1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-nortall-oil alkyl derivs.

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was performed between 23 march 2000 and 11 April 2000.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-nortall-oil alkyl derivs.

EC Number:

263-171-2

EC Name:

1H-Imidazole-1-ethanol, 4,5-dihydro-, 2-nortall-oil alkyl derivs.

Cas Number:

61791-39-7

Molecular formula:

Not applicable (a generic molecular formula cannot be provided for this specific UVCB substance).

IUPAC Name:

2-{2-[(8Z)-heptadec-8-en-1-yl]-4,5-dihydro-1H-imidazol-1-yl}ethan-1-ol; 2-{2-[(8Z)-heptadec-8-en-1-yl]-4,5-dihydro-1H-imidazol-1-yl}ethyl (9Z)-octadec-9-enoate

Details on test material:

Sponsor's identification: PR 9061
Date received: 3 March 2000
Description: light amber liquid
Storage conditions: room temperature in the dark

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Sprague-Dawley CD (Cri : CD ® (SD) IGS BR) strain rats supplied by Charles River (UK) Ltd, Margate, Kent, UK were used. At the start
of the study the males weighed 201 to 211 g, and the females 223 to 231 g, and were eight to twelve weeks old. After an acclimatisation period of at least five days the animals were selected at random and given a number unique within the cage by taiI marking.

The animals were housed in groups of three by sex in solid-floor polypropylene cages furnished with woodflakes. With the exception of an overnight fast immediately before dosing and for approximately three to four hours after dosing, free access to mains drinking water and food (Rat and
Mouse Expanded Diet No.1, Special Diets Services limited, Witham, Essex, UK) was allowed throughout the study.

The temperature and relative humidity were set to achieve limits of 19 to 25°C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 2.15 mL/kg

CLASS METHOD
- Rationale for the selection of the starting dose: The information available suggested a starting dose of 2000 mg/kg.

Doses:

2000 mg/kg

No. of animals per sex per dose:

3 animals of each sex per dose

Control animals:

no

Details on study design:

All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was
calculated according to the fasted bodyweight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each sex to confirm the survival of the previously dosed animals.

The animals were observed for deaths or overt signs of toxicity 1/2, 1, 2 and 4 hours after dosing and subsequently once daiIy for up to fourteen days.

Individual bodyweights were recorded prior to dosing and seven and fourteen days after treatment or at death.

At the end of the observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross pathological examination. This consisted of an external examination and opening of the abdominal and thoracic cavities for examination of major organs. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Results and discussion

Preliminary study:

Not applicable.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 500 mg/kg bw

Remarks on result:

other: Mortalities were noted at 2000 mg/kg bodyweight.

Mortality:

Individual mortality data are given in Table 1 (attached background material).
One female was killed in extremis two days after dosing.

Clinical signs:

other: Individual clinical observations are given in Tables 2 and 3 (see attached background material). Clinical signs of toxicity commonly noted were hunched posture, lethargy, pi lo-erection and decreased respiratory rate with additional incidents of emaciatio

Gross pathology:

Individual necropsy findings are given in Tables 6 and 7 (see atttached background material).
Abnormalities noted at necropsy of the female that died during the study were haemorrhage and sloughing of the gastric mucosa, sloughing of the nonglandular epithelium of the stomach and haemorrhage of the small and large intestines. Abnormalities noted at necropsy of males that were killed at the end of the study were stomach adhered to the liver and/or white foci present over all of the non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of females that were killed at the end of the study.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute oral median lethal dose (LD50) of the test material, in the Sprague Dawley CD strain rat was estimated to be greater than 2500 mg/kg bodyweight.
Mortalities were noted at 2000 mg/kg bodyweight.

Executive summary:

A study was performed to assess the acute oral toxicity of the test material following a single oral administration to the Sprague-Dawley CD strain rat. The method followed that in the OECD Guidelines for Testing of Chemicals No. 423 "Acute Oral Toxicity - Acute Toxic Class Method" (adopted 22 March 1996) and Method B1 tris of Commission Directive 96/54/EC (which constitutes Annex V of Council Directive 67/548/EEC) .

Using all available information, 2000 mg/kg bodyweight was selected as the starting dose.

A group of three fasted females was treated with the starting dose. This was followed by a group of three fasted animals of the other sex at the same dose level.

The undiluted test material was administered orally. The animals were observed ¹/₂, 1, 2 and 4 hours after dosing and then once daily for up to fourteen days. Bodyweights were recorded on Day 0 (day of dosing) and on Days 7 and 14, or at death. At the end of the observation period the surviving animals were killed by cervical dislocation and all animals were subjected to gross necropsy.

One female was killed in extremis two days after dosing.

Clinical signs of toxicity commonly noted were hunched posture, lethargy, piloerection and decreased respiratory rate with additional incidents of emaciation, diarrhoea, dehydration, ptosis, gasping, laboured and noisy respiration and staining around the eyes, mouth and snout. Surviving animals recovered four to seven days after dosing.

The surviving animals showed expected gains in bodyweight over the study period except for one female which showed slight bodyweight loss during the first week and expected gain in bodyweight during the second week of the study.

Abnormalities noted at necropsy of the female that died during the study were haemorrhage and sloughing of the gastric mucosa, sloughing of the non-glandular epithelium of the stomach and haemorrhage of the small and large intestines. Abnormalities noted at necropsy of males that were killed at the end of the study were stomach adhered to the liver and/or white foci present over all of the non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of females that were killed at the end of the study.

The acute oral median lethal dose, (LD₅₀) of the test material, in the Sprague-Dawley CD strain rat, was estimated as being greater than 2500 mg/kg bodyweight. Mortalities were noted at a dose level of 2000 mg/kg bodyweight.

No symbol and risk phrase are required according to EU labelling regulations.