, O.H.  (1958)  Persistence of Tedion
residues on fruits.  J. agric. food Chem., 6(12): 908-910.

SINGER, P., SMILEY, K., & WHEATLEY, A.  (1984)  Pesticide and
PCB levels in fish from Alberta (Canada).  Chemosphere, 13(1):

DE LANGE, N., VINCENT, W.R., & POST, L.C.  (1975)   Disposition
 of 35 S-tetradifon in the rat, Weesp, Netherlands, Duphar BV,
(Unpublished Proprietary Report No. 56654/20/75).

DEN TONKELAAR, E.M. & VAN ESCH, G.J.  (1974)  No-effect levels
of organochlorine pesticides based on induction of microsomal
liver enzymes in short-term toxicity experiments.  Toxicology,
2: 371-380.

DUPHAR BV  (1960)   Investigation of the toxicity of Tedion
 V18, Weesp, Netherlands, Duphar BV (Unpublished Proprietary
Report No. 77.260)

DUPHAR BV  (1985)  Proprietary data made available to the Task

DURHAM, W.F. & WOLFE, H.R.  (1962)   Measurement of the
 exposure of workers to pesticides, Geneva, World Health
Organization, pp. 75-91 (WHO Bulletin No. 26).

GIJSWIJT, M.J.  (1984a)   The acute toxicity of tetradifon to
 Lebistes reticulatus (Guppy), Weesp, Netherlands, Duphar BV
(Unpublished Proprietory Report No. 56635/11/84).

GIJSWIJT, M.J.  (1984b)   The acute toxicity of tetradifon to
 Daphnia magna, Weesp, Netherlands, Duphar BV (Unpublished
Proprietary Report No. 56635/21/84).

GIJSWIJT, M.J.  (1984c)   Tetradifon and algal growth, Weesp,
Netherlands, Duphar BV (Unpublished Proprietary Report No.

GUNTHER, F.A.  (1969)  Insecticide residues in California
citrus fruits and products.  Residue Rev., 28: 1-119.

HALBERSTADT, J.  (1958)  Some experiments with radioactive
preparations of 2,4,5,4'-tetrachlorodiphenylsulfone, a new
acaricide.  Meded. Landbouwhogeschool Gent., 23: 788-794.

HANYU, I. & TSUJI, T.  (1974)  [Results of investigation on
the effects of agricultural chemicals, especially organo-
phosphorous pesticides on farmers health.]  Koshu Eisei Joho,
4: 20 (in Japanese).

HENDRIKSEN, TH.W.J.  (1956)   Investigation into the toxicity
 of 2,4,5,4'-tetrachlorodiphenylsulfone (Duphar Tedion V18),
Weesp, Netherlands, Duphar BV (Unpublished Proprietary Report
No. 6748/4/56).

(1983)   Analysis of technical and formulated pesticides,
Cambridge, England, Heffers Printers Ltd, pp. 1901 (CIPAC
Handbook Vol. 1B).

(1975)   Lethal dietary toxicities of environmental pollutants
 to birds, Washington DC, US Fish and Wildlife Service, 61 pp
(Special Scientific Report No. 191).

HODGE, H.C. & STERNER, J.H.  (1956)  Combined tabulation of
toxicity classes. In: Spector, W.S., ed.  Handbook of
 toxicology, Philadelphia, Pennsylvania, W.B. Saunders Company.

HORIUCHI, N. & ANDO, Y.  (1978)  Photosensitivity caused by
pesticides. In:  Proceedings of the 7th International Congress
 on Rural Medicine, Salt Lake City, 1978, Oakdale, Utah,
Institute of Agricultural Medicine, pp. 279-284.

(1969) Bioassay pesticides and industrial chemicals for
tumourigenicity in mice: a preliminary note.  J. Natl Cancer
 Inst., 42: 1101-1114.

IRPTC  (1983)   IRPTC legal file 1983, Geneva, International
Register of Potentially Toxic Chemicals, United Nations
Environment Programme (UNEP), Vols. 1 and II.

