Dr. Dostal is a board-certified toxicologist with over 25 years of professional experience in toxicology including 19 years of experience in the pharmaceutical industry and 4 years in consulting. In the pharmaceutical industry she served as a study director, project team representative for general toxicology, manager, and therapeutic area leader for antibacterials. She is a specialist in reproductive and developmental toxicology, juvenile animal toxicology, and nonclinical antibacterial drug development. Dr. Dostal has special expertise in fertility and sperm evaluations for rats, dogs, monkeys and rabbits; as well as proficiency in assessing testicular and epididymal toxicity in animals. She has designed, monitored, and interpreted hundreds of regulatory toxicological studies to support pharmaceutical development for CNS therapeutics (such as Lyrica), anti-inflammation agents, biologicals, and products to improve cardiovascular health (e.g. HMG CoA reductase inhibitors such as Lipitor). Dr. Dostal has reviewed and contributed directly to numerous regulatory documents for IND and NDA submissions, including Investigator Brochures, preIND briefing documents, PIP (Pediatric Investigational Plan) and eCTD submissions for the US and worldwide. Dr. Dostal assists clients in developing and implementing scientific strategies for nonclinical safety testing of new pharmaceutical candidates, particularly in general toxicology, reproductive toxicology, safety pharmacology studies, impurity evaluation, due diligence, nonclinical study planning to support IND submissions, and regulatory submissions in electronic eCTD format.
Dr. Dostal is an active member of the toxicology community. She has served in several leadership capacities in the Society of Toxicology, the Midwest Teratology Association, and the Teratology Society. As President of the Reproductive and Developmental Toxicology Specialty Section of Society of Toxicology, Dr. Dostal provided written comments to the FDA on the proposed amendment to Pregnancy and Lactation Labeling for Human Prescription Drugs, and has contributed to the scientific content of labels for NDA submissions consistent with the expected new labeling guidelines.
Dostal LA, Toverud SU. Enhanced sensitivity of young suckling rats to the toxic effects of 1,25-dihydroxyvitamin D3. Calcif Tissue Int 1983; 35:432–437.
Dostal LA, Boass A, Toverud SU. Effects of high doses of vitamin D3 and 1,25-dihydroxyvitamin D3 in lactating rats on milk composition and calcium homeostasis of the suckling pups. Endocrinology 1983; 112:1631–1638.
Dostal LA, Toverud SU. Effect of vitamin D3 on duodenal calcium absorption in vivo during early development. Am J Physiol 1984; 246:G528–534.
Dostal LA, Toverud SU, Peach R. Renal calcification in suckling rats after high doses of calcitriol (1,25-dihydroxycholecalciferol). Arch Pathol Lab Med 1984; 108:410–415.
Mathews JM, Dostal LA, Bend JR. Inactivation of rabbit pulmonary cytochrome P-450 in microsomes and isolated perfused lungs by the suicide substrate 1-aminobenzotriazole. J Pharmacol Exp Therap 1985; 235:186–190.
Toverud SU, Dostal LA. Calcium absorption during development. Experimental studies of the rat small intestine. J Pediatr Gastroenterol Nutr 1986; 5:688–695.
Dostal LA, Aitio A, Harris C, Bhatia AV, Hernandez O, Bend JR. Cytosolic glutathione S-transferases in various rat tissues differ in stereoselectivity with polycyclic arene and alkene oxide substrates. Drug Metab Disp 1986; 14:303–309.
Brigelius R, Dostal LA, Horton JK, Bend JR. Alteration of the redox state of NADPH and glutathione in perfused rabbit lung by paraquat. Toxicol Ind Health 1986; 2:417–428.
Dostal LA, Jenkins WL, Schwetz BA. Hepatic peroxisome proliferation and hypolipidemic effects of di(2-ethylhexyl) phthalate in neonatal and adult rats. Toxicol Appl Pharmacol 1987; 87:81–90.
Dostal LA, Horton JK, Harris C, Brier DF, Bend JR. Stereoselectivity of cytosolic glutathione S-transferases with arene and alkene oxide substrates in various tissues and isolated hepatic and pulmonary cells of the rabbit. Carcinogenesis 1987; 8:1601–1606.
