Effect of housing conditions, management procedures and traits of the external male reproductive tract on the sexual behaviour of natural mating boars.

Although artificial insemination in pig production is widespread, many farms rely on natural mating (NM). For NM to be successful, adequate sexual behaviour and a sufficient libido level in boars is crucial for appropriate reproductive performance. Therefore, this observational study evaluated the libido level of 59 boars of different breeds used for NM by a scoring system ranging from 0 (no libido) to a maximum of 23 points (perfect libido) and analysed their general and andrological health as well as housing and management factors influencing the libido. The boars showed a mean libido score of 16.7 (SD ± 2.3). Crossbreed (median: 17.5, min: 14.0, max: 21.0) (p < 0.01) and Landrace (median: 17.5, min: 17.0, max: 21.0) (p < 0.05) boars showed significantly higher libido scores compared to Piétrain boars (median: 14.0, min: 13.0, max: 17.0). A non-slippery mating area was found to be positively associated with libido (p < 0.05), whereas disorders such as lameness showed a negative correlation (p < 0.01). In winter, significantly higher libido values (median: 17.0, min: 14.0, max: 21.0) were recorded compared to spring (median: 16.0, min: 11.0, max: 21.0) (p < 0.05). In addition, high number of supports by farmers during natural mating and frequency of use for NM and for stimulation of artificially inseminated sows did not negatively influence the libido score. No significant correlation between the satisfaction of the farmer about the libido level of the boars and the evaluated libido score was detected. This is the first study investigating the effect of housing conditions and management procedures on the libido of boars used for NM under field conditions. The findings may therefore help to establish a successful mating management for herds applying NM on a regular basis. A systematic evaluation of the libido score is needed to detected boars with low libido levels, because it is often overlooked by the farmers. Moreover, genetics, general health condition and flooring in mating areas turned out to be critical parameters that influence the libido score of boars used for NM and therefore should be considered when examining natural mating on farm.

Careers in toxicology in Europe--options and requirements. Report of a workshop organized on behalf of the Individual Members of EUROTOX during the EUROTOX Congress 2000 in London (September 17-20, 2000).

In view of the lack of information regarding careers for toxicologists in Europe, the Individual Members of EUROTOX organised a workshop on careers in toxicology during the EUROTOX Congress 2000 in London. Toxicologists are mainly employed in academia, regulatory agencies, contract research organisations (CROs) and the chemical and pharmaceutical industries. There are also a few governmental institutes involved with toxicological work other than teaching or regulation. Toxicologists can also work as independent consultants, especially for commercial organisations. The requirements for starting a career in any of the above organisations, the need and the advantages and disadvantages of specialisation, and further career prospects are summarised and briefly discussed. The organisations, and also working as an independent toxicology consultant, offer interesting professional work of relevance to modern-day society. There is currently a shortage of toxicologists not only in the traditional field of risk assessment but also especially in new areas, e.g. toxicogenomics. This shortage may be at least in part due to insufficient training opportunities. Further consideration of career opportunities is planned and will be published in due course.

Professional opportunities for toxicologists: the requirements of the private sector for education/teaching.

Toxicology, as a multidisciplinary field, provides career opportunities for graduates with medical (human or veterinarian), pharmacological, pharmaceutical, biological, microbiological, molecular biological, chemical, biochemical, genetic or other backgrounds. However, in today's environment specialists with a university degree in toxicology or a postgraduate training in toxicology have a clear advantage. Postgraduate diplomas are now available in most industrial countries. In addition, to be successful, modern toxicologists in the private sector also need a good understanding of how to turn a scientific project into a successful product, an expertise generally acquired by on-the-job training. Last, but not least, the rapid progress in essentially all toxicology-relevant sciences makes continuous training mandatory.

Are newer scientific concepts in regulatory toxicology used timely and appropriately?

Laws regulating toxicology (e.g. toxic thresholds allowed, poison classes or definition of necessary preclinical testing) might improve health and save lives. Scientific facts will always serve as a mandatory base for political decision-making, but there will also be additional influences (perception and acceptance of risks, possible benefits, economic considerations etc.). These latter factors may vary considerably from one society to another. The Delaney clause prohibited the marketing of any product which was found to be carcinogenic in animals. Due to their benefits, exceptions were made for drugs. In other countries, too, other chemicals could be an exception due to a different perception of the risk or different scientific evaluation. Clear cases of major events always trigger changes in legislation. When in 1937 a newly-marketed sulfanilamide elixir led to severe kidney damage and 70 deaths, the FDA quickly endorsed the propositions of the investigation team set up by the American Medical Association: animal testing in two species with histopathologic examination before a marketing authorization could be granted became mandatory. A similarly rapid reaction followed in Europe when it was detected that Thalidomide was responsible for malformations in the offspring of mothers who had taken the drug in early pregnancy. When the effects are more difficult to link to a chemical, there may be time delays in regulatory actions. However, a sophisticated evaluation system was introduced for better monitoring of drug and chemical hazards. Some examples will be given in order to discuss the difficulties of timely and appropriate use of scientific findings.

Morphological changes produced in rat testis by anticancer drugs.

