Tributylethylammonium ethyl sulphate

Endpoint summary

Description of key information

Skin and eye irritation studies with TBEAES performed in accordance with current OECD/EC test guidelines, showed no skin and eye irritation in rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August - October 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Charles River Deutschland, Kisslegg, Germany.
- Age at study initiation: at least 6 weeks old.
- Weight at study initiation: 1435-1524 grams.
- Housing: Animals were housed individually in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Charles River Breeding and Maintenance DIet for Rabbits, Altromin, Germany). Hay was abailable during the study period.
- 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: 1 to 4 August 2000

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls.

Amount / concentration applied:

0.5 grams of test substance.

Duration of treatment / exposure:

Single four hour application .

Observation period:

72 hours.

Number of animals:

3 males.

Details on study design:

TEST SUBSTANCE PREPARATION
The test substance was heated up to 70°C to facilitate handling. The test substance was allowed to cool down to an estimated temperature of 40°C and dosed undiluted.

TEST SITE
Approximately 24 hours before treatment, the dorsal fur was clipped with electric clippers, exposing an area of approximately 150 square centimeters (10x15 cm). To facilitate scoring, treated skin areas were re-clipped at least 3 hours before the observations.

The test substance was applied to the skin of one flank, using a patch of 2x3 cm.

REMOVAL OF TEST SUBSTANCE
Four hours after the application, the dressing was removed and the skin cleaned of residual test substance using tap water.

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to application).
- Necropsy: No histopathlogy was performed, since the skin reactions were not masked by test substance staining
- Irritation:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours after the removal of the dressings and test substance. The irritation scores and a description of all other (local) effects were recorded.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404.

Irritation parameter:

erythema score

Basis:

other: animal #1 and #2

Time point:

other: 1 hour

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: animal #1 and #2

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: 1 hour

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: animal #3

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: mean

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

other: mean

Irritant / corrosive response data:

Exposure resulted in very slight to well-defined erythema in the treated skin-areas of the three rabbits. The skin irritation had resolved within 24 hours after exposure in all animals
There was no evidence of a corrosive effect on the skin.

Other effects:

No staining of the treated skin by the test substance was observed. No moratlity occured and no symptoms of systemic toxicity were observed in the animals during the test period.

Interpretation of results:

GHS criteria not met

Conclusions:

In an skin irritation study with rabbits, performed according to OECD/EC test guidelines, slight to well-defined erythema was observed, which was fully reversible within 24 h. No oedem was observed. TBEAES does not have to be classified for skin irritation.

Executive summary:

Assessment of primary skin irrition/corrosin was performed with TBEAES in the rabbit using a 4 hour semi-occlusive application according to OECD/EC guidelines and GLP principles. There was no evidence of a corrosive effect on the skin. Exposure to TBEAES resulted in very slight to well-defined erythema in the treated skin-areas of the rabbits, which had resolved within 24 hours. No oedema was observed. No mortality or symptoms of systemic toxicity were observed. Based on the results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), TBEAES does not have to be classified and has no obligatory labelling requirement for skin irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

August - October 2000

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Charles River Deutschland, Kisslegg, Germany.
- Age at study initiation: Animals used withihn the study were 12-14 weeks old.
- Weight at study initiation: Body weights were 2413 - 2605 grams.
- Housing: Individually housed in cages with perforated floors.
- Diet: Free access to pelleted diet for rabbits (Charles River Breeding and Maintenance Diet for Rabbits, Altromin, Germany). Hay was available during the study period.
- Water: Free access to tap water.
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
Set to maintain:
- Temperature (°C): 21±3
- Humidity (%): 30 - 70
- Air changes (per hr): approx 15
- Photoperiod (hrs dark / hrs light): 12/12

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

IN-LIFE DATES: From: 7 august 2000 to 13 september 2000

Vehicle:

unchanged (no vehicle)

Controls:

other: One eye of each animal remained untreated and served as the reference control.

