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    sec-BUTYLAMINE     JMPR 1975

    IDENTITY

    Chemical name

         2-amino butane

    Synonyms

         2-AB, 'Tutane'(R),  'Deccotane'(R), 'Frucote'(R)

    Structural formula

                   CH3CH2CH(NH2)CH3

              Empirical formula:  C4H11N

              Molecular weight:   73.14

              B.P. 63C

              V.P. 135 mm Hg at 20C

              N20 1.394
               D

              d20 0.724
               4

    Other information on identity and properties

         sec-Butylamine is a colourless liquid with an ammoniacal odour.
    It has a boiling point of 63C and a vapour pressure of 135 mm Hg at
    20C. It is miscible with water and most organic solvents.

         sec-Butylamine is an organic base, forming water-soluble salts
    with acids. Having an asymmetric carbon atom, it exists as optical
    isomers. sec-Butylamine occurs together with a number of primary and
    secondary amines as natural components of citrus peel and juice. It is
    stable but corrosive to tin, aluminium and some steels.

         Formulated products include not only the base but the phosphate
    and carbonate salts. The hydrochloride is referred to in some early
    literature but is apparently not used commercially as it corrodes
    equipment. The commercial product contains 25% sec-butylamine or 26%
    of the carbonate equivalent to 15.5% sec-butylamine.

         The product is used alone. Compatibility with other pesticides
    and adjuvants is unknown. Mixed solutions are not stable beyond three
    days and concentrates or mixed solutions require protection from
    direct light or extremes of temperature.

    EVALUATION FOR ACCEPTABLE DAILY INTAKE

    BIOCHEMICAL ASPECTS

    Absorption, distribution and excretion

         Studies were carried out on the distribution of sec-butylamine
    in edible tissues, milk and excretory products of cows.
    sec-Butylamine is apparently rapidly absorbed as evidenced by its
    presence in milk at three days after feeding. The two to three day,
    interval was the first assayed and the level from that time on for the
    remainder of a feeding trial was constant.

         Residues of sec-butylamine were found in muscle, liver, fat and
    kidney in a dose relationship at 100 and 10 ppm (but not 2 ppm) levels
    in the diet fed to cows for up to 28 days. The residues were found in
    samples taken at 0 withdrawal time after feeding (animals were fed
    diets containing sec-butylamine until sacrificed). Data on the
    presence of sec-butylamine in urine and faeces suggest that it is
    readily absorbed into the blood and excreted primarily in the urine
    (Anonymous, 1975).

         No definitive metabolism studies have been performed.

    Biotransformation

         Urinary samples from two dogs treated daily with 5000 ppm or 10
    000 ppm were acidified and distilled. A diphenyl hydrozone was formed
    which corresponded to the product formed from a reaction with methyl
    ethyl ketone. Methyl ethyl ketone formed from the deamination of
    sec-butylamine and appeared to be excreted. The amine nitrogen
    entered the biological pool and was lost (Worth and Meyers, 1965).

    TOXICOLOGICAL STUDIES

    Special studies on pharmacological response

         Groups of dogs were administered sec-butylamine as the
    carbonate or acetate salt and data were recorded an heart rate,
    respiration rate, blood pressure and with an EEG apparatus.
    Intravenous administration of either the acetate or carbonate resulted
    in elevated blood pressure, heart rate and respiration. Intragastric
    administration of larger doses resulted in similar responses. It was
    suggested that the primary acute response is similar to other amines
    producing a standard sympathomimetic response (Worth and Henderson,
    1965).

    Special studies on reproduction

         Rat

         Groups of rats (20 male and 20 female rats per group) were fed
    sec-butylamine acetate at levels of 0, 500 and 2500 ppm in a two
    litter per generation, four generation reproduction study. The Fo
    parents were allowed to bear six additional litters. The F1b, 2b and
    3b litters were used as parents for the following generation and
    maintained for varying periods (162-202 days after weaning their
    respective litters). Reproduction indices, fertility index, gestation
    index, viability index and lactation index, were normal. A reduction
    of growth was noted throughout the study at the high dietary level.
    Reproduction was unimpaired for any of the eight litters produced by
    the Fo generation (Worth et al., 1969a,b).

         Rabbit

         Groups of rabbits were fed sec-butylamine phosphate in the diet
    and subjected to a two generation, one litter per generation
    reproduction study. Two groups of rabbits (10 males and 14 females in
    the treatment group; 5 males and 10 females in the control group) were
    fed for 53-54 days and the females artificially inseminated with semen
    collected from two control and two treated males. The dietary levels
    were 0 and 2500 ppm. The F1a were maintained for six months, divided
    into groups of 6 males and 12 females, fed 2500 ppm sec-butylamine
    phosphate with 5 males and 8 females fed control diets. These animals
    were bred by insemination, allowed to bear young, maintained for 63
    days and discarded. On postpartum day 14 and day 28 milk samples were
    taken and analysed for sec-butylamine.

