Evaluation of the Teratogenic Potential of Octyl Acetate in Rats

Octyl acetate (CAS RN 108419-32-5) was administered via oralgavage to pregnant Sprague-Dawley rats on Gestation Days 6 through15 at dose levels of 0,0.1,0.5, and 1.0 g/kg. The dams wereweighed and observed for clinical signs of toxicity during pregnancy,and food consumption was measured. On Gestation Day 20 the damswere sacrificed and the fetuses were examined for external,visceral, and skeletal malformations and variations. The mid-and high-dose levels resulted in maternal toxicity as evidencedby reductions in body weight gain and food consumption. Therewere no statistically significant effects on embryo-fetal lethalityor fetal growth for any treatment group. The number of litterswith at least one malformed fetus and the mean percentage ofthe litter malformed were significantly (p < 0.05) elevatedin the highdose group only. The results of the present studydemonstrate that octyl acetate produced some evidence of developmentaltoxicity at a dose (1.0 g/kg) that was maternally toxic. Developmentaltoxicity was not observed at the maternally toxic 0.5 gkg doselevel or the maternally nontoxic dose level (0.1 g/kg). Therefore,these data indicate that octyl acetate is not a selective developmentaltoxicant in the rat.     

Subchronic Delayed Neurotoxicity Evaluation of Jet Engine Lubricants Containing Phosphorus Additives

Synthetic polyol-based lubricating oils containing 3% of eithercommercial tricresyl phosphate (TCP), triphenylphosphorothionate(TPPT), or butylated triphenyl phosphate (BTP) additive wereevaluated for neurotoxicity in the adult hen using clinical,biochemical, and neuropathological endpoints. Groups of 17–20hens were administered the oils by oral gavage at a "limit dose"of 1 g/kg, 5 days a week for 13 weeks. A group of positive controlhens was included which received 7.5 mg/kg of one isomer ofTCP (tri-ortho-cresyl phosphate, TOCP) on the same regimen,with an additional oral dose of 500 mg/kg given 12 days beforethe end of the experiment. A negative control group receivedsaline. Neurotoxic esterase (NTE) activity in brain and spinalcord of hens dosed with the lubricating oils was not significantlydifferent from saline controls after 6 weeks of treatment. After13 weeks of dosing, NTE was inhibited 23 to 34% in brains oflubricant-treated hens. Clinical assessments of walking abilitydid not indicate any differences between the negative controlgroup and lubricant-treated hens. Moreover, neuropathologicalexamination revealed no alterations indicative of organophosphorus-induceddelayed neuropathy (OPIDN). in hens treated with the positivecontrol, significant inhibition of NTE was observed in brainand spinal cord at both 6 and 13 weeks of dosing; this groupalso demonstrated clinical impairment and pathological lesionsindicative of OPIDN. In conclusion, the results of the presentstudy indicated that synthetic polyol-based lubricating oilscontaining up to 3% TCP, TPPT, or BTP had low neurotoxic potentialand should not pose a hazard under realistic conditions of exposure.     

Subchronic Toxicity Evaluation of Tridecyl Acetate in Rats

Subchronic Toxicity Evaluation of Tridecyl Acetate in Rats.DAUGHTREY, W. C, SMITH, J. H., HINZ, J. P., AND BILES, R. W.(1990). Fundam. Appl. Toxicol. 14, 104–112. Tridecyl acetatewas administered to male and female Sprague-Dawley rats by oralgavage, 5 days per week for 13 weeks (90 days). Treated ratsreceived daily doses of 0.1, 0.5, or 1.0 g/kg/day and controlrats received distilled water at a dose of 1.0 g/kg/day. After45 days an interim termination was made to evaluate potentialhematologic or hepatic effects of tridecyl acetate. Blood sampleswere collected for routine hematology and serum chemistry determinationsand liver tissue was obtained for histological examination.After 90 days all animals were necropsied. Blood samples wereobtained and selected organs were weighed and prepared for histologicalexamination. Treatment-related effects observed in the mid andhigh dose groups consisted of (1) increased liver weights and/orliver/body weight ratios in both sexes at the interim and 13week termination, (2) increased kidney weights and/or kidney/bodyweight ratios in both sexes at the terminal necropsy, (3) histopathologicevidence of hydrocarbon nephropathy in males, and (4) a slightdecrease in serum glucose levels in male rats at both the interimand terminal necropsies. The increases in liver weight are believedto be a normal physiological response to a chemkal challenge.The nephropathy produced by tridecyl acetate is characteristicof that produced by a diverse group of hydrocarbons and, todate, appears to be limited to male rats. The low dose in thisstudy was a no observed effect level. These results are indicativeof an overall low degree of systemic toxicity following subchronicoral administration of tridecyl acetate at doses up to 1 g/kgbody weight.     

A Subchronic Toxicity Study of Octyl Acetate in Rats

A Subchronic Toxicity Study of Octyl Acetate in Rats. DAUGHTREY,W. C., EUTERMOSER, M., THOMPSON, S. W., AND BILES, R. W. (1989).Fundam. Appl. Toxicol 11, 313-320. The subchronic toxicity ofoctyl acetate was assessed following its administration to ratsvia oral gavage, 5 days per week for 13 weeks. Treated ratsreceived undiluted octyl acetate at doses of 0.1, 0.5, or 1.0g/kg. Control rats received distilled water at a dose of 1.0g/kg An interim termination was made after 45 days of dosingat which time five animals per sex per group were terminatedand necropsied. Blood samples were collected and liver tissueswere prepared for histological examination. After 13 weeks ofdosing all animals were terminated and necropsied. Blood sampleswere obtained and selected organs were weighed and preparedfor subsequent histological examination. Several treatment-relatedeffects were observed in the high-dose group (1.0 g/kg) animals.These effects included slight reductions in body weight andfood consumption, increased liver and kidney weights, and evidenceof hydrocarbon nephropathy in highdose males only. The significanceof these observations is discussed in the report. With the exceptionof increased liver weights in the mid-dose group, no other significanttreatment-related effects were observed in the mid- or low-dosegroups of animals. It is believed that the increases in liverweight which were observed are a compensatory response to anincreased metabolic load, and not a reflection of true hepatotoxicnty.The results of this study indicated that octyl acetate possessedan overall low degree of systemic toxicity when administeredorally to rats for 13 weeks