Late Inhalation Toxicology and Pathology Produced by Exposure to a Single Dose of 2-Chlorobenzylidene Malononitrile (CS) in Rats and Hamsters

1983 ◽  
Vol 23 (4) ◽  
pp. 257-265 ◽  
Author(s):  
T. C. Marrs ◽  
E. Clifford ◽  
H. F. Colgrave

Hamsters and rats exposed to single doses of CS were retained for up to 32 months, together with appropriate controls. Survival was unaffected and in no case was the incidence of histological changes significantly higher in the test animals than corresponding control animals. The overall incidence of neoplastic disease was similar in test and control animals. A high incidence of pituitary acidophil adenomas was detected in the female rats: these tumours were present both in control and test rats and it was concluded that they were probably the result of ad libitum feeding. It was concluded that single doses of CS of 28 800 mg min m−3 administered during 1 hour or 18 000 mg min m−3 administered over 2 hours produced no long-term adverse effects in the two species studied.

2021 ◽  
Vol 22 (16) ◽  
pp. 8899
Author(s):  
Marina Gabaglio ◽  
Erica Zamberletti ◽  
Cristina Manenti ◽  
Daniela Parolaro ◽  
Tiziana Rubino

Cannabis is the most-used recreational drug worldwide, with a high prevalence of use among adolescents. In animal models, long-term adverse effects were reported following chronic adolescent exposure to the main psychotomimetic component of the plant, delta-9-tetrahydrocannabinol (THC). However, these studies investigated the effects of pure THC, without taking into account other cannabinoids present in the cannabis plant. Interestingly, cannabidiol (CBD) content seems to mitigate some of the side effects of THC, at least in adult animals. Thus, in female rats, we evaluated the long-term consequences of a co-administration of THC and CBD at a 3:1 ratio, chosen based on the analysis of recently confiscated illegal cannabis samples in Europe. CBD content is able to mitigate some of the long-term behavioral alterations induced by adolescent THC exposure as well as long-term changes in CB1 receptor and microglia activation in the prefrontal cortex (PFC). We also investigated, for the first time, possible long-term effects of chronic administration of a THC/CBD combination reminiscent of “light cannabis” (CBD:THC in a 33:1 ratio; total THC 0.3%). Repeated administration of this CBD:THC combination has long-term adverse effects on cognition and leads to anhedonia. Concomitantly, it boosts Glutamic Acid Decarboxylase-67 (GAD67) levels in the PFC, suggesting a possible lasting effect on GABAergic neurotransmission.


2016 ◽  
Vol 283 (1839) ◽  
pp. 20161551 ◽  
Author(s):  
Glenn J. Tattersall ◽  
Damien Roussel ◽  
Yann Voituron ◽  
Loïc Teulier

This study aimed to examine thermoregulatory responses in birds facing two commonly experienced stressors, cold and fasting. Logging devices allowing long-term and precise access to internal body temperature were placed within the gizzards of ducklings acclimated to cold (CA) (5°C) or thermoneutrality (TN) (25°C). The animals were then examined under three equal 4-day periods: ad libitum feeding, fasting and re-feeding. Through the analysis of daily as well as short-term, or ultradian, variations of body temperature, we showed that while ducklings at TN show only a modest decline in daily thermoregulatory parameters when fasted, they exhibit reduced surface temperatures from key sites of vascular heat exchange during fasting. The CA birds, on the other hand, significantly reduced their short-term variations of body temperature while increasing long-term variability when fasting. This phenomenon would allow the CA birds to reduce the energetic cost of body temperature maintenance under fasting. By analysing ultradian regulation of body temperature, we describe a means by which an endotherm appears to lower thermoregulatory costs in response to the combined stressors of cold and fasting.


1988 ◽  
Vol 254 (4) ◽  
pp. R616-R621 ◽  
Author(s):  
F. H. Bronson

Female rats were prevented from growing and developing reproductively by restricting their food intake from the time they reached 80-85 g (27-29 days of age) until they were 2 mo old. A return to ad libitum feeding then typically yielded the pubertal ovulation during the third or fourth dark period. Ad libitum feeding for 48 h increased the frequency of luteinizing hormone (LH) pulsing in ovariectomized females. This treatment also depressed the level of circulating estradiol in ovariectomized females implanted with Silastic capsules. It had no effect on the rate at which estradiol was cleared from the blood in a 1-h test, however, nor did it affect the pool of assayable gonadotropin-releasing hormone (GnRH) in the hypothalamus, the pool of assayable LH in the pituitary, the response of the pituitary to GnRH, or the rate at which LH was cleared from the blood. In toto, the present results suggest that food restriction inhibits pubertal development by acting rather specifically on GnRH secretion via an ovarian steroid-independent pathway. The presumed supplemental role for enhanced negative-feedback sensitivity could not be evaluated because of the aberrant results with encapsulated estradiol.


