AGP:1970/M/12/1 WHO/FOOD ADD/71.42 1970 EVALUATIONS OF SOME PESTICIDE RESIDUES IN FOOD THE MONOGRAPHS Issued jointly by FAO and WHO The content of this document is the result of the deliberations of the Joint Meeting of the FAO Working Party of Experts and the WHO Expert Group on Pesticide Residues, which met in Rome, 9-16 November, 1970. FOOD AND AGRICULTURE ORGANIZATION OF THE UNITED NATIONS WORLD HEALTH ORGANIZATION Rome, 1971 TRICYCLOHEXYLTIN HYDROXIDE IDENTITY Chemical name Tricyclohexyltin hydroxide Synonyms DOWCO (R) 213, PLICTRAN (R) Structural formulaOther relevant chemical properties The compound in a white, crystalline powder with an apparent melting point of 245°C. The compound undergoes loss of water at 120-130°C and In converted to the bis (tricyclohexyltin) oxide. The technical product has the following solubilities at 25°C: acetone 0.13 g/100 ml, benzene 1.6 g/100 ml, carbon tetrachloride 2.8 g/100 ml, chloroform 21.6 g/ml, methanol 3.7 g/100 ml and water < 0.0001 g/100 ml. Purity The technical product contains 95-96% tricyclohexyltin hydroxide. It is formulated as a wettable powder. EVALUATION FOR ACCEPTABLE DAILY INTAKE BIOCHEMICAL ASPECTS Biotransformation In the studies with rats and dogs, in addition to the parent compound, dicyclohexyltin oxide and trace amounts of cyclohexylstannoic acid in organic tin were identified (Smith and Fischer, 1970; Anon, 1970a). The metabolic fate of the limited amounts of compound absorbed from the gastrointestinal tract in animals appears to occur by the sequence: (C6H11)3 SnOH---> (C6H11)2 SnO---> C6H11SnO2H---> Sn+4 Absorption, distribution and excretion Two rats received, each in a gelatine capsule, a single oral dose of 5 mg of 119Sn-labelled tricyclohexyltin hydroxide, corresponding to 25 mg/kg body-weight. Essentially quantitative recovery (99.9 and 100 percent) of the total radioactivity was obtained in the excreta collected for ten days after dosing. Most (75-80 percent) was excreted in the first four days after administration. Almost all of the radioactivity occurred in the faeces (97.5 and 98.9 percent versus 1.8 to 2.5 percent in the urine). The practical lack of gastrointestinal absorption was also confirmed by the absence of radioactivity in the bile of two guinea pigs, which were administered the labelled compound and sacrificed, respectively, 24 and 48 hours after dosing (Smith and Fischer, 1970). Groups of rats and dogs of both sexes were fed tricyclohexyltin hydroxide in their diet at rates of 0.75, 3, 6 and 12 mg/kg body-weight per day, for periods ranging from 45 days to two years. Tin compounds, primarily the parent compound, were distributed through the tissues only in trace amounts. As an example: in rats which were fed 3 mg compound/kg/day, the levels were: fat (0.1 ppm tin) < muscle < adrenals < heart < brain <liver kidney (0.8 ppm). The biological half-life of the tin compounds was approximately 5 to 40 days after compound withdrawal from the diet (Anon, 1970a). Dicyclohexyltin oxide, trace amounts of cyclohexylstannoic acid, and inorganic tin were identified as metabolites in rats and dogs. Generally, from 60 to 95 percent of the tin was present as organotin (Smith and Fischer, 1970; Anon, 1970a). Rats were fed 100 ppm of 119Sn-labelled tricyclohexyltin hydroxide for 90 days, and several tissues were analysed for uptake of 119Sn. Continuous uptake resulted in an equilibrium being reached between 40-60 days with the females accumulating slightly more than the males. Tin was eliminated slowly from the tissues upon cessation of feeding, with the brain being one of the slowest tissues. Traces of tin were noted after 115 days, although the major quantity was removed in 20 days (Smith and Fischer, 1970). Effect on enzymes and other biochemical parameters In a series of pharmacological and biochemical studies, intravenous injection to dogs and cats resulted in no effect on blood pressure, pulse rate or cholinesterase levels, and in no potentiation of drugs (epinphrine chloride, norepinephrine bitartrate, tyramine monohydrochloride or nicotine sulfate). The primary effect noted on intravenous injection was stimulation of respiration accompanied by an increase in