Richard Jelínek

Nineteen mycotoxins tested on chicken embryos

Embryos of White Leghorn Fowls incubated for 40 h were injected subgerminally with 19 mycotoxins dissolved in 30% ethanol to provide a range of doses. Embryonic death as well as the incidence of caudal-trunk abnormalities were determined after a further 24 h incubation. Of the substances tested, the maximum toxic effects were exerted by T-2 toxin and diacetoxyscirpenol which produced 100% embryonic mortality at doses as low as 0.01 microgram. 100 micrograms of griseofulvin, on the other hand, were needed to achieve the same effect. Abnormal development of the caudal trunk was observed after T-2 toxin and diacetoxyscirpenol (0.001 micrograms each) and griseofulvin (10 micrograms) administration. Comparison of these data with results published for both cell and tissue culture techniques and for classical rodent acute toxicity tests reveals a high predictive value for the Chick Embryotoxicity Screening Test (CHEST I), at least for mycotoxins.

Comparative assessment of the aflatoxin B1, B2, G1, G2 and M1 embryotoxicity in the chick embryo.

The embryotoxicity of aflatoxins B1, B2, G1, G2 and M1 was investigated after administration to chick embryos on either Day 2, 3 or 4. Treatment resulted mainly in embryolethality and a rank order for embryotoxicity was established where B1 greater than G1 greater than M1 = B2 greater than G2. The sensitivity of embryos to aflatoxin administration decreased with their age. These results document the general cytotoxic character of aflatoxin action upon the embryonic morphogenetic systems, actions that apparently require neither specific metabolic activation nor any specific target.

Embryotoxicity of 25 psychotropic drugs: A study using chest

Twenty five psychotropic drugs were ranked according to the embryotoxicity dose ranges estimated by the Chick Embryotoxicity Screening Test (CHEST). The chick results were compared with some data for common laboratory mammals. In 17 psychotropic drugs a deleterious dose-dependent effect upon the embryonic cardiovascular system was disclosed, terminating in immediate cardiac arrest.

Use of chick embryo in screening for toxin-producing fungi

The toxinogenicity of 720 fungal isolates was evaluated using the Chisk Embryotoxicity Screening Test (CHEST, phase 1). Three hundred and sixteen (43.9%) isolates produced some of the 23 identified mycotoxins, unidentified toxic metabolites were produced by 170 (23.6%), and 234 (32.5%) isolates showed no signs of toxinogenicity. The 24 h lasting chick embryo assay proved very suitable for detecting fungal products with general cytotoxic potential where it yielded results consistent with those obtained with cell cultures and higher organisms. Simplicity, rapidity, and modest laboratory equipment belong to the advantages of this reliable and non expensive screening procedure.

Effect of cycloheximide administered to rats in early postnatal life: correlation of brain changes with behaviour in adulthood

Behavioural deviations have been observed after malnutrition, hypoxia, hormonal disturbances, drugs, irradiation, sensory deprivation, etc., provided the interventions coincided with the critical periods of brain development. One of the significant critical periods the brain growth spurt period 6 is in some species naturally exposed to the extrauterine environment providing a unique opportunity for studying the causes and mechanisms of brain maldevelopment. The morphogenetic processes 8 underlying the brain growth spurt period especially involve intensive proliferation and growth of individual brain cells 2,6 that are accompanied by a conspicuous net synthesis of macromolecules and their fast accumulation in the brainlL It may be expected that the interference with these biochemical processes will be reflected not only m impaired proliferation and growth but also in impaired cytodifferentiation resulting eventually in aberrant structural organization and abnormal function. In this study the relations between altered protein synthesis and structural and/or functional abnormalities were investigated in the developing rat brain. Male hooded rats of the Druckray strain were used. The date of birth was assigned as postnatal day 0. Size of the litter was standardized to 8 animals and littermates were divided randomly to experimental and control groups. On day 7 the experimental animals received 0.02 )~ cycloheximide (CHX) in saline subcutaneously in the suprapelvic region. The same volume of saline was administered to the littermate controls. At the time of injection the litter was weighed and the weighing repeated on days 14, 21, 35, 70, 150 and 300. The cerebrum, cerebellum and olfactory bulbs were dissected, weighed and frozen in liquid Nz. For DNA estimation the tissues were homogenized in 0.4 M perchloric acid and DNA separated from RNA by an alkaline hydrolysis 3. The DNA content was measured by the diphenylamine method 4. Inhibition of protein synthesis following CHX treatment was estimated by means of incorporation of L-(U-14C) leucine. Having received the subcutaneous injection (200 #Ci/kg body weight) of

Efficiency of embryotoxicity testing procedures: I. A compromise approach

Abstract As the alternative to current embryotoxicity screening techniques, an attempt was made to utilize the principles of a procedure used in basic teratological research, for simplification, speed and economy. The effects of substances, administered to rats on days 10 and 11 of pregnancy, on the activity of the caudal morphogenetic system were examined by trunk measurements of embryos harvested on day 13. The caudal morphogenetic system of rat embryos reflected some of the changes induced in the maternal-embryonic complex.

Efficiency of embryotoxicity testing procedures: II. comparison between the official, mest and chest methods

Abstract 17 drugs were tested by 3 different embryotoxicity methods. The official routine procedure showed interspecies variance even between rat and rabbit. Evaluation based on the reaction of a single morphogenetic system after short-term treatment in the rat (MEST) is less laborious, inexpensive and quicker. Good results were obtained with chick embryos which, under strictly defined experimental conditions (CHEST), may prove a useful and reliable model in embryotoxicity screening.

An explanation of the stability of the incidence of inborn defects

We propose a mathematical model for the malformation incidence in a population. The model is based on the assumption that malformations occur in a narrow range of embryotoxic doses for a given toxin and that this range varies in the population. Using this assumption, we exhibit malformation incidence curves which are in qualitative agreement with experimental data.