Dostal LA, Weaver RP, Schwetz BA. Transfer of di(2-ethylhexyl) phthalate through rat milk and effects on milk composition and the mammary gland. Toxicol Appl Pharmacol 1987; 91:315–325.
Dostal LA, Guthenberg C, Mannervik B, Bend JR. Stereoselectivity and regioselectivity of purified human glutathione transferases with alkene and polycyclic arene oxide substrates. Drug Metab Disp 1988; 16:420–424.
Dostal LA, Chapin RE, Stefanski SA, Harris MW, Schwetz BA. Testicular toxicity and reduced Sertoli cell numbers in neonatal rats by di(2-ethylhexyl) phthalate and the recovery of fertility as adults. Toxicol Appl Pharmacol 1988; 95:104–121.
Dostal LA, Schwetz BA. Determination of diphenhydramine in rat milk and plasma and its effects on milk composition and mammary gland nucleic acids. J Pharm Sci 1989; 78:423–426.
Dostal LA, Hopfer SM, Lin S-M, Sunderman FW Jr. Effects of nickel chloride on lactating rats and their suckling pups, and the transfer of nickel through rat milk. Toxicol Appl Pharmacol 1989; 101:220–231.
Dostal LA. Investigation of the mechanisms of the extensive excretion of cimetidine into rat milk. Biochem Pharmacol 1990; 39:207–210.
Dostal LA, Weaver RP, Schwetz BA. Excretion of high concentrations of cimetidine and ranitidine into rat milk and their effects on milk composition and mammary gland nucleic acid content. Toxicol Appl Pharmacol 1990; 102:430–442.
Dostal LA, Brown S, Bleck J, Anderson JA. Developmental toxicity of pentostatin (2'-deoxycoformycin) in rats and rabbits. Teratology 1991;44:325-334.
Dostal LA, Kim SN, Schardein JL, Anderson JA. Fertility and perinatal/postnatal studies in rats with the angiotensin-converting enzyme inhibitor, quinapril. Fundam Appl Toxicol 1991; 17:684–695.
Kamrin MA, Carney EW, Chou K, Cummings A, Dostal LA, Harris C, Henck JW, Loch-Caruso R, Miller RK. Female reproductive and developmental toxicology: overview and current approaches. Toxicol Lett 1994; 74:99–119.
Dostal LA, Schardein JL, Anderson JA. Developmental toxicity of the HMG-CoA reductase inhibitor, atorvastatin, in rats and rabbits. Teratology 1995; 50:387–394.
Dostal LA, Anderson JA. Developmental toxicity study in rats treated with the anticonvulsant, ralitoline. Teratology 1995; 51:11–19.
Dostal LA, Faber CK, Zandee J. Sperm motion parameters in vas deferens and cauda epididymal rat sperm. Reprod Toxicol 1996; 10:231–235.
Seed J, Chapin RE, Clegg ED, Dostal LA, Foote RH, Hurtt ME, Klinefelter GR, Makris SL, Perreault SD, Schrader S, Seyler D, Sprando R, Treinen KA, Veeramachaneni DNR, Wise LD. Methods for assessing sperm motility, morphology, and counts in the rat, rabbit, and dog: a consensus report. Reprod Toxicol 1996; 10:237–244.
Dostal LA, Whitfield LR, Anderson JA. Fertility and general reproduction studies in rats with the HMG-CoA reductase inhibitor, atorvastatin. Fundam Appl Toxicol 1996; 32:285–292.
Dostal LA, Juneau P, Rothwell CE. Repeated analysis of semen parameters in beagle dogs during a 2-year study with the HMG-CoA reductase inhibitor, atorvastatin. Toxicol Sciences 2001; 61:128–134.
Designed and monitored reproductive and developmental toxicology, as well as general toxicology, safety pharmacology, and genetic toxicology studies on new drug candidates at contract research laboratories in compliance with GLPs, ICH guidelines, and global regulatory requirements for Canadian, US, and Japanese pharmaceutical companies.
Monitored and advised small and large pharmaceutical companies on juvenile animal toxicology studies in rodent and nonrodent species to support pediatric clinical trials and approvals of new pharmaceuticals in the US and EU.
Performed due diligence investigations for potential acquisition drugs.
Provided impurity qualification support through nonclinical toxicity studies review.
Contributed to IND safety reports, IND submissions, NDA submissions for NME and biological drugs.