Embryotoxicity

Hydraziae is toxic and readily absorbed by oral, dermal, or inhalation routes of exposure. Contact with hydraziae irritates the skin, eyes, and respiratory tract. Liquid splashed iato the eyes may cause permanent damage to the cornea. At high doses it can cause convulsions, but even low doses may result ia ceatral aervous system depressioa. Death from acute exposure results from coavulsioas, respiratory arrest, and cardiovascular coUapse. Repeated exposure may affect the lungs, Hver, and kidneys. Of the hydraziae derivatives studied, 1,1-dimethylhydrazine (UDMH) appears to be the least hepatotoxic monomethyl-hydrazine (MMH) seems to be more toxic to the kidneys. Evidence is limited as to the effect of hydraziae oa reproductioa and/or development however, animal studies demonstrate that only doses that produce toxicity ia pregaant rats result ia embryotoxicity (164). 

Animal and Human Toxicity. The acute toxicity of lindane depends on the age, sex, and animal species, and on the route of adrninistration. The oral LD q in mice, rats, and guinea pigs is 86, 125—230, and 100—127 mg/kg, respectively. In contrast, most of the other isomers were considerably more toxic (94,95). Some of the other toxic responses caused by lindane in laboratory animals include hepato- and nephotoxicity, reproductive and embryotoxicity, mutagenicity in some short-term in vitro bioassays, and carcinogenicity (80). The mechanism of the lindane-induced response is not known. Only minimal data are available on the mammalian toxicides of hexachlorocyclopentadiene. 

Mebendazole is contraindicated in patients witii known hypersensitivity. Mebendazole is also contraindicated during pregnancy (Category C). The drug, like albendazole, has exhibited embryotoxic and teratogenic effects in experimental animals. Administration of mebendazole with tiie hydantoins and carbamazepine may reduce plasma levels of mebendazole. 

Rat DBTC Gestation days 6-17 atO, 1,2.5, 5, and 10 mg/kg body weight Maternal toxicity embryotoxicity malformations NOAEL = 5 Farr etal. (2001)... 

Schering AG (1991) ZK 30.434. Embryotoxicity including teratogenicity study in the rat after daily intragastric administration from day 6 to day 15 of gestation. Berlin, Schering AG, 25 July (Research Report No. IC18/90). 

Renhof M. 1984. Parathion-methyl (Folidol M actice ingredient) Study for embryotoxic effects on rabbits after oral administration. Bayer AG Institute of Toxicology, Wuppertal, West Germany. Unpublished Report No. 12907. 

Tanimura T, Katsuya T, Nishimura H. 1967. Embryotoxicity of acute exposure to methyl parathion in rats and mice. Arch Environ Health 15 609-613. 

Embryotoxicity and Fetotoxicity—Any toxic effect on the conceptus as a result of prenatal exposure to a chemical the distinguishing feature between the two terms is the stage of development during which the insult occurs. The terms, as used here, include malformations and variations, altered growth, and in utero death. 

EI Dupont deNemours Co. 1973. Maternal toxicity, embryotoxicity and teratogenic potential of neoprene accelerators applied to skin of rats during organogenesis. OTS0556789. Sect 8D. 

Gupta PK, Chandra SV, Saxena DK. 1978. Teratogenic and embryotoxic effects of endosulfan in rats. Acta Pharmacol Toxicol 42 150-152. 

OCDD caused embryotoxicity but was not teratogenic at 500 mg/ kg/day. OCDD and 2,7-DCDD caused neither teratogenicity nor embryotoxicity at 100 mg/kg/day. Khera and Ruddick (7) reported that the administration of 2 mg 2,7-DCDD/kg/day was associated with microscopic myocardial and pericardial lesions in rat fetuses. However, examination of sections of myocardium and pericardium from fetuses of dams treated with 100 mg doses in this study revealed no morphological differences from controls. 

Isomers of a chlorodibenzodioxin can produce different degrees of toxicity 2,3,7,8-TCDD is highly embryotoxic and a potent acnegen, but 1,2,3,4-TCDD is neither embryotoxic nor acnegenic. 

Toxicological Fertility study (one generation) Embryotoxicity (one species) Subchronic/chronic toxicity (one species) Additional mutagenicity... 

Toxicological Chronic toxicity Carcinogenicity Fertility study (multi-generation) Embryotoxicity (non-rodent) Acute/subacute toxicity in 2nd species Toxicokinetics... 

A Russian expert system, PASS (prediction of activity spectra for substances) [84], uses substructural descriptors called multilevel neighborhoods of atoms [85] to predict over 900 different pharmacological activities from molecular structure. These activities include a number of toxicity end points such as carcinogenicity, mutagenicity, teratogenicity, and embryotoxicity. The accuracy of prediction has been shown [86] to range from about 85% to over 90%. One-off predictions can be obtained free of charge on the PASS website [84]. 

Rommereim DN, Sikov MR. 1986. Relative embryotoxicity of 239Pu and241 Am in rats. Teratology 33(3) 93C-94C. 

Rommereim DN, Buschbom RL, Sikov MR. 1985. Comparison of embryotoxic effects of intravenously administered 239Pu and 241Am in rats. Health Phys 49 122-123. 

Sikov MR, Rommereim DN. 1986. Evaluation of the embryotoxicity of uranium in rats. Teratology 33(3) 41C. 

The carcinogenic activity of chemical substances is important as well. They are present in pesticides of different classes OCPs (DDT, aldrine, heptachlor, methoxychlor), thiocarbamates (thiram, zineb, ziram), carbamides (monuron) [3], etc. Even if the official description of a given pesticide does not denote its carcinogenic (mutagenic, teratogenic, embryotoxic, etc.) activity, this merely means that this particular pesticide was not studied sufficiently. 

Several pesticides are embryotoxic, i.e., they pathologically affect the developing fetus. For example, it was established in long-term experiments on animals that polychlorpinen, phosalone and trichlorfon are embryotoxic to mammals, leading to stillbirths [A103]. 

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