Effects of amaranth on F1 generation mice.

The color additive, amaranth, was given in the diet to provide dietary levels of 0 (control), 0.03, 0.09 and 0.27%, from 5 weeks of age in F₀ generation mice to 9 weeks of age in F₁ generation mice, and some reproductive, developmental and behavioral parameters were measured. There was no effect on the parameters of litters, litter size, pup weight and litter weight. The body weight of pups during the lactation period in the treatment groups increased less significantly, and the survival index at postnatal day (PND) 21 of the amaranth 0.27% group was reduced. Developmental parameters, direction of swimming on PND 4 in male pups and olfactory orientation in each sex were significantly reduced in the treatment groups. The dose levels of amaranth in this study influenced some reproductive, developmental and behavioral parameters in mice.     

Effects of piperonyl butoxide on F1 generation mice.

Piperonyl butoxide (PB), used in Japan as a pesticide synergist and food additive, was administered to mice from 5 weeks of age in the F0 generation to 9 weeks of age in the F1 generation, in the diet at levels of 0 (control), 0.15, 0.30 and 0.60%, and some reproductive, developmental and behavioral parameters were measured. Some parameters of open field activity were reduced in the treatment groups; in particular, ambulation and rearing were significantly reduced in F0 generation male mice and in 3-week-old F1 generation male mice. The weight of the pups was significantly reduced and litter weight tended to be reduced in the treatment groups. Body weight of dosed pups was reduced in the lactation period. Of the developmental parameters, olfactory orientation was significantly reduced as compared to controls. The dose levels of PB in this study, therefore, had an effect on some reproductive, developmental and behavioral parameters in mice.     

Reproductive and neurobehavioural effects of phloxine administered to mice

The colour additive phloxine was given in the diet to provide dietary levels of 0 (control), 0.1, 0.3 and 0.9%, from 5 wk of age of the F₀ generation to 8 wk of age of the F₁ generation in mice, and selected reproductive and neurobehavioural parameters were measured. There was little effect of phloxine on either litter size or weight, or sex ratio, whereas the body weight of the pups in the lactation period was significantly increased in all treatment groups. Among the neurobehavioural parameters measured, surface righting at postnatal day 4 of male pups was significantly reduced in all treatment groups. Some parameters of the motor activity of pups at 3 wk of age differed from those of the controls; in particular, the average speed of movement male pups was significantly reduced in all treatment groups. The dose levels of phloxine in this study produced a few adverse effects in reproductive and neurobehavioural parameters in mice.     

Multigenerational exposure to phytosterols in the mouse

Due to beneficial health effects phytosterols (PS) are increasingly added to functional foods. The aim of the present study was to investigate the chronic effects of a dietary PS mixture (5 mg/kg/day), containing mainly β-sitosterol, on the reproduction of the mouse. General reproductive parameters, postnatal development, growth and survival of pups, weight of sex organs, the concentrations of plasma sex steroids and testicular testosterone were monitored across five generations (F₀–F₄). PS exposure increased the plasma levels of testosterone and decreased the relative uterine weights in the pups of F₂ and F₄ generations. Furthermore, PS exposure increased the concentrations of plasma estradiol in the female pups of F₃ generation. PS supplement also increased the testicular levels of testosterone in the male pups of F₂ generation. In spite of these transitory changes, PS exposure caused no permanent deleterious effects on the reproduction of the mouse.     

Caffeine-mediated effects on reproductive health over two generations in rats

The present study was designed to investigate the mechanism(s) underlying previously observed birth weight differences found in the first litter of the second (F₂) generation bred from caffeine-exposed F₁ females. The effect of exposure to caffeine in utero on subsequent sexual receptivity, fertility, gestation length, parturition, nesting activity, maternal behaviour, and reproductive senescence in the F₁ mothers, and the viability of the F₂ offspring was investigated. This information was collected by breeding control or caffeine exposed females for 8 consecutive litters. It was demonstrated that exposure to caffeine did not affect the sexual receptivity, fertility, gestation length, or maternal behaviour of the F₁ females, but parturition was prolonged and the viability of the F₂ generation was seriously jeopardised. Many F₂ pups were born significantly larger than their control counterparts and a significant proportion of litters (after the first two litters) were wholly stillborn. It was concluded that a changed genetic program, mediated via the F₂ fetus, delayed the normal progression of parturition. This, in turn, compromised the F₁ mothers and caused increased mortality of their offspring. The severity of the outcome was dose dependent.     