ISHIDA, K. & SHIRAKAWA, K.  (1969)  [Histopathological studies
of liver and kidney of mice injected with lethal doses of
pesticides.]  Niigata Norin Kenkyu, 21: 183-201 (in Japanese).

MELLIES, M., GARTSIDE, P.S., & MCMILLIN, C.  (1978)  Effects
on chlorinated hydrocarbons on plasma alpha-lipoprotein
cholesterol in rats.  Metabolism, 27:  89-96.

JOHANSEN, C.A.  (1983)  Pesticides and bees.  Environ.
 Entomol., 12(5): 1513-1518.

JOHNSON, W.W. & FINLEY, M.T.  (1980)   Handbook of acute
 toxicity to fish and aquatic invertebrates, Washington DC, US
Fish and Wildlife Service, 75 pp (Research Publications
No. 137).

(1981a)  Pesticide, heavy metal, and other chemical residues
in adult total diet samples. XII. August 1975 - July 1976.
 Pestic. Monit. J., 15: 54-71.

JOHNSON, R.D., MANSKE, D.D., & PODREBARAC, D.S.  (1981b)  Food
and feed: pesticide, heavy metal, and other chemical residues
in infant and toddler total diet samples. II. August 1975 -
July 1976.  Pestic. Monit. J., 15(1): 39-50.

JONES, K.H., SANDERSON, D.M., & NOAKES, D.N.  (1968)  Acute
toxicity data for pesticides (1968).  World Rev. Pestic.
 Control, 7(3): 135-143.

KADIR, H.A. & KNOWLES, C.O.  (1981)  Inhibition of rat brain
monoamineoxidase by insecticides, acaricides, and related
compounds.  Gen. Pharmacol., 12: 239-247.

KELLER, J.G.  (1959)   Tedion technical: repeated oral
 administration to dogs (Report to Niagara Chemical Division -
Hazleton Laboratories, Falls Church, Virginia).

KOOPMAN, T.S.M.  (1985a)   Primary irritation study of
 tetradifon technical to the skin of the male rabbit, Weesp,
Netherlands, Duphar BV (Unpublished Proprietary Report
No. 56645/71/85).

KOOPMAN, T.S.M.  (1985b)   Primary irritation study of Tedion
 EC-8 to the skin of the male rabbit, Weesp, Netherlands,
Duphar BV (Unpublished Proprietary Report No. 56645/74/85).

KOOPMAN, T.S.M.  (1985c)   Primary irritation study of
 tetradifon technical to the eye of the male rabbit, Weesp,
Netherlands, Duphar BV (Unpublished Proprietary Report
No. 56645/72/85).

KOOPMAN, T.S.M.  (1985d)   Primary irritation study of Tedion
 EC-8 to the eye of the male rabbit, Weesp, Netherlands, Duphar
BV (Unpublished Proprietary Report No. 56645/75/85).

LIPPOLD, P.C.  (1960)   Tedion: tests with insects (Internal
Report FMC Niagara Chemical Division, Middleport, New York).

MAAS, W.  (1979)  Influence of particle size on pesticidal
activity.  Adv. Pest. Sci., 3: 772-779.

(1971)  [Chemical and biological determination of 2,4,5-T in
tetradifon formulations.]  Noyaku Kensasho Hokoku, 11: 32-36
(in Japanese).

MITCHELL, L.R.  (1976)  Collaborative study of the determina-
tion of endosulfan, endosulfan sulfate, tetrasul, and
tetradifon residues in fresh fruits and vegetables.  J. Assoc.
 Off. Anal. Chem., 59: 209-212.

SHIRASU, Y.  (1983)  Further mutagenicity studies on
pesticides in bacterial reversion assay systems.  Mutat. Res.,
116: 185-216.

MUELLER, H.  (1959)   [Testing of toxicity for bees: Tedion V18
 emulsion,] (Internal Report from the Federal Biological
Institute, Braunschweig, Federal Republic of Germany) (in

(1972)  [Morphological studies upon shortened chronic akaritox
toxicity in rats.]  Med. Prac., 23: 577-584 (in Polish).

