Oxamniquine displayed low acute toxicity in mice, hamsters, and rabbits. In rats, however, oxamniquine was much more toxic, the female being 8-10 times more sensitive than the male; single doses elicited an idiosyncratic sex-linked hepatic necrosis and bile duct proliferation. Dogs given repeated oral doses of 20 or 30 mglkglday for 5 successive days every 4 weeks for 11 months showed neurological disturbances of short duration, which tended gradually to increase in severity from one dosage period to the next; no histopathological correlate could be found. In chronic studies in mice (18 months) and hamsters (19 months) with intermittent dosage regimens relevant to likely usage in man, no evidence of carcinogenicity potential was observed at dose levels up to 150 mglkg. Oxamniquine displayed no maternal toxicity or teratogenicity in mice and rabbits, and only slight embryotoxicity after high oral doses.

Since the passing of the Mineral Workings Act 1951 there have been (1) changing pursuits in agriculture and improved methods of restoration, (2) continually rising costs of machinery and labour, and (3) nationalization of the steel industry.Recently, a new Act was passed, namely the Mineral Workings Act 1971, to make further provision in relation to contributions to and payments out of the Ironstone Restoration Fund, and to abolish the Advisory Committee on Ironstone Restoration. This Act necessited new regulations as follows:Statutory Instrument 1972 No. 210:‘This Order prescribes the full and reduced rates of contributions to be paid by ironstone operators towards the Ironstone Restoration Fund under section 1 of the Mineral Workings Act 1971, in respect of ironstone extracted on or after 1 April 1971 and the sum which may be deducted from payments made under mining leases and mineral rights orders (in accordance with section 3 of that Act) in respect of full-rate contributions.’Statutory Instrument 1972 No. 211:‘Section 9 of the Mineral Workings Act 1951 provides that the rate of payments out of the Ironstone Restoration Fund to be made to ironstone operators in respect of the restoration of worked ironstone land in compliance with conditions of a planning permission shall represent the amount by which the estimated cost per acre of the work of restoration exceeds such sum per acre as the Minister may determine to be the standard rate. The Ironstone Restoration Fund (Standard Rate) Order 1955 determined that rate to be £110 per acre.This Order made under section 3 of the Mineral Workings Act 1971 prescribes a new rate of £260 per acre in respect of all work completed after 31 March 1972.’

Short Communicationspublic information reports to FDA; a total of 13 reports were reviewed. Factors related to PPA effect, such as basal sympathetic tone, daily dosage, dosage form, and chemical structure of the product, were considered. Data were evaluated using a measure of effect size (d) described by Rosenthal and Rubin (1982) designed to facilitate comparisons across independent clinical studies. Metaanalysis, using clinical results from nearly 2000In the kidney, the proximal renal tubule is the most frequent site of drug-induced damage. Early detection of such damage is difficult and the standard commonly used tests for serum creatinine and urea have relatively low sensitivity and specificityThis study was designed to determine the excretion of 3H-cocaine-derived radioactivity into milk and to compare the blood and tissue concentrations of 3H-cocaine in rat dams and their prog-161 subjects who received a range of doses: placebo, 25 to 50mg immediate release and 75 to 150mg sustained release, suggests that PPA does not pose a unique cardiovascular risk to consumers. ReferenceRosenthal R, Rubin RL. Comparing effect sizes of independent studies. Psychological Bulletin 92: [500][501][502][503][504] 1982 for proximal tubular damage. Among other possible methods, the urinary excretion of N-acetyl glucosaminidase (NAG), expressed as its ratio with urinary creatinine, has been suggested; the results, which form part of a larger study, show the correlation between NAG, serum creatinine and urea, and histopathological changes seen in a series of routine diagnostic biopsies carried out in a hospital renal unit. Results suggest that, in urine samples collected overnight, NAG elevations are closely linked with active damage to proximal tubular cells and reach abnormal levels before creatinine and urea. NAG levels decline with reductions in cell numbers, interstitial scarring and fibrosis, whereas serum creatine and urea levels may at this stage be increased. This emphasises the difference in the functional basis of the respective tests. eny. Soon after birth, each litter was reduced to 8 pups, if necessary by random culling. A single dose of an aqueous solution of 3H-cocaine (100 mg/kg) was administered by gavage to mothers on postpartum days 5 to 7. Dams were allowed to nurse their offspring while the blood and milk concentrations of radioactivity were monitored for up to 24 hours. Radioactivity profiles of blood and milk followed a similar time course, reaching a peak at 6 hours, remaining steady up to 12 hours and declining slowly thereafter. At 24 hours, the mean maternal blood concentrations of 3H-cocaine were 8-fold greater (35.4 vs 4.4 ~gfml) than those of the pup blood. Among the pup tissues examined, the

Toxicity studies with oxamniquine in several laboratory animal species revealed an idiosyncratic sensitivity of rats, females being much more sensitive than males. After single p.o. doses of oxamniquine, rats died up to 14 days after the dose from hepatic failure. At doses near the LD-50, serum transaminases were high and proteins low from 24 h after the dose in females and from 48 h in males; serum and liver triglycerides showed no clear changes. Histologically the livers were characterised by cytoplasmic inclusion bodies, parenchymal necrosis, and bile duct proliferation. Metabolism and pharmacokinetic data were inadequate to explain the sex-dependency of this toxicity, but tissue distribution studies with carbon-14 labelled oxamniquine showed that 72 h after a given dose livers of female rats retained more label than males, and that little of this was due to unchanged drug.