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Description of key information

Xanthan lyase was not tested for acute toxicity, but two closely-related enzymes, pectate lyase and pectin lyase, were tested for acute toxicity.


 


The acute toxicity of pectate lyase and pectin lyase was tested by administration by gavage as a single oral dose to one group of five male and five female rats followed by an observation period of 14 days. No signs of toxicity were observed among the rats treated with a single oral dose of pectate lyase corresponding 2447 mg enzyme concentrate dry matter/kg bodyweight (equivalent to 1526 mg aep/kg bodyweight) or a single dose of pectin lyase corresponding to 2218 mg enzyme concentrate dry matter/kg bodyweight (equivalent to 1428 mg aep/kg bodyweight).


 


Based on the similarity of the tested enzymes with xanthan lyase - all belonging to the same enzyme sub-subclass - it can be concluded that similar results are expected for xanthan lyase.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
read-across based on grouping of substances (category approach)
Adequacy of study:
supporting study
Study period:
February 22, 1999 to May 5, 1999
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Read-across to pectate lyase is applied. Data on pectate 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.
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Version / remarks:
1992
Deviations:
no
Qualifier:
according to guideline
Guideline:
other: EEC directive 92/69/EEC
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Møllegaard Avlslaboratorium, Ejby, DK
- Females (if applicable) nulliparous and non-pregnant: Yes
- Age at study initiation: Not specified
- Fasting period before dosing: 20 hours prior to dosing and until 1 hour after the last dosing procedure.
- Housing: Barriered rodent facility with control of temperature and humidity. Five of the same sex per cage in transparent plastic boxes with wire grid tops with aspen wood chips as bedding.
- Weight at the end of the acclimatisation period: Males 172-184 g, females 137-147 g.
- Diet: Altromin rat/mouse Breeding 1320 diet pellets ad libitum
- Water: Tap water added citric acid to pH 2-3 ad libitum
- Acclimation period: 5 days

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

IN-LIFE DATES: From: 1999-02-26 To: 1992-03-12
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Undiluted test material.
Doses:
Dose volume was 24 mL/kg bodyweight. The animals were dosed twice with 12 mL/kg bodyweight within 2 hours.
24 mL/kg bodyweight is equivalent to 2447 mg enzyme concentrate dry matter/kg bodyweight (corresponding to 1526 mg aep/kg bodyweight).
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 symptoms after the first and second dosing procedure and 2 hours after the last dosing. Thereafter clinical observations were carried out once a day for the following 14 days. Animals were weighed on day 1 (before dosing) and on day 8 and before necropsy on day 15.
- Necropsy of survivors performed: yes
Statistics:
No
Sex:
male/female
Dose descriptor:
LD0
Effect level:
>= 2 328 mg/kg bw
Based on:
other: mg enzyme concentrate dry matter
Mortality:
No animals died during the observation period.
Clinical signs:
No clinical symptoms were seen during the observation period.
Body weight:
No effect was observed on the body weights.
Gross pathology:
Effects on organs:
Macroscopic examination of animals killed on Day 15 of the observation period did not reveal any treatment-related findings.
Interpretation of results:
GHS criteria not met
Conclusions:
No signs of toxicity were observed for pectate lyase tested on rats treated with a single oral dose of 2447 mg enzyme concentrate dry matter/kg bodyweight (corresponding to 1526 mg aep/kg bodyweight), which was the highest possible dose at dose volume 24 mL/kg, using the undiluted test item.
Executive summary:

The objective of the study was to assess the acute toxicity of pectate lyase when administered by gavage as a single oral dose to one group of five male and five female rats followed by an observation period of 14 days.


The study was conducted in accordance with the OECD Guideline No 401, 1987 “Acute Oral Toxicity”. The limit test was used. The test item was supplied as a brown liquid ready to use. The dose volume administered was 2x12 mL/kg bodyweight of the undiluted test material.


No clinical signs 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 2447 mg enzyme concentrate dry matter/kg bodyweight (corresponding to 1526 mg aep/kg bodyweight).

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.
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
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
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
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.
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).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Toxicological data has been generated within the enzyme producing industry during the last 40 years. Substantial documentation on the safety of the production strains have been generated, and the enzyme test materials are thoroughly characterized. High quality studies for all relevant endpoints, in vivo studies as well as in vitro studies, show that industrial enzymes from well-known and well-characterized production strains have very similar safety profiles across the catalytic activities. Read-across can therefore be applied for the majority of toxicological endpoints. The database can thus be considered of high quality.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Justification for classification or non-classification

Based on the results from the two acute toxicity tests with pectate lyase and pectin lyase, xanthan lyase is not classified.