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I Chahoud

Publications and source records attributed to I Chahoud.

62 records · Page 4Linked to original sources
PubMedDate not supplied

Developmental toxicity of an octyltin stabilizer in NMRI mice.

The octyltin stabilizer ZK 30.434 is a mixture of 80% dioctyltin diisooctylthioglycolate (DOTTG) and 20% of monooctyltin triisooctylthioglycolate (MOTTG) and is used as stabilizer for rigid polyvinylchloride (PVC) materials. One of the applications of such stabilized films is the packaging of foodstuffs. Exposure to humans occurs via migration of DOTTG/MOTTG from PVC materials. In the present study the developmental toxicity of DOTTG/MOTTG in NMRI mice was investigated. Dams were treated orally with doses of 20, 30, 45, 67, or 100 mg/kg/day DOTTG/MOTTG from gestation day 6 through 17 (plug = day 1). Resorption rates were significantly increased and fetal weights significantly reduced in the study group at the 2 highest doses. External anomalies, such as bent forelimbs, cleft palate, and exencephaly were reported in the group treated with 100 mg/kg/day DOTTG/MOTTG, with the 67-mg/kd dose also exhibiting a significant increase in cleft palate. Moreover, an increase in skeletal anomalies was reported in fetuses exposed to 100 mg/kg/day. The doses of 20, 30, and 45 mg/kg/day elicited a significant increase in supernumerary lumbar ribs. It can be concluded that DOTTG/MOTTG is embryo-fetotoxic and induces developmental effects. The study revealed the need for the establishment of different No-Observed Adverse Effect Levels (NOAEL) for the endpoints investigated.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Embryotoxicity of meglumine antimoniate in the rat.

Meglumine antimoniate (MA) is a pentavalent antimonial (Sb(V)) drug used to treat leishmaniasis. Despite the fact that Sb(V) organic compounds have been used in clinical practice for more than 50 years, information on their safety during pregnancy is still scanty. This study was undertaken to evaluate the embryo/fetotoxicity of MA in the rat. Wistar rats were treated subcutaneously (s.c.) with MA (300 mg Sb(V)/kg body wt/day) on days 6 through 15 of pregnancy or with a higher dose (3 x 300 mg Sb(V)/kg body wt) on day 11 only. A control group treated with saline on days 6 through 15 and an untreated control group were evaluated as well. Cesarean sections were performed on day 21. No maternal toxicity and no reduction of fetal weight were noted in the groups treated with MA. The repeated administration of MA (days 6 through 15), but not the acute treatment (day 11), enhanced embryolethality. Treatment with MA on days 6 through 15 also caused a higher incidence of an atlas bone anomaly that occurs spontaneously at very low frequencies in our rat strain. These findings indicated that repeated administration of MA was embryolethal and teratogenic in rats.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

Harmonisation of rat fetal skeletal terminology and classification. Report of the Third Workshop on the Terminology in Developmental Toxicology. Berlin, 14-16 September 2000.

The initial efforts of the Federal Institute for Health Protection of Consumers and Veterinary Medicine (BgVV) and the Free University of Berlin to standardise terminology in the field of developmental toxicology began in 1995. Procedures were undertaken to harmonise the terminology used by the International Federation of Teratology Societies (IFTS) and the International Programme on Chemical Safety (IPCS). This article reflects these activities and is a report on the Third Workshop on the Terminology in Developmental Toxicology held in September 2000. This Workshop served as a forum to discuss the results of a survey on the classification of skeletal anomalies that had been previously sent to scientists active in the field. Although high agreement was reached among the evaluators for several terms, the use of a number of terms was rather variable. Therefore, the discussions at the workshop among the experts from research institutions, regulatory agencies, and industry were mainly focussed on those terms for which there was disagreement and/or uncertainties and the possible reasons. Pictures provided by the participants for the illustration of "grey zone" anomalies constituted the basis for detailed discussions. In many of the cases with lower agreement, decisions were facilitated by the provision of the corresponding picture. The main reasons for lower agreement were imprecise terms, insufficient knowledge on postnatal consequences, theoretical terms that are unlikely to occur in isolation, and the possibility of observing a range of severity that might be decisive for the classification of either a malformation or variation. The attendees concluded that "grey-zone" anomalies will never disappear completely and that for the assessment, the grade of severity and/or the frequency of the observation can be decisive for the terminology chosen. A Joint IPCS/IFTS Project was proposed to further consensus of terminology and classification and to link these anomalies to pictures at different skeletal sites. In order to support the harmonisation of regulatory decisions, it was proposed to establish a "Clearinghouse" System under the umbrella of the IPCS. The Clearinghouse could be contacted either by the regulatory authorities or by any company to clarify their queries, particularly with regard to registration or authorisation processes. Finally, it was recommended to also carry out a similar survey on "soft tissue anomalies" and "external findings." The results of this survey will be discussed at a Joint IPCS/IFTS Workshop in Berlin in 2002.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

