Fatty acids, C18-unsaturated, 1,6 Hexanediol Diester

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:

27 September - 07 November 1993

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Sensory reactivity to stimuli, assessment of grip strength and motor activity assessment was not conducted.

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1996

Reference 2

Reference Type:

secondary source

Title:

Dibutyl adipate CAS N°: 105-99-7

Author:

OECD

Year:

1996

Bibliographic source:

SIDS Initial Assessment Report for SIAM 4; Tokyo, Japan, 20-22 May 1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

other: Guidelines for 28-Day Repeat Dose Toxicity Test of Chemicals (Japan)

Deviations:

no

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

yes

Remarks:

Sensory reactivity to stimuli, assessment of grip strength and motor activity assessment was not conducted.

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Dibutyl adipate

EC Number:

203-350-4

EC Name:

Dibutyl adipate

Cas Number:

105-99-7

Molecular formula:

C14H26O4

IUPAC Name:

dibutyl adipate

Details on test material:

- Name of test material (as cited in study report): Dibutyl adipate
- Analytical purity: 99.8%

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories Japan, Inc., Yokohama, Japan
- Age at study initiation: 5 weeks
- Weight at study initiation: 131 - 155 g
- Fasting period before study: No
- Diet: MF by Oriental Yeast Co., Ltd., Itabashi-ku, Japan, ad libitum
- Water: filtered and UV-irradiated tap water, ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 40 - 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

VEHICLE
- Amount of vehicle: 5 mL/kg

Analytical verification of doses or concentrations:

no

Duration of treatment / exposure:

28 days

Frequency of treatment:

once daily, 7 days/week

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

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

Doses / concentrations 2

Dose / conc.:

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

Doses / concentrations 3

Dose / conc.:

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

No. of animals per sex per dose:

6 (main study)
6 (satellite control and high-dose groups)

Control animals:

yes, concurrent vehicle

Details on study design:

- Post-exposure recovery period in satellite groups: 14 days

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Once a week

BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 7, 15, 21, 28 during treatment, days 35 and 42 during recovery time

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/animal/day: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Day 29 and 43
- Anaesthetic used for blood collection: Yes (Sodium thiopental)
- Animals fasted: No
- How many animals:
6 (main study)
6 (satellite control and high-dose groups)
- Examined parameters: red blood cell (RBC), hemoglobin, hematocrit, mean corpuscular volume (MCV), mean corpuscular hemoglobin (MCH), mean corpuscular hemoglobin concentration (MCHC), white blood cells (WBC), platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), differential count of leukocytes (neutrophils, eosinophils, basophils, monocytes, lymphocytes)


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Day 29 and 43
- Animals fasted: No
- How many animals: 6 (main study)
6 (satellite control and high-dose groups)
- Examined parameters: total protein, albumin, albumin/globulin ratio (A/G ratio), blood urea nitrogen (BUN), creatinine, glucose, total cholesterol, triglycerides, alkaline phosphatase (ALP), alanine aminotransferase, aspartate aminotransferase, gamma-glutamyltransferase, inorganic phosphor, Ca, Na, K, Cl

URINALYSIS: Yes
- Time schedule for collection of urine: 3 week after commencement of treatment
- Metabolism cages used for collection of urine: No
- Animals fasted: No
- Examined parameters: pH, protein, glucose, ketones, bilirubin, occult blood, urobilinogen

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes, control and high dose group

Statistics:

Barlett's test, Dunett's test, Scheffe's test, Kruskal-Wallis test and chi-square test.

Results and discussion

Results of examinations

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

1000 mg/kg bw/day: Slight salivation was observed frequently in high dose group animals after administration (non-adverse).

Mortality:

mortality observed, treatment-related

Description (incidence):

1000 mg/kg bw/day: Slight salivation was observed frequently in high dose group animals after administration (non-adverse).

Body weight and weight changes:

no effects observed

Food consumption and compound intake (if feeding study):

no effects observed

Food efficiency:

not examined

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

not examined

Ophthalmological findings:

not examined

Haematological findings:

no effects observed

Clinical biochemistry findings:

no effects observed

Urinalysis findings:

no effects observed

Behaviour (functional findings):

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

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
During treatment slight salivation was observed in males and females in 1000 mg/kg bw/day. This change disappeared during recovery period.

BODY WEIGHT AND WEIGHT GAIN
Body weight and weight gain was not affected by the treatment.

FOOD CONSUMPTION
Food consumption did not differ between the control and treatment groups.

HAEMATOLOGY
No treatment related effects were observed.

CLINICAL CHEMISTRY
No treatment related effects were observed.

URINALYSIS
No treatment related effects were observed.

ORGAN WEIGHTS
No treatment related effects were observed.

GROSS PATHOLOGY
No treatment related effects were observed.

HISTOPATHOLOGY: NON-NEOPLASTIC
No treatment related effects were observed.

Effect levels

Key result

Dose descriptor:

NOAEL

Effect level:

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

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: salivation (non-adverse)

Target system / organ toxicity

Key result

Critical effects observed:

no