blood lactate and a decrease in blood pCO2, without changes in either pH or pO2 in the blood (Hine at al., 1969). TOXICOLOGICAL STUDIES Special studies on reproduction Japanese Quail Investigations were started on four groups of birds, each containing eight to ten females plus an equal number of males. Dietary levels of 0, 1, 10 or 100 ppm of tricyclohexyltin hydroxide were given to the adults (ten weeks of age) of the first generation, and, afterwards, through the entire life cycle of the second and the third generation. Body and egg weights, food-consumption, survival of live chicks from eggs, adult mortality, general physical condition and appearance and gross observation of the ovaries and gonads were comparable to the controls for all dietary levels. Similarly, no gross teratogenic or lenticular effects were observed in any of the treated groups. Definite effects on embryonic mortality, egg production, fertility and hatchability were observed at the 100 ppm dietary levels. At 10 ppm, there were effects of questionable significance on egg fertility and hatchability. None of those criteria was affected at the level of 1 ppm (Stevenson and Kenaga, 1969). Rabbit Groups of pregnant New Zealand white rabbits, 28 in all, received oral doses of respectively 0, 0.75 or 3 mg tricyclohexyltin hydroxide/kg body-weight/day on the eighth to the 16th day inclusive of gestation. There was no evidence of significant adverse effects due to the compound as judged by indices of fertility, gestation, viability and lactation or by examination of the foetuses for teratogenic effects (Hine at al., 1969b). Rat A three generation (two litters per generation) reproduction, fertility and teratology study was conducted in groups of 10 male and 20 female rats maintained continuously on diets containing 0, 12.5, 50 or 100 ppm of tricyclohexyltin hydroxide (the uppermost dietary level corresponds to approximately 4 to 6 mg test compound/kg body-weight/day on the basis of adult and female rats). There was no evidence of significant adverse effects due to the compound under test when judged by indices of fertility, gestation, viability and lactation, or by examination of the foetuses for teratogenic effects (Hine et al., 1969a). Special studies on metabolites and photodecomposition products In addition to having been identified as metabolites in animals (Smith and Fischer, 1970), dicyclohexyltin oxide and cyclohexylstannoic acid occur as a relatively minor proportion of the residues on fruit, having been formed by sunlight degradation (Getzendaner, 1968) (see 'Fate of Residues, in plants'). LD50 values for dicyclohexyltin oxide, as determined in five studies involving varying strains of rats, averaged 355 mg/kg body-weight (Anon, 1970c). Cyclohexylstannoic acid exhibits low toxicity to rats with an LD50 value of < 3 600 mg/kg body-weight (Hine, 1967). Male and female rats were fed dicyclohexyltin oxide in their diet for 90 days at dose levels of 0, 1, 3 and 6 mg/kg body-weight/day. No unusual alterations in behaviour and appearance occured during this study nor were any pharmacodynamic or toxic signs exhibited which could be related to the feeding of the test compound in the diet. No compound related variations were found in haematological and biochemical values, in gross and microscopic examination of tissues and in organ-weights and ratios (Wazeter et al., 1968). Acute toxicity TABLE I Summary of acute toxicities by various workers LD50(mg/kg) Animal Route body-weight Reference Chick (M) Oral 650 Olson, 1964 Mouse, Peromyscus Oral 7101/ Kenaga, 1968 Mouse, Swiss White Oral 10701/ Kenaga, 1968 Rat Oral 5402/ Anon, 1970b Rat ip 13 Hine et al., 1969a Guinea pig (M) Oral 780 Olson, 1964 Guinea pig (M) ip 9 Norris, 1968 Rabbit Oral >500,<1000 Olson, 1964 Rabbit ip >126 Norris, 1968 Dog iv 14 Hine et al., 1969a Cat iv 6 Hine et al., 1969a 1/ Approximate lethal dosage (100 percent deaths) 2/ Average LD50 value from 10 studies in both sexes of three strains These data reveal that acute toxicity by the oral route is, because of very poor gastrointestinal absorption, considerably lower than by the parenteral route. The compound appears to be principally a depressant of