the active ingredient of the present invention , that is , epichlorohydrin , can be prepared by the reaction of 1 , 3 - dichloro - 2 - propanol with sodium hydroxide as disclosed in org . syn ., 3 , 47 ( 1923 ). the pharmaceutical preparations are prepared by mixing the epichlorohydrin with compatible , edible diluents , e . g ., magnesium oxide , zinc oxide and aluminum oxide . ( compatible diluents are those which do not contain free hydroxyl or amino groups , that is , water , alcohols , sugars and the like are chemically incompatible with the active ingredient .) animal baits can be prepared by first micro encapsulating the epichlorohydrin by methods known to the art , e . g ., coacervation and then mixing with animal bait carriers , for example , oatmeal or other cereal grains or proteinaceous foods , e . g ., fishmeal and the like . parenteral forms are prepared by dispersing the epichlorohydrin in suitable fluid diluents , for example , paraffin , mineral oil , vegetable oils such as peanut oil , corn oil and cottonseed oil . all dosage forms as heretofore described , contain from about 0 . 01 gram to about 2 . 5 grams of the epichlorohydrin per unit dose , but are not limited thereto , since within such range they include , for example , 0 . 5 gram , 1 . 0 gram , and 2 . 0 grams . sterile parenteral forms for injection contain from about 0 . 5 % weight / volume to 50 % weight / volume of epichlorohydrin . for animal baits the concentration is from about 0 . 1 % weight / weight to about 50 % weight / weight of epichlorohydrin . these dosage forms provide , generally , the dosage range of essential active ingredient from about 0 . 1 to about 2 . 5 grams per day . the daily oral and parenteral doses for rendering a male sterile are approximately the same except for sustained parenteral dosage forms which contain from about 0 . 1 gram to 0 . 5 gram of epichlorohydrin per milliliter and are given once a month intramuscularly . the usual oral and parenteral forms are to be administered once per day or in the case of baits allowed to be fed ad lib . mature virgin male rats are checked for ability to mate by placement with immature female rats primed with gonadotropic factor of pregnant mare &# 39 ; s serum . those males which mate are used for subcutaneous injection or oral administration of the novel pharmaceutical preparations . the essential active ingredient is prepared as a 30 mg ./ ml . dispersion in 0 . 25 % aqueous methylcellulose in sterile vehicle . this pharmaceutical composition is administered to each of three mature mating males , a half ml . per day subcutaneously or orally for 8 days . these treated males are exposed to receptive mature females for mating and mating is checked by the presence of sperm with or without a plug in the vagina of the female . approximately ten days thereafter , the females are examined for the presence and number of implantation sites , and the ability of the pharmaceutical compositions to prevent impregnation by the mature male is shown by the absence of implantation sites at autopsy . the following examples illustrate the manner and process of making and using the invention but are not to be construed as limiting . epichlorohydrin was prepared as a 3 % sterile dispersion in 0 . 25 % aqueous methylcellulose . one - half ml . was injected subcutaneously into each of three mating male rats for 8 days . thereafter , the treated males were subjected to the aforesaid procedure to determine the ability of the preparation to prevent impregnation of female rats by the males , and the preparation was found to be effective . an oral pharmaceutical preparation containing 1 % of epichlorohydrin in 0 . 25 % methylcellulose was administered orally to mating mature male rats daily for 7 weeks at a daily dose of 5 mg ./ rat . this preparation induced inability in the males to impregnate receptive females by the first week , and this infertility remained throughout the treatment . post - treatment , the ability to impregnate receptive females returned the first week of post treatment and bred females had a normal number of implantation sites . a soft gelatin capsule is prepared to contain 0 . 01 gm . of epichlorohydrin . an oral daily dose of 1 capsule is effective to prevent impregnation of a receptive female by mature male rats . cottonseed oil is used as a sterile vehicle to prepare a sterile dispersion of epichlorohydrin , 250 mg ./ ml . injection of 1 ml . daily is effective to prevent impregnation of receptive female monkeys by a mature male . other oils , such as peanut oil or mineral oil could also be used . cottonseed oil is used as a sterile vehicle to prepare a sterile dispersion of epichlorohydrin , 250 mg ./ ml . injection of 1 ml . daily is effective to prevent impregnation of receptive female monkeys by a mature male . ability to impregnate returns during the first week after cessation of treatment . additional embodiments of the present inventive concept are compositions , i . e ., rations , for oral ingestion by rodents , especially rats , and methods of controlling rodent population , especially the rat population . such rations contain the essential active ingredient and , in amounts that are attractive to the animals in the sense that they are not repelled thereby , edible dietary constituents such as protein , fat , carbohydrate , minerals , and vitamins . the medicated ration must not repel the rodents although it does not necessarily have to attract in the sense of being absolutely preferred over other rations . hence , the medicated ration retains the natural flavor of the dietary constituents after the essential active ingredient is incorporated therein . such incorporation provides a final mixture or blend throughout which the active ingredient is uniformly distributed . such active ingredient can be added to the ration by mixing both as solids or as liquids , by addition to a solid ration of the active ingredient itself , by adding the active ingredient in a compatible liquid which is then removed to leave a dry solid mixture , for example , a solution or suspension in chloroform , methylene chloride , or acetone ; by adding the active ingredient in the form of coated particles or pellets , coated , for example , by coacervation with pvp , or by coating with an acetone solution of a oil - soluble type of peg - ester . the final ration containing the coated particles or pellets is the preferred form because of its tendency to better mask any undesirable taste of the essential active ingredient . the rations contain the essential active ingredient in a concentration sufficient to control fertility or cause lesions in the excurrent duct ( epididymal lesions ) and permanent infertility in otherwise fertile male animals , especially rats , when they ingest the compositions in their usual manner of providing for their metabolic needs . illustratively , most mature male rats that ingest an amount of the ration providing at least about 30 mg . per kilogram of rat body weight become irreversibly infertile as shown by epididymal lesions and by sterile matings with fertile females . as will be apparent , rats eating ad libitum will consume different amounts of the active ingredient - containing rations . hence , to provide about 30 mg . per kilogram in a rat eating a smaller amount of the effective ration , a more concentrated ration must be provided than for a rat consuming a larger amount of the same ration . in the latter case , a less concentrated ration is operable . for example , in rats weighing about 200 to 250 gm . and consuming about 10 to 25 gm . of ration at one feeding , the ration may contain 0 . 