Amount / concentration applied:

average 47.4 ± 0.6 mg (a volume of approximately 0.1 mL)

Duration of treatment / exposure:

Single instillation on Day 1.

Observation period (in vivo):

The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 days after instillation of the test substance

Number of animals or in vitro replicates:

3 males

Details on study design:

TREATMENT
Each animal was treated by instillation of the test substance in the conjunctival sac of one of the eyes after gently pulling the lower lid away from the eyeball.

REMOVAL OF TEST SUBSTANCE
-Washing: No

OBSERVATIONS
- Mortality/Viability: Twice daily.
- Toxicity: At least once daily.
- Body Weight: Day of treatment (prior to installation).
- Necropsy: No histopathology was performed
- Irritation:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours and 7 days after instillation of the test substance.
The irritation scores and a description of all other (local) effects were recorded.The irritation was assessed according to OECD 405.

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other: animal #3 iris score 1 at 1 hour which was fully reversible within 24 hours

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #1

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.7

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.7

Max. score:

3

Reversibility:

fully reversible within: 7 days

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.3

Max. score:

4

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritant / corrosive response data:

Irritation
Instillation of test substance into one eye of each of three rabbits resulted in effects on the iris and conjunctivae. Iridial irritation (grade 1) was observed in one animal after 1 hour only. Irritation of the conjunctivae was seen as redness, chemosis and discharge which had completely resolved within 72 hours in one animal and within 7 days in the other two animals.

Corrosion
There was no evidence of ocular corrosion.

Other effects:

No staining of peri-ocular tissues by the test substance was observed.
No symptoms of systemic toxicity were observed in the animals during the test period and no mortality occured.

Interpretation of results:

GHS criteria not met

Conclusions:

In an eye irritation study with rabbits, performed according to OECD/EC test guidelines, no corrosion was observed. Irritation of the conjunctivae was seen as redness, chemosis and discharge which had completely resolved within 72 hours (one animal) or within 7 days (two animals). No corneal opacity or corneal epithelial damage was observed. Based on these results TBEAES does not have to be classified and has no obligatory labelling requirements.

Executive summary:

Assessment of acute eye irritation/corrosion was performed with TBEAES in the rabbit according to OECD/EC guidelines and in accordance with GLP principles. Installation of single samples of TBEAES into one eye of each of three rabbits resulted in effects on the iris and conjunctivae. Iridial irritation (grade 1) was observed in one animal after 1 hour only. Irritation of the conjunctivae was seen as redness, chemosis and discharge which had completely resolved within 72 hours in one animal and within 7 days in the other two animals. There was no evidence for ocular corrosion. No corneal opacity or corneal epithelial damage was observed. Based on these results and according to the EC criteria for classification and labelling requirements for dangerous substances and preparations (Guidelines in Commission Directive 93/21/EEC), TBEAES does not have to be classified and has no obligatory labelling requirements for eye irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

Assessment of primary skin irritation/corrosion was performed with TBEAES in the rabbit using a 4 hour semi-occlusive application according to OECD/EC guidelines and GLP principles. There was no evidence of a corrosive effect on the skin. Exposure to TBEAES resulted in very slight to well-defined erythema in the treated skin-areas of the rabbits, which had resolved within 24 hours. No oedema was observed. No mortality or symptoms of systemic toxicity were observed. Based on these results TBEAES was concluded to be not irritating.

Eye:

Assessment of acute eye irritation/corrosion was performed with TBEAES in the rabbit according to OECD/EC guidelines and in accordance with GLP principles. Installation of single samples of TBEAES into one eye of each of three rabbits resulted in effects on the iris and conjunctivae. Iridial irritation (grade 1) was observed in one animal after 1 hour only. Irritation of the conjunctivae was seen as redness, chemosis and discharge which had completely resolved within 72 hours in one animal and within 7 days in the other two animals. There was no evidence for ocular corrosion. No corneal opacity or corneal epithelial damage was observed. Based on these results TBEAES was concluded to be not irritating.

Justification for classification or non-classification

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