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Mutagenic studies of aziridine derivatives derived from various diamines.

Various aziridine derivatives derived from diamines were studied in several biological systems to evaluate their effects on reproduction and as potential mutagens. Considerable variations in the biological activities of these compounds were seen among animal species and among the varied chemical structures. In general, mutagenic responses paralleled the antifertility effects in mice and houseflies and the anticancer effects in mice. The lack of an antifertility effect by N,N'-bis(aziridinylacetyl)-1,8-octamethylenediamine in the rat was quite unexpected in view of its chemosterilant activity in houseflies and mice.

Animals↗

Development of a system for sterilizing tsetse flies, Glossina spp., in the field.

Various autosterilizing systems were evaluated on natural populations of Glossina pallidipes Austen and G.morsitans morsitans Westwood in Zimbabwe. These involved a clear plastic tower of two or three chambers mounted at the cage position on a trap. Inside one chamber flies could be exposed to the vapour phase of the chemosterilant bisazir, P,P-bis (1-aziridinyl)-N-methylphosphinothioic amide. The system was designed to encourage flies to enter the sterilizing chamber, delaying their exit for sufficient time to expose them to a sterilizing dose. This was accomplished in the most effective system by restriction of the exit to one small hole (6 mm diameter) at the roof-side junction. The number of flies remaining in the chamber declined exponentially. The rate of exit was directly proportional to the density of flies in the sterilizing chamber and to the number of exit holes. The probability of a fly being in this chamber for at least 1 or 7 min (the times taken for female and male G.m.morsitans respectively to receive an ED50) was 0.84 and 0.67 respectively with one fly present. With sixteen flies, these probabilities were 0.76 and 0.18 respectively. Results suggest that it may be possible to develop a cheap, safe and efficient autosterilizer for use on tsetse traps.

Animals↗

The mating ability of males of Culex pipiens fatigans Wiedemann sterilized with apholate or tepa.

The chemosterilants apholate and tepa are known to induce a high degree of sterility in the males of Culex pipiens fatigans. The studies reported show that 36-hour-old apholate-and tepa-sterilized laboratory-bred males can inseminate the same number of laboratory-bred or wild females as can normal laboratory or wild males in the first 48 hours of their lives. Males sterilized by either compound were found to be more competitive in mating with normal laboratory females than were the normal laboratory males. When normal virgin females were mated first with sterile and then with normal males or vice versa, the sperms of the first mating always decided the fate of eggs. Apholate-sterilized laboratory males were not only compatible with wild females but could even induce the same level of sterility in them and were fully as competetive in mating as normal wild males. The authors stress that it has still to be ascertained whether these encouraging laboratory findings would apply in field conditions.

Animals↗

[Genetic control of Blattella germanica].

Based on a literature survey, the possibilities of a genetic control of the German cockroach (Blattella germanica) are shown. First, an oversight is given on the cytogenetics of the German cockroach, including some important mutations. Then the control methods by genetic mechanisms are explained. This chapter begins with analysing the relevant biological pecularities. In control measures, the dominant lethal mutations (induced by rays rich with energy and by chemosterilants) have only a chance if they can be applied in the scope of autosterilization of natural populations. Reciprocal translocations may expect maximum consideration in the future of the control of the German cockroach. Some of these are already available in the heterozygote state. But the establishment of homozygous strains was not yet successful up to now. The possibilities of the application of translocation-heterozygotes are discussed. Such mutant strains of cockroaches which bear several translocations in the heterozygous state, offer the most promising way of control. This may even include the population's eradication. A long-lasting regulation of the population may be achieved with the introduction of insects mutated in this manner even in the case if a complete eradication is not attainable. It might be expected that also other genetic mechanisms may contribute, in future, to the improvement of cockroach control. Such mechanisms may be conditional lethal factors, sex distortions, and others more.

Chemosterilants↗

[Development of resistance in Pharaoh's ant (Monomorium pharaonis)].

