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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 5 December 2011 to 26 December 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2012
Report Date:
2012

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Deviations:
yes
Remarks:
relative humidity 18 to 61%, 1 animal not weighed at time of death
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes
Test type:
up-and-down procedure
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid
Details on test material:
No further details
Specific details on test material used for the study:
- Name of test material (as cited in study report): XTJ-568
- Substance type: Clear colorless liquid
- Physical state: liquid
- Analytical purity: 97% (primary amine)
- Composition of test material, percentage of components: water (0.03%), acetylatable (9.2 meq/g), total amine (8.7 meq/g)
- Lot/batch No.: 0G704
- Stability under test conditions: no data
- Storage condition of test material: 21 - 26.7°C

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan
- Age at study initiation: 9 to 10 weeks at start of dosing; records of dates of birth for animals used in this study are retained in the Calvert archives.
- Weight at study initiation: 191 - 202 grams
- Fasting period before study: Animals were fasted overnight prior to dose administration.
- Housing: Animals were group housed by sex upon receipt and individually housed upon assignment to study in compliance with the National Research Council " Guide for the Care and Use of Laboratory Animals". Calvert is a USDA registered and fully AAALAC accredited facility. The room in which the animals were kept was documented in the study records. no other species were kept in the same room.
- Diet (e.g. ad libitum): ad libitum with fasting overnight prior to dose administration
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days prior to dosing

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19 to 22°C
- Humidity (%): 18 to 61%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours light/12 hours dark

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Dose preparation: An initial preparation of the test article in distilled water resulted in an undoseable suspension with a pH of 13. Therefore, the proper amount of the test article was measured according to volume since it was a liquid, and was allocated/dosed neat as received from the Sponsor with a pH of 10. The stock bottle was inverted several times prior to dispensing.

Dose volumes (specific density 1 g/ml): 0.32, 0.55, 1 and 2 ml/kg.
Doses:
320, 550, 1000 or 2000 mg/kg
No. of animals per sex per dose:
A total of six rats received the substance.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
mortality/morbidity: manually recorded once daily
clinical observations: clinical observations were collected manually. On the day of dosing (Day 1) animals were observed prior to dosing and approximately 30 minutes and 4 hours post-dose. Animals were observed once daily thereafter (Days 2-15).
body weight: Animal weights were manually recorded prior to dosing on Day 1, and on Day 8 and 15, or upon death.
- Necropsy of survivors performed: yes. The necropsy included examination of: the external body surface, all orifices, the cranial, thoracic and abdominal cavities and their contents. All surviving animals were euthanized by CO2 asphyxiation.
Statistics:
The LD50 was calculated for the main test using AOT425StatPgm developed by Westat May, 2001.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
1 000 mg/kg bw
Based on:
test mat.
95% CL:
>= 275.7 - <= 2 580
Mortality:
Mortality was not observed in any of the animals dosed at 320 or 550 mg/kg of the substance. Two of three animals receiving the test article at 1000 mg/kg were found dead as well as the single animal dosed at 2000 mg/kg.
Clinical signs:
Clinical observations observed included piloerection at 30 minutes in the single animal at 320 mg/kg and in the surviving animal at 1000 mg/kg. no clinical signs were observed prior to death in the two other animals at 1000 mg/kg. Piloerection, decreased activity, decreased body tone and abnormal gait and stance were observed at 4 hours in the animal treated at 550 mg/kg. At 2000 mg/kg, decreased body tone and abnormal gait were observed at 30 minutes and death was observed at 4 hours.
Body weight:
No biologically significant effect was seen on body weights of the surviving animals on Days 8 and 15.
Gross pathology:
Terminal necropsy revealed no visible lesions in the animals at 320, 550 or the surviving animal at 1000 mg/kg. Necropsy of two animals found dead at 1000 and 2000 mg/kg revealed dark red fluid-filled intestines. The third animal found dead had no visible lesions.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
Based on the results of this study, the oral LD50 for the substance in rats was estimated to be 1000 mg/kg (95% PL Confidence interval of 275.7 to 2580 mg/kg).