the central nervous system, but not nearly to the same extent as the triethyltin acetate in comparable doses. Neither interperitoneal, intravenous nor oral administration resulted in cerebral oedema or significant pathologic lesions (Hine at al., 1969). Death usually occurred within two to seven days after administration. Acute signs of poisoning in rats include anal wetting, piloerection, wet nares and mouth, lethargy, hyporeflexia, arching, depressed respiration, emaciation, diarrhoea and flexure of all four limbs when picked up by the scruff of the neck. Gross examination of the dead animals showed that the adrenal gland of rats was 2-3 times heavier than the controls and the spleen was 0.3-0.4 time heavier than the controls (Hine, 1966). Short-term studies Dog A total of 96 beagle dogs, half male and half female, averaging eight months of age, were fed tricyclohexyltin hydroxide in the diet, at levels adjusted to give ingestion rates of 0, 0.75, 3 or 6 mg/kg body-weight/day, for two years, or of 12 mg/kg/day for six months. Animals were sacrificed in each group after 3, 6, 12 or 24 months. All diets containing the compound under test were rejected by the animals to some extent during the first stages of the treatment, particularly at the highest levels. Diets designed to administer 12 mg/kg/day were very unpalatable; many dogs completely refused diets at this level, most progressively lost weight and some died of starvation. Ingestion of 6 mg/kg/day for two years caused no direct toxic effect on tissues, but did cause an apparent reduction in final body weight, which in turn affected organs to body-weight ratios, but no pathological changes were found. At the 3 mg/kg/day dietary level, mortality, behaviour, food intake, growth rate, gross and microscopic pathology, haematology and biochemical values were comparable to the controls. The same conclusion applies to organ-weights and ratios, except for statistically significant increased heart to body-weight ratio averages, but not actual heart weights, in both sexes, and average liver weight and ratio in the males only. These observations were not associated with significant alterations in these two organs at either the interim or final necropsy periods or upon microscopic examination. Copper content in the urine was decreased at all dose levels examined. A notable undefined effect in dogs was a tanning or brown discoloration of the serosal surface of the small intestine in dogs fed 3 and 6 mg/kg levels. This effect was not noted at 0.75 mg/kg. Measurement of tin content indicated higher levels of tin in all tissues examined. Levels in the males were lower than in the females and were proportional in both sexes to the dietary intake. An equilibrium level was apparently reached between six and 12 weeks of feeding and remained constant for the remainder of the testing. Tissues of rats and dogs contained similar concentrations of tin, except for the liver of dogs, which contained five to 14 times the tin content of rats and a higher proportion of inorganic tin. No signs of toxic injury were observed at the level of 0.75 mg/kg (Hine, 1970). Rabbit Tricyclohexyltin hydroxide administered to the conjunctival sac resulted in irritational corneal injury which subsided in one week (Olson, 1964). Groups of rabbits (ten male and ton female) were treated dermally at doses of 0, 1.2, 6, 12 or 60 mg/kg/body-weight/day, five days per week for three weeks. All animals developed erythema, oedema, atonia, desquamation and fissuring of the skin. The signs of toxicity were severe at all done levels examined. Other than dermal problems, no other effects were noted (Wazeter, 1969). Rat Exploratory experiments in rats showed that an oral dose of 12.5 mg/kg body-weight/day did not produce tissue damage when given daily by gavage for 19 days. A dose of 25 mg/kg/day was toxic within two weeks, and doses of 50 and 100 mg/kg/day were toxic within one week. Rats that received 12 mg/kg body-weight/day for ten or 16 weeks showed no direct toxic effects. Poor weight gain observed at this dietary level was judged to be caused by unpalatability of diets containing tricyclohexyltin hydroxide. Due to diet unpalatability, higher