1995 ◽  
Vol 145 (2) ◽  
pp. 363-369 ◽  
Author(s):  
M-W Wang ◽  
D L Crombie ◽  
D E Mais ◽  
J S Hayes ◽  
R B Heap

Abstract Passive transfer of a monoclonal antibody against progesterone produces a high incidence of maternal rejection in mice after recovery from antibody-induced infertility. To investigate the mechanisms involved in this reduction of maternal care, we have examined whether the effect is due to long-term exposure to antibody. Antibody was administered i.p. either on day 2 or day 17 of pregnancy. When a low dose (1·0 nmol) was given on day 2, pregnancy proceeded normally but 44·8% pups delivered at term were rejected compared with 12·7% in the control group. When a higher dose (4·5 nmol) of antibody was given on day 17, pregnancy continued normally to term and the rejection rate was 48·8% (control: 11·1%). When the same amount of antibody was injected after delivery (day 1 of lactation), no detrimental effect was found on subsequent maternal care to the young, the rejection rate being comparable between antibody-treated and control groups (5·3% vs 4·6%). To determine if the presence of antibody interfered with lactation or suckling, a bolus injection of 10 μCi [3H]H2O was given to mice treated at day 17 with antibody or saline. The levels of radioactivity present in both mothers and pups and the first 5-day pup growth curves showed identical patterns, indicating that milk availability and the suckling process were not affected. Crossfostering studies revealed that antibody-treated mothers rejected 25·5% of fostered pups compared with 8·5% found in the control females when antibody was administered on day 17 of pregnancy and the entire litters were crossfostered between the two groups immediately after delivery. Detailed analyses using a retrieval test further demonstrated that the reduction in maternal care was most pronounced during the first 3 days after delivery. These results demonstrate that antibody-treated mothers show a higher frequency of pup rejection which is (i) not restricted to their own litter; (ii) not due to lack of milk; and (iii) not a result of defects in the pups. They are consistent with the hypothesis that anti-progesterone antibody interferes with the priming mechanism(s) necessary for the onset of maternal behaviour during the 3-day period prior to delivery, leading to impaired maternal care after parturition. Journal of Endocrinology (1995) 145, 363–369


1983 ◽  
Vol 23 (1) ◽  
pp. 51-63 ◽  
Author(s):  
Françoise VANDERMEERSCHEN-DOIZÉ ◽  
J.-C. BOUCHAT ◽  
Marie-Antoinette BOUCKOMS-VANDERMEIR ◽  
R. PAQUAY

2018 ◽  
Vol 3 (1) ◽  

Radioactive iodines emitted following nuclear accidents are responsible for the dramatic increase of the late-onset thyroid cancer. Until the Fukushima disaster, a single dose of potassium iodide (KI) has been considered as an efficient countermeasure. Indeed, recently it has been suggested that repeated administration of KI may be necessary to ensure adequate protection in case of protracted exposure. Whereas, the effect of a single dose of KI has largely been studied ensuring its safety, studies regarding adverse effects of repeated iodine thyroid blocking (ITB) administration are scarce. Our objective was to assess the long term overall impact of KI in adult rats after repeated intake. Adult Wistar rats were subjected to either KI or saline solution over eight days. Biochemical homeostasis, hormones level, autoimmunity status, thyroid morphology and thyroid transcriptome profile were analyzed thirty days after the discontinuation of KI administration. Biochemical parameters, plasma levels of TSH; thyroid hormones; anti-TPO and anti-Tg did not differ between treated and control rats, the thyroid histology was not affected by the treatment and no long term transcriptome signature attributable to the treatment was noticed. Based on these data, we conclude the safety of repeated KI intake in adult rats; these data are prominent and may contribute to the ongoing development of KI guidelines and marketing authorization.


1990 ◽  
Vol 259 (1) ◽  
pp. R25-R31 ◽  
Author(s):  
F. H. Bronson ◽  
P. D. Heideman

These studies focused on the phenomenon of "catch-up" pubertal development. Circulating levels of several hormones were characterized in 8-wk-old female rats whose growth and reproductive development had been blocked before puberty by restricting their food intake. Some of these females were fed ad libitum for 24 h to initiate rapid pubertal development. Blood levels of luteinizing hormone (LH) and growth hormone (GH) were suppressed by food restriction and then partially restored to adult diestrus levels by 24 h of ad libitum feeding. Prolactin titers were also suppressed by food restriction but not significantly elevated by 24 h of ad libitum feeding. Circulating levels of follicle-stimulating hormone (FSH) and thyroid-stimulating hormone (TSH) were unaffected by either treatment. It is concluded that GH could play an active supplementary role to LH in eliciting catch-up pubertal development but that FSH and TSH could play only passive roles at best. The role of prolactin remains uncertain. On a finer time scale, when food-restricted females were examined in relation to the time of day at which they were fed, most showed high-amplitude LH pulses 2-4 h after eating but rarely at any other time. Thus under some conditions LH secretion can be modulated by food intake on an almost hour-by-hour basis. Overall, blood levels of corticosterone were generally but not always inversely correlated with the frequency of LH pulsing in these experiments. Finally, the present results argue against the concept that puberty is dependent on a critical whole body characteristic.(ABSTRACT TRUNCATED AT 250 WORDS)


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