glucan 1,4-alpha-maltohydrolaseIUBMB 3.2.1.133

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

From December 14, 1983 to March 27, 1984

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

- Principle of test: Rats were deprived of food approximately 18 hours before dosing. Rats were dosed once orally by gavage and observed 30 minutes, 2 hours and daily after dosing for a period of seven days. Control and the group receiving the highest dose were observed daily for a period of 14 days after dosing. All rats were given the same volume 20 mL/kg b.w.
- Short description of test conditions: Animals weighed 69-81g at the time of dosing. Rats were caged in Macrolon cages (type IV) at 22-26 degrees centigrade and 24-38% relative humidity. They were offered a standard rodent diet (Brood Stock Feed for Rats and Mice - R3- Ewos) and tap water (adjusted to approximately pH 3.0 with citric acid) ad libitum.
- Parameters analysed / observed: 30 minutes and 2 hours after dosing rats were observed for any signs of reaction to dosing, especially the following symptoms: Death, increased and decreased respiration, ptosis, salivation, lachrymation, piloerection, head drop, tail constantly erected, increased or decreased motoric activity, abduced hind legs, unsteady gait, convulsion, writhing movements, tremor, high gait and diarrhea. Followed by daily observations for seven days. Control and high dose group were observed for another seven days and thus for a period of 14 days, whereas animals of all other groups were sacrificed after seven days.

GLP compliance:

no

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Active enzyme protein of glucan 1,4-alpha-maltohydrolase (CAS no.160611-47-2, EC name: Cellulase, Enzyme Class no. 3.2.1.133)

Molecular formula:

Not available. Please see 'Remarks'.

IUPAC Name:

Active enzyme protein of glucan 1,4-alpha-maltohydrolase (CAS no.160611-47-2, EC name: Cellulase, Enzyme Class no. 3.2.1.133)

Test material form:

liquid

Details on test material:

- Substance type: UVCB
- Physical state: Liquid
- Lot/batch No.: ABF 7
- Expiration date of the lot/batch: 1985
- Stability under test conditions: The test material is stable for at least 4 hours at room temperature
- Storage condition of test material: In refrigerator (below 5 °C)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Møllegaard Breeder Center Ltd, Skensved, Denmark
- Fasting period before dosing: 18 hours fasting prior to dosing.
- Housing: Groups of 5, 2, 2, 2, 2 and 5 males and females respectively were caged in standard Macrolon cages (type IV).
- Weight at the time of dosing: 69 - 81 g
- Diet: Standard rodent diet (Brood Stock Feed for rats and mice - R3 - Ewos) ad libitum.
- Water: Tap water (adjusted to approximately pH 3.0 with citric acid) ad libitum.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-26 °C
- Humidity (%): 24-38%

IN-LIFE DATES: From: 1983-12-14 To: 1983-12-28

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration of test substance in vehicle: 0, 8.3, 16.7, 25.0, 50.0 or 100.0% (v/v)

Doses:

Dose volume was 20 mL/kg bw for all animals.
Concentration of test substance were: 0, 8.3, 16.7, 25.0, 50.0 or 100.0% (v/v) corresponding to mg test substance given in dry matter/kg bw: 0, 250, 500, 750, 1500 and 3000 mg/kg bw.

No. of animals per sex per dose:

5, 2, 2, 2, 2 and 5 males and females, respectively for the dosage groups 0, 250, 500, 750, 1500 and 3000 mg dry matter/kg bw.

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 7 days.
- Frequency of observations and weighing: 30 minutes and 2 hours after dosing.
- Necropsy of survivors performed: Yes.

Statistics:

No

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 3 000 mg/kg bw

Remarks on result:

other: No effects were observed

Mortality:

No animals died during the study.

Clinical signs:

other: No clinical signs were observed in any of the rats.

Gross pathology:

The post mortem examination showed no macroscopic findings.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Remarks:

Migrated information

Conclusions:

No signs of toxicity were observed among the rats dosed with a single oral dose of up to 3000 mg/kg bw. Therefore, a LD50 could not be estimated.

Executive summary:

The objective of this study was to evaluate the acute oral toxicity of the enzyme TS-25-Amylase batch ABF7 in rats. The liquid test substance was diluted with tap water and given once orally in doses of 0, 250, 500, 750, 1500 and 3000 mg/kg bw to groups of 5, 2, 2, 2, 2 and 5 male and female Wistar rats, respectively.

Thirty minutes and 2 hours after dosing and daily in the following period of the study the rats were observed for any signs of response to treatment. The rats were weighed at weekly intervals. After 7 days the four intermediate groups were sacrificed and a macroscopic examination was performed. All rats from the highest dose level and the control group were observed for another 7 days and sacrificed and macroscopically examined.

No rats died during the study and no signs of toxicity or reactions to treatment were seen. Group mean values of body weight and body weight gain showed no differences in the period of the study. No dose-related organ changes were seen in any of the rats.

No signs of toxicity were observed among the rats treated with a single oral dose of up to 3000 mg/kg bw. Therefore, a LD50 could not be calculated.