Biomedical subjects

C Ricciardi

Publications and source records attributed to C Ricciardi.

At least 19 recordsLinked to original sources

PubMed2000

[Bioethics and toxicology].

Human activity, involving nature and environment, alters the ecosystems in which we live; the question is whether this activity can be the source of risk and/or the origin of damages to human health. Risk assessment and risk management, connected with its protection, are not only a scientific and technical problem: hazards are real, but risks are social constructions. The role of toxicologists shows subjective features connected with different affiliations (industry, research, government); thus the assumptions and interpretations of risk assessment need to be integrated with wider psychological, social and political perspectives, in particular with ethical choices and values. Within public health personal subjectivities (genetic, biological and social) an adequate value should be given contrary to an abstract and collective entity which may erase and sacrifice subjectivities in favour of a statistical point of view. Public health should be considered as a whole of individual health conditions with regard to prevention, treatment and care.

Bioethics↗

PubMed1999

Problems in testing and risk assessment of endocrine disrupting chemicals with regard to developmental toxicology.

Endocrine disrupting chemicals (EDCs) may affect mammalian development either indirectly (by impairing implantation, placental development, lactation, etc.) or directly, altering the maturation of target tissues. Current regulatory tests for reproductive/developmental toxicity should be carefully evaluated with regard to risk assessment of EDCs, considering hazard identification (are relevant endpoints being assessed?) and dose-response assessment (are sensitive NOEL/dose-response curves being provided?). Many in vitro and in vivo assays for sex steroid disruption are available; provided that the metabolic capacities of the assays are defined, they could be integrated in a sensitive battery for early detection of steroid-disrupting potentials. The screening battery should address further regulatory in vivo tests (e.g. what specific parameters have to be investigated). As regards dose-response, qualitative differences may be observed between lower and higher exposures, showing primary hormone-related effects and frank embryotoxicity, respectively. Other problems concern (a) the identification of critical developmental windows, according to hormone concentrations and/or receptor levels in the developing target tissues; (b) the potential for interactions between chemicals with common mechanism/target (e.g. xenoestrogens); (c) most important, besides sex steroids more attention should be given to other mechanisms of endocrine disruption, e.g., thyroid effects, which can be highly relevant to prenatal and postnatal development.

Animals↗

PubMed1998

Evaluation of the placenta: suggestions for a greater role in developmental toxicology.

Both in human and in rat, two types of placenta are present: the yolk sac (YS) and the chorioallantoic placenta. Histiotrophy, alpha-fetoprotein synthesis and blood cell formation occur in YS of both species. Besides, the midgut, primordial germ cells and possibly immunological structures originate from the YS tissue. The specialised cells of the chorioallantoic placenta attach the embryo to the uterus and form the vascular connections necessary for the nutrient transport. The placenta redirects maternal endocrine, immune and metabolic functions to conceptus advantage. These complex activities are sensitive to direct toxicity. Indirect effects on the placental functions might be elicited by immunomodulators and endocrine disrupters. Some experimental models could be utilised to identify possible toxic effects on placenta. Among the in vitro models the rodent giant yolk sac culture may be used to study the transport of materials, morphological and/or biochemical alterations and biotransformation activity of the visceral YS epithelium. Other in vitro approaches utilise human derived trophoblastic cells and tissues to investigate implantation and perimplantation toxicology. Besides specific studies, in vivo reproductive toxicity tests could pay more attention to the evaluation of placental tissues. Nowadays, some physiologically based pharmacokinetic models for developmental toxicity are also available to describe the disposition of toxic substances and their metabolites during pregnancy in rodents. Thus, more detailed studies on the embryo-foetal placenta may provide an important tool to understand developmental toxicity mechanisms, with particular regard to embryolethality and delayed development.

Allantois↗

PubMed1998

Developmental toxicity of carbendazim: comparison of no-observed-adverse-effect level and benchmark dose approach.

The benchmark dose (BD) approach has been applied to foetal data from four gavage segment II studies (rat studies 1 and 2, rabbit study, hamster study) on the teratogenic benzimidazole carbendazim. Nineteen parameters were assessed using the log-normal model as a practical tool to derive BDs; good model fitting was observed for all except two parameters. Data were evaluated on a 'per-implant/foetus' basis; BDs were derived from response rate increases of 1, 5, and 10%. The values were compared to the lowest-observed-adverse-effect levels (LOAELs) and no-observed-adverse effect levels (NOAELs) obtained by Fisher's exact test on a 'per-implant/foetus' basis. Frank effects observed only at the top dose and/or small sample size tended to increase the 95% confidence limits and this influenced the determination of BD. Generally, the BD approach provided slightly more conservative estimates than NOAEL; overall, BD01 and BD05 were similar to NOAEL, or even lower for several parameters. The LOAEL in most cases was similar to BD10. Reference doses obtained by dividing BD01 by a 10 or 100 uncertainty factor, corresponded to residual risks of 10(-5) or below. For two critical parameters (hydrocephalus in rat study 1 and resorption rate in the rabbit study) a NOAEL could not be found, whereas a BD was always determined.

