6,6'-di-tert-butyl-4,4'-diethyl-2,2'-methylenediphenol

Specific investigations: other studies

Administrative data

Endpoint:

specific investigations: other studies

Remarks:

anticoagulant properties

Type of information:

experimental study

Adequacy of study:

other information

Study period:

1954

Reliability:

3 (not reliable)

Rationale for reliability incl. deficiencies:

other: Non GLP study which meets basic scientific methods however details on used method and results are not provided in the report.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1954

Report date:

1954

Materials and methods

Test guideline

Qualifier:

no guideline followed

GLP compliance:

no

Type of method:

in vivo

Endpoint addressed:

other: Influence of dietary Vitamin K on prothrobin time

Test material

Test material information

Constituent 1

Reference substance name:

6,6'-di-tert-butyl-4,4'-diethyl-2,2'-methylenediphenol

EC Number:

201-814-0

EC Name:

6,6'-di-tert-butyl-4,4'-diethyl-2,2'-methylenediphenol

Cas Number:

88-24-4

Molecular formula:

C25H36O2

IUPAC Name:

2-tert-butyl-6-[(3-tert-butyl-5-ethyl-2-hydroxyphenyl)methyl]-4-ethylphenol

Test material form:

solid: particulate/powder

Test animals

Species:

rat

Strain:

other: albino rats

Sex:

male

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

42 days (animals receiving diet with Vitamin K)
23 days (animals receiving diet without Vitamin K)

Frequency of treatment:

daily

No. of animals per sex per dose:

10 male animals per treatment

Control animals:

yes, plain diet

Details on study design:

A group of 30 young, male, albino rats was maintained for 2 weeks on a synthetic diet containing 50 ppm menadione as the sole source of vitamin K. Concurrently a group of 30 males was fed the identical diet with the exception that all menadione was omitted. There was no significant difference in either food intake or weight gain between the two groups over this initial period. At the end of this period, the groups were further subdivided:
1. Vitamine K present
A. 10 animals, Controls: no change in diet
B. 10 animals, 1% Antioxidant 425 added to diet
C. 10 animals, 1% Antioxidant 2246 added to diet (results not further discussed here)
1. Vitamine K omitted
A. 10 animals, Controls: no change in diet
B. 10 animals, 1% Antioxidant 425 added to diet
C. 10 animals, 1% Antioxidant 2246 added to diet (results not further discussed here)

Results and discussion

Details on results:

Addition of 1% Antioxidant 425 to the diet in the presence of VItamin K caused a reduction in food consumption and growth rate in comparison to the corresponding controls. In addition, the animals appeared hyper-irritable and exhibited rapid respiration and diarrhea of 1 to 2 weeks duration. None of the animals of this sub-group died; 2 were sacrificed after 22 days feeding and the remainder after 42 feeding. Gross autopsy revealed mild gastrointestinal irritation in 2 cases, and hyperemic kidneys in about half of the group. However, no evidence of bleeding was observed. Prothrombin times and hematocrit values were within normal limits and comparable to those of the controls.
Addition of 1% Antioxidant 425 to the diet in absence of vitamin K resulted in a marked recution of food intake and growth rate. During the second week of feeding of the antioxidant, dyspnea, irritability and diarrhea developed among the animals, and one death occurred on the 9th day. Subsequently, depression, paleness of the ears and tail, and blood about the anal region were observed. Additional deaths occurred; 2 on the 18th day, 1 on the 19th day and 1 on the 21st day. The survivors were sacrificed after 22 to 23 days feeding. Autopsy of the animals sacrificed disclosed vascular congestion of the brain, with small blood clots in the transverse and sagittal sinuses in one case; hemorrhagic arreas about testes, epidimides, and surrounding fatty tissue; clotted blood in the peritoneal cavity; and subcutaneous hemorrhage about the front and hind limbs and in the neck region. Prothrombin times were prolonged in all of the 5 rats sacrificed. In the case of the 3 animals in which hematocrits were obtained, the values were within normal limits.

Applicant's summary and conclusion

Conclusions:

Based on the results of this study it was concluded that Antioxidant 425 does not possess anticoagulant properties.

Executive summary:

Male albino rats were maintained on a synthetic diet containing menadione at a concentration of 50 ppm as the sole source of Vitamin K. The addition of Antioxidant 425 to this diet at a concentration of 1 % (equivalent to approx. 0.63 gm/kg/day) over a period of 42 days resulted in a significant reduction in food intake and weight gain. However, prothrombin times and hematocrit values were not affected. There were no deaths, and no gross evidence of hemorrhagic tendencies. All animals were sacrificed at termination of the period of feeding, and gross autopsy revealed no evidence of internal bleeding. When vitamin K was omitted in the diet, the prothrombin times in the group that received 1% Antioxidant 425 in the diet for 23 days, was prolonged in all animals. Based on the results of this study it was concluded that Antioxidant 425 does not possess anticoagulant properties.