Registration Dossier

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

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1984
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

Reference
Name:
Unnamed
Type:
Constituent
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).