         Mortality of several rabbits was evident at an original dose
    level of 5000 ppm. After the rabbits on this level were switched to
    the 2500 ppm regimen, mortality and growth of all animals was normal.
    The dietary level of 2500 ppm had no effect on fertility, duration of
    gestation, delivery of live progeny or lactation indices in both
    generations examined. Growth of progeny in the F1 generation was
    normal while it was slightly depressed in the F2. There were no
    effects noted on survival of offspring in either generation. There was
    a constant level of sec-butylamine found in milk at both the 14 and
    28 days ranging from 20 to 77 ppm in the F1 and 19 to 84 in the F2.
    (The analytical method used in the study is sufficient to detect
    sec-butylamine in milk but the sensitivity is questionable as food
    samples containing 2500 ppm were found to contain 1770-1820 ppm or a
    recovery of 72%. The study suggests that the F1 and F2 generation were
    exposed to the pesticide from parturition.) The presence of 2500 ppm
    sec-butylamine in the diet had no effect on reproduction in the
    rabbit (Gibson et al., 1970).

    Special studies on teratogenicity

         Rabbit

         Groups of Dutch Belted does (10 rabbits per group) were
    administered sec-butylamine acetate at a dose of 0, 75 and 150 mg/kg
    daily from day 8 through day 18 of gestation. On day 28 the does were
    sacrificed and half of the foetuses were examined for gross and
    skeletal abnormalities. Half of the foetuses were incubated for 24
    hours to assess viability after which they were examined and
    discarded. Mean foetal weight appeared lower than controls and a
    decreased viability of live foetuses was noted at the high dose level.
    There were no differences from controls with respect to reproduction,
    sex distribution of foetuses or in the number of malformations
    observed (Worth et al., 1966).

    Acute toxicity

                                                                                                    

                                    LD50               Chemical
    Species            Route        (mg/kg)            form                     Reference
                                                                                                

    Mouse              Oral         660                base             Worth and Anderson, 1965
                                    1750-2470          salt*                        "
                       iv           225                base                         "

    Rat                Oral

      Newborn                       350                base                         "
      Weanling                      350                base                         "
      Adult                         380                base                         "

      Newborn                       430-690            salt*                        "
      Weanling                      1270-1660          salt*                        "
      Adult                         1510-4600          salt*                        "

                       Inhalation   3.5 mg/L           salt & base*                 "

    Guinea-pig         Oral         880                salt*                        "

    Dog                Oral         250                base                         "

                                    250-500            salt                         "

    Rabbit             Dermal       2500               base & salt*                 "
                                                                                                

    *Little differences were noted in four salt forms (acetate,
    phosphate, carbonate, and HCl) and the range for these is presented.
    
         Signs of poisoning in rat included salivation for two hours
    before convulsion. In rats and mice acute gastritis, excessive mucus
    secretion and respiratory paralysis were noted. In dogs foamy bloody
    vomitus, depression tremors and mydriasis were observed. In primary
    dermal irritation studies, salts of sec-butylamine were
    non-irritating while the base administered at 0.7 mi/animal was a
    primary irritant.

    Short-term studies

         Rat

         Groups of rats (10 male and 10 female rats per group) were fed
    sec-butylamine acetate in the diet for three months at levels of 0,
    312.5, 625, 1250, 2500 and 5000 ppm. A significant growth reduction
    was noted at 5000 ppm. A dose-dependent leukopenia in both males and
    females was recorded although no other effects on clinical chemistry
    parameters were observed. Gross and microscopic examination of tissues
    and organs showed no adverse effects of dietary sec-butylamine
    (Worth et al., 1965).

         Rabbit

         A group of rabbits (6 males and 6 females) were treated dermally
    for 20 days at a daily dose of 2 ml/kg of a 10% solution of
    sec-butylamine acetate. A surfactant was present in the aqueous
    solution. The skin of half of the animals was abraded prior to
    initiation of the study. There was no mortality and only one animal of
    the abraded group showed adverse reactions (diarrhoea) during the
    study. Growth, clinical chemistry, haematology and gross and
    microscopic examination of tissues and organs were normal (study
    reported in summary only) (Worth et al., 1965).

         Dog

         Groups of mongrel dogs (2 male and 2 female dogs per group) were
    administered sec-butylamine acetate by capsule for 91 days at levels
    equivalent to 0, 1250, 2500 and 5000 ppm of the diet. (No indication
    of whether treatment was for five or seven days/week.) No effects were
    noted in this study on growth (body weight stability), haematology,
    clinical chemistry or gross and microscopic examination of tissues and
    organs (Worth et al., 1965).