NIOSH  (1977)   Registry of toxic effects of chemical
 substances, Cincinnati, Ohio, US National Institute of
Occupational Safety and Health, pp. 883.

Residues of dicofol and tetradifon in tea leaves.  Plant Crops,
9: 124-125.

ROGER, S.  (1968)   Essais de toxicite a l'egard de l'abeille
 de produit Tedion V-18 emulsion 8 (Unpublished Report of the
"Station de Recherche sur l'abeille et les insectes sociaux",
Bures sur Yvette, France).

PRIODE, B.M.  (1977)  Supplementation of apple pomace with
non-protein nitrogen for gestating beef cows. IV. Pesticide
accumulation in cows.  J. anim. Sci., 46: 543-550.

RUTTER, H.A.  (1976)   A two-generation reproduction study on
 rats. Tedion. Final report, Vienna, Virginia, Hazleton
Laboratories (Project No. 681-109) (Proprietary data for
product registration purposes made available by Duphar BV to
the IPCS).

RUTTER, H.A.  (1982)   A two-generation reproduction study on
 rats. Tedion. Addendum to final report, Vienna, Virginia,
Hazleton Laboratories (Project No. 681-110) (Proprietary data
for product registration purposes made available by Duphar BV
to the IPCS).

SANDERS, O.  (1969)   Toxicity of pesticides to the crustacean
 Gammarus lacustris, Washington DC, US Fish and Wildlife
Service, Bureau of Sport, Fish and Wildlife, 18 pp (Technical
Paper No. 25).

SHERMAN, M. & SANCHEZ, F.F.  (1968)  Further studies on the
toxicity of insecticides and acaricides to the papaya.  Hawaii
 Agric. Exp. Stn Univ. Hawaii. Tech. Bull., 74: 5-63.

(1976)  Mutagenicity screening on pesticides in the microbial
system.  Mutat. Res., 40: 19-30.

TERAMOTO, S., & KADA, T.  (1977)  Mutagenicity screening on
pesticides and modification products: a basis of carcino-
genicity evaluation. In: Hiatt & Watson, ed.  Origins of human
 cancer. A. Incidence of cancer in humans, Cold Springs
Harbour, New York, Cold Springs Harbour Laboratories.

SOBTI, R.C., KRISHAN, A., & DAVIES, J.  (1983)  Cytokinetic
and cytogenetic effect of agricultural chemicals on human
lymphoid cells  in vitro. II. Organochlorine pesticides.  Arch.
 Toxicol., 52: 221-231.

STERNER W., KORN, W.D., & PFENNIG, K.D.  (1978)   [Testing the
 acute toxicity of technical tetradifon for fresh-water fish,]
Hanover, Federal Republic of Germany, International Bio
Research (Unpublished Report No. 1-8-210-78).

(1971)  Induction by different inducers: structure-activity
relationships among DDT analogues. In:  Proceedings of the 2nd
 International IUPAC Congress of Pesticide Chemistry, Israel,
 22-26 February 1971, New York, Gordon and Breach Science
Publishers, pp. 237-256.

(1973)  Separation and identification of 20 pesticides in
mixtures.  Agric. Biol. Chem., 37: 1959-1962.

SUZUKI, K., NAGAYOSHI, H., & KASHIWA, T.  (1974)  The systemic
separation and identification of pesticides in the first
division. Agric.  Biol. Chem., 38: 279-285.

US FDA  (1968)   The regulation of pesticides in the United
 States, Washington DC, US Department of Agriculture, US
Department of Health, Education and Welfare, Food and Drug

VAN DIJK, L.P., WIESE, I.H., & MULLEN, J.E.C.  (1982)
Management and determination of pesticide resides in South
Africa.  Residue Rev., 82: 38-121.

