3,9-dicyclohex-3-enyl-2,4,8,10-tetraoxaspiro[5.5]undecane

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Principles of method if other than guideline:

3,9-Di-3-cyclohexen-1-yl-2,4,8,10-tetraoxaspiro[5,5]undecane was administered by gavage to 5 male and 5 female Wistar rats per dose group in daily doses of 0, 100, 300 or 1000 mg/kg body weight for 29 days.
The animals were regularly observed and weighed and food and water intakes were determined. In addition, clinical pathology of blood samples was performed. Organs and tissues were subjected to gross and histopathological investigation. Functional observational battery (FOB) and motor and locomotor activity measurements (MA/LMA) were done.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3,9-dicyclohex-3-enyl-2,4,8,10-tetraoxaspiro[5.5]undecane

EC Number:

229-542-8

EC Name:

3,9-dicyclohex-3-enyl-2,4,8,10-tetraoxaspiro[5.5]undecane

Cas Number:

6600-31-3

Molecular formula:

C19H28O4

IUPAC Name:

3,9-bis(cyclohex-3-en-1-yl)-2,4,8,10-tetraoxaspiro[5.5]undecane

Test material form:

other: solid

Details on test material:

Test Item: 3,9-Di-3-cyclohexen-1-yl-2,4,8,10-tetraoxaspiro[5,5]undecane
Synonym: Vulkazon AFS, Vulkazon AFS/LG
CAS No.: 6600-31-3
Trade Name Vulkazon AFS
Molecular Formula C19H28O4
Chemical Name 3,9-Di-3-cyclohexen-1-yl-2,4,8,10-tetraoxaspiro[5,5]undecane
Molecular Mass 320.4
Purity: 96.7% (not considered for formulation)
Appearance: brownish solid
Storage: Room temperature

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Solutol HS 15®/ Ethanol/ Tap Water (4:1:5 v/v/v)

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 100, 300 or 1000 mg/kg body weight
Basis:
other: nominal

No. of animals per sex per dose:

5 male and 5 animals/dose

Control animals:

yes, concurrent vehicle

Results and discussion

Effect levels

Dose descriptor:

NOEL

Effect level:

300 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: based on effects on body weight development and food consumption (males) at 1000 mg/kg

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

There were no intercurrent deaths up to 1000 mg/kg.

Daily in cage and detailed weekly clinical observations including OFO revealed no findings induced by treatment with the test item. In addition, functional observations gave no indication of test item-related effects up to 1000 mg/kg. During Motor and Locomotor activity examination only in 1000 mg/kg females slightly reduced motor/locomotor activity was seen.

Body weights were unaffected up to 300 mg/kg body weight in males and in all female dose groups. At 1000 mg/kg body weights of male rats were transiently significantly reduced.

The test item had no effect on food and water intake of all treated females and of low and mid dose males. High dose males consumed more food and water related to body weight.

Hematology revealed no changes of red and white blood count or of blood coagulation.

Clinical chemistry and histopathology were not indicative of hepato- and nephrotoxicity up to 1000 mg/kg. Slightly higher liver weights of high dose rats are hence considered to be rather a chance result.

Slightly decreased thymus weights (mid and high dose males) are considered a chance result due to missing dose relation and correlating histopathological findings.

Organ weight measurements revealed no changes beyond those described.

In the whole dose range there were no test item-related morphological changes in all organs/ tissues investigated.

Applicant's summary and conclusion

Executive summary:

3,9-Di-3-cyclohexen-1-yl-2,4,8,10-tetraoxaspiro[5,5]undecane was administered by gavage to 5 male and 5 female Wistar rats per dose group in daily doses of 0, 100, 300 or 1000 mg/kg body weight for a period of 29 days. As vehicle Solutol HS 15®/ Ethanol/ Tap Water (4:1:5 v/v/v, = vehicle) in a dosing volume of 10 ml/kg body weight was used.

The animals were regularly observed and weighed and food and water intakes were determined. In addition, clinical pathology of blood samples was performed. Organs and tissues were subjected to gross and histopathological investigation. Functional observational battery (FOB) and motor and locomotor activity measurements (MA/LMA) were done.

Test substance formulations were stable during the period use. Content checks during the study revealed correct concentrations of the test substance in the formulations used.

There were no intercurrent deaths up to 1000 mg/kg.

Daily in cage and detailed weekly clinical observations including OFO revealed no findings induced by treatment with the test item. In addition, functional observations gave no indication of test item-related effects up to 1000 mg/kg. During Motor and Locomotor activity examination only in 1000 mg/kg females slightly reduced motor/locomotor activity in interval 2-5 were seen.

Body weights were unaffected up to 300 mg/kg body weight in males and in all female dose groups. At 1000 mg/kg body weights of male rats were transiently significantly reduced.

The test item had no effect on food and water intake of all treated females and of low and mid dose males. High dose males consumed more food and water related to body weight.

Hematology revealed no changes of red and white blood count or of blood coagulation.

Clinical chemistry and histopathology were not indicative of hepato- and nephrotoxicity up to 1000 mg/kg. Slightly higher liver weights of high dose rats are hence considered to be rather a chance result.

Slightly decreased thymus weights (mid and high dose males) are considered a chance result due to missing dose relation and correlating histopathological findings.

Organ weight measurements revealed no changes beyond those described.

In the whole dose range there were no test item-related morphological changes in all organs/ tissues investigated.

Under the conditions described the no-observed-adverse-effect-level (NOAEL=NOEL) for 3,9-Di-3-cyclohexen-1-yl-2,4,8,10- tetraoxaspiro[5,5]undecane is set at 300 mg/kg based on effects on body weight development and food consumption (males) at 1000 mg/kg.