Tributylethylammonium ethyl sulphate

Endpoint summary

Description of key information

Acute oral and dermal studies with TBEAES performed in accordance with current OECD/EC test guidelines and GLP principles, showed LD50 values >2000 mg/kg bw for acute oral and dermal toxicity in rats.

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:

December 1999 - January 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:

1996

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1996

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Species:

rat

Strain:

other: Crl:(WI) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 7 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (males 260 - 277 grams, females 172-188 grams).
- Fasting period before study: Food was witheld overnight (for maximum of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance.
- Housing: Group housing of 3 animals per cage in labeled polycarbonate cages containing purified sawdust as bedding material.
- Diet: Free access to pelleted rodent diet (from Carfil Quality BVBA, Oud-Turnhout, Belgium).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
set to maintain:
- Temperature (°C): 21
- Humidity (%): 30 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Deviations from these optimal conditions were noted, but were considered not to have affected study integrity.

IN-LIFE DATES: From: 28 December 1999 tot 13 January 2000

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Details on oral exposure:

GAVAGE METHOD: stainless steel stomach tubes.

Frequency: single dosage, on Day 1.

- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED: 2000 mg/kg (10 mL/kg) body weight.

DOSAGE PREPARATION: The formulations (w/w) were prepared within 4 hours prior to dosing. The test substance was heated up to 70°C immediately prior to formulation. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of vehicle.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 females and 3 males in a stepwise manner

Control animals:

no

Details on study design:

Animals were deprived of food overnight prior to dosing and until 3-4 hours after administration of the test substance. Water was available ad libitum.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15.
Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.
- Necropsy of survivors performed: At the end of the observation period. Descriptions of all internal macroscopic abnormalities were recorded
- Other examinations performed: none.

Statistics:

No statistical analysis was performed (The method used is not intended to allow the calculation of a precise LD50 value).

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured

Clinical signs:

other: In one female, uncoordinated movements were noted on day 1. No clinical signs were noted in the remaining two females. Among males, tremors and/or uncoordinated movements were noted on day 1.

Gross pathology:

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

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute oral toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.

Executive summary:

Assessment of acute oral toxicity of TBEAES was performed in Wistar rats according to OECD/EC guidelines and GLP principles. TBEAES was administired in a single dose to rats of both sexes at 2000 mg/kg body weight. No mortality occured. In one female, uncoordinated movements were noted on day 1. No clinical signs were noted in the remaining two females. Among males, tremors and/or uncoordinated movements were noted on day 1. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. the oral LD50 value of TBEAES in Wistar rats was established to exceed 2000 mg/kg body weight. Based on these results TBEAES does not have to be classified and has no obligatory labelling requirements for oral toxicity according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The study has been performed according to OECD and/or EC guidelines and according to GLP principles (Klimisch 1).

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:

August to October 2000

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:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

yes

Species:

rat

Strain:

other: Wistar strain, Crl:(WI) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Source: Charkes River Deutschland, Sulzfeld, Germany.
- Age at study initiation: Young adult animals (approx. 8 weeks old)
- Weight at study initiation: Body weight variation was within +/- 20% of the sex mean (males 315-370 grams and females 202-233 grams).
- Housing: Individually housed in polycarbonate cages.
- Diet: Free access to pelleted rodent diet (Carfil Quality BVBA, Oud-Turnhout, Belgium).
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
set to maintain:
- Temperature (°C): 21
- Humidity (%): 50
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

Deviations from these optimal conditions were noted, but were considered not to have affected study integrity.

IN-LIFE DATES: From 9 August 2000 to 23 August 2000

Type of coverage:

occlusive

Vehicle:

propylene glycol

Details on dermal exposure:

VEHICLE
- Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at NOTOX and on test substance data supplied by the sponsor.

Dose volume: 10 mL/kg body weight.

DOSAGE PREPARATION
To facilitate preparation, the test substance and test substance formulation (w/w) were heated up to 70°C within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made for specific gravity of vehicle. The temperature of the formulation at time of dosing was 30-40°C.

One day before exposure (Day -1) an area of approximately 5x7 cm on the back of the animal was clipped.

The formulation was applied in an area of approx. 10% of the total body surface, i.e. approx. 25 cm² for males and 18 cm² for females. The formulation was held in contact with the skin with a dressing. A piece of Micropore tape was additionally used for fixation of the bandage in females only.

Frequency: Single dosage, on Day 1.

Washing: tap water.

Duration of exposure:

24 hours.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

Duration of observation period following administration: 14 days
Frequency of observations and weighing:
- Mortality/Viability: Twice daily
- Body weights: Days 1 (pre-administration), 8 and 15
- Clinical signs: At periodic intervals on the day of dosing (Day 1) and once daily thereafter, until Day 15.

- Necropsy of survivors performed: At end of the observation period. Descriptions of all internal macroscopic abnormalities were recorded.
- Other examinations performed: none.

Statistics:

None.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured

Clinical signs:

other: Chromodacryorrhoea was noted in two males and one female on days 1 and/or 2. Focal erythema was seen in the treated skin-aera of two males and two females during the observation period.

Gross pathology:

No abnormalities were found at macroscopic post mortem examinations of animals.

Interpretation of results:

GHS criteria not met

Conclusions:

In an acute dermal toxicity study with rats, performed according to OECD/EC test guidelines, an LD50 >2000 mg/kg bw was determined.

Executive summary:

Assessment of acute dermal toxicity with TBEAES in the rat was performed according to OECD/ EC guidelines and according to GLP principles. TBEAES was administired to five Wistar rats of each sex by dermal application at 2000 mg/kg bw for 24 hours. No mortality occured. Chromodacryorrhoea was noted in two males and one female on days 1 and/or 2. Focal erythema was seen in the treated skin-area of two males and two females during the observation period. The changes noted in body weight gain in males and females were considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals.The dermal LD50 value of TBEAES in Wistar rats was established to exceed 2000 mg/kg bw. Based on these results, TBEAES does not have to be classified and has no obligatory labelling requirement for dermal toxicity according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Quality of whole database:

The study has been performed according to OECD and/or EC guidelines and according to GLP principles (Klimisch 1).

Additional information

Oral

Assessment of acute oral toxicity of TBEAES was performed in Wistar rats according to OECD/EC guidelines and GLP principles. TBEAES was administered in a single dose to rats of both sexes at 2000 mg/kg body weight. No mortality occurred. In one female, uncoordinated movements were noted on day 1. No clinical signs were noted in the remaining two females. Among males, tremors and/or uncoordinated movements were noted on day 1. The body weight gain shown by the animals over the study period was considered to be normal. No abnormalities were found at macroscopic post mortem examination of the animals. The oral LD50 value of TBEAES in Wistar rats was established to exceed 2000 mg/kg body weight.

Dermal

Assessment of acute dermal toxicity with TBEAES in the rat was performed according to OECD/ EC guidelines and according to GLP principles. TBEAES was administered to five Wistar rats of each sex by dermal application at 2000 mg/kg bw for 24 hours. No mortality occurred. Chromodacryorrhoea was noted in two males and one female on days 1 and/or 2. Focal erythema was seen in the treated skin-area of two males and two females during the observation period. The changes noted in body weight gain in males and females were considered not indicative of toxicity. No abnormalities were found at macroscopic post mortem examination of the animals.The dermal LD50 value of TBEAES in Wistar rats was established to exceed 2000 mg/kg bw.

Justification for classification or non-classification

Based on the available studies, TBEAES does not have to be classified for acute toxicity according to CLP Regulation EC (No.) 1272/2008.