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

Acute Toxicity: dermal

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

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

EC Number:

930-859-5

Molecular formula:

C23-25H49-53NO3

IUPAC Name:

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

Test material form:

solid

Remarks:

Amber solid

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

Test animals

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

Administration / exposure

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.

Results and discussion

Effect levels

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.

Any other information on results incl. tables

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

 

Applicant's summary and conclusion

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.