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PubMedDate not supplied

Testing strategies in behavioral teratology: I. Testing battery approach.

Female rats were given drinking water containing 1.5, 5 or 15 mg/l methylmercury chloride from two weeks prior to pairing until the end of the lactation period. The usual reproduction parameters were recorded. The morphological, functional and behavioral development of the offspring was assessed by subjecting them to a routine testing battery in accordance with the English and Japanese guidelines. Due to toxic effects in the high dose group only offspring of the mid and low dose groups were tested. In both groups some motor coordination and learning deficits as well as delayed sexual maturation were noted, although effects were small and varied considerably. Results demonstrated that a routine testing battery can detect behavioral effects in the offspring at a dose where no reproduction effects are observed.

Animals↗

PubMed1979

The effect of age on reproduction in repeatedly mated female rats.

The effects of age and repeated pregnancies on reproduction were studied in Long-Evans rats. Indices of reproduction measured included estrous cycles, successful mating, numbers of rats producing litters, average litter size, average pup weight and serum LH-from a 4 pm proestrous blood sample. There were no differences in these reproductive parameters between rats with serial pregnancies initiated at 2 or 9 mo of age. The percentage of rats producing normal litters was reduced much faster than the percentage of successfully mated rats with normal ovarian cycles. Although 60% of the rats still had normal ovarian cycles and were mated at 17 mo of age, only one rat (4%) produced a litter. Increasing age and multiple pregnancies did not significantly affect the LH concentration of the proestrous blood sample or the average litter size or pup weight of the rats with successful pregnancies. These data suggest post-ovulatory loss of reproduction in the aging rat.

Animals↗

PubMed1995

Early lactation responses of Holstein cows fed a rumen-inert fat prepartum, postpartum, or both.

Primiparous (n = 22) and multiparous (n = 41) cows were randomly assigned by calving date and parity to one of four dietary sequences of supplemental fat from 14 d prepartum to 151 d postpartum. Partially hydrogenated tallow was added to diets at 0% prepartum and postpartum (control); 1% prepartum and 2% postpartum; 0% prepartum and 2% postpartum; and 0% prepartum, 0% from 1 to 34 d postpartum, and 2% from 35 to 151 d postpartum. Inclusion of partially hydrogenated tallow did not influence yields of milk or 3.5% FCM, milk composition, or DMI during the first 151 d postpartum. During the first 35 d postpartum, cows receiving partially hydrogenated tallow starting at parturition yielded milk with a higher fat content than those receiving fat prepartum and postpartum. Addition of partially hydrogenated tallow to diets starting 35 d postpartum resulted in cows being more persistent in yields of milk and 3.5% FCM from 60 to 151 d postpartum. Reproduction parameters measured were unaffected by time of fat addition to diets. Our data suggest that delaying the addition of partially hydrogenated tallow to diets until 35 d postpartum may improve the persistency of lactation.

Animals↗

PubMed1994

Alterations in the ontogeny of rat pup ultrasonic vocalization produced by prenatal exposure to nitrogen dioxide.

Wistar female rats were exposed to low concentrations of nitrogen dioxide, NO2 (1.5 and 3 ppm) from day 0 to day 20 of pregnancy. The results show that prenatal exposure to this oxidant gas produced significant changes in the duration pattern of ultrasonic vocalizations emitted by male pups removed from their nest. In particular, a significant decrease in the length of ultrasonic calls was found in both 10- and 15-day-old rats exposed to NO2 (3 ppm) during gestation. These alterations were found at dose levels which did not significantly affect reproduction parameters, body weight gain and motor activity development. These findings suggest that gestational exposure to NO2, at concentrations below those associated with overt signs of toxicity, induces in rat offspring subtle behavioral changes characterized by altered ontogeny of ultrasonic emission.

Aging↗

PubMedDate not supplied

Ethylene glycol monomethyl ether II. Reproductive and dominant lethal studies in rats.

