3,5,5-trimethylhexan-1-ol

Specific investigations: other studies

Administrative data

Endpoint:

biochemical or cellular interactions

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented publication/study report which meets basic scientific principles. However, there is no CAS number given. The exact chemical structure remains therefore unclear and it cannot be excluded that another isomer was used.

Data source

Reference

Reference 1

Reference Type:

publication

Title:

Unnamed

Year:

1984

Reference 2

Reference Type:

secondary source

Title:

Unnamed

Year:

1963

Report date:

1963

Materials and methods

Test guideline

Qualifier:

no guideline required

Deviations:

not applicable

Principles of method if other than guideline:

Mechanistic study comparing the effects of phthalate and adipate esters with the corresponding alcohols

GLP compliance:

not specified

Type of method:

other: in vivo and in vitro

Test material

Test material information

Constituent 1

Reference substance name:

3,5,5-trimethylhexan-1-ol

EC Number:

222-376-7

EC Name:

3,5,5-trimethylhexan-1-ol

Cas Number:

3452-97-9

Molecular formula:

C9H20O

IUPAC Name:

3,5,5-trimethylhexan-1-ol

Details on test material:

Isononanol was obtained from ICI PLC, Wilton, U.K.
However, there as no CAS number was reported the exact chemical structure remains therefore unclear and it cannot be excluded that another isomer was used, i.e. the test material identity remains unclear.

Test animals

Species:

rat

Strain:

other: Alderley Park Wistar-derived

Sex:

male

Administration / exposure

Route of administration:

oral: gavage

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 days

Frequency of treatment:

daily

Post exposure period:

none

Doses / concentrations

Remarks:

Doses / Concentrations:
1 mmol/kg bw/day (= 130 mg/kg bw/day)
Basis:
actual ingested

No. of animals per sex per dose:

5 rats per test group

Control animals:

yes, concurrent vehicle

Results and discussion

Any other information on results incl. tables

Result of in-vivo experiments:

Table 1

	Controls	Isononanol
Body weight gain	118 ± 8	111 ± 11
Liver: body weight ratio x 100	5.21 ± 0.26	5.59 ± 0.25
Testis: body weight ratio x 100	1.00 ± 0.04	1.01± 0.07
Peroxisomes (No. per 504 µm²)	6.1 ± 2.6	7.7 ± 2.6
Catalase (ks/g)	26.1 ±7.0	32.4 ± 2.0
Cholesterol (mg/100 ml)	43 ± 7	136 ± 26
Triglycerides (mg/100 ml)	114 ±23	137 ± 25
Liver histology Incidence of : Slight centrilobular hypertrophy Slight/moderate glycogen vacuolation Slight/moderate centrilobular “fat”  vacuolation	4/10 9/10 6/10	1/5 5/5 1/5

Table 2

Group	Concentration (mM)	Acyl CoA oxidase (nmol NADH/mg/min)	% Control
control	-	0.71 / 0.844 / 0.774	100
Isononanol	0.1	1.159 ± 0.194*	150

 

control	-	0.71 / 0.844 / 0.774	100
Isononanol	0.1	1.159 ± 0.194*	150

Applicant's summary and conclusion

Conclusions:

Not asignable: test substance identity unclear. In a 2-week oral study, rats dosed with 1 mmol/kg 3,5,5-trimethylhexanol showed some liver enlargement but no testicular atrophy, hepatic peroxisome induction, or hypolipidemia

Executive summary:

 Isononanol was administered by gavage for 14 days to male rats (Alderly Park Wistar-derived) at a dose equivalent to 1 mmol/kg/day (i.e, 144 mg/kg bw/day). This dose was selected, because administration of 6000 ppm DEHP (approx. 1 mmol/kg/day) produced hepatocellular tumors.

It could be demonstrated, that isononanol did not induce testicular atrophy, hepatomegaly, peroxisome proliferation or hypolipidaemia, while DEHP did produce liver effects.

It was therefore suggested that the alcohol does not produce the effects that were seen with the corresponding phthalate ester (Rhodes et al., 1984).