Toxicological effects of Tris (1,3-dichloro-2-propyl) phosphate exposure in adult male rats differ depending on the history of exposure in the neonatal period.

There is increasing concern about multiple high concentration exposure to toxins in disaster and emergency situations. However, conventional toxicology testing methods may not adequately address these situations. Thus, we assessed whether the toxic effects of exposure in the adulthood differ depending on the presence or absence of neonatal exposure to Tris (1,3-dichloro-2-propyl) phosphate (TDCIPP) in male rats to investigate the effects of exposure history of chemicals. In the neonatal stage [postnatal days (PNDs) 1-7], animals were treated with either sesame oil (5 ml/kg/day) as a control or TDCIPP (250 mg/kg/day) dissolved in sesame oil. In adulthood (PND 101-107), animals were treated with either sesame oil (5 ml/kg/day) or TDCIPP (650 mg/kg/day). One day after the final administration, dissection was performed, and body and organ weight, hematology, blood biochemistry, and histopathology were examined. The results demonstrated that the toxic effects of TDCIPP exposure in adulthood on adrenal gland size, serum iron content, and unsaturated iron binding capacity were enhanced by TDCIPP exposure in the neonatal stage. From these findings, it was indicated that the toxic effects of TDCIPP exposure in the adult stage are affected by pediatric exposure. These results suggest that the toxic effects of high-dose and long-term unsteady exposure to chemicals in large-scale disasters may change based on the exposure history of chemicals.

Novel toxicity of tris(1,3-dichloro-2-propyl) phosphate in adult male rats.

The widespread use of tris(1,3-dichloro-2-propyl) phosphate (TDCIPP) as a flame retardant has led to its release to the environment. Thus, the toxicological effects of TDCIPP on humans and animals are of importance. For better understanding of its potential toxicities, TDCIPP (250, 500, or 650 mg/kg/day) or vehicle control was administrated orally to adult male Wistar-Imamichi rats for 7 days. After the final administration of compounds, organ weights, histopathology, blood biochemistry, and hematology were examined. Hepatic toxicity was observed at doses ≥ 500 mg/kg/day of TDCIPP, and renal toxicity was observed at 650 mg/kg/day. The anti-androgenic activity of TDCIPP was previously confirmed in vitro and in vivo, but weights of epididymis, an androgen-dependent organ, were not affected by TDCIPP treatment in adults. Serum alkaline phosphatase activity was significantly decreased in all TDCIPP-treated rats independent of dose. Hemoglobin concentration, hematocrit, red blood cell count, and reticulocyte count were decreased in all TDCIPP-treated rats, but mean corpuscular volume, total iron-binding capacity, and serum iron were normal, suggesting that renal anemia was caused by TDCIPP. Together with previous reports on effects of anti-androgenic substances on red blood cell indices, anemia caused by TDCIPP could be due to its anti-androgenic activity. These considerations will contribute to further assessment of the toxicity of the compound.

The effects of 28-day early-life exposure to triphenyl phosphate (TPhP) on odor preference and sexual behavior in female rats.

Many chemical substances are detectable in house dust, and they are consequently taken into our bodies via the mouth and nose. Triphenyl phosphate (TPhP), a flame retardant that has an estrogen-like effect in vitro, is present in house dust at high concentrations. Estrogen exposure during development has significant influences on reproductive behavior in rodents, and its effects persist until maturity. In the present study, we investigated the effect of early life exposure to TPhP on the reproductive behavior of female rats. Oral treatment with TPhP (25 or 250 mg/kg), ethinyl estradiol (EE; 15 µg/kg) as a positive control, or sesame oil as a negative control, were given to female rats (from birth to 28 days of age). The 8-week-old rats were bilaterally ovariectomized. At 12-15 weeks of age, the rats were subjected to odor preference and sexual behavior tests. In the odor preference test, the oil group showed significantly higher preference for male odor than female odor, but the low-dose TPhP treatment group lost the preference for male odor, indicating a possible outcome of early life TPhP exposure on sexual recognition. In the sexual behavior test, both the EE and TPhP treatment groups displayed significantly less proceptive behavior. These results suggest that early life exposure to TPhP disturbs the normal sexual behavior of female rats.

Relationship between motor function and ultrasonic vocalizations induced by maternal separation in rat pups.

When rat pups are isolated from their mothers, they emit ultrasonic vocalizations (USVs). Although previous studies have reported that USVs are related to anxiety, others have reported that they are related to simple, nonemotional factors, such as physiological reactions to coldness. In this study, we examined the influence of three maternal separations on rat pups. The number of USVs during 5 min of USV test under maternal separation, latency in the righting reflex as motor function, and body temperature were recorded twice (the first and second tests) before and after the pups were put in various environments for 10 min. The environments were no maternal separation (Control: CON), maternal separation with littermates (LMS), and single maternal separation with a heater (SMS). In the second test, the SMS pups had fewer USVs, a lower body temperature, and a more rapid righting reflex than the CON and LMS pups. In addition, there was no strong correlation between USVs and righting reflex. As a result, pups undergoing 10 min of SMS while being kept warm by the heater showed rapid righting reflex. Thus, by a single maternal separation, the number of USVs decreased but the decrease was unrelated to decrease in motor function.

Hatano rats are a suitable metabolic syndrome model for studying feeding behavior, blood pressure levels, and percent body fat.

Currently, metabolic syndrome is a worldwide concern. Thus, it is imperative to understand the mechanism of metabolic syndrome by establishing various metabolic syndrome models. In this study, we used Hatano high-avoidance animals (HAA) and low-avoidance animals (LAA), both derived from Sprague-Dawley rats by selective breeding to determine high- or low-avoidance rates in shuttle-box active avoidance tests. HAA and LAA rats have some strain differences related to eating and appetite. Therefore, we determined whether Hatano rats could be used as a metabolic syndrome model. We compared food intake, body weights, blood pressure levels, plasma component levels, and fat contents between HAA and LAA rats. The HAA rats showed more active eating, higher blood pressure, higher percentage fat, and higher triglyceride levels than the LAA rats-these features correspond to some of the risk factors associated with metabolic syndrome. Our study suggests that HAA rats can be considered as a metabolic syndrome model by focusing on their feeding behavior, blood pressure levels, and percent body fat.