Groups of male and female Sprague-Dawley (CD) rats were exposed to 0, 30, 100, or 300 ppm ethylene glycol monomethyl ether (EGME) vapor 6 hours/day, 5 days/week for 13 weeks. The 0 and 30 ppm groups each contained 30 rats/sex and the 100 and 300 ppm groups each had 20 rats/sex. Following the exposure period, males were bred to unexposed females to evaluate reproductive capability and dominant lethality. Additional matings of control and 300 ppm exposed males were performed during the post-exposure period in order to evaluate the recovery of fertility. Exposed females were bred with unexposed males to assess reproductive parameters. Results of the present study indicate a potential for inhaled EGME to completely suppress fertility in male rats at the 300 ppm level. Fertility of these rats was partially restored at 13 weeks post-exposure. Body weights of animals in the 300 ppm group were reduced as a result of the exposures. No dominant lethal effect or impaired fertility was observed in male rats exposed to 30 or 100 ppm EGME. Treatment-related pathologic alterations were observed only in male rats at the 300 ppm level and induced decreased testicular size and atrophic seminiferous tubules. Female rats tolerated up to 300 ppm EGME without any adverse reproductive effects. Based on these results, it was concluded that the no-adverse effect level of EGME for fertility and reproduction was 100 ppm in rats.

Animals↗

PubMed1984

Reproductive performance of broiler breeders exposed to cycling high temperatures from 17 to 20 weeks of age.

Forty male and 240 female broiler breeders were placed in cages within environmental chambers (20 males or 40 females per chamber) at 14 weeks of age. Chamber temperatures were maintained at 21.3 +/- 2.5 C, and relative humidity (RH) ranged from 40 to 50%. Ventilation rate was approximately 47.2 liters/sec per chamber, and light was provided from 0600 to 1800 hr. Feed was restricted daily according to industry recommendations, and water was provided ad libitum. From 17 to 20 weeks of age, control (C) chambers were kept at constant 21.0 +/- 1.4 C with 45 +/- 5% RH, and heat-treated (HT) chambers were cycled from 24.4 +/- 5.5 C (45 +/- 5% RH) during 1800 to 0800 hr to 36.0 +/- 2.8 C (15 +/- 5% RH) during 0800 to 1800 hr. Body weights were recorded at biweekly intervals. At 18 and 20 weeks of age, blood samples and rectal body temperatures were obtained randomly from five fasted birds per chamber at 0800 and 1400 hr. From 20 to 60 weeks of age, all birds were kept in individual cages in a conventional fan-ventilated house. Maximum temperature never exceeded 30 C, and average RH was 65.0%. Reproductive parameters were monitored and body weights were obtained at 4-week intervals. There were no significant treatment effects for body weight, body temperature, or differential leukocyte counts. Hematocrits were significantly lower for HT females than controls, and heat treatment did not result in consistent changes in plasma glucose or total proteins.(ABSTRACT TRUNCATED AT 250 WORDS)

Age Factors↗

PubMed1995

Retrospective evaluation of production characteristics in Sinclair miniature swine--44 years later.

Three hundred seventy-one litter records collected between 1985 and 1993 from 156 Sinclair S-1 miniature sows, a Hormel-derived strain of miniature swine, were retrospectively analyzed and compared with published records for 1950 to 1952 and 1963 to 1965. The effect of several variables such as season and month of parturition, age of sow, parity, and litter size on reproductive parameters of the Sinclair miniature swine were evaluated. The mean and standard error of the mean for litter size, number of liveborn, number of stillborn, and litter size at weaning of the Sinclair S-1 miniature swine were 7.20 +/- 0.12, 6.57 +/- 0.12, 0.63 +/- 0.06, and 5.75 +/- 0.12 piglets respectively. From a total of 2,436 liveborn piglets, 2,133 (87.56%) were weaned. The litter size at birth was similar to that previously reported for this strain of swine, whereas the litter size at weaning increased (P < 0.001) from 4.7 piglets during 1963 to 1965 to 5.8 piglets in our study. The average birth weight decreased (P < 0.001) from 0.90 kg in 1950 to 1952 and 0.72 kg in 1963 to 1965 to 0.59 kg in our study. Reproductive variables that had a considerable effect on the miniswine reproduction included month of parturition, age of sow, parity, and litter size. Primiparous sows had the smallest litter size and lowest number of weaned piglets. Sows during their second and third parity or sows between 2 and 4 years old had the best reproductive performances. Litter size and number of stillborn increased with parity and age of sow, resulting in fewer piglets weaned in older sows.(ABSTRACT TRUNCATED AT 250 WORDS)

Aging↗

PubMed1987

The effects of aluminium ingestion on reproduction and postnatal survival in rats.

