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Description of key information

Acute oral toxicity study in the rat

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
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Recently conducted OECD Guideline study conducted according to GLP
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
Species:
rat
Strain:
Fischer 344
Sex:
female
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
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.

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.

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).

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
550 mg/kg bw
Quality of whole database:
good

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

The acute oral toxicity of Octanolamine is relatively low, meeting the criteria for classification as Harmful (EU DSD) or Acute Toxicity class 4 (GHS). The oral administration of octanolamine appears to have resulted in the irritation of the gastrointestinal tract (evidenced by discoloration seen during necropsy). This irritancy appears to be due at least in part, to the high pH of the test substance once in solution (pH in excess of 11). Whether this was the cause or a contributing factor in the mortality observed at the mid and high doses is unclear.

Due to the Corrosive properties of octanolamine when applied to the skin it was not possible to conduct an acute dermal toxicity study. Therefore it is not possible to comment conclusively on whether this substance would be acutely toxic following exposure via the dermal route. However the corrosiveness of this substance will limit the potential for acute dermal exposure and thus toxicity in humans.

Due to the low vapour pressure of the material, the irritancy/corrosivity and the potential work place exposure scenarios it was not considered appropriate to conduct testing via the inhalation route.


Justification for selection of acute toxicity – oral endpoint
standard guideline study

Justification for selection of acute toxicity – inhalation endpoint
study waived due to low volatility and corrosivity.

Justification for selection of acute toxicity – dermal endpoint
study waived due to corrosivity

Justification for classification or non-classification

The substance has an acute oral LD50 of 550 mg/kg, this therefore requires classification as Harmful (EU DSD) and Toxic Class 4 (GHS).