title: Urolithiasis in rats consuming a dl bitartrate form of choline in a purified diet.
abstract: Urolithiasis appeared in rats maintained to study the effects of nutrients and methylmercury on development and aging. After a year, the mortality rate was approximately 10%, and by 2 years, it had increased to nearly 30%. Clinical signs and urinary tract pathology were examined as a function of diet, duration on diet, gender, methylmercury exposure, genetics, and other potential risk factors by using survival analyses and qualitative comparisons. Urolithiasis in female rats appeared 15 weeks after beginning a purified diet and after 5 weeks for male rats. After 97 weeks, the mortality rate of female rats was 22% and for male rats was 64%. Lifetime urolithiasis-associated mortality was about 2% in a group of rats that consumed the contaminated diet for < 30 weeks. No urolithiasis occurred in siblings or cohorts of the rats described here that were maintained on a standard rodent chow containing choline chloride. Urolithiasis was traced to racemic, rather than levo-, bitartaric acid in some purified diets shipped in 2001 and 2002. It is unknown when the impurity first appeared in the diet, so estimates of exposure duration are upper limits. Chronic methylmercury exposure increased vulnerability. Some families (dam + offspring) had multiple cases of urolithiasis, but probability models constructed to evaluate familial clustering revealed no evidence for a genetic predisposition to urolithiasis apart from gender. Removing racemic tartaric acid did not decrease mortality once rats had been on the diet for 20 to 30 weeks, but it helped when exposure duration was shorter.
authors.affiliation: Behavioral Toxicology Laboratory, Experimental Psychology, Auburn University, Alabama 36849, USA.
authors.forename: M Christopher
authors.initials: MC
authors.lastname: Newland
authors.forename: Phyllis A
authors.initials: PA
authors.lastname: Reile
authors.forename: Eva A
authors.initials: EA
authors.lastname: Sartin
authors.forename: Michael
authors.initials: M
authors.lastname: Hart
authors.forename: Margaret C
authors.initials: MC
authors.lastname: Craig-Schmidt
authors.forename: Ian
authors.initials: I
authors.lastname: Mandel
authors.forename: Neil
authors.initials: N
authors.lastname: Mandel
mesh_terms: D000821:Animal Feed / Q000633:toxicity; D000818:Animals; D002794:Choline / Q000008:administration & dosage / Q000633:toxicity*; D004032:Diet; D004347:Drug Interactions; D005260:Female; D008297:Male; D008767:Methylmercury Compounds / Q000008:administration & dosage / Q000633:toxicity; D051381:Rats; D020318:Rats, Long-Evans; D012737:Sex Factors; D016019:Survival Analysis; D014545:Urinary Calculi / Q000139:chemically induced* / Q000401:mortality / Q000473:pathology; D014551:Urinary Tract / Q000473:pathology
chemical_list: D008767:Methylmercury Compounds; D002794:Choline