Aluminium nitrate was tested for its effects on reproduction, gestation, and lactation in Sprague-Dawley rats, at dosages of 0, 180, 360 and 720 mg/kg/day. Mature male rats were treated orally for 60 days prior to mating with mature virgin female rats treated for 14 days prior to mating with treatment continuing throughout mating, gestation, parturition, and weaning of the litters. One-half of the dams in each group were killed on day 13 of gestation and the remaining dams were allowed to deliver and wean their offspring. Postnatal development was monitored. No adverse effects on fertility or general reproductive parameters were evident at doses employed in these studies. However, the survival ratios were higher for the control group. Moreover, a dose-dependent delay in the growth of the living young could be observed in aluminium treated groups. Therefore, it would seem that high amounts of aluminium should not be ingested during the periods of gestation.

Aluminum↗

PubMed1995

Developmental toxicity of dibasic esters by inhalation in the rat.

Dibasic esters (DBE) are a mixture of 3 carboxylic acid esters which are used in the paint and coatings industry. In this study, groups of pregnant Crl:CD BR rats were exposed to either 0.16, 0.4, or 1.0 mg DBE/L by inhalation for 6 hr/day from Days 7 through 16 of gestation (day in which copulation plug was detected was designated Day 1G). A control group of chambered pregnant rats was exposed simultaneously to air only. All female rats were euthanized on Day 21G and the fetuses were examined. A suppression of both food consumption and the rate of body weight gain was seen in the 0.4 and 1.0 mg/L groups during the first 6 exposure days. Staining on the fur and perineal area was seen in rats exposed to 1.0 mg/L and liver weight decreases, although not statistically significant, occurred in the 2 high exposure groups. None of the reproductive parameters were altered in any of the groups and no fetal effects were detected. DBE is not a developmental toxin in the rat following inhalation exposures as high as 1.0 mg DBE/L during the period of organogenesis.

Abnormalities, Drug-Induced↗

PubMed1991

Immunotoxicity of 2-methoxyethanol following oral administration in Fischer 344 rats.

The immunotoxicity of the glycol ether 2-methoxyethanol (ME) was evaluated in adult Fischer 344 rats using a variety of in vitro and in vivo immune function assays. In the first phase of this study, male rats were dosed by oral gavage with ME in water, at dosages ranging from 50 to 200 mg/kg/day, for 10 consecutive days. Decreases in thymus weights were observed at dosages of 50-200 mg/kg/day in the absence of decreased body weights. Lymphoproliferative (LP) responses to concanavalin A and phytohemagglutinin were reduced at 50-200 mg/kg/day while pokeweed mitogen and Salmonella typhimurium mitogen responses were reduced at 200 mg/kg/day. No alterations were observed in natural killer cell activity, mixed lymphocyte reaction, or cytotoxic T lymphocyte responses. The frequency of W3/25-positive splenocytes was reduced in rats dosed at 200 mg/kg/day. Interleukin-2 production was reduced in splenocytes from rats exposed to all dosages of ME. The plaque-forming cell (PFC) response to sheep red blood cells was enhanced in rats dosed at 50 mg/kg/day. However, the PFC response to trinitrophenyl-lipopolysaccharide (TNP-LPS) was suppressed at all dosages. Similarly, the PFC response to TNP-LPS was suppressed in adult female rats dosed with ME. A reduction in the expulsion of adult worms was observed in rats dosed at 200 mg/kg/day that were infected with Trichinella spiralis. A number of male reproductive parameters were also evaluated in rats dosed with ME over 10 days. A significant reduction in testicular weight was observed in rats dosed at 200 mg/kg/day. In the second phase of this study, the PFC response to TNP-LPS was employed to assess the role that metabolism of ME to 2-methoxyacetic acid (MAA) plays in the immunotoxicity of this glycol ether. Ten-day oral dosing with MAA resulted in the inhibition of the PFC response to TNP-LPS at dosages of 50-200 mg/kg/day. Concomitant exposure of rats to ME and the alcohol dehydrogenase inhibitor 4-methylpyrazole blocked ME-induced suppression of this PFC response. Attempts to ameliorate ME-induced suppression of the PFC response with serine, which has been shown to reverse ME-induced developmental and reproductive toxicity, were unsuccessful. These results suggest that the immune system may be more sensitive than the reproductive system to the toxic effects of ME. Furthermore, it appears that MAA is the proximate toxicant for ME-induced alterations in the immune system, as has been demonstrated for ME-induced reproductive and developmental toxicity.

