Fig. 1 Mean body weight changes of male rats administered cefaclor orally on fertility study
Table. 1 Serum biochemical analysis in male rats administered cefaclor orally on fertility study The values were expressed as mean } S.D. * P <0.05, ** P <0.01 Significant difference from control (STUDENT's t-test) + P <0.05, ++ P <0.01 Significant difference from control (ASPIN-WELCH's t-test) Table. 2 Relative organ weight of male rats administered cefaclor orally on fertility study The values were expressed as mean } S.D. * P <0.05, ** P <0.01 Significant difference from control (STUDENT's t-test) + P <0.05, ++ P <0.01 Significant difference from control (ASPIN-WELCH's West) Cecum + : Cecum with contents Cecum - : Cecum without contents
Fig. 2 Mean body weight changes of female rats administered cefaclor orally on fertility study Table. 3 Absolute organ weight of pregnant rats administered cefaclor orally on fertility study The values were expressed as mean } S.D. * P <0.05, ** P <0.01 Significant difference from control (STUDENT's t-test) + P <0.05, ++ P <0.01 Significant difference from control (ASPIN-WELCH's t-test) Cecum + : Cecum with contents Cecum - : Cecum without contents
Table 4 Mating and fertility ratio of rats administered cefaclor orally on fertility study * P <0.05, ** P < 0.01 Significant difference from control (STUDENT's t test) + P <0.05, ++ P <0.01 Significant difference from control (ASPIN-WELCH's t test) Significant difference from control (WILCOXON's rank sum test) Significant difference from control (CHI-SQUARE test)
Table 5 Effect of oral administration of cefaclor on rat fetuses on fertility study * P <0.05, ** P <0.01 Significant difference from control (STUDENT's t-test) + P <0.05, ++ P <0.01 Significant difference from control (ASPIN-WELCH's t-test) Significant difference from control (WILCOXON's rank sum test) Significant difference from control (CHI-SQUARE test)
Table 6 Effect of oral administration of cefaclor on skeletal development in rat fetuses on fertility study * P <0.05, ** P <0.01 Significant difference from control (STUDENT's t-test) + P <0.05, ++ P <0.01 Significant difference from control (ASPIN-WELCH's t-test) Significant difference from control (WILCOXON's rank sum test) Significant difference from control (CHI-SQUARE test)
Fig. 3 Mean body weight changes of pregnant and lactating rat dams administered cefaclor orally on perinatal and postnatal study Table 7 Relative organ weight of reared darns administered cefaclor orally on perinatal and postnatal study Sianificant difference from control at P <0.05 (STUDENT's t-test) Significant difference from control at P < 0.01 Significant difference from control at P <0.05 (ASPIN-WELCH's t-test) (WILCOXON's rank sum test) Significant difference from control at P <0.01 (CHI-SQUARE test) Cecum +: Cecum with contents Cecum -: Cecum without contents
Table 8 Effect of oral administration of cefaclor on rat newborns on perinatal study Significant difference from control (STUDENT's t-test) Significant difference from control (ASPIN-WELCH's t-test) Significant difference from control (WILCOXON's rank sum test) Significant difference from control (CHI-SQUARE test) 1) Birth rate : No.of No.of newborns/ implants 2) Suckling rate : No.of Fl pups at 4th day before killed No.of newborns at birth / 3) Weanling rate : No.of Fl pups at 21st day/ No.of Fl pups at 4th day after killed
Table 9 Effect of oral administration of cefaclor on postnatal development of F1 rats on perinatal and postnatal study Significant difference from control (STUDENT's t-test) Significant difference from control (ASPINMELCH's t-test) Significant difference from control (WILCOXON's rank sum test) Significant difference from control (CHI-SQUARE test)
Table 10 Mating and fertility ratio of newborns (F1) on perinatal and postnatal study Significant difference from control (STUDENT's t-test) Significant difference from control (ASPIN-WELCH's t-test) Significant difference from control (WILCOXON's rank sum test) Significant difference from control (CHI-SQUARE test)
Table 11 Effect of cefaclor on rat fetuses of Fl (F2) on perinatal and postnatal study * P <0.05, ** P <0.01 Significant difference from control (STUDENT'S t-test) + P <0.05, ++ P <0.01 Significant difference from control (ASPIN-WELCH'S t-test) Significant difference from control (WILCOXON'S rank sum test) Significant difference from control (CHI-SQUARE test)
Table 12 Effect of cefaclor on rat newborns of Fl (F2) on perinatal and postnatal study * P <0.05, ** P <0.01 Significant difference from control (STUDENT'S t-test) + P <0.05, ++ P <0.01 Significant difference from control (ASPIN-WELCH'S t-test) Significant difference from control (WILCOXON'S rank sum test) Significant difference from control (CHI-SQUARE test)
2) WILSON, J. G. & J. WARKANY : Methods for administering agents and detecting malformations in experimental animals. Teratology-Principles and Techniques. pp.262 3) DAWSON, A. B.: A note on the staining of the skeleton of cleared specimens with arizarin red S. Stain Technol. 1: 123 `124, 1926 4) WILLIAM, C. B.: Early age differences in maze performance in the albino rat. J. Genetic Psychology. 56: 439 `453, 1940 5) HANASONO, G. K.; C. H. DRAPER, T. G. LEWIS, J. K. MARKHAM & D. M. MORTON : Personal communication.
REPRODUCTION STUDIES ON CEFACLOR (CCL) (2) FERTILITY STUDY AND PERINATAL-POSTNATAL STUDY IN RATS TADAKAZU FURUHASHI, AKIRA NOMURA, MASAMI UEHARA, EMIKO KOMURO and HIROSHI NAKAYOSHI Nomura Research Institute Fertility study and peni- and postnatal study on cefaclor (CCL) were carried out using male and female Sprague-Dawley rats (SLC-SD). Cephalexin (CEX) was also examined as a reference compound in either experiment. 1) Fertility study CCL was orally administered daily for 63 days to male rats starting at 6 weeks of age at the doses of 250, 500, 1,000 and 2,000 mg/kg/day. The compound was also administered to mature female rats for 14 days at the same dose levels. After these administrations, male and female rats of the same dosage group were randomly cohabitated for mating. Administration of the compound continued during this period and further until day 7 of pregnancy in mated female rats. CEX was also administered orally to male and female rats at the dose of 2,000 mg/kg/day. By the consecutive administration of CCL, decrease in body temperature, diarrhea and growth retardation were observed in some rats, especially in the highest dosage group. However, mating abilites were normal in either male or female rats, and no abnormalities were observed in ova implantation, fetal growth and viability. Neither external, skeletal nor visceral malformation was observed in all fetuses examined. 2) Peri- and postnatal study CCL or CEX was orally administerd daily from day 17 of pregnancy until day 20 of lactation at the same doses used in fertility study. Maternal death was observed during the administration period in 1 and 4 dams given 2,000 mg/kg/day of CCL and CEX, respectively. The other pregnant rats administered CCL consecutively delivered normally their offsprings and nursed them thereafter without any troubles. The growth, general behavior and reproductive performances of the F1 male and female rats were normal in all groups tested and no abnormalties were observed in F2 fetuses and newborns. These results indicate that CCL has no adverse effect on reproductive ability of rats and on any functions in the next generations at the doses of 1,000 mg/kg/day or less.