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Administrative data

Description of key information

Acute toxicity studies with Alkaterge E are available for the oral and dermal route. The acute oral LD50 of Alkaterge E is greater than 2,000 mg/kg of body weight in female rats. The dermal LD50 value of Alkaterge E in Wistar rats (both sexes) was established to exceed 2000 mg/kg body weight.

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 - March, 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
yes
Species:
rat
Strain:
Fischer 344
Sex:
female
Details on test animals and environmental conditions:
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals (Natl. Res. Council, 2011). Litter paper was placed beneath the cage and was changed at least three times per week.
- Animal Room Temperature and Relative Humidity Ranges: 19-23ºC and 30-45%, respectively.
- Animal Room Air Changes/Hour: 12. Airflow measurements are evaluated regularly and the records are kept on file at Eurofins PSL.
- Photoperiod: 12-hour light/dark cycle
- Acclimation Period: 9-28 days
- Feed: Purina Certified Rodent Diet (PMI #5002)
- Water: Filtered tap water was supplied ad libitum by an automatic water dispensing system.
- Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study. Analysis of the water is conducted regularly and the records are kept on file at Eurofins PSL. The most recent water analysis was conducted in December 2010. Purina Certified Rodent Diet, PMI #5002, Lot Numbers: SEP 23 10 3A, OCT 28 10 1A and NOV 10 10 3A, were analyzed in October and November, 2010.
- Cage: Each cage was identified with a cage card indicating at least the study number, dose level, identification and sex of the animal.
- Animal: A number was allocated to each rat on receipt and a stainless steel ear tag bearing this number was attached to the rat. This number, together with a sequential
Route of administration:
oral: gavage
Details on oral exposure:
Following acclimation, experimentally naive rats were fasted overnight by removing the feed from their cages. During the fasting period, the rats were examined for health and weighed (initial). Five healthy naive female rats (not previously tested) were selected for test.

The test substance was administered to the stomach using a stainless steel ball-tipped gavage needle attached to an appropriate syringe. Following each administration, each animal was returned to its designated cage. Feed was replaced immediately after dosing.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
5 females
Control animals:
no
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived test substance administration.
Body weight:
All animals gained body weight during the study.
Gross pathology:
No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period
Other findings:
Following administration, two rats exhibited ano-genital staining and/or reduced fecal volume, but both animals recovered from these symptoms by Day 4 and, along with the other three animals, appeared active and healthy for the remainder of the observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute oral LD50 of ALKATERGETM- E Oxazoline is greater than 2,000 mg/kg of body weight in female rats.
Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with Fischer 344 rats to determine the potential for ALKATERGE TM- E Oxazoline to produce toxicity from a single dose via the oral route. An initial limit dose of 2,000 mg/kg was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, four additional females received the same dose level, sequentially. Since these animals survived, no additional animals were tested. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for up to 14 days after dosing. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) following dosing. Necropsies were performed on all animals at terminal sacrifice.All animals survived test substance administration and gained body weight during the study. Following administration, two rats exhibited ano-genital staining and/or reduced fecal volume, but both animals recovered from these symptoms by Day 4 and, along with the other three animals, appeared active and healthy for the remainder of the observation period. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Under the conditions of this study, the acute oral LD50 of ALKATERGE TM- E Oxazoline is greater than 2,000 mg/kg of body weight in female rats.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
study scientifically not necessary / other information available
Justification for data waiving:
the study does not need to be conducted because exposure of humans via inhalation is not likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size
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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Specific details on test material used for the study:
Identification: Alkaterge E
Appearance: Brown viscous liquid
Batch: D598F47BC1
Purity/Composition: UVCB
Test item storage: At room temperature
Stable under storage conditions until: 05 April 2020 (retest date)

Additional information
Test Facility test item number: 208794/A
Purity/Composition correction factor: No correction factor required
Chemical name (IUPAC, synonym or trade name: 4-Ethyl-2-(8-heptadecenyl)-2-oxazoline-4-methanol,Alkaterge E
CAS number: 68140-98-7
Molecular formula: C23H43NO2
Molecular weight: 365.60
Specific gravity / density: 0.925 (25°C)
Species:
rat
Strain:
Wistar
Remarks:
Crl: WI(Han)
Sex:
male/female
Details on test animals and environmental conditions:
Housing
On arrival, animals were group housed (up to 5 animals of the same sex together) in polycarbonate cages (Makrolon MIV type; height 18 cm.) and following assignment to the study, animals were individually housed in polycarbonate cages (Makrolon MIII type; height 18 cm.) containing sterilized sawdust as bedding material (Lignocel S 8-15, JRS - J.Rettenmaier & Söhne GmbH + CO. KG, Rosenberg, Germany) equipped with water bottles. These housing conditions were maintained unless deemed inappropriate by the Study Director and/or Clinical Veterinarian. The room(s) in which the animals were kept were documented in the study records. Animals were separated during designated procedures/activities. Each cage was clearly labeled.