Administration, Oral↗

PubMedDate not supplied

Two-generation reproduction study on commercial hexane solvent.

The reproductive effects of inhalation exposure to commercial hexane vapors were evaluated in Sprague-Dawley rats. Males and females were exposed to commercial hexane vapor at target concentrations of 0, 900, 3000 or 9000 ppm for 6 h a day, 5 or 7 days a week, over two generations. In addition to pre-breed exposures of 10 weeks' duration, exposures continued through mating, gestation and lactation. At both the F0 breed to produce F1 litters and the F1 breed to produce F2 litters, reproductive parameters were unaffected by commercial hexane exposure. The mating, fertility and gestational indices, as well as litter size and postnatal survival, were not significantly different between exposure groups. However, reductions in body weight and body weight gain were observed in both F1 and F2 litters exposed to 9000 ppm. Effects on body weight were not observed in offspring exposed to the two lower concentrations of commercial hexane. Histopathological examination of selected tissues revealed hyaline droplet nephropathy in adult F0 and F1 males exposed to 9000 ppm. This finding was anticipated and is not believed to be relevant for the assessment of human health effects. No other treatment-related histopathological lesions were observed. Thus, exposure of rats to commercial hexane for two generations resulted in reduced body weight gains at 9000 ppm but no adverse effects on reproduction. These findings suggest that occupational exposure to commercial hexane vapors at currently recommended threshold limit value concentrations (i.e. TLV for n-hexane is 50 ppm and TLV for other hexane isomers is 500 ppm) should not pose a reproductive hazard.

Administration, Inhalation↗

PubMed1996

Reproductive bionomics of the soft tick, Ornithodoros turicata (Acari: Argasidae).

The effects of different temperatures and relative humidities (RHs) were tested on various reproductive parameters of Ornithodoros turicata, an argasid tick that inhabits gopher tortoise burrows in Florida, USA. The pre-oviposition, oviposition and incubation periods of the ticks decreased as temperature increased. These periods were also affected by the RH. The number of eggs oviposited was affected significantly by the combined effect of temperature and RH. Fewer eggs were laid by ticks in the 24 degrees C regimes and the 27 degrees C/95% RH regime compared to those in the other temperature/RH groups. There was an inverse relationship between the number of eggs oviposited and the percentage of hatched larvae that was correlated with the temperature and RH. Ticks reared at 27 degrees C/90% RH and 30 degrees C/90% RH laid more eggs than those reared in the other combinations of temperature and humidity but fewer larvae hatched from these eggs. The reproductive fitness index (RFI) values were highest in females held in the 24 degrees C groups and the 30 degrees C/95% RH group, although significantly more larvae hatched at the lower temperatures. The optimum reproductive conditions for O. turicata under laboratory conditions appear to be 24 degrees C and 90-95% RH. While mating occurred at all temperatures, none of the females laid eggs at 22 degrees C. The ticks may move preferentially to low temperatures when not feeding to remain above the critical equilibrium humidity and/or below the critical metabolic level necessary for prolonged survival. However, most female ticks oviposited after 45 days when moved to 27 degrees C/95% RH. Ornithodoros turicata females may have a limited capability to delay oviposition until an optimal microenvironment for egg deposition can be located in the burrow.

