Developmental toxicity of clarified slurry oil, syntower bottoms, and distillate aromatic extract administered as a single oral dose to pregnant rats.
Clarified slurry oil (CSO), syntower bottoms (STB), and distillate aromatic extract (DAE) are refinery streams produced by processing crude oil. Each of these refinery streams is rich in both hydrocarbons having carbon numbers of C20 or greater and polycyclic aromatic compounds. Available data indicate that some refinery streams are developmentally toxic (manifested primarily as increased embryolethality and growth retardation) by the dermal route of exposure. However, there is no conclusive evidence for their being teratogenic. The present studies were designed to further explore the suspected teratogenic potency of refinery streams while at the same time limiting embryolethality. To profile teratogenic effects as a function of gestation day, pregnant rats received a single oral dose (2000 mg/kg) of CSO, STB, or DAE on one of gestation days (GD) 11-14; DAE and STB were also administered on GD 15. To profile effects as a dose response function, rats received a single oral dose of CSO, DAE, or STB on GD 12 at 125, 500, and 2000 mg/kg. Control animals were similarly treated but were administered tap water. On GD 20, dams were necropsied and the fetuses evaluated for normal development. In general, evidence of maternal toxicity (i.e., decreased body weight gain, decreased thymus weight) was observed at doses greater than or equal to 500 mg/kg. For each refinery stream tested, the incidence of resorption was greatest on GD 11. A common pattern of fetal malformations was observed for all of the refinery streams tested and included cleft palate, diaphragmatic hernia, and paw and tail defects. The incidence and type of malformation observed were influenced by the gestation day of exposure. The incidences of external and skeletal malformations were greatest on GD 11 and 12 for fetuses exposed to CSO; on GD 13 and 14, the incidence of malformation was comparable for CSO- and STB-exposed fetuses. The incidence of visceral anomalies was greatest on GD 11-13 for fetuses exposed to CSO and STB; on Gestation D 14, the incidence was comparable for each of the refinery streams tested. In general, the ability to produce adverse effects on development was greatest for CSO and least for DAE. Effects produced by STB were comparable to or less severe than those observed for CSO.
Feuston
M H
MH
Stonybrook Laboratories, Inc., Princeton, NJ 08543-1029, USA.
Mackerer
C R
CR
D000014:Abnormalities, Drug-Induced; D000284:Administration, Oral; D000818:Animals; D001835:Body Weight / Q000187:drug effects; D001842:Bone and Bones / Q000002:abnormalities* / Q000187:drug effects; D002227:Carbazoles / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D020964:Embryo Loss; D005314:Embryonic and Fetal Development / Q000187:drug effects*; D005260:Female; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010578:Petroleum / Q000633:toxicity*; D011083:Polycyclic Compounds / Q000008:administration & dosage / Q000633:toxicity*; D011247:Pregnancy; D051381:Rats; D012098:Reproduction / Q000187:drug effects
D002227:Carbazoles; D010578:Petroleum; D011083:Polycyclic Compounds; C101576:syntower bottoms; C052511:clarified slurry oil; C101575:distillate aromatic extract