         Groups of dogs (half the dogs were purebred beagles and half were
    mongrels - 4 male and 4 female dogs per group - 5 males and 3 females
    were used in the low treatment level) were fed or administered
    sec-butylamine acetate by capsule daily for periods of up to two
    years. All animals except four at the highest dose were administered
    capsules containing a dose of 0, 31, 62.5, 125 or 250 mg/kg daily. Two
    male and two female dogs (of the highest dose group) were administered
    the test material in the food (undefined diet reported to be
    equivalent to 10 000 ppm).

         Mortality (4/4) occurred in the highest group of dogs
    administered sec-butylamine acetate by capsule within three weeks of
    the start of the treatment. Mydriasis was reported as evident in all
    treated animals (including controls an one occasion). Lacrimation
    occurred at the highest treatment level accompanied by keratitis in
    three of the four treated animals. Two other deaths occurred (one male
    at 62.5 mg/kg and one male at 125 mg/kg) apparently not attributable
    to the sec-butylamine acetate. Abnormal behaviour was not observed
    in any treatment. Body weights at the termination of the study were
    normal in all animals including those dogs fed 10 000 ppm in the diet.
    Keratitis was observed in three of four dogs fed 10 000 ppm.
    Haematology values were normal except for a reduced haemoglobin and
    haematocrit value (especially in females) at 10 000 ppm. Urinalysis
    and clinical chemistry values were unaffected. Gross examination of
    tissues and organs indicated increased kidney weight and decreased
    spleen weight in females at 10 000 ppm. Leukocyte counts were normal
    as were bone marrow m/e ratios. Microscopic examinations of tissues
    and organs showed no pathological conditions. A no-effect level in
    this study is 125 mg acetate salt/kg body weight/day (equal to 69 mg
    base/kg body weight/day) (Worth et al., 1969b). 

    Long term studies

         Rat

         Groups of rats (30 males and 30 females per group) were fed
    sec-butylamine acetate in the diet for two years at dose levels of
    0, 1250, 2500 and 5000 ppm. Survival of rats over the two years was
    not affected by sec-butylamine acetate. Terminal body weight was
    slightly reduced in males at 5000 ppm. Haematological findings
    recorded at several intervals over the test period were normal.
    Leukocyte count averages at the end of the study were normal but the
    range of values suggested a possible leukopenia at 5000 ppm. Terminal
    male kidney weight was increased while prostate and testes were
    reduced. These changes were not evident in female kidney, ovary or
    uterus. Gross and microscopic examinations of tissues and organs,
    except where noted above, were normal. A no-effect level for this
    study is 2500 ppm acetate salt equal to 686 ppm base (Worth et al.,
    1969b).

    OBSERVATIONS IN MAN

         None.

         No definitive studies have been reported. A series of letters
    from industrial users of the material have been offered as suggestions
    that, although occupational exposure when handling the chemical is
    present, the hazard is low.

    COMMENTS

         sec-Butylamine, an agricultural fungicide, is absorbed in cows
    through the GI tract and distributed widely in the body within two to
    three days of high dietary dosing. An equilibrium level in body
    tissues, milk and excrete was apparent. sec-Butylamine was noted in
    milk of lactating cows and rabbits. sec-Butylamine is degraded by
    oxidative deamination to methyl ethyl ketone in the dog although a
    complete metabolic route has not been differentiated.

         The acute toxicity of sec-butylamine is low with all salt forms
    (acetate, carbonate, phosphate and hydrochloride) by several routes of
    administration. General sympathomimetic signs of acute poisoning have
    been noted in acute studies in rodents and dogs and in pharmacological
    studies in dogs. Reproduction studies in rats and rabbits, including a
    study for teratological potential, were negative. Short- and long-term
    studies suggest a no-effect level of 1250 ppm of the acetate salt in
    rats (equivalent to 63 mg acetate salt/kg/day) and 125 mg acetate salt
    kg/day in dogs. The value of 1250 ppm in rats was based on the effect
    on growth noted in the reproduction study. The no-effect levels were
    recalculated and expressed as the free base. A dose-dependent
    leukopenia, observed in rat, did not appear to be critical. Leukopenia
    was not noted in the dog.

         The carcinogenic potential of sec-butylamine was judged to be
    low based on the long-term feeding study.

         Data were sufficient to estimate a no-effect level and to
    allocate a temporary ADI. A larger margin of safety reflected such
    considerations as the probable occurrence of residues in milk and meat
    and the lack of studies to define the mutagenic potential.

    TOXICOLOGICAL EVALUATION

    Level causing no toxicological effect

         Rat:      686 ppm base (1250 ppm acetate salt) in the diet
                   equivalent to 35 mg base/kg bw (63 mg acetate salt/kg
                   bw).

         Dog:      69 mg base/kg bw/day (125 mg acetate salt/kg bw/day).

    ESTIMATE OF TEMPORARY ACCEPTABLE DAILY INTAKE FOR MAN

         0-0.2 mg base/kg bw.

