4-(2-hydroxyethyl)piperazin-1-ylethanesulphonic acid

Endpoint summary

Description of key information

Oral (OECD TG 423), rat: LD50 > 2000 mg/kg bw (reference 7.2.1 -1)

Dermal (OECD TG 402), rat: LD50 > 2000 mg/kg bw (reference 7.2.3 -1).

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Jul 17 - Aug 28, 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

March 22, 1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

September 30, 1996

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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: F. Winkelmann, 33178 Borchen
- Age at study initiation: 6 - 8 weeks
- Weight at study initiation: 172 (range from 159 to 184) g
- Fasting period before study: 17 hours before dosing
- Housing: separately in Makrolon cages type III with a shelter, placed on mobile racks.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22
- Humidity (%): 54 to 71
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: day 1 To: day 14

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 200 g/L
- Amount of vehicle: 10 mL/kg
- Justification for choice of vehicle: low toxicity, good solubility
- Purity: Aqua pro injectione

CLASS METHOD
- Rationale for the selection of the starting dose: limit dose

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: days 2, 4, 6, 8, 11, 13, and 15
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross pathology

Statistics:

Standard statistical methods have been applied for data processing.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

All rats survived the observation period.

Clinical signs:

other: No signs of toxicity were detected in the 3 male and 3 female rats after treatment.

Gross pathology:

No alterations were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

According to the results of this study the test material is not acute toxic, i.e. the LD50 value is expected to exceed 2000 mg/kg bw.

Executive summary:

The GLP study was performed according to OECD TG 423. The test material was tested for acute toxicity in Wistar rats (3/sex/dose) after oral administration of. A limit dose of 2000 mg/kg body weight was applied. Directly before the administration the test material was prepared with aqua pro injectione as vehicle. The animals were observed for 14 days.

All rats survived the observation period. No signs of toxicity were detected in the 3 male and 3 female rats after treatment with 2000 mg/kg bw. The body weight development was normal. Gross pathology showed no alterations.

According to the results of this study the test material is not acute toxic, i.e. the LD50 value is expected to exceed 2000 mg/kg bw.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study according to OECD TG, RL1.

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Aug 2002 - Dec 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

24th February 1987

Deviations:

yes

Remarks:

animal room temperature outside range --> no effect on study outcome

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

31st July 1992

Deviations:

yes

Remarks:

animal room temperature outside range --> no effect on study outcome

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Janvier, Le Genest-Saint-Isle, France
- Age at study initiation: approximately 9 weeks
- Weight at study initiation: mean body weight ± standard deviation of 284 ± 9 g for the males and 230 ± 10 g for the females
- Housing:
During the acclimation period, one to seven animals of the same sex were housed in polycarbonate cages with stainless steel lid (48 cm x 27 cm x 20 cm).
During the treatment period, the animals were housed individually in polycarbonate cages with stainless steel lid (35.5 cm x 23.5 cm x 19.3 cm).
Each cage contained autoclaved sawdust (SICSA, Alfortville, France).
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 ± 2
- Humidity (%): 30 to 70
- Air changes (per hr): approximately 12
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: 10% of the total body surface
- Type of wrap if used: adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage

REMOVAL OF TEST SUBSTANCE
No residual test item was observed on removal of the dressing.

TEST MATERIAL
- Amount applied: 2000 mg/kg bw
- Constant volume or concentration used: yes
- For solids, paste formed: no

Duration of exposure:

24 h

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: at least once per day
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, macroscopic examination of the main organs

Statistics:

not applicable as no effects observed

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

none

Clinical signs:

other: none

Gross pathology:

No apparent abnormalities were observed at necropsy in any animal.

Other findings:

No cutaneous reactions were observed.

Interpretation of results:

GHS criteria not met

Conclusions:

In a GLP-study according to OECD Test Guideline 402, the test item tested at 2000 mg/kg bw did not induce any mortality. Therefore, the respective LD50 is larger than 2000 mg/kg bw.

Executive summary:

The acute dermal toxicity of the test item was evaluated in rats according to OECD (No. 402, 24th February 1987) and EC (92/69/EEC, B.3, 31st July 1992) guidelines. The study was conducted in compliance with the principles of Good Laboratory Practice Regulations. The test item was applied to the skin of one group of ten Sprague-Dawley rats (five males and five females). The application was performed with the test item in its original form at the dose of 2000 mg/kg. The test site was then covered by a semi-occlusive dressing for 24 hours. Clinical signs, mortality and body weight gain were checked for a period of 14 days following the single application of the test item. All animals were subjected to necropsy. The interpretation of results was carried out according to the classification criteria laid down in Council Directive 67/548/EEC (and subsequent adaptations). No clinical signs and no deaths were observed during the study. A reduced weight gain was seen in all males and in 3/5 females between day 1 and day 8. The body weight gain of the other females was similar to historical control animals. No cutaneous reactions were observed. No apparent abnormalities were observed at necropsy in any animal. Under our experimental conditions, the dermal LD50 of the test item is higher than 2000 mg/kg in rats.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

discriminating dose

Value:

2 000 mg/kg bw

Quality of whole database:

GLP study according to OECD TG, RL1.

Additional information

Acute toxicity: oral

The acute oral toxicity of 4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid was assessed in a study performed according to the acute toxic class method ATC (OECD 423) in Wistar rats (3/sex/dose) (reference 7.2.1 -1). A limit dose of 2000 mg/kg bw was administered. All rats survived the observation period (14 days). No signs of toxicity were detected in the 3 male and 3 female rats after treatment. The body weight development was normal. Gross pathology showed no alterations. According to the results of this study the test material can be allocated to ATC class 0 i.e. the LD50 value is expected to exceed 2000 mg/kg bw.

Acute toxicity: dermal

In a study performed according to OECD 402, 2000 mg/kg bw the test item was applied to the shaved skin of 10 Sprague-Dawley rats (5/sex) and held under a semi-occlusive dressing for 24 hours (reference 7.2.3 -1). No clinical signs and no deaths were observed during the study. A reduced weight gain was seen in all males and in 3/5 females between day 1 and day 8. The body weight gain of the other females was similar to historical control animals. No cutaneous reactions were observed. No apparent abnormalities were observed at necropsy in any animal. The LD50 is considered to be > 2000 mg/kg bw.  

The test substance-related findings were comparable for oral and dermal routes of application in the acute toxicity studies, with the high LD50-values indicating that the test item has a very low potential to cause acute toxicity via these routes.

Justification for classification or non-classification

The available experimental test data is reliable and suitable for classification purposes under Regulation (EC) No 1272/2008. As a result the substance is considered not to be classified for acute oral and dermal toxicity under Regulation (EC) No 1272/2008, as amended for the twelfth time in Regulation (EU) 2019/521.