doses had to be administered by gavage. Direct toxic effects were not achieved until doses of 25 mg/kg bodyweight/day were administered. This level resulted in clinical symptoms, such as severe diarrhoea and weight loss, as well as morphological effects, such as gastroenteritis, intrahepatic and extrahepatic cholangitis, degenerative changes in adrenal glands and toxic nephrosis (Tucker, 1966). Long-term studies Rat A total of 720 rats, half males and half females, aged four weeks, were fed 0, 0.75, 3, 6 or 12 mg tricyclohexyltin hydroxide/kg body-weight/day for up to two years. None of the dietary levels of treatment caused any change in behaviour, mortality records, haematologic and biochemical values, gross appearances and histological characteristics of organs and tissues. Effects observed at the 12 mg/kg level wore decreased weight gains in both sexes and increased organ to body-weight ratios for spleen and liver in the females. The pattern of tumour incidence appeared to be random and not suggestive of a dose relationship. The occurrence of many cysts seen throughout this study at all levels may be related to the particular strain of animals, although in the females at 12 mg/kg, 17 liver cysts and five pituitary cysts were noted as compared to one liver cyst and five pituitary cysts in the controls. At six mg/kg, only a slight decrease of food intake and a related mild depression of growth rate were observed during the first three months on treatment. These effects were absent at the level of 3 mg/kg (Hine, 1970a). OBSERVATIONS IN MAN A wettable powder formulation (50 percent tricyclohexyltin hydroxide) was examined for its irritation and sensitization potential to human subjects. No adverse reactions were observed in 53 females following sensitization applications and a challenge application 20 days later of 0.5 ml of a 0.1 percent emulsion. Tricyclohexyltin hydroxide was not dermally irritating at a concentration of about 0.01 mg/kg body-weight (Laker et al., 1966). COMMENT The Meeting expressed concern that the only toxicological data that had been presented for consideration were unpublished, and had therefore not already been subject to critical scrutiny by the general scientific community. A difficulty with the toxicological evaluation of this compound is that its presence made laboratory diets unpalatable. A need for carefully controlled paired-feeding experiments was therefore evident. Concern was expressed that residual tin remained in the tissues of exposed animals for prolonged periods and that brown discoloration of the serosal surface of the small intestine occurred in dogs fed 3 mg/kg body-weight/day or higher dose levels of the compound. It was noted that, in dogs fed 0.75 mg/kg body-weight/day or more, there was a reduction in urinary copper output. In view of this observation, the need for information on the copper content of the liver of exposed animals was stressed. The observation of an increased incidence of cysts of the liver and pituitary gland of female rats fed 12 mg/kg body-weight/day was regarded with some concern. For these reasons the Committee considered that only a temporary acceptable daily intake could be established. TOXICOLOGICAL EVALUATION Level causing no toxicological effects Dog: level in the diet adjusted to give 0.75 mg/kg body-weight/day Rat: level in the diet adjusted to give 3 mg/kg body-weight/day ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR MAN 0-0.0075 mg/kg body-weight RESIDUES IN FOOD AND THEIR EVALUATION USE PATTERN Pre-harvest treatments Tricyclohexyltin hydroxide is a non-systemic acaricide used or under development for use in several countries to control phytophagous mites on apple and pear trees. The compound exhibits little or no activity against insects,including pollinating bees,and it is relatively harmless to predatory mites. Thus it may be advantageously applied in integrated control schemes (Gray, 1968; Zambelli et al., 1968; Jeppson et al., 1968). Typically, tricyclohexyltin hydroxide is recommended for use in dilute sprays at concentrations of 15 to 30 g/100 litres, the total amount applied per unit area ranging from 0.42 to 1.68 kg/hectare. In