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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non GLP, non-guideline, animal experimental study. Minor restrictions in design and/or reporting but otherwise adequate for assessment.

Data source

Reference
Reference Type:
publication
Title:
Effect of Vitamin B12 on the Metabolism in the Rat of volatile Fatty Acids
Author:
Dryden LP and Hartman AM
Year:
1971
Bibliographic source:
Journal of Nutrition, Vol. 101, pp 589-592

Materials and methods

Principles of method if other than guideline:
Feeding study designed to determine whether vitamin B12 is required for the metabolism of odd-carbon fatty acids higher than propionate and of certain branched-chain fatty acids that lead to propionate.
GLP compliance:
no
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Sodium acetate
EC Number:
204-823-8
EC Name:
Sodium acetate
Cas Number:
127-09-3
Molecular formula:
C2H4O2.Na
IUPAC Name:
sodium acetate
Details on test material:
- Name of test material (as cited in study report): Sodium acetate

Test animals

Species:
rat
Strain:
Wistar
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: No data
- From mothers who were transferred from a stock ration to a vitamin B12 deficient ration at parturition and continued on the deficient ration during lactation.
- Age at study initiation: Approximately 28 days
- Housing: Individually in cages with raised screen floors
- Diet: 25% protein, vitamin B12 deficient diet ad libitum, with or without the addition of fatty acids
- Fatty acids, when fed, replaced an equal quantity of dextrin in the diet. 1.58% acetate moiety (fed as sodium acetate, 3.58% of ration)
- Vitamin B12, when given, was included in the ration at a level of 5 µg/10 g diet
- Water: ad libitum
- Acclimation period: At least 3 days

ENVIRONMENTAL CONDITIONS: no data
IN-LIFE DATES: no data

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
4 weeks
Frequency of treatment:
Continuous
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
3.58% sodium acetate
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
equivalent to 1.58% as the acetate moiety
Basis:
nominal in diet
No. of animals per sex per dose:
6 males (without vitamin B12), 7 males (with vitamin B12)
Control animals:
yes, plain diet

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
Ophthalmological findings:
not examined
Haematological findings:
not examined
Clinical biochemistry findings:
not examined
Urinalysis findings:
not examined
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
not examined
Gross pathological findings:
not examined
Histopathological findings: non-neoplastic:
not examined
Histopathological findings: neoplastic:
not examined

Effect levels

Dose descriptor:
NOAEL
Effect level:
1.58 other: % based on the acetate moiety
Sex:
male
Basis for effect level:
other: The effect on growth of rats fed diet containing 3.58% sodium acetate, with or without vitamin B12, was not significantly changed when compared to rats fed basal diet only.
Remarks on result:
other: see "Overall remarks, attachments"

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Acetate and higher even-carbon fatty acids had no effect on such growth. While the 5-, 7- and 9-carbon straight-chain fatty acids depressed growth on the control ration, as did propionate itself, the extent of depression decreased as the carbon chain lengthened, reflecting perhaps a tendency for the higher acids to be partially metabolized by an alternate pathway. The branched-chain acids (isobutyric, 2-methyl butyric and 4-methyl valeric), depressed growth on the control ration but isovaleric acid did not.

Effect of vitamin B12 on growth of rats fed acetic acid

 

 

 

Average weight gain g (weeks 2-4)

Amount in diet %

# rats per group

Vitamin B12

Basal diet

Basal diet + fatty acid

% change

1.58

6

No

39

45

+15

1.58

7

Yes

125

124

-1

 

Applicant's summary and conclusion

Conclusions:
The effect on growth of rats fed diet containing 3.58% sodium acetate (1.58% acetate moiety) in basal diet, with or without vitamin B12, was not significantly changed when compared to rats fed basal diet only. Accordingly, the NOAEL was determined to be 3.58% sodium acetate or 1.58% based on the acetate moiety. These doses correspond to concentrations of 5370 mg/kg bw/day for sodium acetate and 2370 mg/kg bw/day for the acetate moiety (see "Overall remarks, attachments").

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