Testicular side effects of procarbazine (Proc: 50 or 200 mg/kg i.p.), vincristine (Vin: 0.15 or 0.6 mg/kg i.p.) or busulfan (Bu: 10 mg/kg p.o.) were examined by morphological methods 3 days, 1 week and weekly thereafter until week 10 after a single exposure. With Proc a degeneration of the germ cells, particularly of mid primary spermatocytes, was seen first. Morphogenesis of early spermatids was disturbed, especially of those subcellular elements depending on an intact RNA metabolism. Later, giant cells were frequent. Vin led first to a malformation of late spermatids and arrest of cell division of spermatocytes and especially of spermatogonia, indicating microtubule dysfunction. After 2 and 4 weeks Bu showed a disappearance of spermatogonia and early spermatocytes leading to a depletion of the germinal epithelium by maturation. Late effects were rather similar in all the groups.

Aspects of testicular toxicity induced by anticancer drugs.

Newer histopathologic techniques were used in combination with sperm head counts (SHC) and serial mating (SM) studies to assess different aspects of testicular toxicity. Adult male rats were treated once intraperitoneally (i.p.) with vincristine (Vin: 0.15 and 0.6 mg/kg) or procarbazine (Proc: 50 and 200 mg/kg). Investigations were performed at weekly intervals until 10 weeks after treatment. SHC are a good parameter for cytotoxicity (Vin, Proc) assessed in great detail by morphological examination. Optimal fixation after perfusion and high optical resolution of semi-thin sections also allow the study of early and subtle specific alterations. However, they do not replace SM studies for the assessment of genotoxicity (Proc). In turn, SM studies are poor indicators of cytotoxicity.

Drug-induced histological changes in rat seminiferous tubular epithelium.

It is proposed to divide antispermatogenic compounds into four main groups on the basis of the morphological changes which they cause: a) Radiomimetic substances (e.g., Busulfan). These have a direct effect on spermatogonia and hence also on later sperm development. b) Substances inhibiting the meiotic and postmeiotic phases of spermatogenesis. These cause the seminal epithelium to disappear rapidly except for spermatogonia and Sertoli cells, which apparently remain intact (e.g., 20-438, an indenopyridine derivative). c) Substances acting hormonally (via pituitary). These severely damage Leydig cells, and there is a particularly pronounced degeneration of later stage spermatids. Sertoli cells are also affected. The tunica propria becomes thicker. The weights of the accessory sex glands decrease, and the pituitary weight increases. The peritubular tissue in the epididymis becomes thicker (e.g., 17 beta-estradiol). d) Vasoactive substances (e.g., cadmium chloride). These cause spot-like necrosis. Whole tubuli are destroyed (similar to infarction) whereas others can remain intact. Leydig cells also degenerate, and there is fibroblastic proliferation in the interstitium. The peritubular tissue in the epididymis becomes thicker and the secretion of clear cells is affected. Accessory glands lose weight.

Reversible inhibition of spermatogenesis with an indenopyridine (20-438).

30 mg/kg/day 20-438, an Indenopyridine, induced a complete inhibition of spermatogenesis in male dogs within a few days. The dogs did not develop signs of general toxicity. Erection capability and ejaculation were not inhibited, although the sperm number fell to zero. Histologically the seminiferous tubuli were emptied of spermatides and spermatocytes. After drug withdrawal sperm number and histological appearance returned to normal within 8-11 weeks. In rats, single doses of 50 mg/kg or more induced also an arrest of spermatogenesis. The effect was easily detected by the decrease of testes weights. The weight of seminal vesicles remained unchanged. In chronically treated rats, serum-LH and FSH were slightly increased. The compound has similar effects as other substances acting on spermatocytes (AF 1312/TS, Silvestrini et al., 1975; Boris et al., 1974 or WIN 18446, Coulston et al., 1960). The exact mechanism of action (vascular?) has to be elucidated.

[Relevance of enzyme histochemistry of rat thyroid gland]. / Zur Relevanz der Enzymhistochemie der Rattenschilddrüse.

High doses of aniline analgesics produced increased lipofuscin accumulation in rats thyroid glands after 18 week's treatment. To assess the significance of this change histochemical, biochemical and functional tests have been performed. Increased benzidineperoxidase, decreased acid phosphatase and unchanged leucyl-beta-naphtylamidase activities have been found histochemically and partly confirmed by biochemical methods. 131I-uptake was unchanged and PBI-levels decreased. The selection of appropriate histochemical methods in combination with additional techniques is stressed.

Resolution of three distinct populations of nerve endings from rat brain homogenates by zonal isopycnic centrifugation.

Conditions have been established for the fractionation of subcellular components of rat forebrain homogenates by zonal isopycnic equilibration in continuous sucrose density gradients using a B-XIV rotor. The fractions were analyzed biochemically and by ultra-structural morphometry. Starting from postnuclear supernates of forebrain homogenates, it has been possible to resolve three distinct populations of nerve endings from one another, as well as from free mitochondria and myelin fragments. The three types of nerve endings differ in their apparent specific gravity, their biochemical properties, and their ability selectively to accumulate exogenous transmitter substances in vitro. These three particle populations are likely to represent, in order of increasing modal equilibrium density, (a) cholinergic nerve endings, characterized by their high content of acetylcholine, (b) gamma-amino butyric acid (GABA)-containing nerve endings with high glutamate decarboxylase activity and the ability to accumulate exogenous GABA, (c) adrenergic nerve endings that accumulate exogenous dopamine and noradrenaline and exhibit high monoamine oxidase activity.