    RESIDUES IN FOOD AND THEIR EVALUATION

    USE PATTERN

         sec-Butylamine is a fungicide particularly effective for the
    control of many fruit-rotting fungi. Aqueous solutions of its salts
    containing 0.5-2% amine are used as dips or sprays on harvested fruit
    to prevent decay in transport or storage. The amine has been used
    experimentally to fumigate harvested fruit at 100 ppm by volume for
    four hours or its equivalent. In neutral aqueous solution, the salts
    of the optical isomers show marked differences in fungicidal activity.
    The control of Penicillium decay of oranges is due largely to the 1(-)
    isomer (Eckert et al,, 1972). sec-Butylamine is non-phytotoxic to
    most fruits at 10 times the recommended concentration.

         Since the discovery at the University of California of the
    fungicidal activity of sec-butylamine (Eckert and Kolbezen, 1962),
    many workers have reported outstanding results on the control of a
    variety of post-harvest diseases of many varieties of citrus. The
    following are some of the more important references to the performance
    of sec-butylamine in general and particularly on citrus: Eckert,
    1967, 1969; Eckert and Kolbezen, 1962, 1963, 1964, 1970; Eckert et
    al., 1966, 1969, 1972; Gutter, 1967; Jarrett and Gathercole, 1964;
    McCornack and Brown, 1965; McCornack and Hopkins, 1965; MacLean and
    Dewey, 1964; Pierson, 1966; Seberry, 1969; Seberry and Baldwin, 1968;
    Vanderweyen et al., 1965.

         There are a number of scientific papers indicating the
    suitability of sec-butylamine for the control of post-harvest decay
    of apples, pears, peaches and bananas. These include Eckert and
    Kolbezen (1964), MacLean and Dewey (1964), Pierson (1966).

         The use of sec-butylamine was registered in the United States
    of America in 1972 (EPA, 1972, 1973; Bruner, 1974, 1975).

         The recommendations for the control of Penicillium moulds of
    citrus involve drenching the fruit in boxes or bins in a 1% solution
    of sec-butylamine. For spray treatment on packing lines a 2%
    solution of the active ingredient is recommended. To attain the best
    disease control the fruit must not be rinsed with fresh water after
    treatment. Fumigation treatment, though effective, is not practical
    because of difficulty in maintaining an adequate concentration in the
    fumigation chamber.

         For the control of stem-end rot more intensive treatment is
    required. This involves dipping in a 1% solution for one to five
    minutes, or drenching for at least three minutes. For the control of
    stem-end rot by treatment on packing lines, a much more concentrated
    solution is required. Careful control of the concentration of the
    dipping and spraying fluid is essential. Ph control is essential.

         Although phytotoxic damage is not reported from treatments with
    sec-butylamine, field injury of fruit may be more apparent after
    treatment.

         As far as it is known sec-butylamine has not been registered
    for use on other fruits and there is no indication that it is used
    commercially for fruits other than citrus.

    RESIDUES RESULTING FROM SUPERVISED TRIALS

    Pre-harvest treatments

         There is no indication that sec-butylamine has any pre-harvest
    application to crops, but Kolbezen et al. (1962a, 1969) have shown
    that ripe citrus contains appreciable amounts of endogenous primary
    and secondary amines including sec-butylamine. Results of a typical
    analysis are shown in Table 1,


    TABLE 1. Endogenous amines of Valencia oranges (mg/kg)

                                                      

     Amine          Peel      Juice
                                                      

     methyl         0.36      Tr

     dimethyl       0.42      0.13

     ethyl          5.0       1.3

     isopropyl      0.082     Tr

     sec-butyl      0.029     0.009

     isobutyl       0.13      Tr

     isoamyl        Tr        Tr
                                                      


    Citrus fruit

         The following information is a summary of extensive data provided
    by Elanco (1968a,b).

         The mean level of sec-butylamine residues found in citrus fruit
    following application concentrations of 2% and less was 5.8 mg/kg with
    a range of 0.16-44 mg/kg. A dose-response correlation was observed
    when sec-butylamine was applied by dip or drench methods. However,
    the spray treatment did not show this relationship. The average
    residues, expressed as mg/kg sec-butylamine, resulting from various
    concentrations of treatment and method of application are shown below:

                                                                        

                            Dip or drench              Spray
                                                                        

    Concentration       0.5%    1.0%    2.0%        1.0%    2.0%

    Residue, mg/kg      1.8     3.9     6.6         6.8     6.0
                                                                        

         Separate analysis carried out on peel and pulp clearly indicate
    that the overwhelming majority of the residues is found in the peel
    portions, with the pulp showing only a trace of residue. In many
    instances, the pulp is free from sec-butylamine residue at a
    detectable level.

         The average residue found from many trials in each type of fruit
    from application concentrations of 2% and less is summarized in Table
    2.


    TABLE 2.  sec-Butylamine residues in citrus fruit from application
              concentrations <2%.