The possibility of resistance development in the pharaoh's ant Monomorium pharaonis in regard to insecticides and chemosterilants in general and in the special case of sodium arsenate is discussed. The low number of sexuals and the long duration of generations reduced the possibility of the development of resistance in social insects to a great extent. Although the pharaoh's ant offers relatively good possibilities for the selection of resistance on account of the polygyny, the duration of generations in the range of a whole year under field conditions and the isogeny of the colonies diminished the development of resistance. Experimental investigations for the selection of resistance to sodium arsenate in laboratory colonies with artificially shortened sequence of generations are presented. Following six generations, no enlargement of tolerance or true resistance but a clear sensitivity could be stated. This sensitivity leads to an eradication of the colonies. It is pointed out, that in pharaoh's ant a development of resistance against the lethal action of sodium arsenate and carbaryl is impossible, because of the protection mechanism of the social food chain.

Animals↗

Effects of diazacholesterol dihydrochloride (SC-12937), an avian antifertility agent, on rat testis.

The present study was undertaken to evaluate the effectiveness of an avian chemosterilant, 20, 25-diazacholesterol dihydrochloride (SC-12937), on the rat testis. Adult male rats were injected intraperitoneally with 10 mg (Group 1) or 30 mg (Group 2) of SC-12937/kg/d or with vehicle alone (Group 3) for 10 days, and were killed 24 hours after the last injection. A wide range of variation in the appearance of affected seminiferous tubules was observed in the testis of SC-12937-treated rats at both dose levels. This ranged from apparently normal-looking seminiferous tubules to almost completely atrophied tubules with no cells. Affected tubules exhibited intraepithelial vacuoles of varying size, multinucleated giant cells, germ cell exfoliation, and tubular atrophy. The presence of severely damaged and entirely normal seminiferous tubules adjacent to one another in the same section was noteworthy. The changes appeared to be dose-related. A greater number (34.6%) of affected tubules were observed in rats receiving 30 mg of SC-12937 compared with the ones receiving 10 mg of this compound (19.6%). The Sertoli cells also were affected by this drug and exhibited cytoplasmic vacuolation, a marked increase in the accumulation of lipid droplets and myeloid bodies. Necrotic Sertoli cells also were observed in the severely affected tubules. The possible mechanism of antispermatogenic action of SC-12937 in rats has been discussed briefly.

Animals↗

A preliminary evaluation of antifertility activity of a triterpenoid glycoside (DSS) from Dalbergia saxatilis in female Wistar rats.

Antifertility activity of a triterpenoid glycoside, DSS, isolated from the root of Dalbergia saxatilis was investigated in female Wistar rats of breeding age. When administered by gastric intubation at a dose rate of 200 mg kg(-1)body weight at the premating period, conception was inhibited in 71.4% of the treated animals. Fertility Index (FI) for this group was 107.82 compared with 373.5 value for control rats that received 30% aqueous Tween 20 vehicle. DSS, did not significantly alter the fertility of rats at the first and second trimesters of pregnancy but did cause a significant decrease (P<0.05) in the mean Day 20 foetal crown-rump length when administered at the premating period and at the third trimester of pregnancy; with a concurrent decline in the mean maternal body weights. The potential use of DSS as a chemosterilant in fertility control are discussed.

Animals↗

Control of rickettsial diseases.

Prevention of rickettsial infections is aimed at individual control and epidemic measures (especially in epidemic typhus), vector and rodent control, milk pasteurization (in Q fever), chemoprophylaxis and immunoprophylaxis. In vector and rodent control, the main obstacle is the rise in resistance to insecticides and rodenticides. For this reason in vector control, apart from insecticides, enhancement of the natural immunity acquired by animals in response to tick infestation and vaccination with concealed tick antigens as well as the use of hormones, chemosterilants and genetic manipulation can also be considered. For short-term high-risk exposure, doxycycline may be an effective prophylaxis of illness but may not prevent infection with scrub typhus or spotted fever group rickettsiae. At present, for specific prevention by vaccination, only Q fever vaccines are available for common use. However, development of subunit vaccines, namely immunogenic rickettsial proteins, cloned and expressed in Escherichia coli, seems to be very promising.