VAN KOLFSCHOTEN, A.A.  (1982)   A two-generation reproduction
 study in rats. Tedion. Further evaluation of report No.
 681-109 and Addendum 681-110, Vienna, Virginia, Hazleton
Laboratories (Duphar Report No. 56645/30/82) (Proprietary data
for product registration purposes made available by Duphar BV
to the IPCS).

(1978)  Tetradifon. In: Zweig, G. & Sherma, J., ed.  Analytical
 methods for pesticides and plant growth regulators, New York,
Academic Press, pp. 119-126.

VAN ROSSUM, B., MARTIJN, A., & LAUNER, J.E.  (1981) Gas-liquid
chromotographic determination of tetradifon technical and
formulations: collaborative study  J. Assoc. Off. Anal. Chem.,
64: 829-832.

Toxicity studies on tetrasul. III. Short-term comparative
studies in rats with tetrasul and structurally-related
acaricides.  Toxicology, 1: 113-123.

VIDANO, C. & ARZONE A. (1975)  [Research and considerations on
pesticides demonstrated to be harmless for bees.]  Apicot.
 Mod., 66(5): 163-167 (in Italian).

WHO  (1984)   The WHO recommended classification of pesticides
 by hazard. Guidelines to classification 1984-1985, Geneva,
World Health Organization (Unpublished Report VBC/84.2).

WILLEMS, A.G.M. & DE WINTER, M.L.,  (1985)   Bioaccummulation
 of tetradifon by fish, Weesp, Netherlands, Duphar BV
(Unpublished Proprietary Report No. 56637/77/1985).

WILLEMS, A.G.M. & NIMMO, W.B.  (1981)   The degradation of
14 C-tetradifon in a water/hydro soil system, Weesp,
Netherlands, Duphar BV (Unpublished Proprietary Report
No. 56635/41/81).

WILLEMS, A.G.M. & SMIT J.  (1982)   Movement of tetradifon and
 its degradation products in soil, Weesp, Netherlands, Duphar
BV (Unpublished Proprietary Report No. 56635/28/82).

ed.  (1983)   The Merck Index, 10th ed., Rahway, New Jersey,
Merck and Co., Inc.

WOLFE, H.R.  (1976)  Field exposure to airborne pesticides.
In: Lee, R.E., ed.  Air pollution from pesticides and
 agricultural processes, Florida, CRC Press, pp. 137-161.

WOLFE, H.R., DURHAM, W.F., & ARMSTRONG, J.F.  (1967)  Exposure
of workers to pesticides.  Arch. environ. Health, 14: 622-633.

(1972)  Exposure of spraymen to pesticides. A rch. environ.
 Health, 25: 29-31.

WOOLSON, E.A., THOMAS, R.F., & ENSOR, P.D.J.  (1972)  Survey
of polychlorodibenzo- p-dioxin content in selected pesticides.
 J. agric. food Chem., 20: 351-354.

WORTHING, C.R.  (1979)   The pesticide manual, 6th ed.,
Croydon, British Crop Protection Council (BCPC Publications).

YARON, B., BICLORAI, H., & KLIZER, L.  (1974)  Fate of
insecticides in an irrigated field: azinphosmethyl and
tetradifon cases.  J. environ. Qual., 3: 413-417.

(1972)  [Biochemical changes due to sublethal doses of
tetradifon.]  Igiena, 21: 665-670 (in Rumanian).

ZWEIG, G. & SHERMA, J.  (1972)  Tedion (tetradifon). In:
Zweig, G. & Sherma, J., ed.  Analytical methods for pesticides
 and plant growth regulators. Gas chromatographic analysis, New
York, Academic Press, Vol. 6, pp. 488-492.



A1.1  Main Hazards for Man; Prevention and Protection; First Aid 

     The toxicity of technical tetradifon for man is thought to be 
low, and no adverse health effects from exposure to tetradifon have 
been reported.  The toxicity and hazard of a formulation may 
largely depend on the vehicle used. 