                                                          

                            Residue, mg/kg, average
                                                          

    Citrus type     Dip or drench     Spray     Dip + spray
                                                          

    Oranges         5.6               3.4       12.6

    Grapefruit      3.7               4.9       1.6

    Lemons          9.0               15.1      27.8

    Tangelos        23.5              -         -

    Tangerine       -                 9.5       -
                                                          

         The results of analysis of 250 samples of different citrus
    varieties have been grouped to show the distribution pattern of
    residue levels found in the whole fruit from all treatment levels
    (Table 3).

         A cross-section of extensive data (Table 4, Elanco, 1968a,b)
    shows the wide scatter in residue levels resulting from differing
    types of treatment with different rates of application. Duration of
    dipping, condition of fruit at time of dipping, nature of the pre- and
    post-treatment conditions, as well as concentration of fungicide in
    the dip or spray solution, all appear to affect the level of deposit.
    An analysis of the data suggests that if there is an influence of the
    formulation (carbonate or phosphate) on the level of residues
    deposited then it is frequently overshadowed by the variability in
    fruit and in packing-house practices.

         The method of application must be adapted to suit packing-house
    practice, variety of fruit being handled, amount of harvest injury,
    likely storage requirements and marketing requirements.

         Irrespective of the method of application or the amount of
    sec-butylamine deposited an the whole citrus fruit it is obvious
    from the data summarized in Table 5 that the amount of residue finding
    its way into the pulp is negligible. Eckert (1969) indicates that this
    is probably due to the impermeability of the surface cells of fruit to
    amine cations. Most data indicate that the amount of sec-butylamine
    reported to be found in pulp is at or about the limit of
    determination, and possibly reflects the presence of endogenous
    primary amines.

         Kolbezen et al. (1969) give an indication of the residues
    resulting from an adequate and effective fumigation (150 ppm) and from
    a double-dosage fumigation (300 ppm) when sec-butylamine is
    volatilized into a chamber holding various types of fruit. These data
    (Table 6) show residues broadly similar to those resulting from
    dipping or spraying treatments.

    Other fruits

         Although known to be effective against post-harvest rots of
    fruits other than citrus (Eckert and Kolbezen, 1964; McLean and Dewey,
    1964;  Pierson, 1966), the only information available to show the
    level of residues on other fruit is that given in the paper on
    analytical methods by Day et al. (1966). The tabulated data
    representing typical residues of sec-butylamine in fruit show
    residue levels in apples ranging from 2.3 to 19.3 mg/kg (five
    examples) and in peaches, 3.6 mg/kg (one example).


        TABLE 3. Distribution pattern of residues of sec-butylamine on various varieties of citrus fruits

                                                                                                          

                                   No. of samples of each variety found in range
                                                                                         Total samples
                                                                                             in each range,
       Residues                                                                              as% of total
    (range, mg/kg)     Orange      Grapefruit  Lemon     Tangerine   Tangelo     Total     samples analysed
                                                                                                          

       0-5             62              57      13            10      -           142       56.8

       5.1-10          15              17      8              4      -           44        17.6

       10.1-15         7                5      7              7      -           26        10.4

       15.1-20         5                2      7              3      1           18        7.2

       20.1-25         -                -      4              1      -           5         2.0

       25.1-30         -                1      6              2      -           9         3.6

       30.1-35         -                -      -              -      1           1         0.4

       35.1-40         -                -      -              1      -           1         0.4

       >40             -                -      2              1      1           4         1.6

    Total samples
    of each fruit
    analysed           89              82      47            29      3           250
                                                                                                          

    TABLE 4. sec-Butylamine residues in citrus fruit

                                                                                                       

                                                   Residue, mg/kg, after treatment with
                                                                                                 

                                                      Carbonate                    Phosphate

    Variety      Location            Treatment     1%            2%            1%             2%
                                                                                                       
    Oranges

    Temple       Florida             Dip           1.49                        4.86           11.0

    "            "                   "             1.37                        2.68           11.2

    "            "                   "             4.15                        3.38           8.13

    Pineapple    "                   "             3.20                        11.6           17.0

    "            "                   "             2.98                        7.2            12.4

    "            "                   "             2.41                        5.78           13.9

    "            "                   Drench        5.65          6.10          5.95           6.45

    "            "                   "             3.32          3.80          2.21           3.18

    Valencia     "                   Spray         1.1-2.4

    "            "                   "             2.88          3.44          2.00           2.50

    "            "                   "             4.00          5.45          2.96           3.45

    "            "                   "             2.36          2.78          2.45           2.93

    TABLE 4. (continued)

                                                                                                       

                                                   Residue, mg/kg, after treatment with
                                                                                                 

                                                      Carbonate                    Phosphate

    Variety      Location            Treatment     1%            2%            1%             2%
                                                                                                       

    "            California          Dip           0.58          1.73          0.69           0.69

    "            "                   Spray         1.73          3.76          4.00           6.32

    "            "                   "             3.32          3.06          1.03           2.16