Animals↗

The effect of the intestinal worms and migrating L1 larvae of Trichinella spiralis on the production of antiparasitic IgE antibodies.

The effect of the adult worms and migrating L1 larvae of Trichinella spiralis on the production of specific IgE antibodies was determined in BCF1 mice. To achieve this, we combined the effect of two anthelminthics: thiabendazole, to produce chemosterilization of adult females, and napthalophos, to expel adult worms from the intestine of infected mice on the desired day. Our results demonstrate that when the natural route of infection is used the production of IgE antibodies is not dependent on the infection dose or the number of migrating L1 larvae, and that both intestinal worms and migrating L1 larvae contribute to the production of reaginic antibodies. In addition to this, an extended period of antigenic stimulation (10-12 days) is required for the induction of a detectable, specific IgE response by adult worms. Finally, our results seem to indicate that although the effects of adult worms and migratory L1 larvae on the IgE production are not additive, the presence of adult worms in the intestine of mice may stimulate a secondary exposure to common antigens released by the migrating L1 larvae.

Animals↗

The metabolism of the soil fumigant 1,2-dibromo-3-chloropropane in the rat.

The soil fumigant 1,2-dibromo-3-chloropropane (I) undergoes hydrolysis in the rat to a series of epoxide metabolites. Alkylation of glutathione by these epoxides produces 2 urinary metabolites identified as the mercapturic acids VI (R=COCH3) and VII (R-COCH3). Hydrolysis of the epoxides produces the male antifertility agents alpha-chlorohydrin (IX, X-Cl) and alpha-bromohydrin (IX, X-Br) which are oxidatively metabolized to oxalic acid (XII), thus causing renal damage. These metabolic pathways can explain the toxic nature of the fumigant as a carcinogen, a male chemosterilant and as an agent causing kidney damage.

Animals↗

Equine piroplasmosis: a review.

This review focuses on equine piroplasmosis with specific reference to its distribution, diagnosis and clinical and pathological signs. The more common used drugs are discussed both with reference to treatment and chemosterilization. Areas requiring further research are also briefly mentioned.

Animals↗

Embryopathies due to spermatozoal impairment in Xenopus laevis.

An in vitro test system, involving gametes of Xenopus laevis has been used to study the effect of antifertility agents upon spermatozoa as manifest in developing embryos. Exposure to either the isomeric forms of dimethylmyleran, methyl methanesulphonate or gamma-radiation led to development of a range of embryopathies, whereas treatment with steroidal drugs or the rodent epididymal chemosterilants alpha-chlorohydrin and trimethylphosphate was compatible with production of apparently normal offspring.

Abnormalities, Drug-Induced↗

Ultrasonic potentiation of the sporicidal activity of glutaraldehyde.

Laboratory test data showed a 4.8-fold increase in the sporicidal activity of glutaraldehyde with the incorporation of ultrasound. Projected times required for 100 percent killed of a 20,000 hydrated spore inoculant were reduced from 211 minutes to 44 minutes. Clinical exposure time intervals necessitated a 31/2-hour glutaraldehyde immersion versus a 30-minute cavitated glutaraldehyde chemosterilization to ensure a 100 percent kill. The feasibility of reducing the ADA-required 10-hour soak in glutaraldehyde to ensure sterility with the incorporation of ultrasonic baths is supported by these data. Tests performed also showed that the airborne contamination from an open tank method is minimal. No spores were retrieved from vapor collected by passive vacuum during cavitation of inoculated glutaraldehyde.

Aldehydes↗

Acaricidal and insecticidal activities of cadina-4,10 (15)-dien-3-one.

