Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Recently conducted OECD Guideline study conducted according to GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2007
Report Date:
2007

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
The Test material was Octanolamine ( XU-12314.00)

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
175 mg/kg bw
550 mg/kg bw
2000 mg/kg bw
No. of animals per sex per dose:
175 mg/kg bw - 2 female;
550 mg/kg bw - 3 female;
2000 mg/kg bw - 1 female
Control animals:
no

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
ca. 550 mg/kg bw
Mortality:
550 mg/kg (3 animals):
2 animals died during the study (1 on day 0 and 1 on day 1)

2,000 mg/kg (1 animal):
This animal died within 2 hours of test substance administration.
Clinical signs:
175 mg/kg (2 animals):
Both animals appeared active and healthy during the study - there were no adverse clinical signs, signs of gross toxicity or abnormal behaviour.

550 mg/kg (3 animals):
Clinical signs noted prior to death included hypoactivity, prone posture and/or ocular discharge (clear). Following administration, the surviving rat exhibited clinical signs including ocular discharge (clear), hypoactivity and reduced fecal volume. This animal recovered from the above symptoms by Day 3 and appeared active and healthy for the remainder the study.

2,000 mg/kg (1 animal):
Clinical signs noted prior to death included hypoactivity, hunched posture and piloerection.
Body weight:
175 mg/kg (2 animals):
both animals gained bodyweight during the study.

550 mg/kg (3 animals):
The surviving animal gained weight from day 3 onwards following recovery from the symptoms outlined above.
Gross pathology:
175 mg/kg (2 animals):
There were no abnormalities noted at necropsy.

550 mg/kg (3 animals):
Gross necropsy of the decedents revealed discoloration of the intestines. No gross abnormalities were noted for the euthanized animal necropsied at the conclusion of the 14 -day observation period.

2,000 mg/kg (1 animal):
Clinical signs noted prior to death included hypoactivity, hunched posture and piloerection.

Any other information on results incl. tables

Summary of results:

Animal number

Sex

Dose Level (mg/kg)

Bodyweight (g)

Dose 2 (ml)

Mortality1 (day)

Initial

Day 7

Day 14

3101

F

175

143

150

162

0.029

E

3103

F

130

137

149

0.026

E

3102

F

550

135

-

-

0.082

0

3104

F

123

136

148

0.075

E

3106

F

130

-

-

0.079

1

3105

F

2000

130

-

-

0.29

0

1 - E - Euthanized via CO2 inhalation after weighing on Day 14

2 - The test substance was administered as received. Specific Gravity – 0.897 g/mL.

Applicant's summary and conclusion

Interpretation of results:
harmful
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
XU-12314.00 appears to have moderate to low acute toxicity, with an LD50 of approximately 550 mg/kg.
Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with Fischer 344 rats to determine the potential for XU-12314.00 to produce toxicity from a single dose via the oral route. Under the conditions of this study, the acute oral LD50 of XU-12314.00 was estimated to be 550 mg/kg (the one dose with partial response) of body weight in female rats with a 95% PL confidence interval of 88.94 mg/kg (lower) to 2,430 mg/kg (upper).