    "            "                   Dip & spray                                              11.7-13.5

    Grapefruit

    Marsh        Florida             Dip           2.96          8.65

    "            "                   "             6.92          8.00

    "            "                   "             3.47          10.2

    "            "                   Drench        1.32          2.46

    "            "                   "             1.66          2.22

    Ruby Red     "                   "             2.06          4.58          2.92           2.96

    Duncan       "                   Spray         1.87          1.90          2.29           2.79

    "            "                   "             2.44          4.46          1.15           3.38

    Marsh        California          "                                         -              3.4-10.4

    TABLE 4. (continued)

                                                                                                       

                                                   Residue, mg/kg, after treatment with
                                                                                                 

                                                      Carbonate                    Phosphate

    Variety      Location            Treatment     1%            2%            1%             2%
                                                                                                       

    Lemons

    Eureka       California          Dip           1.93                        1.66

    "            "                   "                                         0.33-24.0      1.15-16

    "            "                   Spray                                                    0.67-44

                                     Dip & spray                                              27.8

    Tangerines

    Orlando      Florida             Dip                                       16.2           30.8

    "            "                   Spray         3.58          5.25

    Dancy        "                   "             1.29          3.46          8.10           13.35
                                                                                                       

    TABLE 5. Distribution of sec-butylamine residues within citrus fruits


                                                       Residue, mg/kg, after treatment with
                                                                                                  

                                                   1% solution                   2% solution
                                                                                                 

    Variety        Location     Treatment      peel    pulp    whole         peel    pulp    whole
                                                                                                  

    Oranges

    Valencia       Florida      Spray          2.34    0.42    1.34

    "              "            "              5.30    0.23    2.48

    "              "            "              2.05    0.39    1.19

    "              "            "              3.02    0       1.35

    Grapefruit

    Marsh          Florida      Dip            6.43    0.09    2.96          18.1    0.31    8.65

    Ruby Red       "            "              8.10    0       3.47          23.4    0       10.2

    Marsh          "            Drench         2.32    0       1.32          5.14    0       2.46

    "              "            "              1.58    0       0.82          5.50    0       2.72

    "              California   Dip            8.7     0       4.26

    "              "            Spray                                        4.18    0.09    2.02

    "              "            "                                            9.53    0.16    4.59

    "              "            Dip & spray    3.42    0       1.57

    TABLE 5. (continued)


                                                       Residue, mg/kg, after treatment with
                                                                                                  

                                                   1% solution                   2% solution
                                                                                                 
    Variety        Location     Treatment      peel    pulp    whole         peel    pulp    whole
    Lemons

    Eureka         California   Dip            29.1    0.32    15.4

    "              "            "              41.5    0.21    24.0          28.3    0.03    16.0

    "              "            Spray                                        24.6    0       14.0

    "              "            "                                            18.5    0       9.2

    Tangerines

    Dancy          Florida      Spray          17.0    0.11    3.58          23.3    0.26    5.83

    "              California   "                                            1.74    0.24    0.92
                                                                                                  
    

         These data are quite inadequate to determine an appropriate
    maximum residue limit.

    FATE OF RESIDUES

    In stored products

         Kolbezen et al. (1969) reported that residues resulting from
    spray, dip or fumigation treatments are contained exclusively in the
    peel and the greater part is in the flavedo. As spray or dip treatment
    solutions are somewhat alkaline (Ph 8.5-9.5), there is normally a
    small loss of residue during the first few days after treatment due to
    volatilization. During this period, the presence of sec-butylamine
    can be detected by its odour. Thereafter, the remaining residues
    persist unchanged in magnitude and identity for many weeks. There is
    no evidence that citrus is able to metabolize sec-butylamine in any
    way. An injection of 3 mg sec-butylamine as an aqueous solution of
    the sulfate salt into lemons showed no changes in quantity or chemical
    nature after eight weeks (Kolbezen et al., 1969).


    TABLE 6.  Residues of sec-butylamine on citrus fumigated for four
              hours with its vapour at two rates

                                                                    

                                ppm sec-butylamine in air

                                150                   300

            Fruit          sec-butylamine, mg/kg, on whole fruit
                                                                    

            Grapefruit          6.1                   13.5

            Tangerines          6.6                   16.5

            Lemons              13.4                  29.3

            Naval oranges       8.7                   15.1
                                                                    


         The same authors referred to the finding of endogenous primary
    amines in citrus. Although, the amount of naturally occurring
    sec-butylamine is relatively low (0.03 mg/kg), there may be from
    5-7.5 mg/kg of ethylamine together with varying amounts of
    methylamine and dimethylamine. The presence of these related products
    give reasonable assurance that residues of sec-butylamine will
    persist unchanged as there is apparently no inbuilt mechanism for
    degradation of amines in citrus.

