Registration Dossier

Administrative data

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

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2011
Report Date:
2018

Materials and methods

Test guideline
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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid: viscous

Test animals

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

Administration / exposure

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

Results and discussion

Effect levels
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.

Applicant's summary and conclusion

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.