Multigeneration reproduction study of policosanol in rats

The hypocholesterolaemic drug policosanol was administered to Sprague-Dawley rats of both sexes throughout three successive generations at concentrations of 0, 5, 50 and 500 mg/kg bw/day by gavage. for each generation two litters were reared until they were at least 3 weeks old. No clinical signs which could be related to the administration of the test substance were observed in the F₀, F_1b and F_2b parents. There were no differences among groups in the number of animals that conceived, the number of pups born live or dead, the rate of male to female pups, the number of pups that survived until weaning and the pups' body weights through the lactancy. The following test showed no treatment-related effects on F3b offspring: righting on a surface, air righting, corneal, pirmal and pain reflexes, auditory startle and visual placing. The results of the present study did not demonstrate any deleterious effects on the fertility, reproductive performance or development of rats administered policosanol at levels of up to 500 mg/kg bw/day over three successive generations.     

Effect of butyl benzyl phthalate in Sprague-Dawley rats after gavage administration: a two-generation reproductive study

Butyl benzyl phthalate (BBP), a plasticizer, has been shown in in vitro studies to be weakly estrogenic, and in in vivo studies to possess testicular toxicity and teratogenicity, but few experimental data on BBP multigeneration effects on reproduction in mammals are available. The present two-generation reproductive study was conducted in male and female Sprague-Dawley rats using oral doses of 0, 20, 100, and 500 mg/kg/day BBP. Endpoints were chosen in order to evaluate both subchronic and reproductive toxicity. In the parent animals (F₀), a decrease in body weight gain was observed in males in the 500 mg/kg/day group, although no significant decrease in food consumption was found. No dose-related changes were observed in estrous cyclicity, fertility, or lactation. A dose-dependent increase in kidney weight in rats of both sexes, an increase in liver weight in males, and a decrease in the weight of the ovaries in females were observed. No macroscopic or microscopic changes were found in the reproductive system of males or females. Oral administration of BBP caused a decrease in the serum concentration of testosterone, and an increase in FSH. In the next generation (F₁), the body weight of male and female offspring at birth in the 100 and 500 mg/kg groups was significantly decreased, and the body weight in the 500 mg/kg group was lower throughout the study, while viability was not affected. Anogenital distance (AGD) at birth was decreased in male pups and was increased in female pups of the 500 mg/kg/day group. Preputial separation for male offspring in the 500 mg/kg/day group was delayed, while vaginal opening for female offspring in this group was not affected. BBP did not affect reproductive ability, including delivery and lactation, at any dose whereas macroscopic and microscopic changes of the testis, and decreased serum concentrations of testosterone were observed in male offspring of the 500 mg/kg/day group after puberty. From these data, it would appear that 20 mg/kg BBP is a no observed adverse effect level (NOAEL) for reproductive effects on parent animals and the next generation.     

Reproductive Toxicity of Triethylene Glycol and Its Diacetate and Dimethyl Ether Derivatives in a Continuous Breeding Protocol in Swiss CD-1 Mice

Triethylene glycol and two of its derivatives were evaluatedfor reproductive toxicity in a continuous breeding protocolwith Swiss CD-1 mice. Triethylene glycol (TEG: 0, 0.3, 1.5,and 3%), triethylene glycol diacetate (TGD: 0, 0.75, 1.5, and3%), and triethylene glycol dimethyl ether (TGDME: 0, 0.25,0.5, and 1%) were administered in drinking water to breedingpairs (20 pairs per treatment group, 40 control pairs) duringa 98-day cohabitation period. Reproductive function was assessedby the number of litters per pair, live pups per litter, proportionof pups born alive, and pup weight. There were no apparent effectson reproductive function in the animals receiving TEG or TGDat doses up to 3% in the drinking water (representing 6.78 or5.45 g/kg, respectively). However, some developmental toxicitywas demonstrated for both TEG and TGD. Continuous exposure ofdams to 1.5 or 3% TEG significantly reduced live pup weightat birth compared to control and 0.3% TEG, while exposure to3% TGD during lactation significantly (but reversibly) reducedpup body weights on Postnatal Days 14 and 21. In contrast, TGDMEwas toxic to the reproductive system as evidenced by decreasesat the highest dose (1% TGDME; 1.47 g/kg) in the proportionof pairs that produced at least one litter, live pups per litter,and proportion of pups born alive, with dose-related trendsseen in the latter two parameters. A crossover mating trialshowed that TGDME was more toxic to the female than the malereproductive system. These data indicate that TGDME (1.47 g/kg)is a reproductive toxicant in Swiss mice while re productivetoxicity was not demonstrated in mice receiving TEG or TGD (atdoses up to 6.78 or 5.45 g/kg, respectively).     