         Day et al. (1968) provide data on typical residues of
    sec-butylamine in fruit measured at varying intervals after
    treatment. There appears to be no significant difference in the level
    of residues determined 28 days after treatment compared with the
    residues three days after treatment. Results obtained at intermediate
    times of storage appear consistent and support the belief that the
    residue is stable.

         Elanco (1968a,b) reports that commercial citrus washing
    procedures remove only a portion of the residual sec-butylamine from
    treated citrus. The data indicate that, depending upon the vigour of
    the wash and the adjuvants used, up to 50% of the residue may be
    removed during washing. Relatively little of the residue is removed
    when citrus is subjected to a solvent waxing process after fungicide
    treatment. Application of water-based wax emulsion does not appear to
    significantly lower the residual deposit of sec-butylamine,
    particularly when the fruit is dried prior to waxing.

    In processing

         Because of the huge quantity of citrus which is processed for the
    extraction of juice and other by-products, numerous studies have been
    conducted to determine the level and fate of sec-butylamine residues
    in the various fractions of processed citrus. Table 7 summarizes the
    residue levels in various components of processed oranges, determined
    during semi-commercial production over three separate seasons (Elanco,
    1968a,b). The use of a five-minute dip in 7% sec-butylamine in the
    1967 studies was merely an attempt to determine the effect of
    excessive treatments and the fate of such residues during processing.
    This amount of sec-butylamine is four to seven times the normal rate
    applied to commercial citrus.


    EVIDENCE OF RESIDUES IN FOOD IN COMMERCE OR AT CONSUMPTION

         sec-Butylamine has not yet been widely used and therefore no
    information is available on residues in food moving in commerce.


        TABLE 7.  Residues of sec-butylamine in various fractions of processed oranges

                                                                                                            

                                             Residue, mg/kg, after specified treatment
                                                                                                          

                             Year      19651                   19661                19671        19682

          Fraction                 1%3       2%3          1%3         2%3           7%4          1%3
                                                                                                            

    Whole fruit                    3.3       8.8          2.96        8.65          23.7         13-17

    Juice (single strength)        0         0            0.4         0.5           0.38         0.18-0.23

    Juice sacs + pulp              0         0            0.18        0.46          0.50         -

    Peel residue                   9.3       11.6         3.60        3.80          26.0         19.4-20.3

    Peel press liquor              6.6       6.8          1.93        2.72          15.8         2.64-2.69

    Molasses                       25.2      27.8         13.1        24.6          82.0         22-25.7

    Dried pulp                     33.3      33.3         16.2        24.9          38.2         45-51

    Cold pressed oil               0         0            0.46        0.50          0            0.26
                                                                                                            

    1 Florida process.

    2 California process.

    3 Normal rate of application.

    4 Excessive rate of application for experimental purposes.
    

    METHODS OF RESIDUE ANALYSIS

         Based on the method of McIntire et al. (1953) as modified by
    Kolbezen et al. (1962b), Day et al. (1966, 1968) developed GLC methods
    for the determination of sec-butylamine residues in fruit. By these
    methods, the amine is distilled from the tissue, reacted with
    1-fluoro-2,4-dinitrobenzene, and determined by gas chromatography with
    an electron affinity detector. Dimethylamine interferes but can be
    separated from sec-butylamine by thin-layer chromatography before
    the final measurement. Of 65 pesticides studied, only ferbam, thiram
    and ziram which produce dimethylamine upon hydrolysis, interfered to
    any degree with the determination. The authors claim that the
    recoveries fall within the 80-100% range. The limit of determination
    of sec-butylamine under the conditions described is about 0.1 mg/kg.
    This concentration yields a peak height of about 0.5 cm. The authors
    draw attention to the fact that there are significant amounts of
    endogenous amines, particularly ethylamine but also including
    sec-butylamine and dimethylamine in citrus and corrections must be
    made for such materials which have not come from chemical treatment.

         Johnson (1968a,b) has modified the procedure of Day et al. in
    order to determine sec-butylamine in citrus oil. The amines in the
    oil sample are isolated by acid extraction and subsequent formation of
    the dinitrobenzene derivative. The various amine derivatives are
    separated by thin-layer chromatography and the sec-butylamine
    content is determined by gas chromatography.

         Kolbezen et al. (1969) using experience gained in the
    microdetermination of amines with 2,4-dinitrofluorobenzene (Kolbezen
    et al., 1962a,b) have drawn attention to important refinements which
    assist in eliminating interference by endogenous amines. The limit of
    determination is reported to be 0.2 mg/kg.

         The United States Food and Drug Administration, in establishing a
    food additive tolerance (FDA, 1973), recommend the method of Day et
    al. (1968) as suitable for the determination of residues covered by
    the tolerance.

         The Environmental Protection Agency (EPA, 1974) published a
    method developed by Elanco Products Company, and submitted with a
    pesticide residue petition. When used for the determination of
    sec-butylamine in milk, recoveries of 70% were obtained at 0.75
    mg/kg and 85% at 1.5 mg/kg. The sensitivity is reported to be 0.02
    ppm.

