Alcohols, C7-9

Repeated dose toxicity: oral

Administrative data

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Research publication, study well documented, meets generally accepted scientific principles, acceptable for assessment. The liver was the only organ examined microscopically.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1984

Materials and methods

Test guideline

Qualifier:

no guideline required

Principles of method if other than guideline:

Research study to investigate effects on peroxisome perliferation in the rat using only one concentration of the test material which was given by gavage for 14 days. Only the liver was examined microscopically at study termination.

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Alcohols, C6-12

EC Number:

271-642-9

EC Name:

Alcohols, C6-12

Cas Number:

68603-15-6

IUPAC Name:

octan-1-ol

Details on test material:

- Name of test material (as cited in study report): Linevol 79, C6-12 alcohols Type C
- Substance type: technical product
- Physical state: liquid
- Analytical purity: no data
- Impurities (identity and concentrations): no data
- Composition of test material, percentage of components: mainly C7-C9 alcohols
- Isomers composition: no data
- Purity test date: no data
- Lot/batch No.: no data
- Expiration date of the lot/batch: no data
- Stability under test conditions: no data
- Storage condition of test material: no data

Test animals

Species:

rat

Strain:

Wistar

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: ICI
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: individually in steel, screen-bottomed cages
- Diet (e.g. ad libitum): conventional, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

polyethylene glycol

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS: test material dissolved in polyethylene glycol 300


VEHICLE
- Justification for use and choice of vehicle (if other than water): no data
- Concentration in vehicle: 12.8 mg/ml
- Amount of vehicle (if gavage): 10 ml/kg bw/day

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

14 days

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
1 mmol/kg bw/day (128 mg/kg bw/day)
Basis:
actual ingested

No. of animals per sex per dose:

5 males - treatment group
10 males - control group

Control animals:

yes, concurrent vehicle

Positive control:

Diethylhexylphthalate (DEHP)

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: no data, but at least weighed pre-dosing and at study termination

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No data

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: at study termination
- Animals fasted: No data
- How many animals: 5 treated group; 10 control group
- Parameters examined: plasma cholesterol and plasma tryglycerides

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

OTHER: liver homogenised and 15000 X g fraction prepared for enzyme assays for total catalase and cyanide (CN)-insensitive palmitoyl CoA oxidation

Sacrifice and pathology:

GROSS PATHOLOGY: No data
HISTOPATHOLOGY: Yes; only the liver was microscopically examined

Other examinations:

weights of liver and testis

Statistics:

none

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Mortality:

no mortality observed

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

not specified

Food efficiency:

not specified

Water consumption and compound intake (if drinking water study):

not specified

Ophthalmological findings:

not specified

Haematological findings:

not specified

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Description (incidence and severity):

testis and liver only were weighed

Gross pathological findings:

no effects observed

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

not examined

Details on results:

CLINICAL SIGNS AND MORTALITY
No deaths occurred during the study and no clinical signs of toxicity were reported

BODY WEIGHT AND WEIGHT GAIN
Body weight gain was similar in the treated and control groups

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study)
No differences in food consuption were reported

FOOD EFFICIENCY
No differences in food efficiency were reported

CLINICAL CHEMISTRY
Levels of plasma and triglycerides were comparable in the treated and control groups

ORGAN WEIGHTS
Liver:bw ratio and testis:bw ratio were similar in the treated and control animals
[It is usual to evaluate absolute testis weight, rather than relative weight; absolute organ weights not reported.]

GROSS PATHOLOGY
No macroscopic findings were reported

HISTOPATHOLOGY: NON-NEOPLASTIC
Minor histological changes, seen as slight centrilobular hypertrophy and "fat" type vacuolation of the liver were evident in both treated and control animals

OTHER FINDINGS
The test substance had no effect on the enzyme catalase or on peroxisome perliferation

Effect levels

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male

Basis for effect level:

other: only one dose level tested; no effect on a limited range of endpoints (testis or liver weights (relative to body weight), peroxisome proliferation, hepatomegaly or hypolipidaemia)

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

In vivo studies: There were no effects on relative testes weight, relative liver weight showed a slight* significant increase with 3,5,7-trimethyl hexanol. The postive control DEHP showed a clearly significant increase** in relative liver weight. There were no significant changes in testes weight relative to controls. Histopathological examination of the liver revealed no treatment related changes. Only the positive control DEHP showed any peroxisome proliferation or effects on cholesterol or triglycerides and catalase was unaffected by treatment.

In vitro levels of palmitoyl CoA oxidase were increased only in the positive control group (MEHP).

None of the alkanols investigated at dose levels of 1 mmol/kg bw showed any evidence of peroxisome proliferation, hepatomegaly, or hypolipidaemia.

Applicant's summary and conclusion

Conclusions:

In a reliable study, conducted to determine the effects of Linevol 79 (C6-12 alcohols Type C) on the testis and the histology and peroxisome activity in the liver, 128 mg/kg bw/day given to male rats daily for 14 days had no effects on testis or liver weights, peroxisome proliferation, hepatomegaly or hypolipidaemia. For the limited range of endpoints evaluated, an NOAEL of 128 mg/kg bw/day was identified.