Teratogenicity of 2-methoxyethanol applied as a single dermal dose to rats.

2-Methoxyethanol (2-ME) was applied as a single dermal dose on the backs of collared, pregnant Sprague-Dawley rats on Gestation Days (GD) 10, 11, 12, 13, or 14 at doses of 0 and 2000 mg/kg, and at doses of 0, 250, 500, and 1000 mg/kg on GD 12. Except for a transient loss in body weight observed the day after 2-ME administration, no signs of maternal toxicity were observed. On GD 20, dams were necropsied and the fetuses evaluated for normal development. Resorptions were significantly (p less than 0.05) increased in dams exposed to 2-ME on GD 10. Fetal body weights were reduced at dose levels of 1000 and 2000 mg/kg, but statistically significant differences were found only on GD 10 and 12. Significant increases in external, visceral, and skeletal malformations were observed in fetuses exposed to 2-ME at dose levels of 500 mg/kg or greater. Defects of the cardiovascular and urinary systems were the prominent visceral malformations observed. Limb defects (especially those pertaining to the digits) and vertebral column defects (primarily of the tail) were the most frequently observed skeletal defects. At the 2000 mg/kg dose level, 2-ME was teratogenic regardless of the GD of administration. Based on the results of this study, the no observed adverse effect level for developmental toxicity for a single dermal dose of 2-ME applied on GD 12 was determined to be 250 mg/kg.

Reproductive toxicity of 2-methoxyethanol applied dermally to occluded and nonoccluded sites in male rats.

12-Methoxyethanol (2-ME), also known as Methyl Cellosolve, was applied on the backs of Sprague-Dawley male rats at dose levels of 0, 625, 1250, or 2500 mg/kg/day on occluded (covered) sites, and 0, 1250, 2500, or 5000 mg/kg/day on nonoccluded (uncovered) sites for 7 consecutive days. Because deaths occurred at a dose level of 2500 mg/kg/day among rats with occluded test sites, dosing of this group was discontinued after 5 days. The number and morphology of caudal epididymal sperm, number of testicular spermatids, and weights of reproductive organs were determined on Weeks 4, 7, 10, and 15; fertility was assessed on Weeks--1, 4, 7, 10, and 14. The effects of treatment were dose-related and included a decline in epididymal sperm count and testicular spermatid count, a reduction in weights of testes and epididymides, an increase in the number of sperm with abnormal morphology, and a reduction in fertility in rats exposed to 2-ME. The above effects were seen with or without occlusion, but they were more severe and recovery proceeded at a slower rate when the skin sites were covered.

Developmental toxicity of Clarified Slurry Oil applied dermally to rats.

Clarified Slurry Oil (CSO), the heavy residual fraction from the fluidized catalytic cracker, was applied to the shaven backs of groups of 10 pregnant rats at doses of 0, 4, 8, 30, 125, and 250 mg/kg/day. All groups received the test material on gestation days 0-19. CSO was applied undiluted and left uncovered on the skin; collars were placed on the rats to minimize ingestion of the test material. Signs of maternal toxicity, some of which were seen at dose levels as low as 8 mg/kg/day, included vaginal bleeding, decreased body weight gain, reduced food consumption, death, increased relative liver weights, atrophy of the thymus, and aberrant serum chemistry. The number of fetal resorptions/deaths was markedly increased and the number of viable offspring decreased by CSO at dosages of 30 mg/kg/day and above. The group receiving 250 mg/kg/day carried no viable offspring. Fetuses from pregnant females exposed to CSO at dose levels in excess of 8 mg/kg/day were smaller than those from control and 4 mg/kg/day groups, and their skeletons showed decreased ossification. Abnormal external development and visceral development were observed in living and dead fetuses exposed in utero to CSO at dose levels as low as 8 mg/kg/day. Based on these data, 4 mg/kg/day represents the No-Observed-Adverse-Effect-Level for both maternal and developmental toxicity.