4-Ethylbiphenyl was studied for oral toxicity in rats in a reproduction/developmental toxicity screening test at doses of 0, 10, 30, 100 and 300 mg/kg/day (12 animals of each sex per group).
In the males, lower body weights were noted in the 100 and 300 mg/kg groups and lower food consumption and higher relative testis weights in the 300 mg/kg group. No changes caused by the substance were evident regarding general signs, body weight, necropsy, sperm examination, or histopathological examination.
In the females, 4 animals died in the 300 mg/kg group. Hypothermia, decrease in locomotor activity, piloerection, soiled fur, and loose stool were also noted in the 300 mg/kg group, with reduction in body weight before mating and during the pregnancy and lactation periods. Transiently lowered food consumption was also noted in the 100 mg/kg group before mating, and lowered food consumption in the 300 mg/kg group before mating and during the pregnancy period. Changes caused by the substance were not noted in organ weights or on histopathological examination.
The NOELs for repeat dose toxicity are considered to be 30 mg/kg/day for both sexes.
Regarding reproductive/developmental toxicity, gestation length was prolonged in the 100 and 300 mg/kg groups. The number of implantation sites was low, and the implantation rate and gestation index tended to be lower in the 300 mg/kg group than in the controls. However, no changes caused by the substance were noted in terms of the copulation index, delivery conditions, nursing conditions, fertility index, or number of corpora lutea.
The NOELs for reproductive performance are considered to be 300 mg/kg/day for males, and 30 mg/kg/day for females.
Regarding the pups, the number of stillbirths was elevated, and the birth and live birth indices were reduced with a tendency for the number of pups born and the viability index to be lowered in the 100 mg/kg group. The number of stillbirths was increased, and the number of pups and live pups born, delivery index, birth index, live birth index, and viability index were lowered in the 300 mg/kg group. The body weight of each sex on day 0 of lactation was lower or tended to be lower than the control in the 300 mg/kg group.
The NOEL for pup development is considered to be 30 mg/kg/day.
| Purity | : | 99.71 % |
| Test species/strain | : | Rat/Crj:CD(SD)IGS |
| Test method | : | OECD Test Guideline 421 |
| Route | : | Oral(gavage) |
| Doses | : | 0(vehicle), 10, 30, 100, 300 mg/kg/day |
| Number of animals/group | : | Males, 12; females, 12 |
| Vehicle | : | Corn oil |
| Administration period | : | Males, 50-52 days Females, from 14 days before mating to day 3 of lactation |
| Terminal kill | : | Males, day 51-53 Females, day 4 of lactation |
| GLP | : | Yes |
Test results:
In the males, lowered body weights were noted in the 100 and 300 mg/kg groups, along with reduced food consumption and high relative testis weight in the 300 mg/kg group. No changes caused by the substance were noted in terms of general signs, body weight, necropsy, sperm examination, or histopathological examination.
In the females, 4 animals died in the 300 mg/kg group. Hypothermia, decrease in locomotor activity, piloerection, soiled fur, and loose stool were also noted in the 300 mg/kg group. Lowering of body weight was noted in the 300 mg/kg group before mating and during the pregnancy and lactation periods. Transiently lowered food consumption was noted in the 100 mg/kg group before mating, and lowered food consumption in the 300 mg/kg group before mating and during the pregnancy period. Changes caused by the substance were not noted in organ weights or an histopathological examination.
The NOELs for repeat dose toxicity are considered to be 30 mg/kg/day for both sexes.
<Reproductive and developmental toxicity>
Gestation length was prolonged in the 100 and 300 mg/kg groups. The number of implantation sites was lower, and the implantation rate and gestation index tended to be lower than the control in the 300 mg/kg group. However, no changes caused by the substance were noted regarding the copulation index, delivery conditions, nursing conditions, fertility index, or number of corpora lutea.
The NOELs for reproductive performance are considered to be 300 mg/kg/day for males, and 30 mg/kg/day for females.
Regarding the pups, the number of stillbirths was elevated, and the birth and live birth indices were reduced, while the number of pups born and viability index tended to be lowered in the 100 mg/kg group. The number of stillbirth was higher, and the numbers of pups and live pups born, delivery index, birth index, live birth index, and viability index were decreased in the 300 mg/kg group. The body weight of each sex on day 0 of lactation was lower or tended to be lower than the control in the 300 mg/kg group.
The NOEL for pup development is considered to be 30 mg/kg/day.
| 1) | The test was performed by Nihon Bioresearch Inc., 6-104 Majima, Fukuju-cho, Hashima, Gifu, 501-6251, Japan. Tel +81-58-392-6222 Fax +81-58-392-1284 |