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Previous research demonstrated the inhalation teratogenicity of the solvent 2-ethoxyethanol in rats and rabbits. As this is one of a class of widely used industrial solvents, we investigated the teratogenicity of five structurally related compounds. Each chemical was vaporized and administered to approximately 15 pregnant rats in one to three concentrations for 7 hr/day on gestation days 7 to 15, and dams were sacrificed on day 20. Fetuses were individually weighed, and two-thirds of them were fixed in Bouin's solution and examined for soft-tissue anomalies. The other one-third were fixed in alcohol, stained with Alizarin Red and examined for skeletal defects. Data were analyzed on a litter basis; three solvents were compared with a pooled group (N = 34) of sham-exposed controls, and the remaining two were compared with a group of 15 controls. At concentrations which were apparently not maternally toxic, 2-methoxyethanol was highly embryotoxic, producing complete resorptions at 200 ppm; increased resorptions, reduced fetal weights and skeletal and cardiovascular defects occurred at both 100 and 50 ppm. 2-ethoxyethyl acetate at 600 ppm induced complete resorption of litters; 390 ppm reduced fetal weights and induced skeletal and cardiovascular defects, but only a single defect was observed at 130 ppm. 2-Butoxyethanol evidenced slight maternal toxicity at 200 ppm but produced no increase in congenital defects at that concentration. Neither 2-(2-ethoxyethoxy)ethanol (100 ppm) nor 2-methylaminoethanol (150 ppm) was maternally toxic or embryotoxic. In summary, shorter alkyl chained glycol ethers produced greater embryotoxicity than those having longer chains, and the ester produced effects equivalent to the ether, both patterns predictable from the biochemical literature.Of the thousands of chemicals to which workers are exposed, only a few have even minimal experimental animal data from which to evaluate or predict reproductive toxicity. One class of chemicals that has demonstrated reproductive toxicity is a class of monoand dialkyl ethers of ethylene glycol and their derivatives, collectively referred to as cellosolves or glycol ethers. Approximately 700 million pounds (318 thousand metric tons) of glycol ethers were produced in 1977, with the ethylene glycol monoethers representing about 78% of the total production (1). Ethoxyethanol, the prototype of this class, has the largest production volume, followed by butoxyethanol and methoxyethanol (1). The glycol ethers are widely used in industry as

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Developmental toxicologists have investigated the interactive effects from concurrent exposures to a variety of chemical and physical agents, including therapeutic drugs, industrial agents, and some biological organisms or their toxins. Of approximately 160 reports of concurrent exposures reviewed in this paper, about one third report no interactive effects (including additive effects--usually referring to response--as opposed to dose-additivity); another one third report antagonistic effects, and the final third report potentiative or synergistic effects. The quality of the studies is highly variable. Frequently, only small numbers of animals were included, and very few dose levels were evaluated. Maternal toxicity was rarely discussed. Time-effect relationships were examined infrequently. In addition, these studies are also inconsistent in the use of terms to describe interactive effects, and more than 90% of the terms were not in harmony with currently accepted definitions in toxicology. Because interaction studies will continue to be important in the future, this paper proposes uniform usage of terms for additivity and interactions in developmental toxicology: additivity (the combined effect of two or more developmental toxicants approximates the sum of the effects of the agents administered separately); antagonism (the combined effect of two or more agents, one or more of which are present at doses that would be developmentally toxic if given individually, is significantly less than the sum of the effects of the agents administered separately); potentiation (the increased effect of a developmental toxicant by concurrent action of another agent at a dose that is not developmentally toxic); synergism (the combined effect of two or more developmental toxicants is significantly greater than the sum of the effects of each agent administered alone); and, interaction if more precise terminology does not apply.