Carcinogenicity study of 1,1-Bis(tert-butylperoxy)-3,3,5-trimethylcyclohexane in B6C3F1 mice

1,1-Bis(tert-butylperoxy)-3,3,5-trimethylcyclohexane (BBTC) is widely used in the manufacture of rubber. The present carcinogenicity study in B6C3F₁ mice was carried out in order to assess its potential to induce tumours. BBTC was administered at dietary levels of 0 (control), 0.25 and 0.5% for 78 wk; these dose levels were selected on the basis of a subchronic toxicity study, in which body weights were depressed to less than 90% of the control group values and swelling of hepatocytes was histologically evident in animals fed 1% BBTC or more in the diet. Neoplasms were found in all groups, including the control group, but there were no significant differences between groups of either sex in mortality, tumour incidences or tumour distribution. All tumours were considered to be spontaneous because of the similarity to background data for B6C3F₁ mice. This study thus provides no evidence of carcinogenicity of BBTC in B6C3F₁ mice.     

EFFECTS ON PUBERTAL GROWTH AND REPRODUCTION IN RATS EXPOSED TO LEAD PERINATALLY OR CONTINUOUSLY THROUGHOUT DEVELOPMENT

The reproductive, endocrine, and growth effects of developmental lead exposure were assessed using a rat model in which 0.6% lead acetate (w/v) was administered in the drinking water ad libitum during different developmental periods to determine if lead actions were a result of direct effects of continuous exposure to the metal ion or secondary to disrupted neonatal "endocrine imprinting." Sprague Dawley rats were exposed to lead: (1) from gestational d 5 through birth; (2) during pregnancy and lactation; (3) during lactation only; (4) from birth through adulthood; or (5) from gestational d 5 through adulthood. Lead effects were measured on the development of aspects of the reproductive system, adult sex steroid levels, and growth rates in both male and female animals. The relative weights of male secondary sex organs in adult offspring were not significantly affected in any of the lead-treated groups. In contrast, female pups exposed to lead from birth through adulthood or from gestational day 5 through adulthood were observed to have significantly delayed vaginal opening and disrupted estrus cycling. These effects on female reproductive physiology were not observed in animals where lead exposure was confined only to pregnancy or lactation. Significant suppression of adult mean serum testosterone levels was only observed in male pups exposed to lead continuously from gestational age 5 d throughout life. Lead decreased birth weight in all animals exposed in utero and mean body weights were significantly decreased in all lead-treated groups up to weaning. Analysis of growth curves revealed that all lead-treated groups had significantly reduced growth rates during lactation. However, in addition, in male pups exposed to lead during pregnancy and lactation, from birth or from gestational age 5 d, growth rates were also significantly reduced during puberty. Postpubertal growth rates were unaffected in any lead-treated group. Thus, delayed female reproductive development and suppression of adult male serum testosterone concentration required continuous exposure to the heavy metal. Little evidence was observed for an alteration of "endocrine imprinting" by lead on either reproductive or growth parameters. Exposure during early development (pregnancy and lactation) resulted in no permanent effects in this model other than small (10%) decreases in the body weight of pups postpuberty.     

Tetrahydrofuran: two-generation reproduction toxicity in Wistar rats by continuous administration in the drinking water.

