acetylxylan esterase

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:

2009

Report date:

2009

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

yes

Remarks:

The body weights of two animals were less than 20% of the mean initial weight of the previously dosed animals. The morning mortality/systemic observations were not performed for one animal on day 18 of the study; the animal appeared normal on day 19.

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

yes

Remarks:

The body weights of two animals were less than 20% of the mean initial weight of the previously dosed animals. The morning mortality/systemic observations were not performed for one animal on day 18 of the study; the animal appeared normal on day 19

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Active enzyme protein of Lipase, triacylglycerol (EC no. 232-619-9, CAS no. 9001-62-1, EC name: Lipase, triacylglycerol, Enzyme Class No.: 3.1.1.3)

Molecular formula:

Not applicable, see remarks

IUPAC Name:

Active enzyme protein of Lipase, triacylglycerol (EC no. 232-619-9, CAS no. 9001-62-1, EC name: Lipase, triacylglycerol, Enzyme Class No.: 3.1.1.3)

Constituent 2

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 3

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 4

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

Constituent 5

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

Test material form:

liquid

Details on test material:

Substance type: UVCB
Physical state: translucent tan liquid

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Ace Animals, Boyertown, PA
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: 61 days old
- Weight at study initiation: Mean = 229 g (Range 188-263 g)
- Fasting period before study: Yes, 16-20 hours before dosing
- Housing: Individually housed in suspended stainless steel wire bottom cages. Paper bedding was placed beneath the cages and changed at least three times/week
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): temperature was controlled, but exact temperature was not reported
- Humidity (%): not reported
- Air changes (per hr): not reported
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

DOSAGE PREPARATION (if unusual): The test substance was thawed in the refrigerator overnight prior to dosing. It was used as received and the dose was based on the sample weight as calculated from the specific gravity.

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Initially, a single female Wistar albino rat was dosed orally by syringe and dosing needle at a dose level of 2000 mg/kg. Since the animal survived, four additional females were dosed at 2000 mg/kg.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed at 15 minutes, 1, 2 and 4 hours postdose and once daily for 14 days for toxicity and pharmacological effects. Animals were observed twice daily for mortality. Body weights were recorded for all animals immediately pretest, weekly, and day 14. Additional body weights for animal #1 were recorded on day 15 through day 19.
- Necropsy of survivors performed: yes

Statistics:

An estimate of the LD50 was made based on the mortality occurring during the study.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the single 2000 mg/kg oral dose.

Clinical signs:

There were no abnormal physical signs noted during the observation period.

Body weight:

Body weight changes were normal in 3/5 animals. Two animals lost weight by day 14. One animal was observed for an additional 5 days due to loss of body weight.

Gross pathology:

Necropsy results were normal.

Applicant's summary and conclusion

Interpretation of results:

Category 5 based on GHS criteria

Conclusions:

The LD50 in female rats of the test substance is greater than 2000 mg/kg, the highest dose tested.

Executive summary:

The acute oral toxicity of the test substance was determined in accordance with OECD Guideline 425. The test substance was used as received and the dose was based on the sample weight as calculated from the specific gravity. Initially, a single female Wistar albino rat was dosed orally by syringe and dosing needle at a dose level of 2000 mg/kg. Since the animal survived, four additional females were dosed at 2000 mg/kg. The rats were observed at 15 minutes, 1, 2, and 4 hours post-dose and once daily for 14 days for toxicity and pharmacological effects. Animals were observed twice daily for mortality. Body weights were recorded for all animals immediately pretest, weekly, and on day 14. Additional body weights for one animal were recorded on day 15 through day 19 due to loss of body weight. All animals were examined for gross pathology.

All animals survived the single 2000 mg/kg oral dose. There were no abnormal physical signs noted during the observation period. Body weight changes were normal in 3/5 animals. Two animals lost weight by day 14. One animal was observed for an additional 5 days due to loss of body weight. Necropsy results were normal. The LD50 of the test substance is greater than 2000 mg/kg of body weight in female rats.