Animals↗

PubMed1991

Reproductive toxicity studies with cis-(-)-2,3,4,4a,5,9b-hexahydro-2,8-dimethyl-1H-pyrido-[4,3-b]indole dipalmitate in rats.

cis-(-)-2,3,4,4a,5,9b-Hexahydro-2,8-dimethyl-1H-pyrido-[4,3-b]indole dipalmitate (stobadin dipalmitate; in the following briefly called STB) a new prospective cardioprotective drug, was evaluated for effects on fertility, general reproductive performance, prenatal and peri-postnatal development in the rat. Doses of 5, 15 and 50 mg/kg/d were administered orally in aqueous suspension to rats in all studies. Daily treatment of male rats for 70 days before mating and female rats for 14 days before mating and during gestation and lactation had no adverse effects on fertility, survival rate and weight gains of parental animals or on prenatal and postnatal development of pups. There was only evidence of slight adult toxicity late in the experiment, significant increase of anomalous foetuses in both the 15 and 50 mg/kg/d doses and decreased body weight of the young at 50 mg/kg/d on day 21 post partum. Daily oral treatment of pregnant rats with STB throughout organogenesis (day 4 to 16) had no overt effects on dams or on embryo-foetal development, except of increased incidence of some skeletal variations in all treated groups. In the peri-postnatal toxicity study treatment of pregnant dams with STB continuously from day 15 of gestation through parturition and lactation had no adverse effects on reproductive parameters of dams or on survival and development of F1 offspring at any dose used. There were only signs of slight maternal toxicity at 50 mg/kg/d, which consisted of sedated behaviour, reduced liver weight and reversible histopathological changes in kidney tissue. The results of these studies did not reveal serious developmental hazard potentials of STB administered to rats in doses up to 50 mg/kg/d.

Animals↗

PubMedDate not supplied

Microsomal enzyme induction, egg production, and reproduction in three lines of Japanese quail fed polybrominated biphenyls.

The sensitivity of three genetic lines of Japanese quail to polybrominated biphenyls (PBBs) was evaluated using criteria of egg production, reproduction, and induction of the hepatic microsomal mixed-function oxidase (MFO) system. Two genetic lines of quail, developed to diverge in their plasma cholesterol response to exogenous adrenocorticotropin (ACTH) (a "Low" line and a "High" line), were compared to a random-bred line ("Random"). ACTH administration caused increases in plasma cholesterol in the Low line that were 15 and 39% below the Random-line values in males and females, respectively, while High-line values were 31% higher in males and 36% higher in females when compared to the respective Random-line values. Hepatic activities of aryl hydrocarbon hydroxylase (AHH) and hexobarbital hydroxylase (HxH) were not significantly influenced by ACTH administration or by genetic line in either sex. PBBs fed at 40 or 80 mg/kg diet for 5 wk resulted in significant increases in hepatic AHH and aminopyrine N-demethylase (APND) activities and cytochrome P-450 concentrations. The induction of AHH, APND, and cytochrome P-450 was significantly less in Low-line males in comparison to Random- and High-line males, while the induction of AHH was less in Low-line females when compared to females from the other two lines, based on covariance analysis. In terms of reproductive parameters, there was a greater adverse effect on egg production at 80 ppm PBBs in Low-line females when compared to the Random and High lines. These data indicate an example in which the biological toxicity of a compound and the induction of a 3-methylcholanthrene-type hepatic enzyme are not directly correlated.

Adrenocorticotropic Hormone↗

PubMed1991

Time of onset of post-partum luteal function and conception in dairy cows.

The following reproductive parameters were studied in 40 Icelandic dairy cows on 2 farms with free stall and tie stall housing: The time of onset of post-partum luteal activity; the time of first post-partum artificial insemination (AI); the time of conception; conception rate to first post-partum AI; the number of AI's per conception; length of gestation; and the number of days between 2 consecutive calvings. Milk for progesterone analysis was sampled 3 times a week from calving until first AI on farm 1, but every day for 90-100 days from calving on farm 2. In this study the average onset of luteal function was 21 days post-partum, the cows were inseminated 62 days and conceived 74 days post-partum. Conception rate to first AI was 71% and number of AI's per conception was 1.6. Significant differences were not found between the 2 farms. The reproductive performance of the cows in this study was greater than found in earlier studies of the Icelandic dairy cows and indicate that this animal has reproductive capabilities comparable to high producing foreign dairy cows.

Animals↗

PubMed1983

The pattern of endemic parvovirus infection in four pig herds.