A1.1.1  Prevention and Protection

     In spite of the low toxicity and hazard of tetradifon, the 
following precautions should be observed during handling and use in 
order to reduce the risk of accidental contamination: 

     (a)  Avoid contact with the skin and eyes.  If eyes become
          contaminated, flush with water.  If irritation
          persists, obtain medical attention.

     (b)  Wash hands and any exposed skin before eating,
          drinking, smoking, and after work.

     (c)  Avoid raising a dust cloud when handling wettable
          powder formulations.

     (d)  Avoid breathing dust from powder products.

     (e)  When unloading and handling containers, wear
          protective PVC or neoprene gloves.

     (f)  When handling leaking containers or when dealing with
          leaks and spills, wear overalls and PVC or neoprene
          gloves and boots.  If overalls become contaminated,
          change and wash them thoroughly before re-use.

     (g)  Store products in original containers out of reach of
          children and away from food and feeding stuffs.

A1.1.2  First aid

     Poisoning by tetradifon is unlikely unless there has been 
gross (negligent) exposure or intentional ingestion.  In cases of 
overexposure, apply routine first aid measures. 

     If material has been spilled on the skin, immediately remove 
the patient from the source of the contamination, remove all 
contaminated clothing, and wash affected areas with soap and 
running water.  If material is in the eyes, flush with clean water 
for at least 15 min.  Keep patient prone and quiet. Start 
artificial respiration immediately if patient is not breathing. 

     Never give anything by mouth to an unconscious person.

     In serious cases, medical attention should be sought.

A1.2  Advice to Physicians

     The human toxicity of tetradifon is believed to be low. There 
is no specific antidote.  Treat symptomatically when required.  In 
cases of ingestion, gastric lavage may be indicated. 

A1.3  Explosion and Fire Hazards and Precautions

     Technical tetradifon is not highly flammable, but liquid 
formulations may be, depending on the solvent used. 

     Fight small fires with CO2, dry powder, or alcohol resistant 
foam.  Confine the use of water spray to cooling of unaffected 
stock only, thus avoiding the accumulation of polluted run-off from 
the site. 

     Fire service personnel should be advised that self-contained 
breathing apparatus may be required, because noxious fumes may be 
generated through a fire. 

A1.4  Storage and Transport Precautions

     All products should be stored in secure buildings, out of 
reach of children and animals, and also comply with any local 
transport regulations.  Containers should be sound and well 

A1.5  Spillage/Disposal Procedures

     Keep spectators away from any leakage.  Prevent contamination 
of other goods or cargo, or nearby vegetation and waterways. 

     Absorb spillage of liquid products with sawdust or sand, sweep 
up and place in separate container. 

     Empty any product remaining in damaged or leaking containers 
into a clean empty container, which should be suitably labelled. 

     Sweep up any spilt powder with damp sawdust taking care not to 
raise a dust cloud.  Place in separate container for subsequent 

     Contaminated absorbents, used containers, surplus product, 
etc., should be burnt in an incinerator designed for pesticide 
disposal.  When no incinerator is available, bury in an approved 
dump or in an area where there is no risk of contamination of 
ground or surface water.  Comply with any local legislation 
applying to waste disposal. 

A1.6  International Chemical Safety Card

     This card should be easily available to all health workers 
concerned and to all users of tetradifon.  It should be displayed 

at, or near, entrances to areas with potential exposure to 
tetradifon, on processing equipment, and on containers.  The sheet 
should be translated into the appropriate language(s).  All persons 
potentially exposed to the chemical should also have the 
instructions on the chemical safety card clearly explained. 


     No effects on the environment have been reported for 

A2.1  Precautionary Measures to Protect the Environment

     Do not contaminate ponds, waterways, and ditches with product 
or used containers.  Puncture empty containers. 


     The information given in this section has been extracted from 
the International Register of Potentially Toxic Chemicals (IRPTC) 
legal file. 

