الفهرس 
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Abstract
Formaldehyde (FA) is a colorless flammable gas with a pungent odor. It is a gas at room temperature, or available as a liquid called formalin. It is used as a disinfectant and as a preservative of biological samples. It is also used as a chemical intermediate in industry e.g. melamine, polyacetate, plywood, particle board, foam insulation, carpet adhesives and wide variety of extruded plastic items.
It has been documented to be naturally present in many common food items, including fruits and vegetables, meats, fish and dried mushrooms etc., at a wide range of levels. It is directly used as bacteriostatic in cheese and milk to prevent Clostridium. The level of formaldehyde can accumulate in certain marine fish during frozen storage.
The aim of this work was to study the developmental effects and possible DNA damaging effects of formaldehyde on the pregnant mice and its teratogenicity on their embryos thereby avoiding the teratogenic potential of FA during pregnancy.
This study was carried out on 50 adult female albino mice, approximately 10 weeks old, obtained from Animal house, Faculty of Medicine, Alexandria University, Alexandria, Egypt.
Bred females which were expected to become pregnant according to the presence of the observed vaginal plug and their fertility, were divided into four equal groups according to an approximate equal mean body weight:
- group I: (control group) included 20 bred mice serving as a control group. They were subdivided into two equal subgroups 10 animals each:
• Subgroup Ia: (negative control group) included 10 bred females received distilled water by orogastric tube on gestational days (GD) 6–13.
• Subgroup Ib: (positive control group) included 10 bred females received colchicine at a dose level of 2 mg/kg body weight per day by orogastric tube on GD 6–13.
- group II: included 10 bred mice receiving 7mg/kg body weight per day of FA dissolved in water by orogastric tube on GD 6–13.
- group III: included 10 bred mice receiving 14mg/kg body weight per day of FA dissolved in water by orogastric tube on GD 6–13.
- group IV: included 10 bred mice receiving 21mg/kg body weight per day of FA dissolved in water by orogastric tube on GD 6–13.
Pregnant females were sacrificed on GD 18. Peripheral blood and bone marrow of dams were examined microscopically for assessment of immature micro-nucleated RBC`S. The uterine horns were examined for resorption sites, and alive or dead fetuses. Extracted live fetuses were examined for external developmental abnormalities and stained for skeletal malformations. The results of the study showed:
• Signs of toxicity including lethargy, decrease in motor activity, and loss of appetite were noted in dams treated with FA compared to both colchicine and negative control groups. These effects progressed throughout the period of treatment.
• Body weight and maternal weight gain were also significantly reduced among the entire period of gestation 6- 18 days simultaneously with reduction in food and water consumption. This indicates maternal toxicity and the reduction in litter size or embryo lethality.
• FA caused increased rate of late resorptions and dead fetuses with a marked decrease in the number of live fetuses and fetal weight reduction indicating its embryotoxicity and fetotoxicity. FA rapidly crosses placental barriers, adversely affecting the mammalian fetal tissue.
• FA resulted in external and skeletal abnormalities indicating that FA is a teratogenic agent. The period from 6th to 13th gestational days in mouse corresponds to the period of organogenesis; from 3rd to 8th week of pregnancy in humans. During this period the embryo is particularly sensitive to teratogenic insults because at this stage there is organ differentiation.
• External abnormalities were in the form of cranial abnormalities and meningeocoele. This is due to FA itself that directly influences brain cell replication and differentiation. Anomalies in other organs such as eyes, ear, body wall, limbs and multiple subcutaneous hemorrhages were noticed.
• Skeletal abnormalities were in the form of cranial retardation, poor ossification and malformed vertebrae and limb bones.
• Exposure to FA at dose of 14 &21mg/kg/day increased the frequency of micronucleated RBCs in peripheral blood and in bone marrow PCEs and increased PCE/NCE ratio. This was due to direct genotoxic effect of FA on the cell genome and formation of DNA–protein cross-links.