Subject teratogenicity

Alcohol sulfates and alcohol ether sulfates were examined many years ago for their carcinogenic, mutagenic, and teratogenic properties. A complete revision of these subjects was carried out by Oba [382]. 

The ability to form carbon—carbon bonds in a controlled manner around an alkene is the subject of continuing intense research [49,134—136], These compounds are stable and, due to the considerably different reactivities of the C—Zr and C—B bonds, allow for selective and sequential reactions with a variety of electrophiles. Temarotene 58 is a retinoid of interest [137] because it shows no sign of hypervitaminosis A and it is not teratogenic, presumably due to the lack of a polar group [138,139], The published synthesis of temarotene-type compounds is long and leads to mixtures of diastereo-isomers, from which the desired product is eventually isolated [140—142], However, the synthesis of temarotene 58 by the method of Srebnik et al. [130] is straightforward, as outlined in Scheme 7.18. 

CR, a mild lacrimatory Irritant, manifests less acute toxicity than CN and CS. At low doses, it causes transient effects. There are a few studies on long-term health effects, including potential mutagenicity and teratogenicity. The available data are insufficient to predict long-term health effects. The small number of exposures and the small number of subjects exposed to CR at low doses at Edgewood make the occurrence of demonstrable effects In these subjects unlikely. 

In 1973, Upshall4 reported tests of CS for teratogenicity in female Porton strain rats and New Zealand White rabbits. He attempted to simulate conditions that exist in riot-control situations, looking for teratogenesis and changes in numbers of offspring in response to aerosol exposure of both species. Control rats were subjected to handling stress and aerosols without CS. 

Saquinavir is subject to extensive first-pass metabolism by CYP3A4 and functions as a CYP3A4 inhibitor as well as a substrate thus, there are many potential drug-drug interactions (Table 49-4). A decreased dose of saquinavir is recommended when -administered with nelfinavir. Increased saquinavir levels when -administered with omeprazole necessitate close monitoring for toxicities. Digoxin levels may increase if co administered with saquinavir and should therefore be monitored. Liver function tests should be monitored if saquinavir is -administered with delavirdine or rifampin. There is no evidence of human teratogenicity from saquinavir there is short-term safety data for both mother and infant. 

The mechanism underlying thalidomide teratogenesis has been the subject of considerable research. Thalidomide exists as two isomers, one intriguing finding is that there is a difference in the toxicity of the two isomers of thalidomide, with only the S- enantiomer being teratogenic and not the R+ enantiomer (Fig. 7.74). 

Dyes such as benzidine-based dyes which are classified as carcinogens, mutagens, or teratogens according to the Directive 67/548/EEC (CMR substances, Table 8.3), are subject of the Council Directive 76/769/EEC (Restrictions on the Marketing and Use of Certain Dangerous Substances and Preparations) and must not be marketed as such or in preparations if they contain more than the maximum concentration of 0.1%. In principle, the directive does not ban the import of articles , e.g., textiles dyed with benzidine-based dyes, because articles are not covered by the directive. 

The February 1987 update of the October 1985 RTECS list of chemicals which cause reproductive hazards, had 6,917 entries. We selected the following T codes T01-T09 (paternal effects), T25 (postimplantation mortality), T31-T59 (effects on embryo or fetus, and specific developmental abnormalities), and T65 (transplacental tumorigenesis). All but the first ones (T01-T09) would fit into a classical definition of teratogens. The paternal effects were included in line with the recommendation by Schardein (vide supra), and also to incorporate the newest data on this long neglected subject. 

It is not surprising that preservatives sometimes prove toxic to humans. To assess the toxicity of any substance, it is necessary to know its acute and cumulative toxicity together with its no effects levels and also to be aware of its mutagenic, teratogenic, and carcinogenic potential. In addition, its local actions as well as its liability to cause hypersensitization might be important. Any new preservative must be subjected to a battery of such mandatory tests to provide these data as must a new application of an established biocide. 

DMAE has also been claimed to be teratogenic. Studies on this subject remain controversial some have shown that DMAE can be teratogenic in mouse embryos at high doses other studies have shown no evidence of toxicity in rodents. In my knowledge nothing has been published on teratogenic effects in humans, and no research has shown teratogenicity in humans, despite the wide use of DMAE in industry. 

No studies have demonstrated that selenium or its compounds are teratogenic in humans. Robertson (1970) reported on the outcome of pregnancies in a laboratory in which workers handled sodium selenite. Of the five pregnancies, four ended in spontaneous abortion and one resulted in an infant with bilateral clubfoot. The urinary selenium levels in all subjects were similar to those in other individuals living in the same area. The limited number of cases, possible exposure to other toxic agents, and other confounding factors leave the relationship between sodium selenite and developmental effects inconclusive. 

---