Toxicity of Mercuric Chloride to the Developing Rat Kidney - II Effect of Increased Dosages on Renal Function in Suckling Pups

Aug 31, 2026

Upload by Himbo

Mercuric chloride exposure was tested to determine how higher doses affect renal function in immature rat pups. Sprague-Dawley pups received single injections at postnatal days 1, 8, or 15 across multiple dose levels, with renal performance assessed at 24–120 hours using urine volume, osmolality, urinary pH, chloride excretion, protein/glucose/hemoglobin, and water-deprivation concentration ability. Increasing age and dose intensified oliguria/anuria, reduced concentrating capacity, lowered urinary pH, altered chloride excretion over time, and increased proteinuria, glucosuria, and hematuria.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages11

Reading Time28 min

AccessFree to download

Toxicity of Mercuric Chloride to the Developing Rat Kidney - II Effect of Increased Dosages on Renal Function in Suckling Pups

Methods

Animals

Renal function evaluation

# Toxicity of Mercuric Chloride to the Developing Rat Kidney.II.Effect ofIncreased Dosages on Renal Function in Suckling Pups GEORGE P.DASTON,¹JACQUEIINE A.GRAY,BRENDA CARVER,AND ROBERT J.KAVLOCK Perinatal Toxicology Branch,Developmental Biology Division,Health Effects Research Laboratory,U.S.Environmental Protection Agency,Research Triangle Park,North Carolina 27711 Received August 30,1983;accepted January 20,1984 Toxicity of Mercuric Chloride to the Developing Rat Kidney.II.Effect of Increased Dosageson Renal Function in Suckling Pups.DASTON,G.P.,GRAY,J.A.,CARVER,B.,AND KAVLOCK,R.J.(1984).Toxicol.Appl.Pharmacol.74,35-45.It has been demonstrated that the sensitivityto HgCl₂nephrotoxicity increases with maturity in the rat,and that neonates are largely unaffectedby a dose of 5 mg/kg.In the present study,immature rat pups were exposed to higher doses ofHgCl to determine whether this effect was attributable to a quantitative or qualitative differencein the renal sensitivity to HgCl₂.Sprague-Dawley rats were injected with a single dose of 5,7.5, 10,12.5,20,or 30 mg/kg on Postnatal Day 1;5,7.5,10,12.5,15,or 20mg/kg on Day 8;or 6.25,7.5,10,or 12.5 mg/kg on Day 15.Renal function was evaluated at 24,48,and 120 hrafter treatment by measuring urine volume,osmolality,urinary pH,and chloride content,theability to concentrate urine during water deprivation,and the presence of protein,glucose,orhemoglobin in urine.Animals were then killed and their kidneys weighed.A dose of 20 mg/kgwas needed to induce mortality in pups treated at 1 day of age,and 15 mg/kg was needed inpups treated at 8 days of age.In contrast,the 6.25-mg/kg dose given to 15-day-old pups producedsome mortality,and all rats given higher doses at 15 days of age died within 2 days.There wasmarked oliguria or anuria in the rats that died.Kidney weight was increased in a dose-relatedfashion at all ages.In those animals not rendered oliguric by the treatment,urine volume increasedand the ability to secrete a more concentrated urine during water deprivation decreased.UrinarypH was decreased in a dose-related manner.Urinary chloride excretion was temporarily decreasedafter HgCl₂treatment on Day 1,but was increased thereafter.Proteinuria,glucosuria,and hematuriawere detected in the treated rats,again increasing in frequency and severity with age and dose. Mercuric chloride is a potent nephrotoxin inthe adult animal.It affects the proximal tubuleand may cause acute renal failure,character-ized by diuresis or,in extreme cases,oliguria,and elevated values for serum creatinine andurea nitrogen(McDowell et al.,1976).Com-paratively little is known,however,of the tox- icity of HgCl₂to the postnatally maturing kid-ney and the reported findings are equivocal.Bidani et al.(1979)reported that 2-week-oldrats had higher serum urea nitrogen levels anda higher rate of mortality after HgCl₂admin-istration than did rats treated at 4 and 8 weeksof age,suggesting that the young rat is moresensitive to HgCl₂exposure.Wold et al.(1977)found no difference in HgCl₂-induced uremiabetween 5-,15-,and 30-day-old and adultrabbits indicating that there is no age differencein the nephrotoxic response in rabbits.Kav-lock(1982)and Kavlock and Gray(1983)in- George Daston is a National Research Council-En-vironmental Protection Agency Research Associate.Towhom requests for reprints should be addressed.Presentaddress:Department of Zoology,University of Wisconsin,P.O.Box 413,Milwaukee,Wisconsin 53201. jected rat pups sc on the day of birth with adose of HgCl₂which is nephrotoxic in theadult rat,but found no alterations in the abilityto excrete a water load or to concentrate urineduring water deprivation.It appears from theseresults that the neonate is less sensitive toHgCl₂toxicity.Recently,Daston et al.(1983)measued numerous renal functional andmorphological parameters in 1-,8-,15-,22-,and 29-day-old rats injected sc with 5 mg/kgHgCl₂.For all parameters measured,neonateswere found to be practically

FAQs

What was the main aim of the study on mercuric chloride toxicity in rat pups?

To test whether higher doses of mercuric chloride would change renal sensitivity in immature suckling pups and clarify whether age-related effects reflect quantitative or qualitative differences.

How were renal functions evaluated after mercuric chloride treatment?

Renal function was assessed 24, 48, and 120 hours after dosing by measuring urine volume, osmolality, urinary pH, chloride content, concentration ability during water deprivation, and urinary protein, glucose, or hemoglobin.

How did dose and postnatal age affect mortality and kidney outcomes?

Mortality increased with both age and dose: 20 mg/kg caused mortality at postnatal day 1, 15 mg/kg at day 8, and all higher doses at day 15 led to death within 2 days. Dying animals showed marked oliguria or anuria, while kidney weight increased in a dose-related manner.

Aug 31, 2026

Upload by Himbo