Glutaraldehyde is commonly used to control physical and biological properties of collagen structure by means of intramolecular and/or intermolecular crosslinking of collagen molecules. Solubility, antigenicity, and biodegradation of naturally occurring or reconstituted collagenous matrices are effectively reduced by glutaraldehyde treatment. Adverse biological reactions to glutaraldehyde have been limited to infrequent contact dermatitis and to biocidal effects which are exploited in chemical sterilization media. In the present study of glutaraldehyde-tanned collagen sponge, the presence of glutaraldehyde was correlated with cytotoxic effects upon fibroblasts in tissue culture and foreign body giant cell reaction to bioimplants of the sponge. Fibroblast growth in tissue culture is 99% inhibited at media concentrations of 3.0 ppm glutaraldehyde. Extracts of glutaraldehyde collagen sponge in aqueous media at pH 7 and 4.5 yielded 6 micrograms and 65 micrograms glutaraldehyde per gram of collagen sponge, respectively. The yield increased tenfold at pH 4.5. Observations indicate that leaching of the glutaraldehyde from glutaraldehyde-tanned collagen sponge is sufficient to produce potentially adverse cellular effects both in vivo and in vitro.
Trichloroethylene and dichloroethylene administered during organogenesis are cardiac, but not general, teratogens. The data indicate that these agents administered in drinking water to pregnant rats caused an increased number of congenital cardiac defects in rat fetuses.
Recent epidemiologic studies have demonstrated a greater than expected number of pediatric patients with congenital heart disease in areas where drinking water was contaminated by halogenated aliphatic hydrocarbons. Trichloroethylene, trichloroethane and dichlorethylene were the principal contaminants in the groundwater. A previous study of chick embryos demonstrated that when injected into the air sacs of fertilized eggs trichloroethylene produced more than three times the number of cardiac defects that are found in control embryos. This mammalian study demonstrates similar effects of trichloroethylene and dichloroethylene when applied under provocative circumstances (that is, solutions delivered through a catheter into the gravid uterus from an intraperitoneal osmotic pump) to the developing rat fetus in utero during the period of organ differentiation and development. Furthermore, the effect is dose dependent for both agents. Although only a very small number of congenital heart anomalies (3%) were found in the control group, 9% and 12.5% were found in the lower dose trichloroethylene and dichloroethylene groups and 14% and 21% in the higher dose groups, respectively (p less than 0.05). A variety of cardiac defects were found. Dichloroethylene appears to be at least as great a cardiac teratogen as trichloroethylene even though it was administered at a 10-fold lower concentration. These agents appear to be specific cardiac teratogens because only a single noncardiac anomaly was found. This study in a rat model demonstrates a dose-dependent relation between fetal exposure to trichloroethylene and dichloroethylene in utero during the period of organogenesis and the appearance of a variety of congenital cardiac defects.
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