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Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
key study
Study period:
03-01-2013 to 05-03-2013
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Read-across to pectin lyase is applied. Data on pectin lyase are considered also to be valid for xanthan lyase, because both enzymes belong to the same enzyme sub-subclass IUB 4.2.2 and are considered to have a similar toxicological profile also with regard to acute toxicity.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2013
Report date:
2013

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
Adopted 17 December 2001.
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
Active enzyme protein of Pectin lyase (EC no. 232-894-5, CAS no.9033-35-6, EC name (1->4)-6-O-methyl-alpha-D-galacturonan lyase , Enzyme class no 4.2.2.10 )
Molecular formula:
n.a.
IUPAC Name:
Active enzyme protein of Pectin lyase (EC no. 232-894-5, CAS no.9033-35-6, EC name (1->4)-6-O-methyl-alpha-D-galacturonan lyase , Enzyme class no 4.2.2.10 )
Constituent 2
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 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:
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.: PPJ34366
- Expiration date of the lot/batch: November 2022

Test animals

Species:
rat
Strain:
other: Crl:CD(SD) albino rats
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (UK) Ltd
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 8-12 weeks
- Weight at study initiation: 218-240 g
- Fasting period before study: overnight fasting prior to dosing and approximately four hours after dosing.
- Housing: They were housed in groups of three rats of the same sex, in solid bottomed polycarbonate cages with a stainless steel mesh lid. Each cage contained a quantity of autoclaved wood flake bedding. Cages, food hoppers, water bottles and bedding were changed at appropriate intervals.
- Diet: standard rodent diet (Rat and Mouse No. 1 Maintenance Diet) ad libitum
- Water: ad libitum
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 23°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 2013-01-16 To: 2013-02-01

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The appropriate dose volume of the test substance was administered to each rat by oral gavage using a plastic syringe and plastic catheter. A record of the weight of each formulation dispensed and the amount remaining after dosing was made. The balance of these two weights was compared with the predicted usage as a check that the doses had been administered correctly. Formulations were stirred before and throughout the dosing procedure.
Doses:
Dose volume was 16 mL/kg bodyweight (equivalent to 2218 mg enzyme concentrate dry matter/kg bodyweight or 1428 mg aep/kg bodyweight).
No. of animals per sex per dose:
6 (female only)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Cages of rats were checked at least twice daily for any mortalities. Observations for clinical signs of effect: soon after dosing, and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The weight of each rat was recorded on Days 1 (prior to dosing), 8 and 15.
- Necropsy of survivors performed: All animals were humanely killed on Day 15 by carbon dioxide asphyxiation. All animals were subject to a macroscopic examination which consisted of opening the cranial, thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.
Statistics:
No

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD0
Effect level:
> 2 218 mg/kg bw
Based on:
other: mg enzyme concentrate dry matter
Mortality:
There were no deaths during the study.
Clinical signs:
There were no clinical signs of reaction to treatment throughout the study.
Body weight:
All animals were considered to have achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No abnormalities were noted in any animal at the macroscopic examination at study
termination on Day 15.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
On the basis of the results for the present study, it was concluded that the acute median lethal oral dose (LD50) to rats of pectin lyase, batch PPJ34366 was demonstrated to be greater than 2218 mg enzyme concentrate dry matter/kg bodyweight (equivalent to 1428 mg aep/kg bodyweight).
Executive summary:

The study was performed to assess the acute oral toxicity of pectin lyase, batch PPJ34366 to the rat. A group of three fasted female rats received a single oral gavage dose of the test substance, ‘as supplied’ at a dose level of 2218 mg enzyme concentrate dry matter/kg bodyweight (equivalent to 1428 mg aep/kg bodyweight). As results at this dose level indicated the acute lethal oral dose of the test substance to be greater than 2218 mg enzyme concentrate dry matter/kg bodyweight, in compliance with the study guidelines, a further group of three fasted females was similarly dosed at 2218 mg enzyme concentrate dry matter/kg bodyweight to complete the study.


There were no deaths during the study. There were no clinical signs of reaction to treatment throughout the study. All animals were considered to have achieved satisfactory bodyweight gains throughout the study. No abnormalities were noted in any animal at the macroscopic examination at study termination on Day 15.


The acute median lethal oral dose (LD50) to rats of pectin lyase, batch PPJ34366 was therefore demonstrated to be greater than 2218 mg enzyme concentrate dry matter/kg bodyweight (equivalent to 1428 mg aep/kg bodyweight).