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Studies of the oral glucose tolerance test performed at 0900 h and 1400 h have shown a diurnal variation of glucose tolerance in normal rabbits and rats. Similar variable responses in a small series of volunteers have also been demonstrated. Carbohydrate-intolerant animals differ from the normal animals studied in that no morning and afternoon variation of response to a constant oral glucose challenge has been observed. Variation diurne de la tolgrance au glucose oral chez des volontaires et des animaux de laboratoire Rdsums Des 6tudes du test de tol6rance au glucose oral, effcctu6 h 9 h et ~ 14 h out montr6 une variation dinrne de la toldrance au glucose chez des lapins et des rats normaux. On a 6galemeut constat6 des r6ponses variables similaires chez un petit hombre de volontaires. Les animaux intoldrants aux hydrates de carbone, diff6rent des animaux normaux par le fair que l'on n'observe pas chez eux de variation diurne de la r6ponse une charge orale constante en glucose. Tageszeitliche Ver~tnderungen der oralen Glucosetoleranz bei freiwilligen Versuchspersonen und Laboratoriumstieren Zusammenfassung. Untersuchungen der oralen Glucose-Toleranz, die um 9 hund 14 h durchgefiihrt wurden, zeig~cn cine yon der Tageszeit abh/ingige Variation bei normalen Kaninchen und l%atten. Bei einer klcinen Anzahl yon freiwilligen Versuchspersonen lie2en sich ahnliche Unterschiede feststellen. Tiere, die intolerant gegeufiber Kohlenhydraten waren, unterschieden sich yon normalen Tieren dadurch, daI~ bei Belastungeu am Morgen und am Nachraittag keine Differenzeu bei konstanter oraler Glucosebelastung zu beobachten waren.

A battery of in vitro and in vivo tests were conducted on HCFC-141b as a vapour. Bacterial gene mutation assays with Escherichia coli and Salmonella typhimurium were negative in all tester strains. In vitro chromosomal aberration assays were positive on CHO cells but negative on human lymphocytes. Moreover, HCFC-141b was negative in vivo in a mouse micronucleus inhalation assay. On the basis of these data and previously reported genotoxicity testing, HCFC-141b is considered non-genotoxic. Groups of 80 male and 80 female Sprague-Dawley rats were exposed, by inhalation (6 hr/day, 5 days/wk) to vapours of HCFC-141b for 104 wk at target concentrations of 0 (control), 1500, 5000 and 20,000 ppm (increased from 15,000 ppm after 17 wk of exposure). No exposure-related effects of toxicological significance were noted with respect to survival, clinical signs, ophthalmoscopy, haematology, clinical chemistry, urinalysis or organ weight analysis. Reduced food intake and body weight gain were noted in both sexes of the 15,000 ppm group during the first 16 wk; thereafter, body weight gains in all groups were similar although the intergroup differences in body weight remained evident. Reduced food intake persisted in both sexes through wk 52 and in females during the second year of exposure. Treatment-related effects on macroscopic pathology were confined to increased incidences of testicular masses and altered appearance. Microscopic pathology examinations confirmed the testes as the target organ with findings of increased incidences of benign interstitial cell tumours and hyperplasia at 5000 and 20,000 ppm. The no-observable-adverse-effect level (NOAEL) was 1500 ppm. The testicular changes at high exposure levels were considered to be due to a change of the senile hormonal imbalance in geriatric rats and of little significance for the assessment of human health effects.

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