Sodium glyoxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 23 May 2008 and 10 July 2009

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Sodium glyoxylate

EC Number:

220-298-8

EC Name:

Sodium glyoxylate

Cas Number:

2706-75-4

Molecular formula:

C2H2O3.Na

IUPAC Name:

sodium oxoacetate

Specific details on test material used for the study:

Name: Sodium glyoxylate (Abbr.: GOA-Na)
Lot number C080501
Appearance: White powder
Purity: 100%
Storage conditions: Room temperature (permissible range: 10° to 30°C, actual value: 16.6° to 22.7°C), in shielded from light, hermetic sealing, headspace of storage container was filled with nitrogen

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

female

Details on test animals or test system and environmental conditions:

Microbial level: SPF

Supplier: Charles River Laboratories Japan, Inc. (Tsukuba breeding center)

Number of animals purchased: 8 females for the first and second administrations

Rationale for the selection of sex: The female was selected in accordance with the OECD Guidelines for the Testing of Chemicals (No. 423).

Quarantine/acclimation: During the 5 days of the quarantine period, animals were observed once daily for their clinical signs, and confirmed to be in good health. In addition, they were subjected to the body weight measurement on arrival and at the end of the quarantine period to confirm their normal body weight gain. After the quarantine period, they were further acclimated and observed once daily for their clinical signs until the day of the administration.

Age at administration: 8 weeks old

Grouping: Animals were assigned to the first and second administration groups using the stratified-by-weight randomization method on the basis of body weights upon completion of quarantine to get almost the same mean body weights for each group.

Body weight at administration: The body weights of animals were within ±20% of the mean body weights on each administration day. Moreover, the mean value at the second administration was within ±20% of the mean value at the first administration. For the first and second administrations, the actual body weights of the animals ranged from 195 to 219 g.

Identification of animals: Animals were identified by marking on the tail (indicated with the number of the last one digit of identification number for the quarantine/acclimation period) with an oil-based ink pen. During the quarantine/acclimation period (before grouping), cages were labeled with a card listing the study number, cage number, animal number for the quarantine/acclimation period, species, strain, and sex. After the grouping, animals were identified anew by marking on the tail (indicated with the mark of the last one digit of animal number) with an oil-based ink pen, and cages were labeled with a card listing the study number, test substance name, group name (dose level), sex, species, strain, and animal number.

Disposition of surplus animals: Surplus animals were euthanized by exsanguinations from the abdominal aorta under anesthesia (sodium thiopental; Ravonal®, Mitsubishi Tanabe Pharma Corporation, i.p.) after the completion of administration of the other animals purchased on the same day.

Animal management
Housing environment
Temperature:
Actual value: 21.6°C - 22.1°C (room 4125, permissible range: 19.0°C - 25.0°C)
Actual value: 22.3°C - 23.0°C (room 2124, permissible range: 19.0°C - 25.0°C)

Relative humidity:
Actual value: 47.4%- 55.3% (room 4125, permissible range: 35.0% - 75.0%)
Actual value: 45.1% - 62.7% (room 2124, permissible range: 35.0% - 75.0%)

Ventilation:
6 to 20 times/hour, all fresh filtered air

Lighting period:
12 hours/day (7:00 - 19:00)

Animal accommodation
Cages:
Autoclave-sterilized polycarbonate cages (265Wx426Dx200H mm, Tokiwa Kagaku Kikai Co., Ltd.) were used and replaced on the days of grouping and Day 8. Furthermore, cages for the animals of second administration were replaced on the day of
the completion of acclimation (the day before administration) as well.

Feeders:
Autoclave-sterilized stainless steel feeders for pellet feed (Tokiwa Kagaku Kikai Co., Ltd.) were used and replaced at the same time as the cages.

Watering bottles:
Autoclave-sterilized polycarbonate watering bottles (700 mL, Tokiwa Kagaku Kikai Co., Ltd.) were used and replaced at the same time as the cages.

Racks:
A steel rack (Tokiwa Kagaku Kikai Co., Ltd.) disinfected with a diluted solution of benzalkonium detergent (Micro Quat®, Ecolab Inc) was used.

Bedding
Type:
Autoclave-sterilized bedding for experimental animals (Beta-Chip®, Charles River Laboratories Japan, Inc.) and autoclave-sterilized stainless steel floor grates (Tokiwa Kagaku Kikai Co., Ltd.) were used and replaced at the same time as the cages.