addition to use on apples and pears, tricyclohexyltin hydroxide is expected to prove useful for control of mites on stone fruits, citrus, grapes and certain other crops. Post-harvest treatments Post-harvest use on apples is under investigation. RESIDUES RESULTING FROM SUPERVISED TRIALS The following typical data (Table II) are extracted from unpublished reports supplied to FAO/WHO by Dow Chemical Company (Getzendaner, 1968; Komblas, 1969; Getzendaner and Corbin, 1969; Anon, 1970b). FATE OF RESIDUES General comments Tricyclohexyltin hydroxide is decomposed by sunlight as evidenced by (1) a half-life of 8 "sunny days" for disappearance from glass slides (Smith et al., 1970c) and (2) detection of inorganic tin as approximately 15 to 30 or more percent of the total tin residues on fruit exposed to 3 or 4 applications of the miticide (Getzendaner and Corbin, 1969). TABLE II Residues found in apples and pears in various countries Rate of Number Post-treatment Residue, total tin, Location application of interval as Cy3SnOH, ppm g/100 l Treatments days average maximum APPLES U.S.A. 15 1 0 0.8 - 8 1.0 - 16 0.6 - 32 0.5 - TABLE II (cont'd) Residues found in apples and pears in various countries Rate of Number Post-treatment Residue, total tin, Location application of interval as Cy3SnOH, ppm g/100 l Treatments days average maximum APPLES U.S.A. 23 4 0 1.7 2.5 14 1.6 2.2 28 1.1 1.5 35 0.9 1.0 Netherlands 25 4 0 1.2 1.9 14 1.2 1.6 28 0.5 0.7 42 0.5 0.7 Italy 30 2 7 1.1 1.3 16 1.2 1.3 28 0.8 1.0 U.S.A. 30 3 17 1.9 - Australia 30 3 0 - 1.94 France 30 1 0 0.7 1.8 15 0.5 0.5 42 0.4 0.4 Japan 33 3 0 2.0 - 14 1.5 - 30 1.1 - PEARS U.S.A. 23 3 0 1.4 2.1 15 1.1 1.4 29 0.7 1.0 42 0.6 0.6 61 0.4 0.6 Australia 23 1 31 - 1.0 Italy 30 2 7 1.0 1.5 16 0.8 1.0 28 0.4 0.6 Photodegradation occurs by the sequence, which is identical with that owing in the animal body:
Tricyclohexyltin hydroxide is not volatile from dry surfaces, but 'co-distils', with water from moist surfaces at a slow but finite rate (Smith et al., 1970). Field experiments show that the half-life of the compound is about four days on grass and about three weeks on apples and pears; the disappearance results from photodegradation, 'co-distillation' with water from moist surfaces and weathering factors (Getzendaner and Gentry, 1970a; Getzendaner and Corbin, 1969). In animals As indicated under "BIOCHEMICAL ASPECTS", tricyclohexyltin hydroxide is not readily absorbed from the gastrointestinal tract. When the miticide is fed daily to rats, dogs or cattle, tin compounds, primarily unchanged tricyclohexyltin hydroxide, accumulate in the tissues to a limited extent, reach equilibrium values in a few months to a year, and are slowly eliminated from the tissues after the compound is withdrawn from the diet. It does not selectively partition into fat, and the distribution pattern in tissues is similar for rats, dogs and cattle (Smith and Fischer, 1970; Anon, 1970a; Getzendaner and Gentry, 1970b). For example, tissues from calves fed 30 ppm of the compound in the diet for 90 days showed 0.07 ppm total tin in fat, 0.09 ppm in muscle, 0.37 ppm in liver and 0.20 ppm in kidney (Getzendaner and Gentry, 1970b). Levels of tricyclohexyltin hydroxide equivalent were 0.05 ppm in milk and 0.4 ppm in cream obtained from cows fed 100 ppm of the compound in the diet for 53 days (Getzendaner and Gentry, 1970c). In plants Residues occurring on apples were identified by a series of extraction techniques followed by analysis. Tricyclohexyltin hydroxide was the main component of the tin residues, comprising 67% (0.66 ppm) of the residue (eight days post-treatment). Small amounts of dicyclohexyltin oxide and cyclohexylstannoic acid were present (5% of each), as well as 23% inorganic tin (Getzendaner, 1968). Tricyclohexyltin hydroxide and its sunlight decomposition products are not translocated in plants to a significant extent. This has been demonstrated by (1) the absence of significant residues of tin compounds in the interior portions of fruit, even after periods of several months between application of the first of up to 5 spray applications and harvest (Getzendaner and Corbin, 1969), (2) the absence of radioactive residues