4-O-β-D-galactopyranosyl-D-glucitol

Repeated dose toxicity: oral

Administrative data

Endpoint:

sub-chronic toxicity: oral

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

4 (not assignable)

Rationale for reliability incl. deficiencies:

abstract

Remarks:

article is in Japanese- abstract only in English

Data source

Reference

Reference Type:

publication

Title:

52-week oral toxicity study of lactitol (NS-4) in rats followed by 9-week recovery test

Author:

Okazaki S, Kobayashi J, Tamura K, Nagatani M, Hamasu Y, and Sumi N

Year:

1994

Bibliographic source:

J Toxicol Sci., 19(Suppl 3):377-404

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

Results of a 52-week oral toxicity study followed by a 9-week recovery in rats was reported.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

4-O-β-D-galactopyranosyl-D-glucitol

EC Number:

209-566-5

EC Name:

4-O-β-D-galactopyranosyl-D-glucitol

Cas Number:

585-86-4

Molecular formula:

C12H24O11

IUPAC Name:

4-O-beta-D-galactopyranosyl-D-glucitol

Test animals

Species:

rat

Strain:

other: Slc:SD

Sex:

male/female

Administration / exposure

Route of administration:

oral: unspecified

Duration of treatment / exposure:

52 weeks with 9-week recovery

Doses / concentrations

Doses / concentrations 1

Dose / conc.:

400 other: mg/kg/day

Doses / concentrations 2

Dose / conc.:

2 000 other: mg/kg/day

Doses / concentrations 3

Dose / conc.:

10 000 other: mg/kg/day

No. of animals per sex per dose:

25

Control animals:

yes

Results and discussion

Results of examinations

Details on results:

Treatment related death, soft stool, diarrhea, decreased body weight and food intake, and increased water consumption were observed in the 10 g/kg group. Urinalysis showed increased Ca excretion in the 2 and 10 g/kg groups. In the 10 g/kg group, there was increased Ca++ excretion and urine specific gravity and decreased K+ and Na+ excretion and urine volume. Hematologic examination showed decreased platelet count in the 10 g/kg group. Biochemical examination revealed higher A/G ratio in the 2 and 10 g/kg groups. In the 10 g/kg group, there were lowered level of total cholesterol, triglyceride, phospholipid, Na+, Cl- and total protein. Distention of the cecum with increased organ weight was seen pathologically in the 2 and 10 g/kg groups. In the 10 g/kg group, caecal mucosa was hyperplasic. The adrenal gland was hypertrophic in the zona glomerulosa in the 2 and 10 g/kg groups. In the 10 g/kg group, the adrenal weight was increased. Dilatation of renal tubules was also found in the 10 g/kg group. The above mentioned changes satisfactorily reversible except for the increased cecum weight in the 10 g/kg group.

Effect levels

Dose descriptor:

NOAEL

Effect level:

>= 0.4 other: g/kg/day

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical biochemistry

food consumption and compound intake

gross pathology

histopathology: non-neoplastic

mortality

organ weights and organ / body weight ratios

urinalysis

Applicant's summary and conclusion

Conclusions:

A 52-Week rat oral study with a 9-week recovery with dosages of 0, 0.4, 2, and 10 g/kg/day of the test substance had a NOAEL of 0.4 g/kg/day.

Executive summary:

Twenty-five male and 25 female Slc:SD rats were given lactitol orally for 52 weeks at dosages of 0, 0.4, 2 and 10 g/kg/day. A 9 week recovery test was conducted after the discontinuation of the drug treatment. Treatment related death, soft stool, diarrhea, decreased body weight and food intake, and increased water consumption were observed in the 10 g/kg group. Urinalysis showed increased Ca excretion in the 2 and 10 g/kg groups. In the 10 g/kg group, there was increased Ca++ excretion and urine specific gravity and decreased K+ and Na+ excretion and urine volume. Hematologic examination showed decreased platelet count in the 10 g/kg group. Biochemical examination revealed higher A/G ratio in the 2 and 10 g/kg groups. In the 10 g/kg group, there were lowered level of total cholesterol, triglyceride, phospholipid, Na+, Cl- and total protein. Distention of the cecum with increased organ weight was seen pathologically in the 2 and 10 g/kg groups. In the 10 g/kg group, cecal mucosa was hyperplasic. The adrenal gland was hypertrophic in the zona glomerulosa in the 2 and 10 g/kg groups. In the 10 g/kg group, the adrenal weight was increased. Dilatation of renal tubules was also found in the 10 g/kg group. The above mentioned changes satisfactorily reversible except for the increased cecum weight in the 10 g/kg group. Based on the results obtained, the NOAEL of this study was 0.4 g/kg/day.