Eye malformation induced by carbamazepine in fetus of Balb/c mice: Histological findings

etters

D22Assessment of the occupational ototoxicity of n-hexane

Adolf Vyskocil 1,∗, Tony Leroux 1, Ginette Truchon 2, FrancoisLemay 2, Martine Gendron 1, France Gagnon 1, Naïma El Majidi 1,Claude Viau 1

1 Université de Montréal, Montréal, QC, Canada, 2 Institut derecherche Robert-Sauvé en santé et en sécurité du travail, Montréal,QC, Canada

The ability of chemicals to produce hearing loss themselves orto promote noise-induced hearing loss has been demonstratedfor some organic solvents. The objective of this study was toreview the literature on the effects of low-level exposure to n-hexane on the auditory system and consider its relevance forthe occupational settings. Both human and animal investigationswere evaluated only for realistic exposure concentrations basedon the permissible exposure limits. In Quebec, the Time-WeighedAverage Exposure Value (TWAEV) for 8 h is 50 ppm. In humans,the upper limit for considering ototoxicity data relevant to theoccupational exposure situation was set at 5 times the TWAEV.Animal data were evaluated only for exposure concentrations upto 100 times the TWAEV. There is no convincing evidence ofn-hexane-induced hearing losses in workers. In rats, n-hexaneseems to affect the auditory function. However, the site of thesealterations cannot be determined from the present data. Furtherstudies with sufficient data on the n-hexane exposure of work-ers are necessary to make a definitive conclusion. In the interim,we recommend considering n-hexane as a possibly ototoxicagent.

doi:10.1016/j.toxlet.2008.06.371

D23Combined effect of ethylene glycol monoethyl and monobutylethers in Aldh2 null and wild mice

Rui-Sheng Wang 1,∗, Katsumi Ohtani 1, Toshihiro Kawamoto 2,Tamie Nakajima 3

1 National Institute of Occupational Safety and Health, Kawasaki,Japan, 2 Department of Environmental Health, University ofOccupational and Environmental Health, Kitakyushu, Japan,3 Department of Occupational and Environmental Health, NagoyaUniversity, Nagoya, Japan

Ethylene glycol ethers have been used industrially as a solvent inmultiple purposes. Ethylene glycol monoethyl ether (EGEE), one ofthe ethylene glycol ethers, is known to be toxic to reproductive sys-tem. Ethylene glycol monobutyl ether (EGBE), with similar formulato EGEE, is much less toxic compared with EGEE, and used in somecases as an alternative solvent. This study investigated the effect onthe reproductive and myelopoietic systems of EGEE and EGBE whenadministrated separately or in combination. Male mice were orallytreated with 600 mg/kg/day of each EGEE, EGBE or both compoundsfor 14 consecutive days. In wild type mice, the motility of sperm inthe spermaducts was significantly damaged in EGEE group, and tothe same extent also in the group of combination treatment. How-ever, such damage was not observed in EGBE group. These findingswere also true as to testes atrophy. In Aldh2 null mice, no effect onmotile sperm and testes weight was observed in any group. On theother hand, calculus in the bladder was found only in the groupswith EGBE treatment, and its rate was about 75% in wild and 50%in Aldh2 null mice. These results suggested that the reproductivetoxicity when co-administrated with the two ethylene glycol etherswas due to EGEE and this effect was only in wild mice; the calculus

180S (2008) S32–S246

was caused only by EGBE, possibly with different severity betweenthe wild and Aldh2 null mice.

doi:10.1016/j.toxlet.2008.06.372

P10 Pharmaceutical Safety

P01Eye malformation induced by carbamazepine in fetus of Balb/cmice: Histological findings

Mohammad Afshar ∗, Adel Moallem, Majid Jalilian, Mohammadja-far Golalipoor

Birjand University of Medical Science, Birjand, South East ofKhorasan, Islamic Republic of Iran

Introduction: Carbamazepine(CBZ) is an antiepileptic drug that isused widely for the treatment of epileptic seizures. Associationbetween maternal use of carbamazepine and congenital eye mal-formation is a new subject in teratology.

Design: To reveal this association this drug was administered viaintraperitoneal (IP) injection during organogenesis period.

Materials and methods: 40 BALB/c pregnant mice were dividedinto four experimental and control groups. Two experimentalgroups received daily IP injection of 30 mg/kg (I) or 60 mg/kg(II) of CBZ on gestational days (GD) 6–15. All drugs resolved inTween20.Two control groups received normal saline or Tween 20.Dams were dissected on GD18 and embryos were collected. Afterobservation of eye malformation in fetuses, we employed routinehistological processes to prepare paraffin blocks of the head of thesemalformed fetuses. Serial sections trimmed from the head followedby Hematoxlin and Eosin (H&E) staining was performed. Imageswere taken by OLYMPUS SZX light microscope.

Results: Premature opening of one or both eyelids with mildto severe exophthalmos occurred in the two experimental groups(I and II). Control groups did not show any malformations. Thefetuses with malformed eye had smaller crown lump and lowerweight than fetuses in the control groups. Histological examina-tion showed the following malformations in the affected eyes:deformed lens, retinal folds with undeveloped layers, corneal foldwith absence of surface epithelium.

Conclusion: This study revealed that IP administration of CBZcould induce eye malformation in mice that deserves to be studiedin more detail.

doi:10.1016/j.toxlet.2008.06.327

P02Dynamics of the biochemical parameters in heroine addictpatients during the methadone substitution therapy

Daniela Luiza Baconi ∗, Anne-Marie Ciobanu, Denisa Margina, Car-olina Negrei, Maria Barca, Mihaela Ilie, Dan Balalau

University of Medicine and Pharmacy, Bucharest, Romania

Aim: Monitoring the biochemical profile of heroine addict patientsduring the methadone substitution therapy

Methods: 112 heroine addict patients were selected for thestudy, according to the clinical and psychological established cri-teria; the following biochemical parameters were evaluated: totalcholesterol (CT), HDL-cholesterol, LDL-cholesterol, triglicerides,creatinine, uric acid, gama-glutamiltransferase (GGT) and totalproteins. The patients received methadone substitution therapy(methadone detoxication and methadone maintenance therapy);at 10 days, 6 weeks, 6 months, and 12 months, the patients were