Analysis of contaminants:
Analysis data by Eurofins Scientific, to which Charles River Laboratories Japan, Inc. contracted the work, were provided by Charles River Laboratories Japan, Inc. On the basis of the analysis data, it was confirmed that the levels of the environmental contaminants, such as residual pesticides in the chip used in this study were all within the permissible levels of the SOP of the test facility.

Feed
Type:
Pellet feed for experimental animals (l'v1F, Oriental Yeast Co., Ltd.)

Feeding:
ad libitum; the feed was replaced at the same time as the feeders. The animals were fasted from the evening on the day before the administration (approximately 18 hours predose) to 3 hours postdose.

Analysis of contaminants:
Analysis data by Eurofins Scientific, to which Oriental Yeast Co., Ltd. contracted the work, were provided by Oriental Yeast Co., Ltd. On the basis of the analysis data, it was confirmed that the levels of environmental contaminants, such as residual pesticides in the lot (Lot No. 080318) used in this study were within the permissible levels of the SOP of the test facility.

Drinking Water
Description:
Tap water filtered through 5-μm filter and irradiated by UV light.

Water supply method:
ad libitum; the water was replaced at the same time as the watering bottles.

Analysis:
The tap water is analyzed periodically (twice a year) by Dia Analysis Service Inc. From the analytical data, it was confirmed that the quality of the water met the specifications of the SOP of the test facility.

Animals per cage
Animals were housed 4 animals per cage before grouping, and 3 animals per cage after group mg.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5 w/v% CMC-Na solution

Details on oral exposure:

An oral administration by gavage was conducted using a disposable syringe equipped with a gastric tube to the animals fasted for approximately 18 hours from the evening on the day before the administration. At the administration, the dosing suspension was stirred using a magnetic stirrer. The animals were fasted for approximately 3 hours after the administration.

Doses:

2000 mg/kg (10 mL/kg)

No. of animals per sex per dose:

two groups of 3 females

Control animals:

no

Details on study design:

Observations and measurements
The following observations and measurements were performed. The day of the initial administration was designated as Day 1.
- Clinical observation: All animals were observed for their mortality and clinical signs before the dosing and at 10 and 30 minutes, 1, 3, and 6 hours postdose (6 times in total) on the day of the administration and once daily for 14 days thereafter.
- Body weight measurement: All animals were subjected to the body weight measurement just before the administration (Day 1) and on Days 4, 8, and 15 using an electronic balance (EB-3200S, Shimadzu Corporation). Moreover, the body weight gain between each measurement day was calculated.

Necropsy
All animals were euthanized by exsanguinations from the abdominal aorta under anesthesia (sodium thiopental; Ravonal®, Mitsubishi Tanabe Pharma Corporation, i.p.), and then subjected to necropsy on Day 15. The organs were not collected.

Results and discussion

Effect levels

Dose descriptor:

LD50

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No deaths were noted.

Clinical signs:

other: Diarrhea was noted in I animal of first dosing group from 1hr after administration until 6hr after administration and slight decreased locomotor activity was noted in all animals (6 animals) of at the first and second dosing groups from 3hr after administ

Gross pathology:

No abnormalities in necropsy findings were noted in any animals at the first and second administration.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

This study was conducted to assess the acute toxicity of GOA-Na in female rats by single oral gavage administration at the single dose of 2000 mg/kg (for the first and second dosing groups).
As a result, no death was noted at the dose level of 2000 mg/kg. In conclusion, the approximate lethal dose 50% (LD50) of GOA-Na under the conditions of this study was estimated to be 2000 mg/kg or above.

Executive summary:

Single oral administration by gavage of GOA-Na was conducted to female SD (Crl:CD( SD)) rats aged 8 weeks old to evaluate its acute oral toxicity in accordance with the OECD Guidelines for Testing of Chemicals (No. 423). 2000 mg/kg was employed as a dose for the first and second administration. GOA-Na was suspended in 0. 5 w/v% CMC-Na solution to make a dosing suspension at a concentration of 200 mg/mL. This suspension was given at 10 mL/kg to the animals fasted from the evening of the day before administration.

As a result, no deaths were noted. Diarrhea and decreased locomotor activity were noted on the day of administration; however, these abnormal changes disappeared by Day 3. One animal with body weight loss on Day 4 showed hunchback position; however, it recovered on Day 8. No abnormalities were found in any animals in the necropsy. In conclusion, the approximate lethal dose 50% (LD50) of GOA-Na under the conditions of this study was estimated to be 2000 mg/kg or above, and was classified into Category 5 (>2000-5000 mg/kg b.w.) in accordance with the Globally Harmonized Classification System (GH S).