Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From February 03, 1997 to August 08, 1997
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1997
Report date:
1997

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
and EEC directive 92/69/EEC.
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

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)
Cas Number:
9001-62-1
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:
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 4
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 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:
- Lot/batch No.: PPW 5756
- Expiration date of the lot/batch: 02 December 2006

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Source: Møllegaard Breeder, Ejby, Denmark
- Fasting period before dosing: overnight fasting prior to dosing
- Housing: Five of the same sex in transparent plastic boxes (Type IV 590 MAK overall dimensions 59 x 38 x 20 cm) with wire grid tops and aspen wood chips bedding. In a barrier maintained animal room with control of temperature and humidity
- Weight at the end of the akklimatization period: Males 154-156 g, females 124-131 g.
- Diet: Altromin rat/mouse Breeding 1320 diet pellets ad libitum
- Water: Water ad libitum
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22±3°C
- Humidity (%): 30-70%
- Air changes (per hr): 8-12
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 12 February 1997 to 26 Februay 1997

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Undiluted test material
Doses:
Dose volume was 20 mL/kg bw, corresponding to a dose of 2740 mg enzyme concentrate dry matter/kg bw.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observations for clinical signs of effect: before dosing, twice after dosing (day 1) and thereafter once per day for the following 14 days. Weighing immediately before dosing at day 1, day 8 and Day 15.
- Necropsy of survivors performed: yes
Statistics:
No

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
other: Fixed dose method - no effects were seen
Effect level:
20 mL/kg bw
Based on:
test mat.
Key result
Sex:
male/female
Dose descriptor:
other: Fixed dose method - no effects were seen
Effect level:
> 2 740 mg/kg bw
Based on:
other: Enzyme concentrate dry matter
Mortality:
No animals died during the study.
Clinical signs:
No clinical signs were observed in the dose group.
Body weight:
No effect was observed on the body weights.
Gross pathology:
Effects on organs: No macroscopic alterations were observed at the terminal post mortem examination.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
No signs of toxicity were observed among the rats treated with a single oral dose of 2740 mg enzyme concentrate dry matter/kg bw (equivalent to 1940 mg active enzyme protein/kg bw), which was the highest possible dose at dose volume 20 mL/kg, using the undiluted test item.
Executive summary:

The study was conducted in accordance with the OECD Guideline No 420, "Acute Oral Toxicity - Fixed dose Method" and EEC directive 92/69/EEC.

The test item was supplied as a brown liquid ready to use. The dose volume administered was 20 mL of the undiluted test material per kg body weight, corresponding to a dosage of

2.74 g enzyme concentrate dry matter/kg bw. A group of five male and five female rats received the test material by a single oral administration (gavage). The animals were subjected to clinical observations daily for a fourteen day observation period and at termination of the study, gross necropsy of all animals was carried out.

No clinical effects 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 2740 mg enzyme concentrate dry matter/kg bw (equivalent to 1940 mg active enzyme protein/kg bw).