In a two-generation reproduction toxicity study, 25 male and 25 female Wistar rats per dose group and generation were exposed continuously to tetrahydrofuran in the drinking water for at least 70 days prior to and during mating, gestation, parturition and lactation to weaning, at concentrations of 0, 1000, 3000 or 9000 ppm (approximately 100, 300 and 700 mg/kg/day in males and females premating, 100, 300 and 800 mg/kg/day in females during gestation, and 200, 500 and 1300 mg/kg/day in females during lactation) through two successive generations. In both generations and sexes, water consumption was dose-relatedly reduced at all doses; food consumption and body weight were reduced at 9000 ppm. Necropsy kidney weights were increased in 9000 ppm F0 males. Pup body weight gain during lactation was reduced in both generations (F1 and F2 pups) and eye opening delayed in the first generation (F1 pups) at 9000 ppm; there were no treatment-related malformations. The NOAEL of tetrahydrofuran in drinking water is 9000 ppm for parental fertility and reproductive performance, and 3000 ppm for systemic parental and developmental toxicity.     

Impaired behaviour, learning and memory, in adult mice neonatally exposed to hexabromocyclododecane (HBCDD)

Brominated flame-retardants (BFRs) are a diverse group of global environmental pollutants. In the present study, we show that neonatal exposure to hexabromocyclododecane (HBCDD) can cause developmental behavioural defects that are similar to those recently reported for PBDEs and certain PCBs. Furthermore, HBCDD appears to be as potent as PBDEs in inducing developmental neurotoxic effects in mice.

In this study, neonatal NMRI mouse pups were given either a single oral dose of 0.9 mg HBCDD/kg body weight, 13.5 mg HBCDD/kg body weight, or a 20% fat emulsion vehicle on postnatal day 10. At the age of 3 months, the mice were observed regarding spontaneous behaviour and concerning learning and memory capability. Mice exposed to 0.9 mg HBCDD or to 13.5 mg HBCDD/kg body weight showed a significantly altered spontaneous behaviour, manifested as a hyperactive condition and reduced habituation. Learning and memory, as observed in a Morris water maze, was also significantly affected in mice given the higher dose of HBCDD.     

Acute toxicity of textile dye wastewaters (untreated and treated) of Sanganer on male reproductive systems of albino rats and mice

This study reports on the toxic effects of 15-days oral administration of untreated (Influent) and treated (Effluent) textile dye wastewaters on male reproductive systems of adult Swiss albino rats (age: 85–90 days) and mice (40–50 days). Textile dye wastewaters decreased body weight (7–25%) and reproductive organ weight (testis, epididymis, prostate gland and seminal vesicle, 2–48%). Similar trends were noted for total protein (14–70%), cholesterol (14–91%) and total lipid (10–30%) content of reproductive organs and spermatozoa, and for fructose levels in seminal vesicle (18–44%). Acid phosphatase activity in prostate however, was increased (11–44%) in the wastewater-exposed animals. Histopathological studies of treated animals revealed altered spermatogenesis, with higher sperm abnormalities, reduction in sperm counts (10–59%), and altered motility (14–56%). The magnitude of these abnormalities was stronger in rats versus mice, while among treatments, it was stronger in the Influent animals. Adverse effects improved when treated rats were allowed to recover 45 days in the control condition. Only recovered Effluent rats were capable of fertilizing normal females indicating that treated wastewater was less toxic; however, in comparison to control rats, litter size and body weight gains of F₁ and F₂ generations were adversely affected. Thus, the present study has established toxicity of both untreated and treated textile dye wastewater on reproductive biology of male Albino mice and rats.     

Developmental and reproductive toxicity evaluation of toluene vapor in the rat. I. Reproductive toxicity

The reproductive toxicity of toluene was evaluated in a 2-generation test in which male and female Sprague–Dawley rats, parental (F0) and first generation (F1), were exposed to toluene via whole body inhalation, 6 h/day, 7 days/week for 80 days premating and 15 days of mating at concentrations of 0, 100, 500 and 2000 ppm (0, 375, 1875 and 7500 mg/m³). Toluene was administered at 2000 ppm to both sexes, or to females or males only to be mated with untreated partners. Pregnant females at all dose levels were exposed from gestation day (GD) 1–20 and lactation day (LD) 5–21. At LD5, females were removed from their litters for daily exposure and returned when 6 h of exposure was completed. F1 pups selected to produce the F2 generation were treated for 80 days beginning immediately after weaning (LD21) and initially mated at a minimum of 100 days of age. F2 pups were not exposed to toluene by inhalation.

