Dextransucrase

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Lipids as a constituent of enzyme deriving from the fermentation or extraction process

Molecular formula:

Not available. See remarks.

IUPAC Name:

Lipids as a constituent of enzyme deriving from the fermentation or extraction process

Constituent 2

Reference substance name:

Carbohydrates constituent of enzyme deriving from the fermentation or extraction process

Molecular formula:

Not available. See remarks.

IUPAC Name:

Carbohydrates constituent of enzyme deriving from the fermentation or extraction process

Constituent 3

Reference substance name:

Active enzyme protein of Amylase, gluco- (EC no. 232-877-2, CAS no. 9032-08-0, EC name: glucan 1,4-alpha-glucosidase, Enzyme Class no. 3.2.1.3)

IUPAC Name:

Active enzyme protein of Amylase, gluco- (EC no. 232-877-2, CAS no. 9032-08-0, EC name: glucan 1,4-alpha-glucosidase, Enzyme Class no. 3.2.1.3)

Constituent 4

Reference substance name:

Protein as a constituent of enzyme deriving from the fermentation or extraction process

Molecular formula:

Not available

IUPAC Name:

Protein as a constituent of enzyme deriving from the fermentation or extraction process

Constituent 5

Reference substance name:

Inorganic salts as a constituent of enzyme deriving from the fermentation or extraction process

Molecular formula:

Not available. See remarks.

IUPAC Name:

Inorganic salts as a constituent of enzyme deriving from the fermentation or extraction process

Test material form:

liquid

Details on test material:

Substance type: UVCB
- Physical state: liquid
- Lot/batch No.: trg08050/52
- Expiration date of the lot/batch: At least stable until January 2011
- Stability under test conditions: The test material and dilutions in water (25% and 50%) are stable for
at least 5 hours at room temperature, 7 days at 4 degrees Celcius and 90 days at minus 20 degrees
of Celcius
- Storage condition of test material: minus 20 degrees of Celcius

Test animals

Species:

rat

Strain:

other: HanTac:WH

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Taconic Europe, DK-4623 Lille Skensved, Denmark
- Females nulliparous and non-pregnant: not specified
- Age at study initiation:
- Weight at study initiation: 147 - 152 g
- Fasting period before study: overnight and 3 h after treatment
- Housing: transparent polycarbonate cages (floor area 1500 cm2, height 21 cm) with 2 animals in each cage. Cages were cleaned and the bedding changed 2x a week.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C ± 3°C
- Humidity (%): 55% ± 15%
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12h light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 1996.3 mg total protein/kg as this was the highest posible dose at dose volume 10 mL/kg, using the undiluted test item.

The starting dose level of 1996.3 mg/kg was based on information from the Sponser.

Doses:

1996.3 mg/kg

No. of animals per sex per dose:

5

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observed 15 minutes, 1, 3, and 6 hours after administration and thereafter daily. Weighed on days 1, 2, 3, 8 and 15
- Necropsy of survivors performed: yes

Results and discussion

Preliminary study:

The sighting study was one female at the dose rate of 1996.3 mg/kg. The animal had an overall body weight gain. The animal appeared normal at all observations. The post-mortem inspections of the animal revealed no abnormalities.

Effect levels

Effect levels 1

Key result

Sex:

female

Dose descriptor:

other: limit test - no effects were seen

Effect level:

>= 2 263.7 mg/kg bw

Based on:

other: enzyme concentrate dry matter

Effect levels 2

Sex:

female

Dose descriptor:

other: Limit test - no effects were seen

Effect level:

> 1 604.96 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: active enzyme protein

Effect levels 3

Sex:

female

Dose descriptor:

other: : Limit test - no effects were seen

Effect level:

> 1 996.3 mg/kg bw

Based on:

other: total protein

Mortality:

No mortality.

Clinical signs:

other: No clinical signs.

Gross pathology:

Post-mortem inspections revealed no abnormalities.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

No signs of toxicity were observed among the rats treated with a single oral dose of 1996.3 mg/kg based on total protein, which was the highest possible dose at dose volume 10 mL/kg, using the undiluted test item. he dose of 1996.3 mg/kg is equivalent to 1604.96 mg active enzyme protein/kg bw or 2263.7 mg enzyme concentrate dry matter/kg bw.

Executive summary:

The objective of this study was to assess the acute toxicity of Glucoamylase when administered as a single oral dose to rats followed by an observation period of 14 days. A preliminary sighting study using one female animal was included to estimate the dose effect for toxicity and to provide information on dose selection for the main study. The dose of 1996.3 mg/kg is equivalent to 1604.96 mg active enzyme protein/kg bw or 2263.7 mg enzyme concentrate dry matter/kg bw.
The study was conducted in accordance with the OECD Guideline No 420, “Acute Oral Toxicity – Fixed Dose Procedure”. The limit test was used. The test item was supplied as a brown liquid ready to use. The dose volume administered was 10 mL/kg.
The study was initiated with a sighting study at dose level 1996.3 mg/kg based on total protein, using one female animal. This was the highest possible dose level at dose volume 10 mL/kg, using the undiluted test item. On the basis of the results of the sighting study, the main study was performed in four additional female rats given a dose of 1996.3 mg/kg body weight. No clinical signs were observed and the overall body weight gain during the study was considered to be normal. The post-mortem inspection revealed no abnormalities.
In conclusion, no signs of toxicity were observed among the rats treated with a single oral dose of 1996.3 mg/kg based on total protein, which was the highest possible dose at dose volume 10 mL/kg, using the undiluted test item.