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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:
other information
Reliability:
3 (not reliable)
Rationale for reliability incl. deficiencies:
other: Does not meet important criteria of today standard methods (test period 7 days, only 1 concentration tested, examination confined to thoracic and gastro-intestinal cavities and forestomach)

Data source

Reference
Reference Type:
publication
Title:
Unnamed
Year:
1991
Report date:
1991

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Subacute 7 days feeding study in order to investigate the early lesion occuring in the forstomach of rats, mice and hamsters following dietary exposure butyric acid.
GLP compliance:
not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Butyric acid
EC Number:
203-532-3
EC Name:
Butyric acid
Cas Number:
107-92-6
Molecular formula:
C4H8O2
IUPAC Name:
butyric acid
Details on test material:
- Name of test material (as cited in study report): butyric acid (BA)
- Analytical purity: approx. 99% (purchased from Sigma Chemicals Co., Poole, Dorset, UK)

Test animals

Species:
other: Three animal species used: rat, mouse, Syrian hamster
Strain:
other: Wistar; C3B6F1; outbred Syrian golden hamster
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: breeding unit of the University of Surrey, Guilford, UK
- Age at study initiation: no data
- Weight at study initiation: rats: males 155 - 215 g, females 150 - 195 g
mice: males 24 - 26 g, females 19 - 23 g
hamsters: males 77 - 94 g, females 86 - 121 g
- Housing: animals were housed 5 to a cage (single sex)
- Diet (e.g. ad libitum): ad libityum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: yes, several days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 23 - 25
- Humidity (%): 58 - 68
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
DIET PREPARATION
- Butyric acid was incorporated into powdered rodent breeding diet (LAD-2 supplied by Labsure, Manea, Cambs., UK) to give a test material concentration of 4% (w/w).
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
7 d
Frequency of treatment:
continuous
Doses / concentrations
Remarks:
Doses / Concentrations:
4 % in food, no doses (mg/kg/day) reported
Basis:
nominal in diet
No. of animals per sex per dose:
5
Control animals:
yes, concurrent no treatment

Examinations

Sacrifice and pathology:
GROSS PATHOLOGY: Yes (only cranial, thoracic and abdominal cavity, forestomach)
HISTOPATHOLOGY: Yes (only forestomach)

Results and discussion

Results of examinations

Gross pathological findings:
effects observed, treatment-related
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Details on results:
GROSS PATHOLOGY
Damage and cellular proliferation in the forestomach was noted. These effects were related to the irritating nature of butyric acid.

HISTOPATHOLOGY: NON-NEOPLASTIC
In the forestomach, acanthosis, edema of the lamina propria and increased numbers of mitotic figures occurred more frequently than in the controls. Furthermore, ulceration associated with epithelial hyperplasia was observed.

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Rat proved to be the most sensitive one among the three tested species. Daily dose is estimated to have been >=2000 mg/kg bw/d.

Applicant's summary and conclusion

Conclusions:
After oral administration of butyric acid (4% in diet) to groups of 5 male and female rats, mice and hamsters for 7 days, lesions in the forestomach were observed (acanthosis, edema of the lamina propria and increased numbers of mitotic figures). For rats, acanthosis, epithelial vacuolation and ulceration (with associated marked epithelial hyperplasia) was prevalent. Rats proved to be the most sensitive of the three tested species.

The formation of lesions in the gastro-intestinal tract caused by the oral application of butyric acid was to be expected due to the acidic nature of the test substance. This effect can be understood as local action of the acidic form of the test substance.