Toluene exposure did not induce adverse effects on fertility, reproductive performance, or maternal/pup behaviors during the lactation period in males and females of the parental or first generation, but did inhibit growth in F1 and F2 offspring in the 2000 ppm (both sexes treated) and 2000 ppm (females only treated) groups. Caesarean section of selected 2000 ppm (both sexes treated) dams at GD20 showed reduced fetal body weight and skeletal variations. Exposure to toluene caused decreased pup weights throughout lactation in F1 and F2 2000 ppm (both sexes treated), and 2000 ppm (females only treated) groups. Exposure at 2000 ppm to male parents only did not induce similar weight inhibition in offspring. The toluene offspring NOAEL is 500 ppm in groups in which maternal animals were exposed, and 2000 ppm for male only treated groups.     

Studies of the toxicological potential of tripeptides (L-valyl-L-prolyl-L-proline and L-isoleucyl-L-prolyl-L-proline): VI. Effects of Lactobacillus helveticus-fermented milk powder on fertility and reproductive performance of rats

The objective of these studies was to assess the effects of the tripeptides, L-valyl-L-prolyl-L-proline (VPP) and L-isoleucyl-L-prolyl-L-proline (IPP), on reproductive capabilities of male and female rats. The specific goals of the experiments were (1) to determine the effects of orally administered tripeptides on (a) fertility and reproductive behavior in both sexes of rats, (b) embryo-fetal development in pregnant rats, and (c) pre- and postnatal development of rats exposed to tripeptides in utero and during lactation; and (2) to estimate the no-observable-adverse-effect doses of tripeptides in maternal and fetal rats. During the conduct of these classical segment I, II, and III studies, the test material was powdered Lactobacillus helveticus-fermented milk (FM), which contains the tripeptides, VPP and IPP. FM (0, 500, 1000 or 2000 mg/kg body weight [BW]/day--equivalent to 0, 0.8, 1.6, or 3.3 mg/kg BW/day of VPP plus IPP) was administered to males by oral gavage from 4 weeks prior to mating until sacrifice, and to females from 2 weeks prior to mating through day 20 of lactation. Evaluative parameters included monitoring grossly observable clinical signs; food consumption and body weight gains; mating behavior and fertility indices of both sexes; implantation and maintenance of embryos; sex ratio of live pups; fetal viability; incidences of external, visceral or skeletal variations; growth and behavioral development; as well as reproductive capabilities of F1 offspring exposed to FM during gestation and lactation. All animals were subjected to macroscopic examination at termination of their segment of the studies. Clinical signs, body weights, and food consumption were unaffected by administration of FM. During segment I, the test agent had no effect on estrus cycle, mating behavior, fertility index, or reproductive competence of either males or females. The results of segment II experiments revealed no effects of FM on postimplantation survival-loss, sex ratio or birth weights of live fetuses, and there was no evidence of treatment-associated developmental or teratological effects. During segment III, FM was without effect on pup viability, behavioral and sexual maturation, and reproductive capability of the F1 generation. Under the conditions of these experiments, the no-observable-adverse-effect level (NOAEL) of FM on reproductive performance in male and female rats is greater than 2000 mg/kg BW/day, the equivalent of 3.3 mg/kg BW/day of VPP plus IPP.     

Developmental toxicity and psychotoxicity of potassium iodide in rats: A case for the inclusion of behaviour in toxicological assessment

Potassium iodide (KI) was fed to male and female rats before and during breeding, to females only during gestation and lactation, and to their offspring after weaning (day 21 after birth) through to day 90, at levels of 0, 0.025, 0.05 or 0.1% (w/w) of the diet. Dams in a fifth group (positive controls) were given 4 mg/kg ip of the anti-mitotic/cytotoxic drug 5-azacytidine on day 17 of gestation. All offspring were reared by their natural dams and were evaluated blind with respect to treatment in a battery of standardized behavioural tests between 3 and 90 days of age. KI produced no significant reductions in parental body weight or food consumption, though it significantly reduced litter size and increased offspring mortality at the highest dose, and decreased weight gain at the two highest doses throughout the first 90 days after birth. Functionally, KI delayed auditory startle at the two highest doses, delayed olfactory orientation to the home-cage scent at the middle dose and decreased female running-wheel activity at all dose levels. In rats killed on day 90 after birth KI reduced brain and body weight at a dose of 0.1% of the diet, and reduced body but not brain weight at a dose of 0.05% of the diet. No significant effect was found on absolute or relative thyroid weight at 90 days of age. Several additional behavioural effects were observed in the low-dose KI group, but because these effects were not dose-dependent, they were not regarded as reliable. 5-Azacytidine produced evidence of substantially greater developmental toxicity than KI. It was concluded that KI produced evidence of developmental toxicity consistent with a picture of impaired thyroid function. The inclusion of tests of functional development added useful evidence to the overall picture of KI developmental toxicity.     

