N,N-bis(2-hydroxyethyl)-3-[(C16-18)alkoxy]-1-propanamine

Endpoint summary

Description of key information

Based on the results of this study, the test material elicited evidence of toxicity at a dose of 2000 mg/kg, but the LD50 is > 2000 mg/kg.  As such, the test material does not meet the criteria for classification.    

The topical application of the test material at a dose level of 2000 mg/kg showed no consistent evidence of systemic toxicity.

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:

January 4, 1995 to February 6, 1995

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Expiration date of the lot/batch: August 1999

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

OTHER SPECIFICS: Amber solid

Species:

rat

Strain:

other: Crl:CD (BR)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Males: approximately 10 weeks; Females: approximately 11 weeks
- Weight at study initiation: Males: 290 to 363 g; Females: 230 to 250 g
- Fasting period before study: After recording animal body weights, all food was removed during the evening immediately prior to the day of administration of the test material. Food was withheld until completion of dosing the following morning.
- Housing: Single housed during the study period in suspended stainless steel and wire mesh caging with absorbent paper below cages.
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 23 d

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68 to 76
- Humidity (%): 40 to 70
- Photoperiod (hrs dark / hrs light): 12/12 by automatic timer

IN-LIFE DATES: From: January 5, 1995 To: January 19, 1995

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

The undiluted test material was warmed until it was doseable. The temperature of the water bath was 49 °C. The test material was administered as a single oral intubation via syringe and a stainless steel, stright, ball tipped feeding needle.

Doses:

2000 mg/kg fasted body weight

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: The animals were examined for viability twice during during the week and once dialy during weekends. Body weights were recorded on the day prior to dosing (pretest), the day of dosing (Day 0), on Day 7, Day 14, and at death for animals which succumbed prior to study termination.
- Necropsy of survivors performed: yes
- Other examinations performed: Clincila observations were made as to the nature, onset, severity, and duration of toxicoloigical signs at 1, 2, 4, and 6 h after dosing, and once per day thereafter for a total of 14 d. The time of death was recorded, as precisely as possible, for animals which succumbed prior to study termination.

Statistics:

Statistical analysis included means and standard deviations of body weight and body weight change by group and sex.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

Two female animals died prior to study termination. On Days 0 and/or 1, one of the animals was observed with oral and ocular discharge, dyspnea, wet rales, and hypoactivity. The other animal was observed with abdominal/ anogenital staining and soft stool. Both animals were found dead on Day 2.

Clinical signs:

other: Clinical signs of the 8 animals wich survived to study termination included oral or nasal discharge, decreased food consumption, emaciated, staining of the skin/ fur, and /or stool abnormalities. These signs were observed primarily from Day 2 to Day 7, b

Gross pathology:

All animals whcih survived to study termination were without gross abnormalities at postmortem examination.

Gross postmortem observations of the 2 females that succumbed included doscoloured liver and/or lungs, consolidated lungs, this/ discoloured stomach lining, roughened glandular portion of the stomach, distended/ discoloured small intestine, and/or staining of the skin/ fur.

Please see the attached tables:

Table 1: Individual inlife observations

Table 2: Individual body weight

Table 3: Individual body weight changes

Table 4: Individual gross postmortem observations

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral toxicity of the test material was assessed in accordance with OECD Guideline 401. Overt signs of toxicity were apparent at a dose level of 2000 mg/kg in all animals as indicated by adverse clinical signs and/or body weight gain suppression, as well as mortality in 2 of the 10 animals. All surviving animals appeared to recover by Day 12. Based on the results of this study, the test material elicited evidence of toxicity at a dose of 2000 mg/kg, but the LD50 is > 2000 mg/kg. As such, the test material does not meet the criteria for classification.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Key

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:

April 15, 1993 to September 22, 1993

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Remarks:

It is unknown whether the stability, identity, strength and compostion or other characteristics which appropriately identifies the test material has been determined in a GLP compliant manner.