075 % by weight of the active ingredient . thereby , the 250 gm . rat consuming 10 gm . of the treated edible preparation ingests 7 . 5 mg . of the active ingredient equivalent to about 30 mg . per kilo . with this same ration containing 0 . 075 % active ingredient , a 200 gm . rat eating 25 gm . at one feeding ingests 18 . 75 mg . of the active ingredient , equivalent to about 93 . 75 mg . per kilo . such variations will occur due to the eating habits of the rats . hence , various embodiments of the rodent - control preparations are within the inventive concept provided they contain an effective amount of the essential active ingredient to cause the males to acquire the epididymal lesions of infertility . the aforesaid embodiments of this inventive concept provide a method of controlling fertility of male rodents , especially rats , which consists essentially of providing in locales available to and frequented by said male rodents , rations supplying an effective amount of the compound epichlorohydrin for preventing impregnation of receptive sexually mature female rodents by the male counterparts thereof . preferably , the rations supply to the recipient at least about 30 mg ./ kilogram of body weight thereof . at this level most rats acquire irreversible infertility and a reduction in rat population ensues in time . expressed as percentage by weight of the edible composition , the active ingredient amounts to from about 0 . 05 % to about 0 . 5 %, such range being not limited thereto for it includes within the range the other percentages such as 0 . 1 %, 0 . 2 %, 0 . 3 %, and 0 . 4 %. a more concentrated preparation , say up to about 2 % or even 5 %, is satisfactory provided it is , upon use , diluted with the aforesaid edible dietary constituents to provide operative amounts of the essential active ingredient without wasting active material . these embodiments of the inventive concept are made available to the animals , especially rats , for control of the population thereof by placing the preparation in and about the locales available to and frequented by the rodents . in accordance with these and other embodiments of the inventive concept , the following are additional examples of the manner and process of making and using the invention but are not to be construed as limitations . a rat ration containing the usual dietary ingredients , protein , carbohydrate , fat , minerals and vitamins is medicated by incorporating therein a sufficient quantity of epichlorohydrin to provide a concentration of about 0 . 25 % by weight . this ration is placed in and about a grain storage area where wild rats are observed and considerable loss of grain occurs . there follows a gradual reduction in rat population in the area such that contamination of the grain and loss thereof are both significantly reduced . although not necessary to the several embodiments heretofore described , other active ingredients can be included in the preparations and methods . the amounts of such ingredients are determined in reference to their known biological and physiological properties . such ingredients are anticoagulant - rodenticides e . g ., 2 - diphenyl - acetyl - 1 , 3 - indandione , and its salts ( u . s . pat . no . 2 , 900 , 302 ), 3 -( alpha - ethylbenzl )- 4 - hydroxycoumarin and its chloro derivative , 3 -( alpha - ethyl - p - chlorobenzl )- 4 - hydroxycoumarin , 3 -( alpha - acetonyl - 4 - chlorobenzyl - 4 - hydroxycoumarin , 3 -( alpha - acetonyl - furfuryl )- 4 - hydroxycoumarin , 2 - pivalyl - 1 , 3 - indandione , calcium salt of 2 - isovaleryl - 1 , 3 - indandione and the like ; stomach poisons , e . g ., sodium fluoroacetate , alpha - naphthylthiourea , thallium sulfate , zinc phosphide , arsenic trioxide , strychnine , and red squill ; estrogens , e . g ., mestranol , ethinyl estradiol , diethyl stilbestrol , and chlorotrianisene ; androgens , e . g ., fluoxymestrone and methyltestosterone ; and progestogens , e . g ., melengestrol acetate , eithisterone , medroxyprogesterone acetate , and norethindrone . depending upon locale , e . g ., farm , urban , business , and type of pest to be controlled and desired effect thereupon , these additional active ingredients are beneficial in controlling vertebrate pests , e . g ., such as rats , gophers , dogs , hares and coyotes . in rat control the use of the additional anticoagulant active ingredient reduces the rat population sooner than expected . similar beneficial effects attend the use of the additional stomach poison active ingredient . a rat bait containing yellow corn meal is medicated by incorporating therein a sufficient quantity of epichlorohydrin to provide a concentration of about 0 . 25 percent by weight . this bait is placed in and about a grain storage area or meat packing plant where wild rats are observed and considerable loss of grain or meat occurs . there follows a gradual reduction in rat population in the area such that contamination of the grain and meat and loss thereof are both significantly reduced . additional baits can be made from a mixture of oatmeal and dried fish meal ; whole corn , oatmeal and dried fish meal ; oatmeal and ground beef , or yellow cornmeal and ground beef .
pharmaceutical preparations in dosage forms and animal feeds consisting essentially of compatible , pharmaceutically acceptable carriers , oral and injectable , compounded with a sub - lethal , yet effective , amount of epichlorohydrin for inducing sterility in male mammals . methods for preventing impregnation of females by male mammals which comprises administering systemically to male mammals a sterilizing amount of epichlorohydrin , also identified as γ - epichlorohydrin .