3,5-dihydroxy-2,6,6-tris(3-methylbuten-2-yl)-4-(3-methyl-1-oxobutyl)cyclohexa-2,4-dien-1-one

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Intragastric administration of lupulone. Publication useful for assessment since it contains data for experiments on rats, rabbits, guinea pigs and monkeys. In view of all of these animal experiments having been published, further animal studies are not warranted.

Data source

Reference

Reference Type:

publication

Title:

Toxicology and Pharmacology of Lupulon

Author:

Y-C Chin and HH Anderson

Year:

1950

Bibliographic source:

Arch. int. pharmacodyn (1950) LXXXII, No. 1, pp. 1-15

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Subacute intragastric toxicity was studied in young male rats, with lupulone administered once daily fo 12 days. All surviving animals were sacrificed and specimens were investiagted for pathology. Similar studies were made in rabbits, guinea pigs and monkeys, but no monkey was sacrificed.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

3,5-dihydroxy-2,6,6-tris(3-methylbuten-2-yl)-4-(3-methyl-1-oxobutyl)cyclohexa-2,4-dien-1-one

EC Number:

207-405-3

EC Name:

3,5-dihydroxy-2,6,6-tris(3-methylbuten-2-yl)-4-(3-methyl-1-oxobutyl)cyclohexa-2,4-dien-1-one

Cas Number:

468-28-0

Molecular formula:

C26-H38-O4

IUPAC Name:

Lupulone

Specific details on test material used for the study:

Lupulone was suspended in 6% gum acacia in proper concentrations.

Test animals

Species:

rat

Sex:

male

Details on test animals or test system and environmental conditions:

Tests were also made on rabbits, guinea pigs and monkeys.

Administration / exposure

Route of administration:

other: Intragastric

Duration of treatment / exposure:

12 days

Frequency of treatment:

Once per day

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

150 mg/kg bw/day (actual dose received)

Doses / concentrations 2

Dose / conc.:

300 mg/kg bw/day (actual dose received)

Doses / concentrations 3

Dose / conc.:

450 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

6

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

Stated in the publication: "Only one rat fed 300 mg per kg bw per day died on the twelfth day. Grossly there were no observable lesion in any animal."

Also: "Rats, rabbits, guinea pigs and monkeys tolerated repeated daily intragastric doses for 2 weeks without showing apparent ill effects. The growth of the rats receiving the top two doses was reduced in the second week. Laboratory findings showed no significant changes. The pathologic sections of about half the animals revealed a spotty mononuclear-leukocytic infiltration in the lungs, usually around bronchi and bronchioles."

Effect levels

Key result

Dose descriptor:

dose level: Only one rat fed 300 mg per kg bw per day died on the twelfth day. Grossly there were no observable lesion in any animal. The growth of the rats receiving the top two doses was reduced in the second week. Laboratory findings showed no significant changes.

Effect level:

ca. 300 mg/kg bw/day (actual dose received)

Based on:

act. ingr.

Sex:

male

Basis for effect level:

body weight and weight gain

Target system / organ toxicity

Key result

Critical effects observed:

no

Applicant's summary and conclusion

Conclusions:

The publication shows that rats, rabbits, guinea pigs and monkeys tolerated daily intragastric doses of lupulone for two weeks without showing apparent ill effects.
The dose rate for rats was 1/4, 1/6 and 1/12 of the LD50.