3-cyclohexylaminopropane-1-sulphonic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2014-09-12 - 2014-12-17

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD guideline study under GLP without relevant deviations on the registered substance itself.

Cross-reference

Reason / purpose for cross-reference:

data waiving: supporting information

Reference

Endpoint:

skin corrosion: in vitro / ex vivo

Remarks:

and in vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because an acute toxicity study by the dermal route does not indicate skin irritation up to the relevant limit dose level (2 000 mg/kg body weight)

Justification for type of information:

JUSTIFICATION FOR DATA WAIVING
No pathological changes on the treated skin of male and female rats were found in a acute dermal toxicity test at a dose of 2000 mg/kg.

Reason / purpose for cross-reference:

data waiving: supporting information

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

valid from 2014-07-11

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3-(Cyclohexylamino)-propane sulfonic acid

IUPAC Name:

3-(Cyclohexylamino)-propane sulfonic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): 3-(Cyclohexylamino)-propane sulfonic acid
- Substance type: Pure compound
- Purity test date: 2014-09-03
- Batch No.: 08140015/107
- Expiration date of the lot/batch: 2017-08-15
- Storage condition of test material: in a container made of plastic, at temp. 15-25°C
- Other: Date of production: 2014-08-13

Test animals

Species:

rat

Strain:

other: Wistar (Crl: WI(Han); outbred)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Experimental Medicine Centre at the Medical University in Białystok
- Age at study initiation: 9 weeks (males), 8 weeks (females)
- Weight at study initiation: average 280 g (males), 213 g (females)
- Fasting period before study: no
- Housing: The animals were housed in plastic cages covered with wire bar lids. The dimensions of cages were 58 x 37 x 21 cm (length x width x height). After application of the test item, each animal was housed individually. After the removal of the test item from the animals’ skin, there were five rats per cage. Each sex was kept separately. UV-sterilized wood shavings were used as bedding.
- Diet (e.g. ad libitum): “Murigran” standard granulated laboratory fodder produced by Wytwórnia Koncentratów i Mieszanek Paszowych AGROPOL, Motycz (Batch No 3/14 and 4/14) ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 40-85%
- Air changes (per hr): about 16 times/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunks
- % coverage: 10% of the body surface area
- Type of wrap if used: The test item was applied to gauze patches. The patches were laid on the prepared skin and covered with PVC foil. An elastic bandage and a sticking plaster were used to make a circular protecting band.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- For solids, paste formed: no

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5/sex/dose

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Observation of all animals for mortality and morbidity was conducted twice a day or once a day (on days off). The detailed clinical observations were made on the application day (day 0) at hourly intervals up to 5 hours. From the 1st to the 14th day of the experiment, the detailed clinical observations were performed once a day.
- Necropsy of survivors performed: The detailed gross examination comprised the observation of the external body surface, all natural apertures, and the cranial, thoracic, and abdominal cavities with their contents.
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Effect levels 2

Sex:

male/female

Dose descriptor:

LD0

Effect level:

>= 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: All animals survived the single application of 2000 mg/kg bw.

Mortality:

All animals survived the experiment.

Clinical signs:

Following single application of the test item, the animals did not show any general clinical signs. No pathological changes on the treated skin were found in males and females.

Body weight:

During the 14-day experiment, body weight gain was found in all animals.

Gross pathology:

The gross examination did not reveal any pathological changes in the examined animals.

Applicant's summary and conclusion

Interpretation of results:

other: EU GHS criteria not met

Conclusions:

The study was conducted under GLP according to OECD guideline 402 on the registered substance itself. The method is to be considered scientifically reasonable with no deficiencies in documentation. Hence, the results can be considered as reliable to assess the acute oral toxicity in rats.
Following single application of 3-(Cyclohexylamino)-propane sulfonic acid at a dose of 2000 mg/kg bw, the animals did not show any general clinical signs. No pathological changes on the treated skin of males and females were found. All animals survived the experiment. During the 14-day experiment, body weight gain was found in all animals. Gross examination did not reveal any pathological changes in the examined animals. So it may be stated that the median lethal dose (LD50) of 3-(Cyclohexylamino)-propane sulfonic acid is greater than 2000 mg/kg b.w. Since no animal showed at no observation time any pathological changes on the treated skin or other signs of irritation, it may be concluded that, under the conditions of this test, 3-(Cyclohexylamino)-propane sulfonic acid, does not need to be considered as irritating to rat skin.
According to the Regulation (EC) No. 1272/2008, it may be concluded that 3-(Cyclohexylamino)-propane sulfonic acid is beyond categorization.

Executive summary:

In an acute dermal toxicity study (OECD 402), groups of 8-9 weeks old Wistar (Crl: WI(Han); outbred) rats (5/sex) were dermally exposed to unchanged 3-(Cyclohexylamino)-propane sulfonic acid for 24 hours on 10% of body surface area at a dose of 2000 mg/kg bw under occlusive coverage. Animals then were observed for 14 days.

 

Following single application of the test item, the animals did not show any general clinical signs. No pathological changes on the treated skin of males and females were found. All animals survived the experiment. During the 14-day experiment, body weight gain was found in all animals. Gross examination did not reveal any pathological changes in the examined animals. Hence, the following results could be gained:

 

LD0(dermal) ≥ 2000 mg/kg bw

LD50(dermal) > 2000 mg/kg bw

 

3-(Cyclohexylamino)-propane sulfonic acid is of lowToxicity based on the LD50 determined. Since no animal showed at no observation time any pathological changes on the treated skin or other signs of irritation, it may be concluded that, under the conditions of this test, 3-(Cyclohexylamino)-propane sulfonic acid does not need to be considered as irritating to rat skin.

According to Regulation (EC) No. 1272/2008, it may be concluded that 3-(Cyclohexylamino)-propane sulfonic acid is beyond categorization.