Allan R. Beaudoin

Toxicity of polybrominated biphenyls (Firemaster BP-6) in rodents

Abstract Pregnant rodents were fed concentrations of a mixture of polybrominated biphenyls (Firemaster BP-6) during the pregnancy. The material appears to be weakly teratogenic, causing exencephaly and cleft palate in mice. Decreasing birth weight with increasing dosage of the material was seen in both mice and rats. Nonpregnant mice fed 1000 ppm Firemaster BP-6 for 11 days had a marked increase in liver size and weight.

Teratogenicity of polybrominated biphenyls in rats

Abstract The teratogenic potential of a mixture of polybrominated biphenyls (PBB) was investigated. Pregnant Wistar albino rats were given single doses of PBB in seasame oil by gavage on one day of pregnancy, from day 6 through 14 (sperm day = 0). The dose ranged from 40 to 800 mg/kg maternal body weight. At autopsy (day 20) fetuses were recovered and subsequently examined for skeletal and soft-tissue abnormalities. Resorptions followed treatment at all days. No skeletal malformations were seen at any dose level. The majority of soft tissue defects were found following 800 mg/kg PBB at day 11, 12, or 13. Only two malformations were produced, cleft palate and diaphragmatic hernia. It is concluded that a single high dose of PBB can be embryolethal and teratogenic to the rat embryo.

THE TERATOGENICITY OF CONGO RED IN RATS.

Summary The teratogenicity of Congo red was investigated in the Wistar Albino rat. Female rats received a single intraperi-toneal injection of a 2% aqueous solution of Congo red on the 8th day of pregnancy. Dosages used were either 14 mg/100 g, 30 mg/100 g or 40 mg/100 g maternal body weight. A dose of 20 mg/100 g was found to be teratogenic, 15.4% of the survivors being malformed. A dose of 40 mg/100 g was lethal, all pregnant rats dying within 5 days after injection. The malformations produced were hydrocephalus, hydronephrosis and ocular defects. Multiple malformations were rare. The teratogenic dose of Congo red did not produce any alteration in maternal serum protein components during the expected period of teratogenic activity. This is contrasted to the situation found following treatment with trypan blue.

Teratogenic action of platinum thymine blue

The teratogenic activity of the antitumor agent cisplatinum-2-thymine (platinum thymine blue) was investigated in rats. Pregnant Wistar-derived albino rats were given single ip injections of an aqueous solution of platinum thymine blue (PTB) at one day of pregnancy from day 5 through day 14 (sperm day=day 0). The dosages used ranged from 20 to 80 mg/kg maternal body weight. At autopsy (day 20) fetuses were recovered and subsequently examined for skeletal and soft-tissue abnormalities. PTB was embryolethal and teratogenic at several stages during rat gestation. Embryonic death occurred following all doses, and was dose dependent, except at day 5. The majority of malformed fetuses, however, were observed only after treatment at day 6 or 7 following injection with 50, 60, or 80 mg/kg. Eye defects were the predominant abnormality followed by hydrocephalus, gastroschisis, and ectopia cordis. The skeleton was only slightly affected. PTB is a potent inhibitor of DNA synthesis, but its mechanism of teratogenic action is unknown.

Effect of Adenosine Triphosphate and Adenosine Diphosphate on the Teratogenic Action of Trypan Blue in Rats

The effect of adenosine diphosphate (ADP) and triphosphate (ATP) on the teratogenic action of trypan blue was investigated in the Wistar rat. On day 8 (sperm day = day 0) each experimental animal received intraperitoneal injections of trypan blue (140 mg/kg or 5 mg/kg) plus either ADP or ATP in dosages ranging from 50 μg to 300 mg per animal. The fetuses were recovered at day 20 and examined. It was found that ADP and ATP may enhance, reduce, or have no effect on the incidence of trypan blue-induced malformations.

A developmental toxicity evaluation of gossypol

In utero development was analyzed in pregnancies that resulted from matings between gossypol-treated male rats and untreated female rats, and in pregnancies in which gossypol was administered to the pregnant rat only. Gossypol treatment of males had no effect on the outcome of pregnancy. There was no significant effect on resorption, fetal growth, or malformation rate. Similarly, gossypol administered to pregnant dams at stages during organogenesis had no observable effect on pregnancy. Under the conditions of this experiment, gossypol administered to either the breeding male rat or the pregnant female rat had no demonstrable adverse effect on development in utero.

A Reproduction and Teratology Study with Gossypol

Following the initial report from China in 1978 of the antifertility effect of gossypol in human males [1], antifertility studies have been conducted in various species: rats [2, 3, 4, 5], mice [6], hamsters [7, 8, 9], rabbits [10, 11], and monkeys [12]. Differential susceptibility among species exist: hamsters appear to be the most susceptible and mice and rabbits the least susceptible to the antifertility effects of gossypol [13, 14, 15]. The physiological and medical aspects of gossypol have been reviewed [16].

Teratogenic Activity of Six Disazo Dyes in the Wistar Albino Rat

Summary The teratogenic action of six disazo dyes was investigated in the Wistar albino rat. Appropriate dosages administered during day 8 of gestation showed the most potent teratogenic dye to be trypan blue followed by Evans blue, Niagara blue 4B, Niagara sky blue 6B, Congo red, and Niagara blue 2B. The diversity in types of malformations produced in the offspring of dye-treated mothers varied with the potency of the dye injected. Trypan blue caused the greatest number of different types of malformations and Niagara blue 2B the least. Ocular defects and hydrocephalus were the two most frequent abnormalities following treatment with each dye. There was no consistent correlation between dye action and maternal weight at the onset of treatment, maternal weight gained during pregnancy, maternal age, parity, fetal weight at autopsy, or placental weight.

The effect of citric acid on the teratogenic action of trypan blue

Trypan blue has been shown to be teratogenic when injected into the r~zbgerminal cavity or yolk sac of the developing chicken egg (1,2,3,4) . The most common abnormality observed after such treatment is rumplesaneas . The mechanism of aotion of this dye ie not known, although, it has been proposed that it acts primarily on the mesoderm (3,4) . Landauer has obtained evidence which shows that certain teratogena are active during chick development by interfering with metabolic processes . He has demonstrated that~the teratogenic effeeta of some compounds can be prevented, or lessened, by supplying the embryos with compounds that play a role in metabolism (5) . The present study was undertaken to determine if a metabolic compound could modify the teratogenic effects of trypan blue in the chicken egg. Citric acid was selected for testing because of its effectiveness in preventing induced rumplessnesa . Materials and Methods Fertile eggs of trhe YVhite Leghorn chicken were obtained from

Interference of Niagara Blue 2B with the Teratogenic Action of Trypan Blue.

Summary The results demonstrate that the non-teratogenic disazo dye, Niagara blue 2B, can afford some measure of protection to the embryo against the lethal and teratogenic action of trypan blue when injected prior to trypan blue in Sherman rats, over a selected range in dye concentration. This protection was not complete.