Reaction mass of 6-O-alfa-D-glucopyranosyl-D-fructofuranose and 1-O-alfa-D-glucopyranosyl-D-fructofuranoseand D-fructofuranose

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Based on well documented journal article translated into English from the original Japanese

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1987

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

A chronic toxicity test was conducted in which the substance was administered orally to male and female rats for 26 weeks. Since the doses were well above the usual acute toxicity test limit dose, and no mortality or marked clinical signs were observed, the study demonstrates the lack of acute toxicity.

GLP compliance:

not specified

Remarks:

Not stated but appears to be in compliance with GLP

Test type:

other:

Limit test:

no

Test material

Reference

Name:

Unnamed

Type:

Constituent

Details on test material:

Palatinose syrup (same as isomaltulose greens) is a byproduct of the process used to manufacture the reducing disaccharide palatinose. It is a monosaccharide/oligosaccharide composite principally composed of 1-O-2-D-glucosyl-D-fructose and palatinose. It contains 71.2% sugars, such as fructose, glucose, sucrose, palatinose, trehalulose, and isomaltose. It is equivalent to isomaltulose greens.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Four-week-old Sprague-Dawley SPF rats (Crj: CD) were obtained from Charles River Laboratories Japan, Inc. and placed under quarantine for a preliminary period of 1 week for acclimation. The animals were kept in a controlled indoor barrier system equipped with 12-hour light cycle systems at 24+/- 1 degrees C and humidity 55 +/- 5%. Each rat was placed inside a metal cage with a wire-mesh floor and allowed free access to the commercial solid feed Rodent Diet CE-2 (CLEA Japan, Inc.) and tap water. At the beginning of the experiment the rats' body weights ranged from 97-118 g (females) and 114-131 g (males).

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Doses were administered orally once a day for a period of 26 weeks (female: 183 days, male: 184 days) using gastric tubes. The palatinose syrup was stored at room temperature. The 4,500 mg/kg syrup was as received from the manufacturer and was dosed undiluted. Solutions for the 3,000 and 1,500 mg/kg groups were prepared by placing the appropriate amount of concentrated syrup in a graduated cylinder and adding distilled water until the w/v ratios of 64.4% and 32.2%, respectively, were achieved.

Doses:

Control, 1,500, 3,000, and 4,500 mg/kg, with a volume of 4,663 ml/kg body weight

No. of animals per sex per dose:

Four groups of 14 rats (male/female) were exposed to each dose level.

Control animals:

yes

Details on study design:

In addition to checking daily for mortality, general clinical symptoms, toxicity symptoms, and macroscopic feces and urine qualities for each rat were made once a week throughout the study. Body weight and individual food consumption were measured once a week for the first 13 weeks and then every two weeks thereafter. Additional measurements were made on regular schedules related to urinalysis, ophthalmological examination, hematological examination, blood biochemistry evaluation, and pathological examination.

Statistics:

Measured values are expressed as mean +/- SD. Student's t-test was used for statistically significant difference from the control group (P<0/05). In cases with unequal variance, the Aspin-Welch t-test was used to test for statistical significance.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 4 500 mg/kg bw

Based on:

test mat.

Mortality:

No treatment related mortalities were observed during the entire 26 week exposure. Two female rats did die in weeks 13 and 14 of the study, but these were believed to be caused by perforation of the esophagus due to administration failure and were not treatment related.

Clinical signs:

No clinical signs of toxicity believed to have been caused by test material administration were observed.

Body weight:

A slight deceleration in weight gain was observed in the 4,500 mg/kg group in week 21 as compared to the control group. No other group showed any significant acceleration or deceleration in weight gain during the 26-week study period.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material is practically non-toxic to rats when given high doses.

Executive summary:

A toxicity test was conducted in which the substance was administered orally to male and female rats for 26 weeks. Doses (1,500, 3,000 and 4,500 mg/kg) were administered orally once a day. Two female rats did die in weeks 13 and 14 of the study, but these were believed to be caused by perforation of the esophagus due to administration failure and were not treatment related. No other mortalities were observed. Since the doses were well above the usual acute toxicity test limit dose, and no mortality or marked clinical signs were observed, the study demonstrates the lack of acute toxicity.