Registration Dossier

Administrative data

Description of key information

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
2012
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Justification for type of information:
Read across to an analogue based on structural similarity. An analogue justification is attached to section 13 of the dataset
Reason / purpose:
read-across: supporting information
Reason / purpose:
read-across source
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
yes
Species:
rat
Strain:
Fischer 344
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories, Inc., Frederick, MD
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 142-168 grams
- Fasting period before study: overnight
- Housing: The animals were singly housed in suspended stainless steel caging with
mesh floors
- Diet (e.g. ad libitum): Harlan Teklad Certified Global 16% Protein Rodent Diet® #2016C. The diet
was available ad libitum
- Water (e.g. ad libitum): Filtered tap water was supplied ad libitum by an automatic water dispensing
system.
- Acclimation period: 21-29 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-23ºC
- Humidity (%): 42-70%
- Air changes (per hr): 14
- Photoperiod (hrs dark / hrs light): 12-hour light/dark cycle

IN-LIFE DATES: May 7-31, 2012
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 50% w/w mixture in corn oil
Doses:
2000 mkd
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: Individual body weights of the animals were recorded prior to test substance administration
(initial) and again on Days 7 and 14 (termination) following dosing. The animals were observed for mortality, signs of gross toxicity, and behavioral changes
during the first several hours post-dosing and at least once daily thereafter for 14 days after dosing.
- Necropsy of survivors performed: yes
- Other examinations performed: Gross
necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal
cavities, and the stomach and its contents were examined.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
All animals survived test substance administration, and the 14-day observation period.
Clinical signs:
All animals appeared active and
healthy during the study. There were no signs of gross toxicity, adverse pharmacologic effects, or
abnormal behavior.
Body weight:
All animals gained weight over the 14-day observation period.
Gross pathology:
No gross abnormalities were noted for any of the animals when necropsied at
the conclusion of the 14-day observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
Under the conditions of this study, the acute oral LD50 of XU-18838.00 is greater than 2,000
milligrams per kilogram of body weight in female rats.
Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with female Fischer 344 rats to determine the potential for XU-18838.00 to produce toxicity from a single dose via the oral route. Under the conditions of this study, the acute oral LD50 of the test substance is greater than 2,000 mg/kg of body weight in female rats. 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 sequentially received the same dose level. 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 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, gained body weight, and appeared active and healthy during the study. There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior. No gross abnormalities were noted for any of the animals when necropsied at the conclusion of the 14-day observation period.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
One High quality study on similar material available.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

An acute oral toxicity study is not available for this substance. The endpoint is therefore addressed using data on a structural analogue. The analogue approach justification is provided in a document attached to Section 13 of this dossier.

In the study using the analogue material, the LD50 was determined to be >2000 mg/kg bw in rats.

No signs of mortality or clinical/phological observations were observed.

Justification for classification or non-classification

The acute oral toxicity study in rats on the analogue material did not detect any mortality or other effects at 2000 mg/kg bw. The substance is not classified for acute oral toxicity.