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The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Toxicological information

Repeated dose toxicity: oral

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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

Constituent 1
Chemical structure
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.