in bean and maize plants grown in soil treated with exaggerated amounts (3 lb/acre) of 119Sn-labelled miticide or its degradation (Smith at al. 1970), and (3) the essential absence of translocation across the narrow thickness of the leaf of cotton plants as determined by bioassay experiments (Allison, 1969). In soil Tricyclohexyltin hydroxide is markedly absorbed by soil and it is not leached from soil, as demonstrated by soil-column leaching studies and by study of the transfer from water to soil (Smith et al., 1970a, Smith and Taylor, 1970; Whitney, 1966). No significant amounts of the miticide will remain in or on the soil from one growing season to the next. In storage and processing Results of several residue trials, involving separate analysis of peel and pulp or surface extraction, indicate that at least 90% of the residue in or on apples and pears is on the surface of the fruit (Getzendaner, 1968; Komblas, 1969; Getzendaner and Corbin, 1969). Typically, about 0.1 ppm tricyclohexyltin hydroxide equivalent may be expected in fruit when the peeling is removed. Mild water washing removed up to 50% of the residue from apples and pears with an average of >20% removed (Getzendaner and Corbin, 1969). Evidence of residues in food in commerce or at consumption No information is available. METHODS OF RESIDUE ANALYSIS Corbin (1970) recently published a method suitable for determination of the total organotin and inorganic tin present in fruit The sample is subjected to a wet oxidation treatment with sulfuric and nitric acids to destroy organic matter, remove volatile acids and halogens and convert the tin to a soluble inorganic form. The tin is then separated from elements which would interfere in the colorimetric method (heavy metals) and from non-interfering salts. This separation involves extracting tin as SnI4, with n-hexane from a strong sulfuric solution of KI. Evaporation of hexane and conversion to sulfate leaves the tin in a form measurable by a dithiol colorimetric method. Sensitivity of the method is 0.01 ppm. Optional steps are included in the method for removal of arsenic and antimony, if these elements are suspected of being present in amounts which might cause interference (> 0.15 mg and > 2 mg, respectively). A complementary method has been developed for determining residues of organotin in fruit by M & T Chemicals (Anon, 1969). Tri-, di-, and monocyclohexyltin are solubilized by treatment of the fruit sample with hydrochloric acid (9 molar) and then extracted with chloroform from inorganic tin and heavy metals, which remain in the acidic aqueous phase. The organotin compounds are then oxidized and determined colorimetrically. NATIONAL TOLERANCES Tolerances have been established (provisional) or are proposed for residues of tricyclohexyltin hydroxide in or on apples and pears in various countries including the following: Country Tolerance Withdrawal between ppm treatment and harvest, days Australia1 3 2 Belgium 12 28 Italy 1 20 Israel 1 30 Netherlands 1 28 U.S.A. 23 14 1 Stone fruits 2 Proposed 3 Tolerance proposed on 23 June 1970 Use of the miticide is registered for apples and pears in Chile, France and Korea, but without provision for tolerance. APPRAISAL Tricyclohexyltin hydroxide is a non-systematic acaricide now used in many countries and likely to be used worldwide on apples and pears, with indications of future use on citrus, stone fruits and other crops. Post-harvest use on apples is under investigation. The compound is relatively harmless to beneficial insects and mites, and it is usefully applied to integrated control schemes. Tricyclohexyltin hydroxide is used as wettable powder at a rate of about 0.5 to 1.5 kg per hectare. Comprehensive residue data on tricyclohexyltin hydroxide on apples and pears are available from the United States and from five other countries, which are consistent with those from the U.S.A. Residue data on other crops were not available to the Meeting. When apples and pears are peeled, most of the tricyclohexyltin hydroxide residue is removed; only 0.1 ppm may be expected in the fruit flesh. Washing is found to remove 20-50% of the residues, more from apples than from pears. Field experiments