Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
August 18, 2014 to December 9, 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2014
Report date:
2014

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Version / remarks:
2008
GLP compliance:
yes (incl. QA statement)
Test type:
up-and-down procedure
Limit test:
no

Test material

Constituent 1
Reference substance name:
Active enzyme protein of catalase (EC no. 232-577-1, CAS no. 9001-05-2, EC name Catalase, Enzyme class no. 1.11.1.6)
Molecular formula:
Not applicable, see remarks
IUPAC Name:
Active enzyme protein of catalase (EC no. 232-577-1, CAS no. 9001-05-2, EC name Catalase, Enzyme class no. 1.11.1.6)
Constituent 2
Reference substance name:
Protein as a constituent of enzyme deriving from the fermentation or extraction process
Molecular formula:
Not available. See remarks.
IUPAC Name:
Protein as a constituent of enzyme deriving from the fermentation or extraction process
Constituent 3
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 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:
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: light brown liquid
- Stability under test conditions: The neat test substance was demonstrated to be stable under the conditions of the study.

Test animals

Species:
rat
Strain:
other: Crl:CD(SD)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories International, Inc., Raleigh, North Carolina, U.S.A
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: approximately 10 weeks old
- Weight at study initiation: 240±5 grams
- Fasting period before study: The rats were fasted approximately 15-17 hours prior to dosing, with food being returned to the rats approximately 3 hours after the first dose
- Housing: Animals were housed individually in solid-bottom caging with bedding and appropriate species-specific enrichment.
- Diet (e.g. ad libitum): PMI® Nutrition International, LLC Certified Rodent LabDiet® 5002 ad libitum except during fasting
- Water (e.g. ad libitum): water ad libitum except during fasting
- Acclimation period: The rats were weighed and observed for general health during the 6-day quarantine period.

ENVIRONMENTAL CONDITIONS
- Temperature: 20-26ºC
- Humidity: 30-70%
- Air changes: 12-hour light/dark cycle

IN-LIFE DATES: From September 9, 2014 to September 26, 2014

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test substance was administered by oral gavage to fasted female rats at a dose of 5000 mg/kg, adjusted for the percentage of total protein in the neat test substance. The neat test substance was delivered in two fractions to each animal, approximately two hours apart, on a single day. The rats were dosed one or two at a time, at a minimum of 48-hour intervals.

The rats were approximately 10 weeks old on the day of dosing. The rats were fasted approximately 15-17 hours prior to dosing, with food being returned to the rats approximately 3 hours after the first dose. Individual dose volumes were calculated using the test substance composition of 167.41 mg total protein/mL and the fasted body weights obtained prior to dosing. The rats were dosed with the neat test substance at an approximate volume of 30 mL per kg of body weight, divided into two fractions of approximately 15 mL/kg each. Based on the exact volume located in the study database and the specific gravity in the COA, the total dose of the neat test substance was calculated as 31957 mg/kg. The weight of each animal was within the ±20% of the mean weight of any previously dosed animals. The neat test substance was inverted prior to the dosing procedure.
Doses:
The neat test substance was administered at a total dose level of 31957 mg/kg bw (equivalent to 5000 mg TP/kg bw or 6443 mg TOS/kg bw) at a volume of approximately 30 mL/kg, which was delivered in two fractions to each animal on a single day. The rats were dosed one or two at a time, at a minimum of 48-hour intervals.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
Daily animal health observations were conducted throughout the study for mortality and signs of illness, injury, or abnormal behavior. Animals were weighed on test days -1, 1, 8, and 15, and were observed for clinical signs at the beginning of fasting, just before dosing (test day 1), once during the first 30 minutes after the first dose, and 2 more times on the day of dosing, and once each day thereafter. On test day 15, the rats were euthanized and necropsied to detect grossly observable evidence of organ or tissue damage. The rats were euthanized by exsanguination while under isoflurane anesthesia

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
other: TP (Total protein)
Remarks on result:
other: no effects observed
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 6 443 mg/kg bw
Based on:
other: TOS (Total Organic Solids)
Remarks on result:
other: no effects observed
Mortality:
No deaths occurred
Clinical signs:
There were no clinical abnormalities observed throughout the study.
Body weight:
There were no overall bodyweight losses observed throughout the study
Gross pathology:
No gross lesions were present in the rats at necropsy.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the oral LD50 for Catalase was greater than 5000 mg TP/kg bw (equivalent to 6443 mg TOS/kg bw) for female rats.
Executive summary:

The study was conducted to assess the acute oral toxicity of Catalase in accordance with the OECD Guideline 425 in compliance with GLP.

 

The test substance was administered by oral gavage to fasted female rats at a dose of 5000 mg/kg bw, adjusted for the percentage of total protein in the neat test substance. The neat test substance was a solution that was administered at a total dose level of 31957 mg/kg at a volume of approximately 30 mL/kg, which was delivered in two fractions to each animal on a single day. The rats were dosed one or two at a time, at a minimum of 48-hour intervals. All rats were observed for mortality, body weight effects, and clinical signs for 14 days after dosing. The rats were necropsied to detect grossly observable evidence of organ or tissue damage.

 

No incidents of mortality, overall bodyweight loss or clinical signs were observed. No gross lesions were present in the rats at necropsy.

Under the conditions of this study, the oral LD50 for Catalase was greater than 5000 mg TP/kg bw (equivalent to 6443 mg TOS/kg bw) for female rats.