摘要:

Several strains of laboratory rats have a high background incidence of mammary tumors and develop a persistent, anovulatory estrus condition at about 12 mo of age. The increased tumor incidence is believed to be associated with elevated estradiol (E2) and prolactin during the period of persistent estrus. A pharmacodynamic estrus cycle (PD-EC) model for the Sprague-Dawley rats has been developed in an attempt to analyze the physiological basis of early-onset persistent estrus and to examine the potential sites of interactions in the hypothalamic-pituitary-ovarian axis for endocrine-modulating xenobi- otics that accelerate the onset of persistent estrus. This initial estrus cycle model focused solely on cyclical changes in E2 and luteinizing hormone (LH). An LH surge was scheduled when a hypothetical estrus cycle-related protein (EC-RP) under transcriptional control by the E2 receptor reached a critical concentration. In the model, aging-related cumulative hypothalamic E2 exposure impaired the LH surge by reducing the rate of production of the EC-RP. The progressively decreasing intercycle resynthesis rate leads first to longer, variable-length cycles and finally to persistent estrus at about 12 mo of age. This model construct is consistent with early-onset persistent estrus related to neonatal E2 exposures, with acyclicity associated with high-dose E2 exposure in the adult, and with persistent estrus conditions associated with exposures to xenobiotic endocrine modulators that are either weak E2 antagonists or weak E2 agonists. With further development these pharma-codynamic estrus cycle models should bejuseful in aiding risk assessments for compounds causing mammary-tissue tumors associated with persistent estrus states.

ISSN:0098-4108    

DOI:10.1080/00984109708984060

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

Hydrodesulfurized kerosine (HDS kerosine), applied dermally, was tested for reproductive and developmental toxicity in Sprague-Dawley rats, using a modified OECD Guideline 421, Reproductive/Developmental Toxicity Screening Protocol. A preliminary acute dermal irritancy test demonstrated that dilution of HDS kerosine in either a light (100 Saybolt universal seconds, SUS) or moderate viscosity (340 SUS) USP mineral oil reduced irritation of the neat material comparably. Similar dermal absorption was observed in vitro for neat HDS kerosine or diluted in either of the mineral oils. HDS kerosine diluted to 494 (60%), 330 (40%), or 165 (20%) mg/kg/day in Squibb mineral oil (340 SUS) was applied daily at 1 ml/kg to the shaved backs of rats for 7 wk (premating, mating to d 19 of gestation) to females and 8 wk to males. Dams and litters were sacrificed on postpartum d 4 and males were sacrificed within the following week. HDS kerosine produced slight to moderate skin irritation at the highest dose in both sexes but no apparent maternal, reproductive, or developmental toxicity. No clinical signs of toxicity and no effects on body weight, food consumption, or absolute organ weights were observed. Relative kidney weights were heavier in male rats at the high dose. Skin changes were observed microscopically in male rats in all groups and in females at the high dose. No microscopic changes were observed in reproductive organs of parental animals. There were no differences in mean number of corpora lutea, implantation sites, and live pups per litter, and no gross anomalies were observed. Pups born from treated dams showed comparable body weights and weight gains to controls. The viability index on postpartum d 4 was >93%. In conclusion, the no observable adverse effect level (NOAEL) for HDS kerosine for reproductive and developmental toxicity in rats is 494 mg/kg/d.

ISSN:0098-4108    

DOI:10.1080/00984109708984061

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

The adjuvant effects of various fine particles [Kanto loam dust, fly ash, carbon black, diesel exhaust particles (DEP), and aluminum hydroxide (alum)] on immunoglobulin E (IgE) antibody production in female BDF) mice were examined. In experiment 1, animals both received 25 pg of each particle intranasally and were exposed to aerosolized Japanese cedar pollen allergens (JCPA) for 30 min/d at 1-wk intervals for the first 8 wk. This was followed by exposure for 30 min every 3 wk for the next 9 wk. As parameters of allergic rhinitis, measurements were made of JCPA-specific IgE and IgG antibody titers, the protein-adsorbing capacity of each type of particle, and nasal rubbing movements. The increases in anti-JCPA IgE and IgG antibody production in mice treated with aerosolized JCPA plus respective particles were significantly greater than that found with aerosolized JCPA alone. This was associated with no marked differences in the other allergic rhinitis parameters. In experiment 2, after the administration of particles as in experiment 1, about 160,000 grains of Japanese cedar pollen (JCP, native dry pollen) were dropped onto the tip of the nose of mice twice a week for 16 wk. Six weeks after the first immunization, the anti-JCPA IgE antibody titers of groups treated with the respective particles were greater than 1:20, whereas those of mice treated with JCP alone were 1:10. No significant differences in the anti-JCPA IgE and IgG antibody productions, nasal rubbing counts, or histopathological changes were observed after 18 wk. These results suggested the nature of the particles, their capacity to adsorb antigens, and/or their size may not be related to enhancement of IgE antibody production nor symptoms of allergic rhinitis. However, IgE antibody production seemed to occur earlier in mice treated with particles than in mice immunized with allergens alone.

