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Toxicological information

Repeated dose toxicity: oral

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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

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1996
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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
other: Guidelines for 28-Day Repeat Dose Toxicity Test of Chemicals (Japan)
Deviations:
no
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

Constituent 1
Chemical structure
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 / concentrationsopen allclose all
Dose / conc.:
20 mg/kg bw/day (actual dose received)
Dose / conc.:
140 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:
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

Applicant's summary and conclusion