Decane-1,10-diol

Endpoint summary

Description of key information

A 4-week toxicity study is available on 1,6-hexanediol, an analogue substance of 1,10 -decanediol.

The oral administration (by gavage) of 1,6-hexanediol in dose levels of 100, 400 and 1000 mg/kg bw/d to Wistar rats caused no substance-related effects.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June to October 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1981

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Limit test:

no

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Dr Karl Thomae GmbH, Biberach/Riss, FRG

- Age at study initiation: 42 day old
- Weight at study initiation: 183 g (males), 147 g (females)
- Fasting period before sacrifice
- Housing: singly
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days

DETAILS OF FOOD AND WATER QUALITY:

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24 °C
- Humidity (%): 30-70%
- Air changes (per hr): "fully air-conditioned room"
- Photoperiod (hrs dark / hrs light): 12/12

Route of administration:

oral: gavage

Details on route of administration:

Volume of administration: 10 ml/kg bw

Vehicle:

water

Details on oral exposure:

The test substance was administered as a solution in doubly distilled water.

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

Investigations to characterize the test substance in respect of purity and homogeneity were carried out before the start if the study.
The stability of the test substance over a period of 17 months was proven. Due ti the short study duration a reanalysis after the experiemental phase of the study was not considered to be necessary.
The preparations were not stored for longer than 4 hours.
At the start of the study, one sample of each concentration was sent to the analytical laboratory for determination of the correctness of the concentration of the test preparations.

Duration of treatment / exposure:

28 days

Frequency of treatment:

daily

Dose / conc.:

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

Dose / conc.:

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

Dose / conc.:

1 000 mg/kg bw/day (actual dose received)

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: based on acute data

Positive control:

no

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes, twice a day (one day on Saturdays and Sundays)
DETAILED CLINICAL OBSERVATIONS: Yes, once week
BODY WEIGHT: Yes at day 0, then weekly
FOOD CONSUMPTION : yes, weekly
OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: at the end of the styudy, in the morning from non-fasted
- Anaesthetic used for blood collection: no data
- Animals fasted: Yes
- How many animals: 5 animals/group

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood:t the end of the styudy, in the morning from non-fasted
- Animals fasted: Yes
- How many animals: 5 animals/group

URINALYSIS: Yes
- Time schedule for collection of urine: at the end of the study
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes
- How many animals: 5 animals/group

NEUROBEHAVIOURAL EXAMINATION: no
IMMUNOLOGY: no

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes

Other examinations:

no

Statistics:

The data were evaluated statistically on the computer systems of the Department of Toxicology of BASF Aktiengesellschaft.

Clinical signs:

effects observed, non-treatment-related

Description (incidence and severity):

No signs attributable to the applications of the test substance were observed throughout the study period, with the exception of animal No . 19 (dose group 3 - 1000 mg/kg body weight/day), which showed paresis in both hindlimbs from day 17 to the end of the study.
Due to the isolated nature of the finding, it has to be regarded as an incidental one without being substance-related .

Mortality:

no mortality observed

Description (incidence):

No animal died during the course of the study.

Body weight and weight changes:

effects observed, non-treatment-related

Description (incidence and severity):

The slightly decreased body weight (6% lower than the concurrent control value) and the slight depression in body weight gain (about 13 % lower than the concurrent control value) of the high dose males at the end of the study have to be seen in context with the slightly reduced food consumption mentioned before. It is likely that these observations were mainly caused by animal No.19. Therefore, they are not regarded as substance-related effects.
In the female animals of dose groups 1- 3 (100, 400 and 1000 mg/kg) slight to moderate decreases in body weight and body weight gain were found. These findings are considered to be of spontaneous nature because a clear dose-response relationship is missing. This includes also the statistically significantly lower mean body weight of female animals of the 400 mg/kg dose group on study day 28 (about 13 % lower than the concurrent control group values) and the statistically significantly diminished body weight gain of the 400 and 1000 mg/kg dose group females (about 31 % and 25 % lower when compared with the concurrent control group values) at the end of the study.
Body weight and body weight gain developed in dependence on the the respective food consumption values of the dosed and the control animals . Consequently these values were lower than the concurrent control values.
However, the body weight values of the dosed animals are fully in the range of the historical control data. Thus, the observations made for body weight and body weight gain are not regarded as substance related effects.

Food consumption and compound intake (if feeding study):

effects observed, non-treatment-related

Description (incidence and severity):

Food consumption values of the male animals of dose group 3 (1 000 mg/kg body weight) and female animals of dose groups 1 - 3 (100 ; 400 ; 1000 mg/kg body weight) were slightly decreased during the course of the study when compared with the concurrent control values.
The food consumption value of the high dose males on study day 21 was about 8 % lower than the corresponding control value. This finding is probably related to the clear reduction of food consumption in animal No. 19. This animal showed paresis of both hindlimbs from study day 17 to the end of the study. Therefore, the finding of marginally decreased food consumption values of the high dose male animals is regarded to be incidental and not related to the test substance administered .
The reduced food consumption values of female animals of dose groups 1 - 3 are regarded as being of spontaneous nature due to the missing dose-response relationship. Moreover, all food consumption values of the dosed females are fully in the range of the historical control data, whereas the respective values of the concurrent control group are at the upper level of the historical control range.
Thus, the reduced food consumption values of female animals of dose groups 1- 3 in comparison to the concurrent control group values are regarded as being of spontaneous nature and not related to the test substance administration.