Environmental Conditions
Target temperatures of 18 to 24°C with a relative target humidity of 40 to 70% were maintained. The actual daily mean temperature during the study period was 21 to 22°C an actual daily mean relative humidity of 49 to 72% (see deviations in Appendix 3). A 12 hour light/12 hour dark cycle was maintained. Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms.

Food
Pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany) was provided ad libitum throughout the study, except during designated procedures. The feed was analyzed by the supplier for nutritional components and environmental contaminants.

Water
Municipal tap-water was freely available to each animal via water bottles.
Type of coverage:
occlusive
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
Alkaterge E, was administered as received. Adjustment was made for specific gravity of the test item. No correction was made for the purity/composition of the test item.

A single dose of test item was administered to the appropriate animals by dermal application on Day 1. One day before dosing, an area of approximately 5x7 cm on the back of the animals was clipped. The test item was applied in an area of approximately 10% of the total body surface, i.e. approximately 25 cm² for males and 18 cm² for females. The test item was held in contact with the skin with a dressing, consisting of a surgical gauze patch (Surgy 1D), successively covered with aluminum foil and Coban elastic bandage. A piece of Micropore tape was additionally used for fixation of the bandages in females only. The application period was 24 hours, after which the dressing was removed and the skin cleaned of residual test item using water or an appropriate vehicle.
Duration of exposure:
24 hours
Doses:
2000 m/kg bw
No. of animals per sex per dose:
5 males, 5 females
Control animals:
not required
Details on study design:
Throughout the study, animals were observed for general health/mortality and moribundity twice daily, in the morning and at the end of the working day. Animals were not removed from cage during observation, unless necessary for identification or confirmation of possible findings.

Post-dose observations were performed at periodic intervals on the day of dosing (at least three times) and once daily thereafter. The observation period was 14 days. All the animals were examined for reaction to dosing. The onset, intensity and duration of these signs was recorded (if appropriate), particular attention being paid to the animals during and for the first hour after dosing.

Animals were weighed individually on Day 1 (pre-dose), 8 and 15.

All animals were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities were recorded.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred.
Clinical signs:
Hunched posture, quick breathing, chromodaccryorrhoea (snout) and/or piloerection were noted for the animals between Days 1 and 6. Scabs (back and left flank) and/or focal erythema (back and left flank) were noted for the animals between Days 2 and 11. General erythema, scales, scabs, thickened area and brown discoloration were seen in the treated skin-area of the animals during the observation period. These local effects were considered not to have affected the conclusion of the study.
Body weight:
The body weight gain during the observation period was within the range expected for rats used in this type of study.
Gross pathology:
No abnormalities were found at macroscopic post mortem examination of the animals.
Interpretation of results:
GHS criteria not met
Conclusions:
The dermal LD50 value of Alkaterge E in Wistar rats was established to exceed 2000 mg/kg body weight.
Executive summary:

Alkaterge E was administered to five Wistar rats of each sex by a single dermal application at 5000 mg/kg body weight for 24 hours. Animals were subjected to daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15).

 

No mortality occurred. Hunched posture, quick breathing, chromodaccryorrhoea (snout) and/or piloerection were noted for the animals between Days 1 and 6. Scabs (back and left flank) and/or focal erythema (back and left flank) were noted for the animals between Days 2 and 11. General erythema, scales, scabs, thickened area and brown discoloration were seen in the treated skin-area of the animals during the observation period. These local effects were considered not to have affected the conclusion of the study. The body weight gain during the observation period was within the range expected for rats used in this type of study. No abnormalities were found at macroscopic post mortem examination of the animals.

 

The dermal LD50 value of Alkaterge E in Wistar rats was established to exceed 2000 mg/kg body weight.

Based on these results, Alkaterge E does not have to be classified and has no obligatory labelling requirement for acute dermal toxicity according to the Globally Harmonized System of Classification and Labelling of Chemicals (GHS) of the United Nations (2015) (including all amendments) and Regulation (EC) No 1272/2008 on classification, labelling and packaging of items and mixtures (including all amendments).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

Justification for classification or non-classification

The available data on acute toxicity of the test substance do not meet the criteria for classification according to the CLP/GHS Regulation (EC) 1272/2008, and are therefore conclusive but not sufficient for classification.