4-(cyclohexylamino)butane-1-sulfonic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 Aug 2019 - 16 Oct 2019

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2019

Report date:

2020

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

December 2001

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Version / remarks:

May 2008

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Guidelines, including the most recent revisions.

Version / remarks:

2000

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-(cyclohexylamino)butane-1-sulfonic acid

EC Number:

629-080-0

Cas Number:

161308-34-5

Molecular formula:

C10 H21 N O3 S

IUPAC Name:

4-(cyclohexylamino)butane-1-sulfonic acid

Test material form:

solid

Details on test material:

Physical Description: White solid
Storage Conditions: At room temperature

Test animals

Species:

rat

Strain:

other: Crl:WI (Han)

Sex:

female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at the initiation of dosing: Young adult animals (approx. 8-9 weeks old)
- Weight at the initiating of dosing: 150 to 198 g
- Fasting period before study: Animals were deprived of food overnight (for a maximum of 20 hours) prior to dosing and until 3-4 hours after administration of the test item.
- Housing: Group housing of 3 animals of the same dosing group in polycarbonate cages (Makrolon MIV type), containing sterilized sawdust as bedding material equipped with water bottles.
- Diet: Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 18 – 24 (actual daily mean: 21)
- Humidity (%): 40 - 70 (actual daily mean: 33 - 68)
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

GAVAGE METHOD: syringe with a plastic gavage cannula attached

Frequency: single dosage, on Day 1.

VEHICLE
The vehicle was selected based on trial preparations.

DOSAGE PREPARATION
Test item dosing formulations (w/w) were homogenized to visually acceptable levels at appropriate concentrations to meet dose level requirements. The dosing formulations were kept at room temperature until dosing (and used within 4 hours after preparation). The dosing formulations were stirred until and during dosing.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

2 groups of 3 females in a stepwise manner

Control animals:

no

Details on study design:

The toxicity of the test item was assessed by stepwise treatment of groups of 3 females. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups. The first group was treated at a dose level of 2000 mg/kg. Based on the results, one additional group was dosed at 2000 mg/kg.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Moribundity checks: Twice daily, in the morning and at the end of the working day.
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (at least 3 times) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
- Other examinations performed: none.

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

other: Hunched posture and/or piloerection were noted for all animals between Days 1 and 6.

Body weight:

lower than 10% body weight loss

Remarks:

The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.

Gross pathology:

No abnormalities were found at macroscopic post mortem examination of the animals.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study with the substance in 6 female rats, performed in a stepwise manner according to OECD/EC test guidelines, an LD50 of >2000 mg/kg bw was determined. As no mortality occurred, the LD50 cut-off value was considered to be 5000 mg/kg body weight according to the OECD 423 test guideline.

Executive summary:

The acute oral toxicity of 4-(cyclohexylamino)butane-1-sulfonic acid was determined in accordance with OECD guideline 423 (2001) and according to GLP principles. The substance was administered by oral gavage to two consecutive groups of three female Wistar Han rats at 2000 mg/kg body weight. No mortality occurred. Hunched posture and/or piloerection were noted for all animals between Days 1 and 6. The body weight gain shown by the animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain. No abnormalities were found at macroscopic post mortem examination of the animals. The acute oral toxicity (LD50) was determined to be > 2000 mg/kg bw.