show that the residues of tricyclohexyltin hydroxide declined to half in about three weeks on apples and pears. The disappearance is due to photodegradation, codistillation with water and weathering factors. The residues are found to occur on the surface of the treated plants. The degradation of tricyclohexyltin hydroxide is found to produce dicyclohexyltin oxide and monocyclohexylstannoic acid and finally inorganic tin salts. The absorption of tricyclohexyltin hydroxide from the gastrointestinal tract of animals is small. The distribution patterns of the compound are determined in rats, dogs and cattle. When cows were fed residues of 30 and 100 ppm, the residues found in milk were less than 0.1 ppm and in various tissues less than 0.5 ppm. Limited feeding of apple and pear pulp to cows is not expected to produce detectable residues in meat or milk. A colorimetric method with a detectability of 0.01 ppm tin is available to determine tricyclohexyltin hydroxide and its organic degradation products. The method is not able to distinguish between the various compounds,but reflects the total amount of the compounds in the sample analyzed. RECOMMENDATIONS FOR TEMPORARY TOLERANCE The tolerance is expressed in terms of tricyclohexyltin hydroxide. The organic degradation products and the inorganic tin salts derived from tricyclohexyltin hydroxide are not included in the tolerance. A temporary tolerance of 2 ppm, based on an interval of two weeks from the last treatment to the harvest, is recommended for apples and pears. FURTHER WORK OR INFORMATION REQUIRED (by June 1973) 1. Further studies on the effects of exposure to tricyclohexyltin hydroxide on copper balance and, in particular, on the copper content of the liver. 2. Further information on the occurrence of liver and pituitary gland cysts in female rate fed the compound. 3. Further information on the effect of the compound on the rate of body-weight gain after allowing for the unpalatability of test diets. 4. Further information on the significance of the brown discoloration of the serosal surface of the intestine of treated animals. 5. Establishment of analytical procedures capable of distinguishing qualitatively between tricyclohexyltin compounds and other organotin compounds, particularly the fentin compounds, and, where possible, of quantitative measurement of the separate compounds. DESIRABLE Data on residues of tricyclohexyltin hydroxide on apples and pears moving in international commerce. REFERENCES Allison, W.E. (1969) An evaluation of the systemic (soil and foliar) acaricidal activity of tricyclohexyltin hydroxide. Unpublished report from the Dow Chemical Co. Anon. (1969) Determination of small amounts of organotin in macerated fruit. Method No. TA-2-2. Unpublished report from M & T Chemicals, Inc. Anon. (1970a) Tin content of tissues of rats and dogs fed varying amounts of tricyclohexyltin hydroxide in the daily diet for two years. Unpublished report from the Dow Chemical Co. Anon. (1970b) Compilation of studies on residues of tricyclohexyltin hydroxide in or on apples and pears: Australia, France, Netherlands, and Japan. Unpublished report Anon. (1970c) Dicyclohexyltin oxide: summary of acute oral toxicity tests. Unpublished report from the Dow Chemical Company Corbin, H.B. (1970) Separation and determination of trace amounts of tin present as organotin residues on fruits. J. Assoc. Offic. Anal. Chemists, 53: 140-146 Getzendaner, M.E. (1968) A review of residue information on tricyclohexyltin hydroxide. Unpublished report from the Dow Chemical Co. Getzendaner, M.E. and Corbin, H.A. (1969) Residue study: inorganic and organic tin compounds in or on apples and pears from field applications of PLICTRAN(R) miticide. Unpublished report from the Dow Chemical Co. Getzendaner, M.E. and Gentry, W.M. (1970a) Determination of tin residues in orchard grass exposed to tricyclohexyltin hydroxide miticide. Unpublished report from the Dow Chemical Co. Getzendaner, M.E. and Gentry, W.M. (1970b) Determination of tin residues in beef calves fed tricyclohexyltin hydroxide for ninety days. Unpublished report from the Dow Chemical Co. Getzendaner, M.E. and Gentry, W.M. (1970c) Determination of