N,N,4-trimethylpiperazine-1-ethylamine

Endpoint summary

Description of key information

Acute oral toxicity: In an acute oral toxicity in Wistar (SPF) rats, following the acute toxic class method in accordance with the OECD guideline 423, the LD50 was determined to be in the range 200-2000 mg/kg for both females and males (K1, Huygevoort A, 2002).

Acute dermal toxicity: in an acute dermal toxicity study in Albino rabbits, the LD50 was determined to be 0.51mL/kg. The test substance is classified as acute dermal toxicant category 4. As the substance is corrosive to skin, no additional acute toxicity testing is required.

Acute inhalation toxicity: An acute inhalation toxicity study does not need to be performed as the substance is corrosive to the skin.

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:

From 2002-01-03 to 2002-01-17

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study without detailed documentation

Qualifier:

equivalent or similar to guideline

Guideline:

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

Deviations:

not specified

GLP compliance:

not specified

Test type:

acute toxic class method

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: 180601
- Expiration date of the lot/batch: 2002-10-25

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: At room temperature in the dark

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

no details provided

Route of administration:

oral: gavage

Details on oral exposure:

no details provided

Doses:

200 mg/kg ; 2000 mg/kg body weight

No. of animals per sex per dose:

2 groups:
2 females - 2000 mg/kg body weight
2 females - 200 mg/kg body weight

Control animals:

no

Details on study design:

Animals were subjected to daily observations and weekly determination of body weight.
All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

>= 200 - <= 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Two females were found dead within 5.5 hours post-treatment (2000 mg/kg). No further mortality occured.

Clinical signs:

other: One decedent showed lethargy, hunched posture, uncoordinated movements, slow breathing, piloerection and ptosis. No clinical signs of toxicity were noted in the other decedent. Animals given 200 mg/kg showed lethargy on day 1.

Gross pathology:

Dark red discoloration of the glandular mucosa of the stomach and dark red discoloration of the forestomach was noted in one animals that died during the study, at macroscopic post mortem examination. The other decedent showed dark red discoloration of the forestomach and the jejunum and ileum contained hemorrhagic fluid. Macroscopic post mortem examination of the other animals did not reveal any abnormalities.

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The oral LD50 value for female rats was established to be within the range of 200-2000 mg/kg body weight.
Based on these rsults and according to the CLP Regulation, the test substance is considered classified as acute oral toxicant category 3.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

200 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

other:

Clinical signs:

other:

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Link to relevant study records

Reference

Reference 1

Endpoint:

acute toxicity: dermal

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

the study does not need to be conducted because the substance is classified as corrosive to the skin

Reference 2

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

supporting study

Study period:

1966

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

test procedure in accordance with national standard methods with acceptable restrictions

Qualifier:

no guideline followed

Principles of method if other than guideline:

The study was performed according to accepted scientific methods.

GLP compliance:

not specified

Limit test:

no

Species:

rabbit

Strain:

other: Albino

Sex:

male

Type of coverage:

not specified

Vehicle:

not specified

Details on dermal exposure:

The product as receive was held in continuous 24-hour contact with the shaved skin

Duration of exposure:

24 hrs

Doses:

0.313, 0.625, 1.25 mL/kg

No. of animals per sex per dose:

No data

Control animals:

no

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

0.51 mL/kg bw

Based on:

test mat.

95% CL:

>= 0.39 - <= 0.67

Mortality:

1.25 mL/kg: 5/5 animals died within 6-24 hrs
0.625 mL/kg: 4/5 animals died (3 animals on day 3, 1 animals on day 5)
0.313 mL/kg: 0/5 animals died

Clinical signs:

other: signs of intoxication observed: depression

Gross pathology:

Gross pathology of surviving animals was performed, and no abnormalities were observed.

Other findings:

signs of irritation observed: eschar formation

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

An LD50 value of 0.51 mL/kg was established. The test substance is considered classified as acute dermal toxicant category 4 according to CLP Regulation.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Quality of whole database:

LD50 was established at 0.51mL/kg.

Additional information

Acute oral toxicity:

The study aimed to assess the acute oral toxicity of the test substance to the rat using the acute toxic class method in male and female Wistar (SPF) rats, according to the OECD guideline 423 (K1, Huygevoort A, 2002).

Initially, one group of Wistar rats, consisting of two females, received a single oral dose of 2000 mg/kg body weight (dose volume 2.27 ml/kg). Due to mortality, one additional group of two females was dosed at 200 mg/kg (dose volume 0.23 ml/kg). Animals were subjected to daily observations and weekly determination of body weight. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded. 

Two females were found dead within 5.5 hours post treatment (at 2000 mg/kg). No further mortality occurred. One decedent showed lethargy, hunched posture, uncoordinated movements, slow breathing, piloerection and ptosis. No clinical signs of toxicity were noted in the other decedent. Animals given 200 mg/kg showed lethargy on day 1. Body weight gain of the animals during the 8 -day study period was considered to be normal. Dark red discolouration of the glandular mucosa of the stomach and dark red discolouration of the forestomach was noted in one animals that died during the study, at macroscopic post mortem examination. The other decedent showed dark red discolouration of the forestomach and the jejunum and ileum contained hemorrhagic fluid. Macroscopic post mortem examination of the other animals did not reveal any abnormalities. The oral LD50 value for female rats was established to be within the range of 200-2000 mg/kg.

Acute dermal toxicity:

In addition to the oral route of exposure, for substances other than gases, the information mentioned under REACH section 8.5.2 to 8.5.3 shall be provided for at least one other exposure route (REACH Regulation, column 2 adaptation of Annex VIII). As this substance is classified as corrosive to skin (Cat 1A), the dermal route of exposure can be waived.

A K2, supporting study is available (1966). In this study, LD50 is calculated at 0.51mL/kg in male albino rabbits.

Acute inhalation toxicity:

In addition to the oral route of exposure, for substances other than gases, the information mentioned under REACH section 8.5.2 to 8.5.3 shall be provided for at least one other exposure route (REACH Regulation, column 2 adaptation of Annex VIII). As this substance is classified as corrosive to skin (Cat 1A), the inhalation route of exposure can be waived.

Justification for classification or non-classification

The substance is classified as Acute oral toxicant Category 3 and acute dermal toxicant category 4 according to EU CLP Regulation.

No acute inhalation toxicity testing is performed, as the substance is classified as corrosive to skin according to EU CLP.