3-methoxybutyl acetate

Repeated dose toxicity: oral

Administrative data

Endpoint:

chronic toxicity: oral

Type of information:

other: experimental result putative metabolite

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non GLP, non guideline, animal experimental study, predates implementation of GLP and/or development of study guidelines but otherwise acceptable for assessment.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1967

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Sprague-Dawley rats were fed diets containing 0, 1, 3 or 10% butanediol for up to 2 years. Clinical observations, bodyweight, food and compound consumption were recorded regularly throughout the study. Haematological assessments and urinalysis was undertaken on six occasions during the study. After one year 10 rats/sex/group, and after two years all surviving rats, were killed and examined post mortem. Representative organs were weighed and a range of tissues were examined histopathologically.

GLP compliance:

no

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butane-1,3-diol

EC Number:

203-529-7

EC Name:

Butane-1,3-diol

Cas Number:

107-88-0

Molecular formula:

C4H10O2

IUPAC Name:

butane-1,3-diol

Details on test material:

- Name of test material (as cited in study report): butanediol
- Source: The Celanese Corporation of America, New York
- No further details

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: no data
- Age at study initiation: weanlings
- Housing: individually in metal cages
- Diet: Purina Rat Chow (Ralston Purina Company, St. Louis, Missouri, USA) ad libitum
- Water: ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- according to the Principles of Laboratory Animal Care (no further details)

IN-LIFE DATES: no data

Administration / exposure

Route of administration:

oral: feed

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DIET PREPARATION
- No data

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

Two years

Frequency of treatment:

Continuous

Doses / concentrations

Remarks:

Doses / Concentrations:
0, 1.0, 3.0 and 10% by weight
Basis:
nominal in diet

No. of animals per sex per dose:

60/sex in the control group; 30/sex for the butanediol-treated groups

Control animals:

yes, plain diet

Examinations

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: "regularly"

DETAILED CLINICAL OBSERVATIONS: No data

BODY WEIGHT: Yes
- Time schedule for examinations: "regularly". Data reported for initial weight and at 4, 20 and 52 weeks

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study): Yes
- No further details

OPHTHALMOSCOPIC EXAMINATION: No data

HAEMATOLOGY: Yes
- Time schedule for collection of blood: 6 times during the study
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: "representative animals"
- Parameters examined: erythrocyte count, total and differential leukocyte count, haematocrit and haemoglobin concentration

CLINICAL CHEMISTRY: No

URINALYSIS: Yes
- Time schedule for collection of urine: 6 times during the study
- Metabolism cages used for collection of urine: No data
- Animals fasted: No data
- Pooled samples examined
- Parameters examined: specific gravity, pH, protein, sugar, acetone, urobilinogen, bilirubin and occult blood measured
- Gross appearance and microscopic examination of sediment

NEUROBEHAVIOURAL EXAMINATION: No

Sacrifice and pathology:

GROSS PATHOLOGY: Yes
- 10 animals/group were killed after one year and all surviving animals killed after two years.

HISTOPATHOLOGY: Yes
- Adrenals, bone (with marrow), brain, gonads, heart, kidney, lung, liver, pancreas, pituitary, spleen, stomach, small and large intestine, thyroid and urinary bladder.
- Representative organs were weighed

Statistics:

Analysis of variance or F test according to Snedecor 1956 or Ostle 1956 (5% probability); survival by Sachs 1959.

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):

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:

not examined

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:

no effects observed

Effect levels

Dose descriptor:

NOEL

Effect level:

10 other: % by weight in diet

Sex:

male/female

Basis for effect level:

other: No adverse effects seen in male or female rats after 2 years.

Target system / organ toxicity

Critical effects observed:

not specified

Any other information on results incl. tables

No adverse effects of treatment were seen.

Applicant's summary and conclusion

Conclusions:

In a 2 year feeding study in male and female rats, the NOEL of 1,3-butanediol was greater than 10% (by weight) in diet.

Executive summary:

Male and female Sprague-Dawley rats were fed 1,3 -butanediol in diet at concentrations of 0, 1, 3 or 10% for up to two years. Clinical observations, bodyweights and food consumption were recorded frequently and blood was sampled for haematological and clinical chemistry changes at intervals throughout the study. 10 animals/group were killed after 1 year and the remainder of the survivors were killed at the end of the 2 year feeding period. Representative organs were weighed and examined histopathologically. There were no observed signs of treatment-related toxicity and no treatment related histopathological findings. The no observed adverse effect level of 1,3 butanediol in rats over 2 years was greater than 10% (by weight) in diet.