Dibutyl terephthalate

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data taken from OECD SIDS and from ECETOC Report

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1986

Reference 2

Reference Type:

secondary source

Title:

n-Butanol (CAS No. 71-36-3)

Author:

ECETOC

Year:

2003

Bibliographic source:

ECETOC JACC No. 41, ISSN-0773-6339-41, December 2003

Reference 3

Reference Type:

secondary source

Title:

OECD SIDS n-Butyl Alcohol

Author:

OECD

Year:

2001

Bibliographic source:

OECD SIDS, UNEP Publications

Materials and methods

Principles of method if other than guideline:

Four groups of male and female rats (30/sex/group) were administered daily by gavage 0, 30, 125 or 500 mg/kgbw/d for either 6
or 13 weeks.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Butan-1-ol

EC Number:

200-751-6

EC Name:

Butan-1-ol

Cas Number:

71-36-3

Molecular formula:

C4H10O

IUPAC Name:

butan-1-ol

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:
Dosing solutions of butanol in deionized water were used.

VEHICLE
- Concentration in vehicle: not specified
- Amount of vehicle (if gavage): 10 ml/kg was the constant dosing volume

Analytical verification of doses or concentrations:

not specified

Details on analytical verification of doses or concentrations:

no data

Duration of treatment / exposure:

6 or 13 weeks

Frequency of treatment:

daily

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 30, 125, 500 mg/kg bw
Basis:
actual ingested

No. of animals per sex per dose:

30

Control animals:

yes, concurrent vehicle

Positive control:

no data

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: twice daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: twice daily

BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were recorded weekly


FOOD CONSUMPTION: Yes
-Time schedule: Food consumption was recorded weekly


OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: Ophthalmic examination was conducted prior to treatment and during week 13 before final necropsy.
- Dose groups that were examined: no data


HAEMATOLOGY: Yes
- Time schedule for collection of blood: before the start of the study, during week 6 and during week 13
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: 10 males and 10 females
- parameters: hemoglobin ( HGB), hematocrit (PCV), erythrocyte count (RBC), mean cell volume (MCV), mean cell hemoglobin (MCH),mean cell hemoglobin concentration (MCHC) total and differential leucocyte counts (WBC), estimated platelet count (PLT)


CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: before the start of the study, during week 6 and during week 13
- Animals fasted: No data
- How many animals: 10 males and 10 females
- parameters: alkaline phosphatase (Alk phos). blood urea nitrogen (BUN), glutamate pyruvate transaminase (SGPT), glutamate oxalacetate transaminase (SG0T), glucose (Gluc), total protein (TP), albumin( Alb), A/G ratio (calculated), globulin (calculated), total bilirubin (Tot. bili.), sodium (Na), potassium (K ), chloride (Cl), calcium. (Ca), inorganic phosphate (Phos), carbon dioxide (TCO2), total serum cholesterol (Chol), creatinine.


URINALYSIS: Yes
- Time schedule for collection of urine: before the start of the study, during week 6 and during week 13
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- parameters: pH, specfic gravity, glucose, protein, ketones, bilirubin, urobilinogen, microscopy of sediment


NEUROBEHAVIOURAL EXAMINATION: No data

Sacrifice and pathology:

GROSS PATHOLOGY: Yes: Ten male and ten female rats from each group were necropsied on study days 43 to 44 and the remaining animals on study days 92 to 93 . Gross pathology of all animals was assessed and organs from animals necropsied on study days 92 to 93 were weighed.
HISTOPATHOLOGY: Yes: A complete histopathological investigation was made of all animals of the control and high-dose groups . In the low and mid-dose groups, histopathology included the liver, kidney, and heart from all animals and all gross lesions . All animals found dead or killed in extremis
were also microscopically examined.

Statistics:

no data

Results and discussion

Results of examinations

Details on results:

CLINICAL SIGNS AND MORTALITY
Ataxia and hypoactivity (lasting less than 1 h) were observed 2 to 3 minutes after dosing in both sexes of the high-dose group (500 mg/kg bw/d)
during the final 6 weeks of dosing. Such ataxia and hypoactivity are typically seen following high oral doses of alcohols . The rapid
induction/remission of these effects and the reported increased incidence after the interim kill may be due to the fact that personnel
were able to collect post-dose observations more quickly since fewer animals required dosing.
No significant changes between treated groups and controls were observed concerning mortality.

BODY WEIGHT AND WEIGHT GAIN
no significant changes between treated groups and controls were observed

FOOD CONSUMPTION
no significant changes between treated groups and controls were observed

OPHTHALMOSCOPIC EXAMINATION
no significant changes between treated groups and controls were observed

HAEMATOLOGY
no significant changes between treated groups and controls were observed

CLINICAL CHEMISTRY
no significant changes between treated groups and controls were observed

URINALYSIS
no significant changes between treated groups and controls were observed

ORGAN WEIGHTS
no significant changes between treated groups and controls were observed

GROSS PATHOLOGY
no significant changes between treated groups and controls were observed

HISTOPATHOLOGY: NON-NEOPLASTIC
no significant changes between treated groups and controls were observed

Effect levels

1

Dose descriptor:

NOAEL

Effect level:

125 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: no effects observed

2

Dose descriptor:

LOAEL

Effect level:

500 mg/kg bw/day (nominal)

Sex:

male/female

Basis for effect level:

other: clinical signs of SNC depression (ataxia and hypoactivity)

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No dose-related differences were observed between treatment or control rats in 
body or organ weight changes, food consumption or mortality, gross pathology, 
and histopathological and ophthalmic evaluations. Ataxia and hypoactivity 
(lasting less than 1 h) were observed 2 to 3 minutes after dosing in both sexes 
of the high-dose group (500 mg/kg bw/d) during the final 6 weeks of dosing. Such 
ataxia and hypoactivity are typically seen following high oral doses of alcohols.
The rapid induction/remission of these effects and the reported increased 
incidence after the interim kill may be due to the fact that personnel were able 
to collect post-dose observations more quickly since fewer animals required
dosing. nBA was not expected to persist or accumulate over time. 
No treatment-related signs were observed in the 30 or 125 mg/kg bw/d treatment 
groups, the latter value being the no-observed adverse effect level (NOAEL).