Teratologic evaluation of styrene given to rats and rabbits by inhalation or by gavage

Risk of Congenital Malformations Associated with Proximity to Hazardous Waste Sites

“…This is particularly important with regard to embryologic development, because the embryo and fetus constantly have cells in the growth phase (1). Animal studies have shown that chemical exposures can cause congenital malformations (2)(3)(4)(5). Occupational studies have identified similar effects in humans.…”

NTP‐CERHR Expert Panel Report on the reproductive and developmental toxicity of styrene

“…It may be used only as corroboration for other studies. Murray et al (1978), supported by companies affiliated with the Manufacturing Chemists Association, treated pregnant Sprague-Dawley rats and New Zealand white rabbits with styrene (minimal purity 99.5%, 2-5 ppm tert-butylcatechol added to inhibit polymerization). Rats were exposed by inhalation 7 hr/day from GD 6-15 (plug 5 GD 0) to 0 or 300 ppm styrene in the first experiment and to 0 or 600 ppm styrene in a second experiment (n 5 29 or 30/dose group).…”

“…There is one regulation-compliant (for its time) developmental toxicity series of studies in rats using inhalation and gavage exposures and in rabbits using inhalation exposures (Murray et al, 1978). A rat study (Daston et al, 1991) using a single dose administered one time and a smaller number of litters than is typical for a developmental toxicity study was useful in showing a distinction between maternal toxicity and embryotoxicity.…”

“…There are two pivotal studies, one in rats and one in rabbits, that evaluate the potential prenatal developmental toxicity of styrene. Murray et al (1978) treated pregnant Sprague-Dawley rats by inhalation 7 hr/day from GD 6-15 with 300 or 600 ppm styrene (each with its own 0 ppm control group). Additional rats were given styrene in peanut oil by gavage on GD 6-15 at 0, 180, or 300 mg/kg bw/day in two divided doses.…”

“…Maternal LOAEL 180 mg/kg bw/day (kbody weight gain) Developmental LOAEL4300 mg/kg bw/day Murray et al, 1978 Rat, strain not indicated Gavage at 0 or 200 mg/kg bw/ day during gestation or lactation period or both…”