[No public or meaningful name is available]

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

September 4, 2018 to October 29, 2018

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2018

Report date:

2018

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Sulfonic Acids, C18-alkane hydroxyl and C18-alkene, potassium salts

Cas Number:

2210238-56-3

IUPAC Name:

Sulfonic Acids, C18-alkane hydroxyl and C18-alkene, potassium salts

Test material form:

cream / paste

Remarks:

Pale yellow paste at 50℃, This sample was obtained from the original liquid form by removing water.

Specific details on test material used for the study:

Storage Condition: Store container tightly closed in well-ventilated place. Store in corrosive resistant/container with a resistant inliner. Store locked up. Don' t store with acids.

Test animals

Species:

rat

Strain:

Crj: CD(SD)

Remarks:

SPF

Sex:

female

Details on test animals or test system and environmental conditions:

First delivery: 7 Weeks old, 178-188 g
Second delivery: 7 Weeks old, 174-188 g


The rat was selected because it is widely used in acute toxicity studies of rodents and recommended in the relevant guideline.


Quarantine period: For 4 days after receipt
Acclimatization period: First delivery, For 5-7days after receipt Second delivery, For 6 days after receipt
Observation of general condition: Once daily
Body-weight measurement: The animals were weighed on the day of receipt, next day of receipt, final day of the quarantine period, and day of grouping.
Observation of the general condition and body-weight measurement were performed during the quarantine and acclimatization period; all the animals considered healthy were used for grouping.


The animals were weighed on each day before administration, and 3 heaviest ones were selected. The body weights of the animals for the second and third administration were within the range of 土 20% of the mean weight of the first-administration group. The surplus animals were excluded from the study.


Housing room: Quarantine and acclimatization period, Clean Room 1 (first delivery) and Clean Room 5 (second delivery). Acclimatization and test period, Clean room 1
Temperature: Actual values, 21.7°C - 27.8°C (set value, 23°C; acceptable range, 20°C - 26°C) . The temperature temporarily deviated; however, it is not considered to have affected the reliability of the study because it was a slight deviation and because no abnormalities were noted in the animals' general condition.
Relative humidity: Actual values, 45.7% - 65.8% (set value: 50%; acceptable range: 30% - 70%)
Ventilation frequency: 12 times/hour (all fresh air)
Light period: 12 Hours/day (on at 6:00 AM, off at 6:00 PM)
Cage: Polycarbonate flat-bottomed cage (W260 x D420 x HI 80 mm; Natsume Seisakusho Co., Ltd.). Cages were changed more than once weekly with bedding.
Rack: Five-shelf stainless-steel rack
Feeder: Cage-lid-integrated stainless-steel feeder
Housing: During the quarantine and acclimatization period, animals were housed 3 or 4 per cage; after grouping, 3 per cage.
Feed: Pellet diet MF (Lot No. 180327, 180531; Oriental Yeast Co., Ltd.) was offered ad libitum. The animals were fasted for a certain period in conformity to the under described administration method.
Drinking water: Municipal tap water filtered through a 5-µm cartridge filter and sterilized with an ultraviolet sterilizer was offered ad libitum through an automatic water-supply system.
Bedding: Pulp bedding (Paper Clean; Lot No. 1806; Japan SLC, Inc.) was used. It was removed during the fasting period.


The analytical results of each lot of feed were obtained from Oriental Yeast Co., Ltd., and the levels of contaminants in the feed were confirmed to meet the acceptable standards specified in SOP.


Water was analyzed with respect to the water quality criteria stipulated by the Waterworks Law (once/year) and the quality of purified water (once/month) by the Saitama-ken Environmental Analysis & Research Association, and the levels of contaminants in the water were confirmed to meet the acceptable standards specified in SOP.


Bedding was analyzed by the manufacturer, and the results of the analysis were obtained. The levels of contaminants in the bedding were confirmed not to be greater than the acceptable level specified in SOP.


The housing rooms were cleaned and disinfected with an amphoteric surface-active sterilizer(Nissan Anon; NOF CORPORATION) daily, except on holidays.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

The animals were transferred into polycarbonate flat-bottom cages, on which only flooring nets were placed, and fasted from around 4 PM on the day before administration through 3 hours after the completion of administration.


8 Weeks old (193 - 204 g). The body weights of the animals in the second- and third administration groups ranged within 士 20% of the mean weight of the first-administration group, and the difference was not noteworthy.


The volume of the dosing formulation was calculated for each animal based on the body weight of the day of administration. Oral gavage administration was performed with a metal stomach tube connected to a 2.5 mL syringe between 9:43 AM and 9:45 AM for the first administration, between 9:41 AM and 9:43 AM for the second administration, and between 9:32 AM and 9:33 AM for the third administration.

Doses:

First administration: 2000 mg/kg based on active ingredients.
Second administration: 300 mg/kg based on active ingredients.
Third administration: 300 mg/kg based on active ingredients.

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

According to the Guidance Document on Acute Oral Toxicity, Guideline No. 423 (OECD Guideline for Testing of Chemicals, Acute Oral Toxicity - Acute Toxic Class Method. Adopted: December 17, 2001) and the sponsor's request, 2000 mg/kg was selected as the starting dose.


The name of the groups, number of animals are shown below.
Group name Number of animals
First-administration group 3
Second-administration group 3
Third-administration group 3


The procedures of the initial administration and thereafter were in accordance with the Annex 2d of the Guidance Document on Acute Oral Toxicity, Guideline No. 423 (OECD Guideline for Testing of Chemicals, Acute Oral Toxicity - Acute Toxic Class Method. Adopted: December 17, 2001).


The dose volume was 10 mL per 1 kg in body weight. The volume of the dosing formulation for each animal was calculated on the basis of the body weight measured on the day of administration.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

act. ingr.

Mortality:

Shown in table 1 of attachment.

Clinical signs:

other:

Body weight:

other body weight observations

Remarks:

Shown in table 3 of attachment.

Gross pathology:

Shown in table 4 of attachment.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 of Sulfonic acids, C18-alkane hydroxy and C18-alkene, potassium salts is considered to be in the range between 300 and 2000 mg/kg.

Executive summary:

Acute oral toxicity of Sulfonic acids, C18-alkane hydroxy and C18-alkene, potassium salts (synonym: C18K) was investigated in rats.

According to the Guidance Document on Acute Oral Toxicity, Guideline No. 423, 3 animals of the first-administration group received a 2000-mg/kg dose. Since 2 animals died at the first administration, 3 animals of the second administration received a 300-mg/kg dose. After confirming no animal died at the second administration, the same dose was given to 3 third-administration-group animals. Observation for mortality and general condition was performed for 14 days after administration, and body weights were measured during the period. After the completion of the observation period, gross observation of organs was performed as a necropsy.

As results, 2 animals died in the first administration at the dose of 2000 mg/kg. Those animals had soiled perinea! region and loose stool, and died 1 day after administration. In necropsy, black spots and smoothing were found in the mucosa of the glandular stomach. Although the survived animal also had soiled perineal region and loose stool, these signs disappeared by 1 day after administration. Its body weight decreased 1 day after administration, and increased from 2 days after administration. Necropsy revealed no changes suggesting the influence of the test-substance administration.

In the groups of the second and third administration at the dose of 300 mg/kg, no animal died. Although soiled perineal region and loose stool were noted, these signs disappeared by 1 day after administration. Body weights satisfactorily increased from 1 day after administration. Necropsy revealed no changes suggesting the influence of the test-substance administration.

Based on the above, the LD50 of the test substance is considered to be in the range between 300 and 2000 mg/kg under the conditions of this study.