No abstract

The number of chemicals in commerce which have not been evaluated for potential developmental toxicity is large. Because of the time and expense required by conventional developmental toxicity tests, an abbreviated assay is needed that will preliminarily evaluate otherwise untested chemicals to help prioritize them for conventional testing. A proposed short-term in vivo assay has been used in a series of studies in which a total of 60 chemicals were tested. Some were independently tested two or four times each. In this preliminary test, pregnant mice were dosed during mid-pregnancy and were then allowed to deliver litters. Litter size, birth weight, and neonatal growth and survival to postnatal day 3 were recorded as indices of potential developmental toxicity. Results in this assay and conventional mouse teratology tests were generally concordant. Conventional data were available for 14 chemicals (ten teratogens, one fetotoxin, three nonteratogens), of which 11 (nine teratogens, one fetotoxin, one nonteratogen) produced evidence of developmental toxicity. This included conventional data for three chemicals (ethylene glycol, diethylene glycol dimethyl ether, and triethylene glycol dimethyl ether) that were untested before the present study. As high priority candidates for conventional testing on the basis of results here, all were subsequently studied in a standard teratology assay and were confirmed to be teratogenic in mice. Additionally, one of them (ethylene glycol) plus a fourth high priority candidate for conventional study (diethylene glycol monomethyl ether) were subsequently tested in rats and were found to be teratogenic in that species.

Previous subchronic and/or chronic inhalation studies of unleaded gasoline and a variety of petroleum naphthas, solvents, and distillates have shown that these complex materials are capable of inducing a distinctive nephropathy which appears limited to male rats. Therefore a series of gavage screening studies using male F-344 rats was conducted on components of gasoline to more clearly identify the major contributors to this nephrotoxicity. The dosing regimen consisted of 20 doses administered once daily, 5 days per wk for 4 wk. Tested were 15 pure hydrocarbon compounds typically found in unleaded gasoline boiling range, 4 naphtha streams representative of those commonly used to blend gasolines and 3 distillation fractions covering the less volatile portions of gasoline. The results revealed that the alkane (paraffin) components were primarily responsible for the nephrotoxic activity seen in unleaded gasoline, with a positive structure-activity response relating the degree of alkane branching to the potency of the nephrotoxic response. In addition, the nephrotoxic activity observed with the naphtha streams and distillation fraction correlated well with the proportion of branched alkanes contained in each.

No abstract

Fifteen glycol ethers were investigated for their potential to cause adverse reproductive toxic effects using an in vivo mouse screening bioassay. Pregnant mice were orally dosed once per day on days 7 through 14 of gestation at concentrations causing 0 to 41% maternal mortality. Reproductive endpoints included pup survival in utero (percent of live litters/pregnant survivors), pup perinatal and postnatal survival (number of live pups per litter, number of dead pups per litter, and pup survival to 2.5 days of age), and pup body weight statistics (weight at birth and weight at 2.5 days of age). The study was conducted in two phases: a dose range-finding phase using nonpregnant female mice, and a definitive reproductive phase using time-mated mice. The range-finding phase sought to identify, for each chemical, the maternal LD10 as the target dose. However, based upon reproductive phase results, such an exact dose was impractical to achieve. Thus, a range from the LD5 to the LD20 was considered a sufficient challenge dose that would not affect results due to high mortality, i.e., greater than the LD20. Glycol ethers were assigned to groups having different priorities for further testing based upon whether a sufficient challenge dose was administered and the degree of effects recorded for each chemical.(ABSTRACT TRUNCATED AT 250 WORDS)