The novel assignment of 13C and 1H NMR data for cadina-4,10(15)-dien-3-one obtained from Hyptis verticillata is presented. The study revealed that cadina-4,10(15)-dien-3-one possesses chemosterilant activities against the economically important cattle tick, Boophilus microplus, and toxic action against adult Cylas formicarius the most destructive pest of sweet potato (I pomoea sp.).

Animals↗

Sterilisation of avian embryos with busulphan.

The chemosterilant drug busulphan (1, 4-butanediol dimethane sulphonate) has been applied to embryos of the domestic fowl at doses of from 1 to 500 micrograms after 48 hours incubation. Direct application caused a number of teratological effects. These could be avoided by injecting the drug in sesame oil directly into the yolk. Embryos treated in this way could be sterilised with an efficiency of over 95 per cent with minimal side effects to the young embryo. The technique provides a method for destroying primordial germ cells that will facilitate studies of germ cell/stroma interactions in the gonad and facilitate the production of transgenic birds.

Abnormalities, Drug-Induced↗

1,2-dibromo-3-chloropropane (DBCP)-induced infertility in male rats mediated by a post-testicular effect.

The potential for the chemosterilant 1,2-dibromo-3-chloropropane (DBCP) to reduce male fertility by acting at a site in the genital tract beyond the testis was evaluated in male, Fischer 344 rats. A single sc treatment with 100 mg/kg DBCP reduced fertility in male rats 2 to 7 days postexposure without affecting mating frequency. Doses of 10, 20, or 40 mg/kg DBCP given sc once daily for 7 days caused a dose-dependent reduction in the metabolism of glucose to CO2 by epididymal sperm, as measured in vitro. Conversion of glucose to lactate was not reduced, indicating inhibition of energy metabolism at a step post-glycolysis. No clinical signs of toxicity were observed in these studies. Direct addition of DBCP to epididymal sperm being incubated in vitro also inhibited the metabolism of glucose to CO2. Inhibition was concentration related, and the minimal inhibitory concentration was 0.316 mM. These data indicate that DBCP may cause a nearly immediate infertility via a direct effect on post-testicular sperm. A possible mechanism of this infertility is inhibition by DBCP of glucose metabolism in the ejaculated sperm.

Animals↗

Reproductive toxicity of 2,4-dinitrotoluene in the rat.

The present study was undertaken to evaluate the effects of the chemosterilant 2,4-dinitrotoluene (DNT) on the rat testis. Adult male rats were fed control, or 0.1%, or 0.2% DNT for 3 weeks. An ultrastructural study of the testes was performed, serum was assayed for testosterone and gonadotropins, and sperm reserve count was determined. A marked change in Sertoli cell morphology was found after 3 weeks of 0.2% DNT exposure. Varying sized vesicles associated with swollen mitochondria and distended endoplasmic reticulum were visible in cells from DNT-treated animals. Circulating levels of follicle stimulating hormone and luteinizing hormone were increased in 0.2% DNT-treated animals. Reduced weights of the epididymides and decreased epididymal sperm reserves were observed in DNT-treated animals. These results indicate that DNT is capable of inducing testicular injury, of directly or indirectly disturbing pituitary function, and of exerting a toxic effect at the late stages of spermatogenesis. These findings suggest that a locus of DNT action is the Sertoli cell, resulting in both inhibition of spermatogenesis and changes in testicular-pituitary endocrine activity.

Animals↗

Dominant lethal mutations in Tilapia mossambica (Peters) elicited by myleran.

Tilapia mossambica (Peters) Teleostei, Cichlidae, is of commercial importance being farmed for human consumption. An effective means of sterilization would be of value since prolific breeding under farming conditions reduces growth rate. The possibility of using the antileukaemic drug myleran as a chemosterilant has been investigated previously, however the present study indicated that it can induce dominant lethal mutations in this species.

Animals↗