tin residues in milk, cream, and body tissue of dairy cows fed tricyclohexyltin hydroxide. Unpublished report from the Dow Chemical Co. Gray, H.E. (1968) PLICTRAN miticide - new approach to mite control. Down to Earth, 23 (4): 3-5 Hine, C.H. (1966) Acute oral toxicity of tricyclohexyltin hydroxide in Long Evans strain rats (17 March 1966). Unpublished report from the Hine Laboratories, Inc. to Dow Chemical Co. Hine, C.H. (1967) Acute oral toxicity: Cyclohexylstannoic-acid, dicyclohexyltin oxide, tetracyclohexyltin, hexacyclohexylditin. Unpublished report from the Hine Laboratories, Inc. Hine, C.H., Brownlow, E.K., Cummins, J.T., Eisenlord, G.H. and Wong, L.C.K. (1969) Studies on the mechanism of action of DOWCO 213. Unpublished report from the Hine Laboratories, Inc. Hine, C.H., Eisenlord, G.H. and Laudel, A. (1969a) DOWCO 213 reproduction and teratology studies in rats. Unpublished report from the Hine Laboratories, Inc. Hine, C.H., Eisenlord, G.H. and Laudel, A. (1969b) DOWCO 213 reproduction and teratology studies in rabbits. Unpublished report from the Hine Laboratories, Inc. Hine, C.H. (1970a) Results of two-year dietary feeding study with tricyclohexyltin hydroxide (DOWCO 213) in dogs. Unpublished report from the Hine Laboratories, Inc. Hine, C.H. (1970b) Results of two-year dietary feeding study with tricyclohexyltin hydroxide (DOWCO 213) in rats. Unpublished report from the Hine Laboratories, Inc. Jeppson, L.R., Jesser, M.J. and Complin, J.O. (1968) Responses of the pacific spider mite and the citrus red mite to laboratory and field applications of tricyclohexyltin hydroxide. J. Econ. Entomology, 61: 1502-1505 Kenaga, E.E. (1968) The rodent toxicity and repellency of tricyclohexyltin compounds to two species of mice. Unpublished report from the Dow Chemical Co. Komblas and Kostas N. (1969) Determination of residues of PLICTRAN acaricide on apples and pears in Italy. (Translation of report of Societá Italo-Americana Prodotti Antiparassitari, Balliera/Bologna, Italy). Unpublished report from the Dow Chemical Co. Laker, T.L., Elsea, J.R. and Ede, M. (1966) Repeated insult patch test on M-2527 and cloth material TE98-SEU3501. Unpublished report from Hill Top Research, Inc. Norris, J.M. (1968) Toxicity of tricyclohexyltin hydroxide via i.p. route in laboratory animals. Unpublished report from the Dow Chemical Co. Olson, K.J. (1964) Results of range finding toxicological tests on tricyclohexyltin hydroxide. Unpublished report from the Dow Chemical Co. Smith, G.N., Axelson, R.J. and Schiesser, L.H. (1970) The loss of PLICTRAN(R) miticide from various soils. Unpublished report from the Dow Chemical Co. Smith, G.N. and Fischer, F.S. (1970) Metabolism of PLICTRAN(R) miticide. Observations on the absorption, distribution, and excretion of tricyclohexyltin-Sn119 hydroxide in white rats. Unpublished report from the Dow Chemical Co. Smith, G.N., Fischer, F.S. and Axelson, R.J. (1970) The volatilization and photodecomposition of PLICTRAN(R) miticide. Unpublished report from the Dow Chemical Co. Smith, G.N. and Taylor, Y.S. (1970) The absorption and translocation of PLICTRAN miticide and its decomposition products in bean and corn plants. Unpublished report from the Dow Chemical Co. Stevenson, G.T. and Kenaga, E.E. (1969) The effects of dietary feeding of tricyclohexyltin hydroxide on the life stages of the Japanese Quail. Unpublished report from the Dow Chemical Co. Tucker, W.E. (1966) Oral toxicity studies of tricyclohexyltin hydroxide in rats. Unpublished data from the Dow Chemical Co. Wazeter, F.X., Buller, R.H., Geil, R.G. and Long, J.E. (1968) Dicyclohexyltin oxide: 90-day feeding study in the Long-Evans rat. Unpublished report from the International Research and Development Corporation Wazeter, F.X. (1969) 21-day dermal study in,albino rabbits-PLICTRAN M-3180 miticide. Unpublished report from the International Research and Development Corporation Whitney, W.K. (1966) Leaching tests with DOWCO 213 in soil Zambelli, N., Komblas, W. and Kovacs, A. (1968) PLICTRAN miticide for the control of spider mites in Italy. Down to Earth, 24(3): 25-31
See Also: Toxicological Abbreviations Tricyclohexyltin hydroxide (WHO Pesticide Residues Series 3)