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, non-treatment-related

Description (incidence and severity):

No treatment-related changes were observed in the results of hematology examinations of both sexes.
No treatment-related changes were observed in the results of the clotting analyses of both sexes.

There is only one statistically significant intergroup
difference in the results of clinical pathology
testing (Table 009 ; males ; test group 2 ; HCT) . This
finding is considered to be of no toxicological
concern, because it is sporadic, inconsistent, when
compared with the other sex, and lacks dose-response
relationship .

Clinical biochemistry findings:

no effects observed

Description (incidence and severity):

No treatment-related changes were observed in the results of the serum enzyme examinations of both sexes .
No treatment-related changes were observed in the results of blood chemistry examinations of both sexes.

There is only one statistically significant intergroup difference in the results of clinical pathology testing (test group 2 ; HCT) . This finding is considered to be of no toxicological concern, because it is sporadic, inconsistent, when compared with the other sex, and lacks dose-response relationship .

Urinalysis findings:

no effects observed

Description (incidence and severity):

No treatment-related changes were observed in the results of the urinalyses of both sexes.

Behaviour (functional findings):

not examined

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

not specified

Gross pathological findings:

no effects observed

Description (incidence and severity):

No substance-related findings were obtained at pathology.

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

not specified

Histopathological findings: neoplastic:

not examined

Other effects:

not examined

Key result

Dose descriptor:

NOAEL

Effect level:

> 1 000 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Remarks on result:

not determinable due to absence of adverse toxic effects

Critical effects observed:

no

Conclusions:

Under the conditions of this 4-week toxicity study, the oral administration (by gavage) of 1,6-hexanediol in dose levels of 100, 400 and 1,000 mg/kg bw/d to Wistar rats caused no substance-related effects .

Executive summary:

1,6 -hexanediol was administered daily to groups of 5 male and 5 female Wistar rats per dose group by gavage as aqueous solution at doses of 0 (vehicle control), 100, 400 and 1000 mg/kg bw/day for 4 weeks. Vehicle was doubly distilled water.

Food consumption and body weight were determined. The state of health was checked each day. During the weekly waighing the animals were subjected to an additional comprehensive clinical examination. Clinicochemical and hematological examinations and urinalyses were carried out towards the end of the administration period. All animals were assessed by gross pathology, followed by histopathological examinations.

There were no substantial substance-related effects concerning food consumption, body weight, body weight change, clinical, clinicochemical, gross pathological and histopathological observations.

The observed statistical significances for the values of body weight and body weight change towards the end of the study in female rats are regarded as incidental, because of missing dose-response relationship. Furthermore, all of them are lying fully in the range of historical controls and are compared to relatively high values of the concurrent controls. Thus, The observed statistical significances for the values of body weight and body weight change towards the end of the study in female rats are regarded as incidental, because of missing dose-response relationship . Furthermore, all of them are lying fully in the range of historical controls and are compared to relatively high values of the concurrent controls. Under the conditions of this 4-week toxicity study, the oral administration (by gavage) of 1,6-hexanediol in dose levels of 100, 400 and 1,000 mg/kg bw/d to Wistar rats caused no substance-related effects .

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

1 000 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

The study is considered to be reliable with a klimisch score of 1

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

28 -day repeated toxicity study on analogue substance :

1,6 -hexanediol was administered daily to groups of 5 male and 5 female Wistar rats per dose group by gavage as aqueous solution at doses of 0 (vehicle control), 100, 400 and 1000 mg/kg bw/day for 4 weeks. Vehicle was doubly distilled water.

Food consumption and body weight were determined. The state of health was checked each day. During the weekly waighing the animals were subjected to an additional comprehensive clinical examination. Clinicochemical and hematological examinations and urinalyses were carried out towards the end of the administration period. All animals were assessed by gross pathology, followed by histopathological examinations.

There were no substantial substance-related effects concerning food consumption, body weight, body weight change, clinical, clinicochemical, gross pathological and histopathological observations.

The observed statistical significances for the values of body weight and body weight change towards the end of the study in female rats are regarded as incidental, because of missing dose-response relationship. Furthermore, all of them are lying fully in the range of historical controls and are compared to relatively high values of the concurrent controls. Thus, The observed statistical significances for the values of body weight and body weight change towards the end of the study in female rats are regarded as incidental, because of missing dose-response relationship . Furthermore, all of them are lying fully in the range of historical controls and are compared to relatively high values of the concurrent controls.

Under the conditions of this 4-week toxicity study, the oral administration (by gavage) of 1,6-hexanediol in dose levels of 100, 400 and 1,000 mg/kg bw/d to Wistar rats caused no substance-related effects .

Justification for classification or non-classification

Based on the 28-day repeated toxicity study, no adverse effect was observed in rats, no target organ was identified, so no classification is required according to the Regulation EC n°1272/2008.