CD rats; 10/sex/group (F0); 15/sex/group (F1); administration in diet during premating, mating, gestation, lactation; 1000, 3000, 9000 ppm (70, 200, 650 mg/kg bw/day for males and 100, 300, 950 mg/kg bw/day for females)
F1 animals were initiated in a 90 day feeding study

1000 ppm (70 mg/kg bw/day for males and 100 for mg/kg bw/day for females) based on reduced body weight gain

NOAEL reproductive performance and developmental effects:
1000 ppm based on reduced bo dy weight gain

At 3000 and 9000 ppm: reduction in body weight gain

Reproduction and offspring:

At 3000 and 9000 ppm: slightly decreased body weight gain

CD rats; 10/sex/group (F0); 15/sex/group (F1); administration in diet during premating, mating, gestation, lactation; 100, 250, 500, 750, 1000 ppm (5,15, 30, 50, 60 mg/kg bw/day for males and 10, 25, 50, 75, 100 mg/kg bw/day for females)
F1 animals were initiated in a 90 day feeding study

1000 ppm (60 mg/kg bw/day for males and 100 mg/kg bw/day for females)

NOAEL reproductive performance and developmental effects: 1000 ppm

Sprague-Dawley rats; 25/sex/group (F0, F1, F2); administration by gavage during premating, mating, gestation, lactation; 0.2, 2, 20, 200 µg/kg bw/day

200 µg/kg bw/day

NOAEL reproductive performance and developmental effects: 200 µg/kg bw/day

Sprague-Dawley rats; 30/sex/group (F0, F1, F2, F3); administration in the diet during premating, mating, gestation, lactation; 0.15, 0.3, 4.5, 75, 750, 7500 ppm (0.001, 0.02, 0.3, 5, 50, 500 mg/kg bw/day for males and females)

75 ppm (5 mg/kg bw/day) based on decreased body weight gain

At 750 and 7500 ppm: moderately to strongly decreased body weight gain (up to 25 %) for F0, F1, F2 parents and F3 retained adults At 7500 ppm only: commonly reduction of absolute organ weights while relative organ weights were increased or unchanged; increased incidences of renal tubular degeneration in kidneys and chronic hepatic inflammation

At 7500 ppm: reduction in implantations and total and live pups/litter at birth for F1, F2 and F3; reduced body weight gain of offspring during lactation beginning on PND 7 for F1, F2 and F3; delayed acquisition of vaginal patency and preputial separation for F1, F2 and F3 offspring considered secondary to decreased body weights (delayed preputial separation also at 750 ppm in F1, but not F2 or F3); reduction in absolute and relative paired ovary weights in F1, F2 and F3

CD-1 mice;

Task 1: preliminary toxicity study (not discussed here);

Task 2: continous breeding phase (controls: 20/sex/group, dosed: 10/sex/group);

Task 3: crossover mating trial (controls and high dose animals only; 17-19/sex/group);

Task 4: reproductive assessment of offspring taken from Task 2 (controls: 40/sex/group, dosed: 20/sex/group); administration in the diet during premating, mating, gestation, lactation; 0.25, 0.5, 1 % in the diet

uptake according to NTP report: 437.5, 875, 1750 mg/kg bw/day

uptake according to EC RAR: 300, 600, 1200 mg/kg bw/day for males and 325, 650, 1300 mg/kg bw/day for

females

< 0.25 % based on histopathological findings in the liver and kidneys of males and females (assessed and found in Task 3 and 4)

NOAEL reproductive performance and developmental effects: 0.25 % based on reduced numbers of litter/pair, litter size and number of live pups/litter (assessed in Task 2, 3 and 4; found in Task 2 and 3)

Task 2: Parental

At 1 %: decreased postpartum body weight of dams (body weights were taken at specified intervals without considering pregnancy status; no assessment of organ weight or histopathology)

Task 2: Reproduction and offspring

At 0.5 and 1 %: reduced numbers of litter/pair, litter size and number of live pups/litter

At 1 %: increased pup lethality in F1 animals which were used in Task 4

Task 3: Parental (only controls and 1 % group tested)