Evaluation of the reproductive and developmental toxicity of a fluoroalkylethanol mixture

The objective of these studies was to evaluate the reproductive and developmental toxicity of a commercial fluoroalkylethanol mixture, which is an intermediate in the production of fluorotelomers. The test substance was administered daily by gavage to Sprague-Dawley rats as a suspension in 0.5% aqueous methylcellulose. In a one-generation reproductive toxicity study, rats (20 per sex per group) were given dosages of 0, 25, 100, or 250 mg kg(-1) day(-1) for a period of 74 days prior to cohabitation, and during mating, gestation, and lactation. Body weights, feed consumption, clinical signs, gross pathology, sperm parameters, estrous cyclicity, and reproductive performance were evaluated for the P1 generation. The F1 offspring were.evaluated during the lactation period for growth and survival and given a gross pathology examination at weaning. A subset of the offspring were retained; body weights, feed consumption, clinical signs, and age at onset of vaginal opening and preputial separation were evaluated, and gross pathology was performed on postnatal day 60. In the developmental toxicity study, groups of time-mated Sprague-Dawley female rats were given the test substance as a suspension in 0.5% aqueous methylcellulose at daily dosages of 0, 50, 200, or 500 mg kg(-1) day(-1) by gavage on gestation days 6-20. During the in-life portion of the study, growth parameters and clinical observations were made. On gestation day 21, dams were euthanized, and the thoracic and abdominal viscera were examined. The uterine contents were removed and examined, and fetuses were evaluated for any alterations. In the reproduction study, litter size at birth, number of live pups per litter on day 0 and 4 of lactation, and pup weights during lactation were reduced in groups administered > or =100 mg kg(-1) day(-1). No other reproductive parameters were affected. There were no adverse reproductive effects observed at 25 mg kg(-1) day(-1). In the developmental toxicity study, reduced maternal body weight parameters, increased perineal fur staining, and increased fetal skeletal alterations were observed at 500 mg kg(-1) day(-1). There was no maternal or developmental toxicity at 50 or 200 mg kg(-1) day(-1). Under the conditions of the studies, the no-observed adverse effect levels for this mixture were 25 mg kg(-1) day(-1) for subchronic toxicity and reproductive parameters and 200 mg kg(-1) day(-1) for developmental toxicity end points. No functional reproductive or developmental effects were observed at dose levels that did not adversely affect adult animals.     

Evaluation of the Reproductive and Developmental Toxicity of a Fluoroalkylethanol Mixture