Animals↗

PubMed1998

[Effects of chemical mixtures on embryonic development: examples of experimental models and problems in risk assessment].

Toxicological risk deriving from the exposure to mixtures of toxic substances, the study of possible interactions among them and their mechanisms of action are of special interest in prenatal toxicology. In fact, embryo is a dynamic complex system whose gradual development substantially modulates the extent and type of damages to which it may be sensitive, through specific, critical periods of sensitivity. In this paper, a number of types of interactions among toxic substances which show the same mechanisms of action and/or the same target site, are analysed. Besides, pharmacokinetic interactions among teratogenic agents and substances modulating their metabolism, need specific evaluations because of the wide variability of possible events. In conclusion, risk assessment in prenatal toxicology has to put greater attention to the various types of effect and pharmacokinetic interaction since they might result in an increasing risk at low doses.

Animals↗

PubMed1997

[Complex biological systems as experimental and prenatal toxicology models].

Experimental biomedical sciences have emphasised the use of model systems in the study and understanding of physiological and pathological processes. Developmental biology, genetics and prenatal toxicology, dealing with cellular differentiation, organogenesis and dismorphogenic alterations, have shown that system models, even those far removed from mammals and humans in the zoological scale (e.g. C. elegans, Hydra, Drosophila), can be useful tools for understanding pathogen mechanisms in developmental toxicology. In particular the study of neural tube and its alterations shows how a biologically complex model (such as the laboratory rodent) necessitates, in turn, a series of models to thoroughly analyse and clarify the limits and levels of research.

Abnormalities, Drug-Induced↗

PubMed1993

Prenatal risks deriving from environmental chemicals.

Hundreds of environmental chemicals affect prenatal development in experimental animals. However, only methylmercury and PCBs have been connected with such effects in humans during localized outbreaks of high exposure. In addition growth and development might also be affected by long-term intake of lead, fluorides or PCBs. Several factors may explain the discrepancy between human and animal data: the actual exposure of the population is below threshold levels, unspecific or delayed effects can be difficult to identify, etc. When experimental data are used to assess the hazards for the conceptus, due consideration should be given to actual ability of the study to detect effects. Thus, the limitations in statistical power, the relevance of the parameters considered and low-dose extrapolation should be taken into account. Finally, understanding toxicokinetics and biological mechanisms is needed to perform interspecies comparisons. Three examples of environmental chemicals showing different prenatal hazards are presented: thiabendazole, a benzimidazole compound with a moderate teratogenic potential, but which could represent a good model for biological extrapolation; nitrofen, a diphenyl ether herbicide which may pose a significant hazard, because of its high potential, toxicokinetics, and specific, hormone-like, teratogenic mechanisms; PCBs, well-known, global, cumulative pollutants which are not teratogenic in the laboratory animals, but may affect the human conceptus at high intake levels.

Abnormalities, Drug-Induced↗

PubMed1992

Tobramycin-induced changes in renal histology of fetal and newborn Sprague-Dawley rats.

Effects on renal development were studied using tobramycin (TBM) as a model compound. Pregnant Sprague-Dawley rats were injected i.p. with TBM at 30 or 60 mg/kg body weight/day on gestational days (GD) 10-19. Kidneys from dams and conceptuses were examined on GD 20 and on postnatal day (PD) 9. The dosing regimen caused in dams moderate proximal tubular alterations and increased concentrations in serum creatinine. Fetal kidneys showed granularity and swelling of proximal tubule cells at the 30 mg/kg dose, poor glomerular differentiation at the 60 mg/kg dose, increased glomerular density at both doses, and no changes on macroscopic examination at either dose. In newborns were observed a moderate developmental delay and tubular lesions at the higher dose, and dose-related increases of glomerular density and relative medullary area at both doses. All findings were more pronounced in males. A maturational disruption of the tubular structures possibly leading to increased glomerular density was attributed to TBM exposure during renal organogenesis in the rat.

