Cyclododeca-1,5,9-triene

Specific investigations: other studies

Link to relevant study record(s)

Reference

Reference 1

Endpoint:

biochemical or cellular interactions

Adequacy of study:

other information

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

documentation insufficient for assessment

Principles of method if other than guideline:

details see reference

GLP compliance:

no

Type of method:

in vivo

Endpoint addressed:

basic toxicokinetics

Species:

guinea pig

Route of administration:

dermal

Vehicle:

unchanged (no vehicle)

Details on exposure:

2 ml of 1,5,9-cyclododecatriene were applied to both flanks of guinea  pigs (5 replicates) three times on alternate days. Three series of  control experiments involving a total of 151 untreated animals were  performed.

Control animals:

yes

Details on results:

The epidermis/dermis dry weight ratio was substantially increased, and  there was also an effect on arginase activity:
- epidermis/dermis dry weight ratio (test/control) = 3.8
- arginase activity (test/control) = appr. 2.3

The morphological effect increases with molecular weight of alicyclic 

 hydrocarbons, saturated and unsaturated substances showing similar effects.

Reference 2

Endpoint:

biochemical or cellular interactions

Adequacy of study:

other information

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

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

Qualifier:

no guideline followed

Principles of method if other than guideline:

see reference

GLP compliance:

not specified

Type of method:

in vivo

Endpoint addressed:

basic toxicokinetics

Species:

mouse

Strain:

other: ICR/Ha mice

Sex:

female

Details on test animals or test system and environmental conditions:

Age: 7 weeks
Number: 5-10 animals per group

Route of administration:

oral: feed

Details on exposure:

Control: diet
TREATMENT
- 30 or 50 µmol/g in diet for 2 weeks

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

2 weeks

Frequency of treatment:

test item in feed

Dose / conc.:

30 other: µmol/g

Remarks:

in diet (nominal concentration)

Dose / conc.:

50 other: µmol/g

Remarks:

in diet (nominal concentration)

No. of animals per sex per dose:

Number: 5-10 animals per group

Control animals:

yes, concurrent no treatment

Examinations:

EXAMINATIONS
- Removal and homogenization of liver, forestomach, and mucosa from small  bowel
- GST activity determination using 1-chloro-2,4-dinitrobenzene as  substrate

Details on results:

None of the compounds elicited increased GST activity in the forestomach.  C6 ring compounds showed no significant effect. C12 ring compounds were  more effective than C8 ring compounds with a decrease in activity in the  order: unsaturated > epoxide > alcohol > saturated. With trans-trans-cis-1,5,9-cyclododecatriene as test substance, the GST  activity in the livers was increased 3.79-, 3.78- and 3.82-fold,  respectively, in three experiments. The increases in the intetinal GST  activity were of similar magnitude.

-----------------------------------------------------------
Test compound          Liver              Small Bowel Mucosa
                    Specific Activity      Specific Activity
------------------------------------------------------------
None                1.96 +- 0.16           0.61 +- 0.04
Cyclododecatriene   7.42 +- 0.53*          2.77 +- 0.29*

None                2.40 +- 0.10           0.65 +- 0.01
Cyclododecatriene   9.06 +- 0.04*          1.74 +- 0.15*

None                1.39 +- 0.05           0.27 +- 0.01
Cyclododecatriene   5.31 +- 0.23*          1.10 +- 0.09*
     * = p <0.005

Description of key information

1984: No guideline followed; pre-GLP; 5-10 ICR/Ha mice; 30 and 50 µmol/g diet; GST activity in liver and intestinal mucosa enhanced (K2)

1971: No guideline followed; pre-GLP; Guinea pigs; undiluted test substance; arginase activity was increased (K4)

Additional information

In an in vivo study using guinea pigs, morphological changes and alterations of the epidermal arginase activity were investigated. The term arginase was used for the soluble enzyme L-arginase amidinohydrolase or L-arginase ureahydrolase. Two ml of the test substance were applied to both flanks of guinea pigs (5 replicates) three times on alternate days. Three series of control experiments involving a total of 151 animals were performed. The epidermis/dermis dry weight ratio was substantially increased, and there was also an effect on arginase activity; epidermis/dermis dry weight ratio (test/control) was 3.8 and arginase activity (test/control) was approximately 2.3 (1971, K4). 

In an in vivo study using female ICR/Ha mice, effects on glutathione S-transferase (GST) activity in the liver, intestinal mucosa, and the forestomach of exposed animals were determined. Therefore, females were assigned to groups of 5-10 mice. The control group received concurrent feed without the test compound. Treatment groups were divided into low and high dose, i.e. 30 and 50 µmol/g of the test substance in the diet. The duration of exposure was two weeks. After treatment, mice were sacrificed and livers, forestomach, and the mucosa from the small bowel removed. With trans-trans-cis-1,5,9-cyclododecatriene as test substance, the GST activity in livers was increased 3.79-, 3.78-, and 3.82-fold, respectively, in three experiments. The increased in the intestinal GST activity were of similar magnitude. No significant differences in the activity of GST in the forestomach of experimental animals was observed compared to the control (1984, K2).