An optimized approach for the assessment of sexual behavior in male rats.

The improvement and optimization of methods used to detect reproductive disorders in experimental animals are among the main challenges facing researchers in this field. The conventional method for testing male sexual behavior uses ovariectomized females rendered sexually receptive by injection of estradiol benzoate and progesterone prior to testing. The receptive females are then mated with exposed male rats during the dark phase of the cycle under dim red light followed by direct visual and momentary observation of the mating activity. The ovariectomized females may respond differently to hormonal injection (individual differences), leading to variations in the intensity of lordosis. Additionally, the data obtained by the direct visual and momentary evaluation of copulatory activity are very subjective and may produce inaccurate results. In the optimized method, the sexual cycles of female rats are determined, and only those in estrus are selected and mated with sexually experienced male rats. The mating activity is videotaped, enabling the correct observation and evaluation of the different components of mating behavior. This method fosters animal welfare by avoiding surgical intervention and enables the videotape to be kept as permanent documentation.

Animals↗
PubMedDate not supplied

Correlation between maternal toxicity and embryo/fetal effects.

It has been widely debated whether embryo/fetal toxicity is secondary to maternal toxicity. This argument has led to great difficulties for administrative decision makers involved in public health evaluation of drugs or chemicals. The present study sought to characterize whether there is a correlation between maternal toxicity and embryo/fetal toxicity. Developmental data from control and treated animals in our laboratory were collected and evaluated. Maternal toxicity, defined here as maternal body weight change, was statistically correlated with embryo/fetal parameters. The result showed that embryo/fetal parameters did not correlate with the body weight change. It can be concluded that maternal toxicity does not always lead to embryo/fetal toxicity; therefore, findings should be handled on a case by case basis and causal relationships should be established.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

In utero exposure to low doses of bisphenol A lead to long-term deleterious effects in the vagina.

The origins of the "endocrine disrupter hypothesis" may be traced to reports on adolescent daughters born to women who had taken the highly potent synthetic estrogen, diethylstilbestrol, while pregnant, and who developed a rare form of vaginal cancer and adenocarcinoma. Bisphenol A (BPA) is an estrogenic chemical that is highly employed in the manufacture of a wide range of consumer products. Some observational studies have suggested that the amounts of BPA to which we are exposed could alter the reproductive organs of developing rodents. We examined the influence of BPA at low doses to address the questions of (a) whether in utero exposure affects the vagina of the offspring and (b) which mechanisms cause the toxic effects. Gravid Sprague-Dawley dams were administered either 0.1 (low dose) or 50 mg/kg per day BPA, the no observed effect level, or 0.2 mg/kg per day 17 alpha-ethinyl estradiol by gavage. Striking morphological changes were observed in the vagina of postpubertal offspring leading us to examine vaginal estrogen receptor (ER) expression because BPA binds to the ER alpha, which is important for growth of the vaginal epithelium. We show that the full-length ER alpha is not expressed during estrus in the vagina of female offspring exposed to either dose of BPA when compared to the control group, whereas ER alpha expression does not differ from the control group during the diestrus stage. ER alpha downregulation seems to be responsible for the observed altered vaginal morphology.

Animals↗