Teratogenic Mixtures

Some single organic solvents, for example, toluene, xylene, and ethanol, are known teratogens. Regretfully, many of the studies in the literature lump all organic solvent exposures together and fail to identify the specific 

One study that overcomes some of the shortcomings of those just cited reported adverse neurodevelopment outcomes following maternal exposures to 19 organic solvents and mixtures of these. 13 In this study, the women were occupationally exposed to the chemicals listed in Table 24.3. Also included in this table are the K, values and whether or not the specific chemical is a known teratogen or a known endocrine disruptor. 5 It is interesting to note that only three of the chemicals in the study—ethanol, trichloroethylene, and mineral spirits (a mixture of hydrocarbon solvents)—are endocrine disruptors. This shows that teratogenic effects can be induced by chemicals and mixtures that are independent of the endocrine system. 

Paternal occupational exposure to organic solvents can also produce teratogenic effects. Painters, automobile body shop workers, printers, and fiberglass workers have all been shown to father children with low birth 

Chemical ow Known Teratogen Known Endocrine Disruptor 

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Semicarbazide hydrochloride (hydrazine carboxamide hydrochloride) [563-41-7] M 111.5, m 173 (dec), 175 (dec), pK " 3.66. Crystd from aqueous 75% EtOH and dried under vacuum over CaS04. Also crystd from a mixture of 3.6 mole % MeOH and 6.4 mole % of water. [Kovach et al. J Am Chem Soc 107 7360 1985.] IR v 700, 3500 cm" [Org Synth Coll Vol I 485 I94I-, Davison and Christie J Chem Soc 3389 I955 -, Thiele and Stange Chem Ber 27 33 I894 pK Bartlett J Am Chem Soc 54 2853 1923]. The free base crystd as prisms from abs EtOH, m 96° [ Curtius and Heidenreich Chem Ber 21 55 1894]. TOXIC ORALLY, possible CARCINOGEN and TERATOGEN. 

Monooctyltin No neurotoxicity reported in 90-day studies Teratogenicity appears to be low (NOAEL = 120 mg/kg body weight per day) based on one study on a monooctyltin/dioctyltin mixture at 67 33 No aromatase inhibition in vitro NOAEL = 0.87 (decreased thymus weight) mg/kg body weight per day (as MOTC/DOTC mixture 65 35 )... 

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. 

Quinn B, Gagne F, Blaise C (2009) Evaluation of the acute, chronic and teratogenic effects of a mixture of eleven pharmaceuticals on the cnidarian, Hydra attenuate. Sci Total Environ... 

Developmental Effects. Oral developmental toxicity studies of deca-, octa-, and pentaBDE have shown no evidence of teratogenicity in animals. Gestational exposure to a high (1,000 mg/kg/day) but maternally nontoxic dose of decaBDE was fetotoxic in rats as shown by subcutaneous edema and delayed skull bone ossification. Commercial mixtures of octaBDE caused skeletal ossification variations in rats and rabbits at maternally toxic levels and other indications of fetotoxicity at lower doses. Effects of gestational exposure to octaBDE included minimally increased postimplantation loss in rats at >10 mg/kg/day, increased resorptions in rats at 25 mg/kg/day, and increased skeletal variations in rabbits at 15 mg/kg/day and rats at 50 mg/kg/day. No evidence of fetotoxicity was found in the only available study of pentaBDE in rats at maternally toxic doses < 200 mg/kg/day. No studies are available on developmental effects of PBDEs in humans. Based on the evidence in animals, PBDEs are unlikely to cause developmental toxicity at expected levels of exposure. 

Figure 6.23 Periods of peak sensitivity to teratogens in the rat. A teratogen administered at the time shown by the arrow would cause a mixture of malformations. It would particularly damage the eyes and brain but would have little or no effect on the palate. Source. Adapted from Ref. 7.

SAFETY PROFILE An experimental teratogen. Other experimental reproduedve effects. Readily forms an explosive peroxide. A very dangerous fire hazard when exposed to heat, flame, or oxidizers. Mixture with lithium tetrahydroaluminate may ignite or... 

SAFETY PROFILE Poison by ingestion, skin contact, and intravenous routes. Experimental teratogenic and reproductive effects. Questionable carcinogen. Mutation data reported. A central nervous system stimulant. Highly toxic to birds, fish, and humans. Many cases of fatal poisoning have been attributed to it. Does not accumulate in human tissue. In humans, ingestion of 1 mg/kg has caused symptoms. A dangerous fire hazard. Mixtures with parathion dissolve very exothermically in petroleum solvents and may cause an air-vapor explosion. See also ALDRIN. 

SAFETY PROFILE Moderately toxic by ingestion, skin contact, intravenous, and intraperitoneal routes. Mildly toxic by inhalation and subcutaneous routes. An experimental teratogen. Other experimental reproductive effects. A mild eye and skin irritant. Combustible when exposed to heat or flame can react with oxidizing materials. Moderate explosion hazard in the form of vapor when exposed to heat or flame. Mixture with hydrogen peroxide + polyacrylamide gel + toluene is explosive when dry. To fight fire, use alcohol foam, dry chemical. See also GLYCOL ETHERS. 

SAFETY PROFILE Mldly toxic by ingestion. An experimental teratogen. Experimental reproductive effects. Questionable carcinogen with experimental mmorigenic data. Mutation data reported. Potentially explosive reaction with potassium nitrate + sodium peroxide when heated in a sealed container. Mixtures with alkali release carbon monoxide when heated. When heated to decomposition it emits acrid smoke and irritating fumes. 

SAFETY PROFILE An experimental teratogen. Explodes on contact with ammonia. Ignites on contact with arsenic. Mixture with acetic anhydride is a sensitive explosive. Incompatible with alcohols. 

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