ISSN:0098-4108    

DOI:10.1080/00984109708984062

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

Raised concentrations of serum bile acids (SBA) following occupational exposure to a number of halogenated aliphatic hydrocarbon solvents and after in vivo exposure of experimental animals to these substances have been reported in several studies in recent years. However, the widely used nonchlorinated aromatic hydrocarbon solvent, toluene, has not been critically examined for its effect on serum bile acids. Accordingly, the effect of in vivo treatment with toluene on SB A and its direct in vitro effects on the transport of bile acids by isolated rat hepatocytes were investigated in this study. In vivo treatment with toluene (2.3 mmol/kg body weight, ip, on each of 3 consecutive days) resulted in a significant rise in the serum concentrations of total and some individual bile acids while other parameters of hepatobiliary function were unaltered. Administration of a higher dose of solvent (9.2 mmol/kg body weight, ip) resulted in a further increase in total SBA levels together with a significant rise in serum activities of some liver enzymes. In vitro application of noncytotoxic doses of toluene in the vapor phase to hepatocytes isolated from untreated rats resulted in a significant inhibition of the initial rate (Vo) of uptake of cholic acid (CA). Similarly, accumulation of CA and taurocholic acid (TC) over an extended incubation time by hepatocytes exposed to toluene was significantly inhibited. Kinetic analysis revealed a noncompetitive inhibition of CA uptake as suggested by a decline in Vmaxand an unaltered Km. In contrast, the initial rate of efflux of these substrates and their continuous efflux from preloaded cells were unaffected by exposure to toluene. Thus, toluene exposure inhibited the transport and accumulation of bile acids by hepatocytes in a manner largely similar to that of halogenated solvents, and this inhibition could explain the raised SBA concentrations following in vivo exposure to this solvent. These findings are consistent with and provide mechanistic data to support previous studies where increased SBA levels (in the absence of any evidence of liver injury as measured by liver enzyme tests) were reported in workers following occupational exposure to this solvent. Additionally, in full agreement with our previous investigations in which SBA levels were found to be a sensitive biological marker of exposure to halogenated aliphatic hydrocarbon solvents, the data support a similar role for SBA on exposure to toluene as well.

ISSN:0098-4108    

DOI:10.1080/00984109708984063

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor

摘要:

The Department of Energy and other federal facilities are reclaiming land through the process of remediation and restoration, and this land will eventually be turned over for future land uses that may involve recreation. Understanding the amount of recreation that is likely (and thus individual exposure) is an essential element in decisions about cleanup standards. In this article the number of days people engage in different recreational activities as a measure of potential exposure is examined. People attending a Mayfest celebration fn = 399) and the Palmetto Sportsmen's Classic (n = 285) in Columbia, SC, were interviewed regarding their recreational activities. In most cases reported in the literature, recreational activities are examined as the mean number of days people engage in each activity per year, but to determine risk it is essential to know the distribution of these activities. In descending order of frequency, people attending the Mayfest reported their activities as birdwatching, photographing, fishing, hiking, camping, and hunting. There were significant gender differences in the frequency of activities, with men spending more days in every activity except birdwatching and photography. There were ethnic differences in recreation, with whites engaging in higher levels of most recreational activities than blacks, but the percentage of black men who reported fishing more than 100 d per year was greater than for white men. Most people reported their participation in most activities less than 30 d per year; however, a higher percentage of people reported participating in photography, birdwatching, and fishing more than 30 d per year compared to the other activities. Further, individuals at the Sportsman's Classic reported far higher rates of hunting and fishing per year than the general public. These data can be used to examine potential exposure of recreationists on remediated and restored land. The data clearly indicate that over 25% of the people engage in at least one recreational activity over 20 d per year, and thus exceed the Department of Energy's 14-d recreation assumption in its future land use document.

ISSN:0098-4108    

DOI:10.1080/00984109708984064

出版商:Taylor & Francis Group    

年代:1997

数据来源: Taylor