The objective of these studies was to evaluate the reproductive and developmental toxicity of a commercial fluoroalkylethanol mixture, which is an intermediate in the production of fluorotelomers. The test substance was administered daily by gavage to Sprague–Dawley rats as a suspension in 0.5% aqueous methylcellulose. In a one-generation reproductive toxicity study, rats (20 per sex per group) were given dosages of 0, 25, 100, or 250 mg kg^{? 1} day^{? 1} for a period of 74 days prior to cohabitation, and during mating, gestation, and lactation. Body weights, feed consumption, clinical signs, gross pathology, sperm parameters, estrous cyclicity, and reproductive performance were evaluated for the P₁ generation. The F₁ offspring were evaluated during the lactation period for growth and survival and given a gross pathology examination at weaning. A subset of the offspring were retained; body weights, feed consumption, clinical signs, and age at onset of vaginal opening and preputial separation were evaluated, and gross pathology was performed on postnatal day 60. In the developmental toxicity study, groups of time-mated Sprague–Dawley female rats were given the test substance as a suspension in 0.5% aqueous methylcellulose at daily dosages of 0, 50, 200, or 500 mg kg^{? 1} day^{? 1} by gavage on gestation days 6–20. During the in-life portion of the study, growth parameters and clinical observations were made. On gestation day 21, dams were euthanized, and the thoracic and abdominal viscera were examined. The uterine contents were removed and examined, and fetuses were evaluated for any alterations. In the reproduction study, litter size at birth, number of live pups per litter on day 0 and 4 of lactation, and pup weights during lactation were reduced in groups administered ≥ 100 mg kg^{? 1} day^{? 1}. No other reproductive parameters were affected. There were no adverse reproductive effects observed at 25 mg kg^{? 1} day^{? 1}. In the developmental toxicity study, reduced maternal body weight parameters, increased perineal fur staining, and increased fetal skeletal alterations were observed at 500 mg kg^{? 1} day^{? 1}. There was no maternal or developmental toxicity at 50 or 200 mg kg^{? 1} day^{? 1}. Under the conditions of the studies, the no-observed adverse effect levels for this mixture were 25 mg kg^{? 1} day^{? 1} for subchronic toxicity and reproductive parameters and 200 mg kg^{? 1} day^{? 1} for developmental toxicity end points. No functional reproductive or developmental effects were observed at dose levels that did not adversely affect adult animals.     

Subchronic, reproductive, and developmental toxicity of a fluorotelomer-based urethane polymeric product

A commercial fluorotelomer-based urethane polymeric dispersion, consisting of polymer, surfactant, and water, was evaluated in subchronic, reproduction, and developmental toxicity studies. The dispersion was administered daily by gavage to rats at dosages of 0, 50, 250, or 1000 mg polymer/kg/day or with 70 mg/kg/day of the sulfonate surfactant. Dose levels of 0, 50, 250, or 1000 mg polymer/kg/day were also used for the reproductive and developmental studies. Nasal olfactory epithelial degeneration and necrosis occurred in all dose groups in the 90-day study. Nasal adhesions were observed only in rats administered surfactant alone. Liver-enzyme alterations at 250 and 1000 mg/kg were considered to be potentially adverse effects. The subchronic no-observed-adverse-effects level (NOAEL) was 50 mg/kg. For the reproduction study, rats were dosed for 10 weeks prior to cohabitation and throughout mating, gestation, and lactation. There were no effects on reproductive function in males or females at any dosage. Thyroid weight was decreased in the 250 and 1000 mg/kg day F(1) groups unaccompanied by microscopic effects. In the developmental toxicity study, female rats were dosed from gestation days 6-20; there was no test-substance-related embryolethality, nor was there any dose-related increase in either fetal malformations. Fetal weight was minimally decreased at 1000 mg/kg/day in the presence of slight maternal toxicity; the NOAEL for developmental parameters was 250 mg/kg/day. The polymeric product was not a specific developmental or reproductive toxin.     

Antigenotoxic effect of Saccharomyces cerevisiae on the damage produced in mice fed with aflatoxin B1 contaminated corn

The potential of Saccharomyces cerevisiae (Sc) was evaluated for reducing the micronucleated normochromatic erythrocytes (MNNE) rate in mice fed AFB₁ contaminated corn. The study included two groups fed AFB₁ contaminated corn (0.4 and 0.8 mg/kg), a control fed uncontaminated corn, another group fed uncontaminated corn and 0.3% of Sc (1 × 10⁸ live cells/g), and two groups fed AFB₁ contaminated corn (0.4 and 0.8 mg/kg) plus 0.3% Sc. Weight and MNNE were determined weekly for six weeks. Subsequently, the same determinations were made for another three-week period, but in mice receiving only a normal diet, without AFB₁ and Sc. Results in the first period revealed the following: control and Sc fed mice had similar constant weight increase, and low MNNE rate; mice fed only AFB₁ showed weight decrease and significant MNNE increase; finally, Sc improved weight gain and reduced MNNE produced by AFB₁. In the second period, results exhibited a tendency similar to that of the previous phase in the control and Sc fed mice; the weight and MNNE values improved in the other groups. We also determined the capacity of Sc for adsorbing and modifying the mycotoxin structure. The mixture was filtered to obtain two phases, and AFB₁ content was measured. Sc revealed a potent adsorbent capacity; however, chromatographic determination suggested no structural modification.