     The file contains regulatory data on chemicals from 12 
countries and recommendations issued by 6 international 

     The reader must be aware that regulatory decisions about 
chemicals taken in a certain country can only be fully understood 
in the framework of the legislation of that country.  A full 
reference to the original national document from which the 
information was extracted can be obtained from the IRPTC. 

     When no effective date appears in the IRPTC legal file, the 
publication year of the national document from which the data are 
taken is mentioned; where appropriate, this is indicated by (r). 

Sample International Chemical Safety Card for Tetradifon (technical) 
(2,4,5,4'-tetrachlorodiphenylsulfone; C12H6Cl4O2S)
Physical properties                                                 Other characteristics
Relative molecular mass               356.04                        slightly yellow crystalline solid;
Melting point                         148 - 149 C                  very stable non-corrosive substance;
Water solubility (20 C)              0.08%                         may emit toxic fumes when heated
Density (20 C)                       1.515                         to decomposition
Octanol/water partition coefficient   4.61
Vapour pressure (20 C)               0.32 x 10-10 kPa
Hazard/symptom                        Prevention and protection     First aid
Skin: mild irritation                neoprene gloves, face shield  remove contaminated clothing;
                                                                    wash with plenty of water
Eyes: marginal irritant              safety goggles, face shield   flush with clean water for
                                                                    at least 15 min
Inhalation: irritation of upper      local exhaust ventilation;    fresh air
            respiratory tract        wear a dust mask

Ingestion: none observed             unlikely professional hazard  gastric lavage may be indicated
Spillage                              Storage                       Fire and explosion
Collect spillage in closed container  store cool and dry in        Fire: not flammable under normal 
or dust bin bag; in the case of       original packing                   conditions
liquid, first use absorbant material;                              Explosion: none
clean up with water                                                Fire extinguishing agents: foam, CO2,
                                                                                             dry chemical
Waste disposal
Should be burnt in an incinerator
designed for pesticide disposal
A3.1  Exposure Limit Values

     Some exposure limit values are given in Table A.1.

A3.2  Specific Regulatory Actions

     In Czechoslovakia (effective date: 1981) and the United 
Kingdom (1983 (r)), the substance is approved as a pesticide or 
acaricide, and specified uses, limitations, and safety precautions 
are listed. In the USSR, the substance is approved as an 
insecticide for agricultural use and application; dose, mode, and 
treatment frequency are specified (effective date: 1982).  In 
Sweden, the substance is an active ingredient in pesticide 
formulations that are registered at the products control board and 
therefore may be marketed and used.  The formulations may be sold 
only to persons authorized to use such formulations (1984 (r)). 

A3.3  Transport and Labelling

     The United Nations Committee of Experts on the Transportation 
of Dangerous Goods classifies tetradifon as a poisonous substance 
(Class 6.1) presenting minor danger for packing purposes when the 
active ingredient constitutes 25 - 100% of the formulation (1982 
(r)).  The recommended label is: 


Table A.1.  Some exposure limit values
Medium  Specification       Country            Exposure limit description          Value    Effective
                                                                                   (mg/kg)  date
Food    plant               Argentina          maximum residue limit               1 - 5    1969
        meat, milk                                                                 0        1969
        mint                                                                       100      1969
        hops                                                                       30       1969
        dried hops                                                                 120      1969

Food    plant (specified)   Brazil             acceptable limit (safety            1 - 5    1981
                                               interval: 14 days)

Food    plant (specified)   Germany, Federal   maximum residue limit               1.5      1978
                            Republic of

        plant (general)                        maximum residue limit               0.05     1978

Food    food products       Kenya              maximum limit                       1 - 100  1978 (r)

Food    fruit, vegetables   Sweden             maximum acceptable concentration    2        1983

Food    food products       USA                residue tolerance                   8 - 120  1981 (r)

        raw agricultural                       acceptable residue limit            0 - 100  1981 (r)

Food    food products       USSR               maximum residue limit               0.1 -    1983
        (specified)                                                                0.7

    See Also:
       Toxicological Abbreviations
       Tetradifon (HSG 11, 1987)
       Tetradifon (ICSC)