Serological surveys were conducted on the gilts and adult sows in 4 herds endemically infected with porcine parvovirus. The study assessed the influence of the type of management of breeders on the spread of virus infection and the influence of endemic parvovirus infection on reproductive parameters of the herd. The practice of holding gilts and sows in groups did not reliably promote infection or maintain a 100% level of active immunity amongst adult sows in 2 of 3 group husbandry herds. In the 4 herds, the prevalence of adult sows (greater than 12 months) with active immune haemagglutination inhibition titres (greater than or equal to 256) ranged between 44% and 100%, while between 0% and 100% of gilts (6 to 12 months of age) had active immune titres. Fully susceptible gilts older than 9 months of age held in groups, failed to become infected by 12 months of age on farms endemically infected with PPV. In 2 herds a continued low infection rate of gilts resulted in increasing the potential of breeding animals becoming susceptible to parvovirus infection as infected sows were replaced by noninfected gilts. In both herds, epidemics of parvovirus infection followed, which were characterised by an increase in reproductive failure. Parvovirus infection during the first 70 days of pregnancy reduced the average number of piglets born alive per litter by 1.6 piglets (p less than 0.05). This was due to the combined effect of more piglets being born dead per litter and an overall reduction in litter size.

Animals↗

PubMedDate not supplied

Testing strategies in behavioral teratology: IV. Review and general conclusions.

Three laboratories collaborated to evaluate and compare different test concepts to be used for routine testing in behavioral teratology. Rat dams were treated orally with methylmercury starting two weeks prior to pairing until weaning of their offspring. In the first laboratory, the usual reproduction parameters were assessed in the dams, and all offspring (96-103 per group) were subjected to a routine developmental and behavioral test battery. After termination of the tests a random selection of these animals was further tested by multiparametric automated techniques in the other two laboratories. In one of these laboratories 12-13 males and females per group (one of each per litter) were tested in a visual discrimination reversal schedule, using nose-poking as operand. In the other laboratory the free behavioral of eight randomly selected males per dose group was studied in a wheel-shaped activity monitor with respect to locomotion magnitude and structure. In the same laboratory eight other males per group were trained in a discrete trial spatial alternation schedule, using lever press as operand. Both the developmental and behavioral testing battery as well as the automated techniques showed some significant effects in the offspring even at the low dose, where no reproduction effects had been noted. However, whereas the testing battery results were of unspecific nature, results of the automated techniques gave precise and specific information. In order to obtain optimal information, it is proposed to combine both approaches for routine testing. This combination could be achieved by using a balanced testing battery in young pups followed by an appropriate operant conditioning schedule in selected young adults.

Animals↗

PubMed1984

Toxicologic, pathologic, and immunotoxic effects of 2,4-dichlorophenol in rats.

2,4-Dichlorophenol (DCP) is a drinking and waste-water contaminant formed by the spontaneous reaction of chlorine with phenols following chlorination of water for disinfection and deodorization. Rats were exposed to 0, 3, 30, or 300 ppm DCP in drinking water either in utero or for 12 wk postnatally following in utero exposure. Toxicity to DCP was assessed by organ and body weight changes, histopathology, and effects on reproduction and immunocompetence. Reproductive parameters measured included conception, litter size, pup birth weight, number stillborn, survival to weaning, and weaning weight. Immune parameters assessed were humoral immunity (antibody production) by an indirect enzyme-linked immunosorbent assay (ELISA), cell-mediated immunity by a delayed-type hypersensitivity response, and macrophage function by phagocytosis of radiolabeled blood cells. Rats that received the combined in utero and postnatal treatment with 300 ppm DCP had significantly increased liver and spleen weights, enhanced humoral immune responsiveness, and depressed cell-mediated immunity. Histopathologic changes were unremarkable in DCP-exposed rats, even in the presence of increased liver and spleen weights. The 6-wk-old progeny of DCP-treated dams had normal immune functions and showed no signs of DCP toxicity, other than increased spleen weights in the 300-ppm exposure group. The results indicate that (1) the immune system may be a sensitive target for chlorinated phenolic compounds, (2) DCP may exert different effects on separate major immune responses, and (3) unlike some other chlorinated phenols, DCP does not appear to alter reproductive performance in rats.

Animals↗