Test type:

fixed dose procedure

Limit test:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material:
- Expiration date of the lot/batch: March 1998

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Preliminary purification step (if any): The test material was assumed 100 % pure for purposes of dosing

FORM AS APPLIED IN THE TEST: Amber solid

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Approximately 12 weeks
- Weight at study initiation: Males: 2.03 to 2.40 kg; Females: 2.21 to 2.53 kg
- Housing: Single housed. Suspended stainless steel and wire mesh with absorbent paper below cages
- Diet (e.g. ad libitum): restricted feeding regimen
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 8 days; animals were examined for viability at least once daily

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 65 to 70
- Humidity (%): 40 to 60
- Air changes (per hr):
- Photoperiod (hrs dark / hrs light): Approximately 12 h light and 12 h dark by automatic timer. Diurnal cycle approximately 07:00 to 19:oo Hours; nocturnal cycle approximately 19:00 to 07:00 Hours.

IN-LIFE DATES: From: To: April 13, 1993 to April 21, 1993

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Preparation of animals: Approximately 24 h prior to topical administration of the test material, the hair of each rabbit on the dorsal surface from the shoulder region to the lumbar region was closely clipped with an electric clipper. Collars were placed around the neck of each rabbit on the day of dosing. The skin of all animals was left intact. Collars remained on the animals for the duration of the study. Animals were reclipped as needed for dermal evaluations.
- Type of wrap if used: A single dose of the test material was applied to the body surface at the appropriate dose, covered with a 10 cm x 20 cm gauze patch and secured with tape. The gauze patch was moistened with 1.0 mL physiological saline per gram of test material. To retard evaporation, to prevent ingestion of the test material, and to keep the substance in contact with the skin, the gauze patch was secured to the trunk of the animal with tape and a plastic sleeve.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): The amount of material remaining was visually estimated and recorded. Residual test material was then removed, with reverse osmosis water and paper towels without altering the exisiting response or the integrity of the epidermis.
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): The dose administered was calculated by multiplying the dose level by the body weight to arrive at the calculated dose.

Duration of exposure:

24 h

Doses:

2000 mg/kg

No. of animals per sex per dose:

5

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Body weights were recorded the day prior to dosing (pretest), the day of dosing (Day 0), on Day 7, and Day 14.
- Necropsy of survivors performed: yes; After the Day 14 observations, all animals were weighed and sacrificed by exsanguination following an intravenous injection of sodium pentobarbital. Gross necropsies were performed on all animals and gross abnormalities were preserved in 10 % neutral buffered formalin.
- Other examinations performed: clinical observations were made as to the nature, onset, severity, and duration of toxicological signs 2 and 4 h after dosing, and once per day thereafter. Dermal responses were evaluated on Day 1 (approximately 45 min after patch removal) and on Day 3, 7, 10 and 14 according to the Draize Method of Scoring.

Statistics:

The means and standard deviations of the body weights and body weight changes were calculated for each weighing period.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived to the study termination and were free of observable abnormalities during the test period.

Clinical signs:

other: - Topical application of the test material elicited erythema in all animals. Erythema was observed in the majority of animals at the 45 min observation interval. The severity of erythema scores increased as the study progressed through Day 7. At the Da

Gross pathology:

The only significant postmortem findings were dermal abnormalities observed in the dose site which were consistent with the dermal findings observed during the inlife phase of the study. Eschar, desquamation, exfoliation, and vascularisation of the skin were observed in one or more animals. In addition, one female was observed with a slightly larger than normal spleen.

Other findings:

- Other observations: An extreme amount of residual test material was apparent in all animals at sleeve removal. One animal vocalised upon dosing.

Please see the attached tables:

Table 2: Individual Supplemental Dermal Observations, Dose 2000 mg/kg

Table 4: Individual body weight (kg), Dose 2000 mg/kg

 

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal toxicity of the test material was assessed in accordance with OECD Guideline 402. The topical application of the test material at a dose level of 2000 mg/kg showed no consistent evidence of systemic toxicity. However, a single dose of the test material did product severe dermal irritation. Based on the tresults of this study, the LD50 appears to be greater than 2000 mg/kg.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Quality of whole database:

Key

Justification for classification or non-classification

No mortality was observed in rats dosed with the test substance at 2000 mg/kg bw by the oral and dermal routes. Therefore, according to the EC regulation No 1272/2008 and former directive 67/548/EEC criteria, no classification is warranted.