Abnormalities, Drug-Induced↗

PubMed1989

Hematotoxic effects in the rat of a toluene dinitro derivative after short-term exposure.

3,5-Dinitro-4-chloro-alpha,alpha,alpha-trifluorotoluene (DNCTT) is an intermediate in the synthesis of dinitroaniline herbicides and was involved in an episode of ground water pollution in 1977. The compound presents a high environmental persistence, which may have possible implications concerning public health. In one experiment male Sprague-Dawley rats were administered DNCTT for 3 days at a dose level of 150 mg/kg body wt by oral gavage. Groups of rats were sacrificed up to 10 days after the end of the administration, at 2-day intervals. Methemoglobin was increased up to Day 7; white blood cells were also increased both in peripheral blood and in bone marrow smears. Spleen relative weights were observed to increase slightly at Days 7 and 10; microscopic examination revealed marked congestion with an increased density of the spleen's white pulp. In a similar scheduled experiment, but at a dose level of 300 mg/kg body wt, the bone marrow white cell series were not affected initially, but were affected after 3 days at the end of the administration. DNCTT has a definite effect on white cells.

Animals↗

PubMed1989

Pre-natal (segment II) toxicity study of cinnamic aldehyde in the Sprague-Dawley rat.

Cinnamic aldehyde (CA) was administered by gavage to Sprague-Dawley rats on days 7-17 of pregnancy at doses of 5,25 or 250 mg/kg body weight/day. Significantly lower weight gain of the dams was observed at the two higher dose levels. No significant dose-related increase of abnormalities was observed: the incidence of poor cranial ossification was significantly increased in all treated groups, while reduced ossification of the tympanic bulla was increased at 25 or 250 mg/kg/day. Significant increases of the incidences of dilated pelvis/reduced papilla in the kidney, dilated ureters and greater than or equal to 2 abnormal sternebrae per foetus were detected in the 2-mg/kg group, which had the highest overall prevalence of minor abnormalities. Since significant increases in the incidences of reduced cranial ossification, dilated ureters and renal variants were observed at 5 mg/kg, a dose at which there was no detectable maternal toxicity, it is suggested that the foetus might be slightly more sensitive than the adult to the action of CA.

Acrolein↗

PubMed1988

Teratogenicity study of ammonium glycyrrhizinate in the Sprague-Dawley rat.

Ammonium glycyrrhizinate (AG), a commercially used salt of glycyrrhizic acid, was administered in the drinking-water to Sprague-Dawley rats on days 7-17 of pregnancy. The actual intakes were 0, 21.33 +/- 1.22, 238.75 +/- 17.50 and 679.94 +/- 69.87 mg AG/kg body weight/day for groups 0, 1, 2 and 3, respectively. AG caused polydipsia in the dams. Foetuses from the treated litters did not present an increase in external malformations, a decrease in weight or a decrease in the degree of ossification. However, there was a slight but significant increase in embryolethality and in the prevalence of external haemorrhages. Skeletal examination revealed a dose-related increase in minor anomalies, especially in the sternebral variants. Renal ectopy also increased significantly at the highest dose. These results indicate that the possible embryotoxicity of aromatizing compounds should be considered.

Aldosterone↗

PubMed1987

Subchronic oral toxicity of 4-chloro-alpha, alpha, alpha-trifluorotoluene in Sprague-Dawley rats.

The subchronic oral toxicity of 4-chloro-alpha, alpha, alpha-trifluorotoluene (CTT) was assessed in Sprague-Dawley rats. Four groups of six male and six female rats were treated daily for 28 days, by gavage, with doses of 0, 10, 100 and 1000 mg CTT/kg body weight using olive oil as a vehicle. No clinical signs were observed, other than salivation in the high-dose group in the last week. The males of this group showed a significant decrease in body-weight gain without a concurrent decrease in food consumption. In males, there were significant dose-dependent increases in blood cholesterol and triglycerides, suggestive of alterations in lipid metabolism. The females showed only a small dose-related increase in serum lactate dehydrogenase. Specific histological alterations were found in the males given 1000 mg/kg/day, namely hyaline droplet nephrosis, along with a significant increase in relative kidney weight, and an increase in lipid vacuoles in the adrenal cortex. Slight nephrosis was also observed in males given 100 mg/kg. Both male and female rats showed a significant increase in relative liver weight at a dose of 1000 mg CTT/kg. CTT appears to have a low subchronic oral toxicity. Neither pathological nor biochemical alterations were found at 10 mg/kg body weight/day and this can be defined as the no-observable-effect level (NOEL).

Administration, Oral↗

PubMed1986