         Kroller (1975) has reported on a method to determine
    sec-butylamine residues in the peel of treated citrus involving
    extraction with acid, concentration on an ion-exchange resin, reaction
    with 1-fluoro-2,4-dinitrobenzene and measurement of the yellow colour
    by spectrophotometry. The limit of determination is quoted as
    0.05 mg/kg.

    NATIONAL TOLERANCES REPORTED TO THE MEETING

         Tolerances for sec-butylamine residues in raw agricultural
    commodities and foods have been established as follows.

                                                                     

    United States of America
                                                                     

    Citrus fruit (from post-harvest
    application)                                           30 mg/kg

    Kidney of cattle                                        3 mg/kg

    Milk and meat, fat and meat
    by-products of cattle (except kidney)                0.75 mg/kg

    Citrus molasses                                        50 mg/kg

    Dried citrus pulp                                      50 mg/kg
                                                                     

    APPRAISAL

         sec-Butylamine has been shown to have good fungicidal and
    fungistatic properties which make it suitable for application to
    citrus and other fruit for controlling post-harvest rots. It is
    effective for inhibiting the germination of Penicillium digitatum
    spores and for controlling organisms which develop resistance to other
    fungicides.

         Primary amines including sec-butylamine are recognized as
    natural components of citrus fruit including orange juice. Although
    the fungicidal properties of sec-butylamine were originally
    discovered in 1962, commercial development has been fairly recent.

         Extensive data available to the Meeting demonstrate the levels of
    residues resulting, in various classes of citrus fruits, from
    different packing-house practices. The level of residues depends as
    much on packing-house practice as on formulation or any other factor,
    and it can be anticipated that commercial citrus will vary
    considerably in its sec-butylamine residue content, depending upon
    the need for treatment and the treatment conditions. Virtually all of
    the residue is deposited in the peel, the amount appearing in the pulp
    and juice being generally less than the amount of naturally occurring
    primary amines which, in the case of ripe orange juice, exceeds
    7 mg/kg.

         Residues of sec-butylamine on citrus remain stable in storage
    and withstand processing of citrus pulp and molasses. Data were
    available to the Meeting to indicate the level of residues at various
    steps in the processing of citrus, figures being provided for juice,
    pulp, dried pulp and molasses. No information is available on the fate
    in cooking citrus fruits for the production of marmalade.

         Whilst sec-butylamine has also been evaluated for the control
    of post-harvest rots of apples, pears, peaches and bananas, little
    data were available on these aspects of its use.

         The feeding of citrus wastes containing residues of
    sec-butylamine can be expected to give rise to transient residues in
    meat, animal tissues and milk but the results of studies known to have
    been conducted were not available to the Meeting.

         Several colorimetric and gas chromatographic methods suitable for
    the determination of sec-butylamine residues in fruit, plant
    products, animal tissues and milk are available and these have been
    extensively used in the evaluation of the performance of
    sec-butylamine, and in studying its fate in packing-house practice.
    Several authors point to the occurrence of natural sec-butylamine in
    citrus fruit and the possible interference of other primary amines in
    the pulp of ripe citrus. Methods for eliminating interference from
    these endogenous amines have been published.

         National tolerances for sec-butylamine residues in citrus,
    citrus pulp and foods of animal origin have been published.

    RECOMMENDATIONS

         The following maximum residue limits are recommended for
    sec-butylamine in the following commodities.

                                                                  

         Commodity                          Limit, mg/kg
                                                                  

         Dried citrus pulp,
         citrus molasses                         50

         Citrus fruits                           30

         Citrus juice                            0.5
                                                                  

    FURTHER WORK OR INFORMATION

    REQUIRED (before 30 June 1978)

         1.   Fate of residues especially after processing of meat and
              milk.

         2.   Quantitative metabolic studies in animals.

         3.   Information on the fate of sec-butylamine residues in
              livestock when citrus pulp and citrus molasses containing
              sec-butylamine are used as components in the ration of
              livestock.

         4.   Information on the use of sec-butylamine for the control
              of post-harvest rot on fruits other than citrus and on
              residues resulting from such uses.

    DESIRABLE

         1.   Mutagenicity studies with techniques currently available.

         2.   Clinical observations in man.

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    Bruner, R. C. (1975) Summary of Industry Committee an Citrus Additives
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    Day, E. W., Holzer, F. J., Tepe, J. B., Eckert, J. W. and Kolbezen,
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    See Also:
       Toxicological Abbreviations
       Butylamine, sec- (Pesticide residues in food: 1977 evaluations)
       Butylamine, sec- (Pesticide residues in food: 1978 evaluations)
       Butylamine, sec- (Pesticide residues in food: 1979 evaluations)
       Butylamine, sec- (Pesticide residues in food: 1980 evaluations)
       Butylamine, sec- (Pesticide residues in food: 1981 evaluations)