4-sec-butyl-2,6-di-tert-butylphenol

Toxicity to reproduction

Administrative data

Endpoint:

screening for reproductive / developmental toxicity

Type of information:

experimental study

Adequacy of study:

supporting study

Results and discussion

Any other information on results incl. tables

Summarization

4-sec-butyl-2,6-Di-tert-butylphenol is mandatorily given to Sprague-Dawley male SPF rats for 14 days before mating and over the mating period till the day before anatomic examination (42 days) and to the females for 14 days before mating and over pregnancy duration till the 4thbreast feeding day (42-46 days) by oral dose by 0 (control group: corn oil), 12, 60 and 300mg/kg/day, and the outlines of repeated dosing toxicity and reproductive and developmental toxicity are discussed.

 

Repeated dosing toxicity

In the 300mg/kg/day dose group, there shows the phenomenon like low body temperature and emaciation in the last phase of pregnancy duration, and occur two cases of death. Through pathological examination, low nutrition condition, liver enlargement, cecal dilatation, thymus miniaturization are seen by naked eyes and two cases of implantation are recognized. Histologically, centrilobular liver cell hypertrophy, empty centrilobular liver cell, bile duct epithelial cell hypertrophy and thymic atrophy are seen.

In the 300mg/kg/day dose group, loose stools can be seen everywhere in case of males and females, the matrixes subject to loose stool, skin etiolation, emaciation, low body temperature and bleeding from anus are seen during breast breeding period, and in case of these matrixes, all the babies fed died after breast-feeding for 2 days. In case of the males in the 300mg/kg/day dose group, the body weight is lower than the control group 2 weeks after dose and it develops, the increase of body weight during dosing period shows to have low value. Within the female animals in the 300mg/kg/day dose group whose feeding babies all died, low nutrition condition, skin etiolation, cecaldilatation, kidney darkening and thymus miniaturization, dark red nest in eye balls, Harder’s gland darkening, lung darkening, miniaturization of sublingual gland and submaxilary, dark red nest in forestomach, miniaturization of spleen are seen by naked eyes, and histologically, bile duct epithelial cell hypertrophy of liver, centrilobular liver cell emptying and necrosis of centrilobular liver cell, ulcers of forestomach and squamous epithelial hyperplasia, acute tubule necrosis of kidney, inflammatory cell infiltration of mesenchyme and glomerular thrombus, thymicatrophy, diffuse mucosa hyperplasia of cecum, increase of porphyrin of Harder’s gland, submandibular gland atrophy, splenicatrophy, cellular infiltration and thrombus of lung, and local hemorrhage in the retina of eye balls are seen. In case of the animals in the 300kg/mg/day dose group which are planned to be killed, cecal dilatation are seen in males and enlargement of liver are seen in females by naked eyes, however, histologically, centrilobular liver cell hypertrophy and bile duct epithelial cell hypertrophy are seen in the livers of males and females.

The weight of liver is recognized to have a high value in males in the 60mg/kg dose group and histologically, centrilobular liver cell hypertrophy are seen in livers of males and females.

The impact of the dose of test substance is not seen in the 12mg/kg dose group.

 

Reproductive and developmental toxicity

In case of parent animals, the dose of test substance is recognized to have no impact on the sexual cycle, the days required till mating, mating rate, fertility rate, conception rate and furthermore, pregnancy duration, corpora lutea count, implantation trace count and implantation rate, however, in the 300mg/kg dose group, the birth rate, number of baby born and inclination of low value in birth rate, inclination of high value in death rate of babies are recognized.

For the babies born, the survival rate 4 days after birth is recognized to be of low value inclination in 300mg/kg dose group, it is not recognized to have impact on the sex ratio of day 0 and day 4 after birth, outside appearance observation of day 0 after birth, what are seen by anatomic examination of day 4 after birth, the weights of males and females of day 0 and day 4 after birth.

From these results, it is judged that the repeated dosing toxicity and no toxic dose for both males and females of test substance are both 12mg/kg, the no-impact dose and no toxic dose for reproductive and developmental toxicity for both male parent animals and baby animals are beyond 300mg/kg, and the no-impact dose and no toxic dose against reproductive and developmental toxicity for female animals are both 60mg/kg.