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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:
18 May - 06 June 2011
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP-guideline study

Data source

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

Materials and methods

Test guidelineopen allclose all
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 (incl. certificate)
Remarks:
National GLP Compliance Monitoring Authority, Department of Science & Technology, New Delhi, India; Food and Consumer Product Safety Authority (VWA), The Hague, the Netherlands; Bundesinstitut für Risikobewertung, Berlin, Germany
Test type:
up-and-down procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): tris amino ultra pure
- Physical state: white crystals
- Analytical purity: 99.9%
- Impurities (identity and concentrations): 0.018 weight% water
- Purity test date: 9 Mar 2011
- Lot/batch No.: XK0731LA1C
- Storage condition of test material: ambient temperature, 18-36 °C
- Other: pH 10.4 (1% aqueous solution)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: inhouse bred (Outbred), Toxicology, Department of Safety Assessment, Advinus Therapeutics Limited, Bangalore 560 058, India
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 177.3-180.3 g (range)
- Fasting period before study: yes, overnight (16-18 hours)
- Housing: the rats were housed individually in standard polysulfone cages (approximately L 425 mm x B 266 mm x H 175 mm) with stainless steel top grill, with facilities for pelleted food and water; steam sterilised corn cob bedding was used and changed along with the cage twice weekly
- Diet: Ssniff rats/mice pellet food, manitenance meal (Ssniff Spezialdiaten GmbH, Soest, Gemany), ad libitum
- Water: deep bore-well water passed through activated charcoal filter and exposed to UV-rays in Aquaguard on-line water filter-cum-purifier (Eureka Forbes Ltd., Mumbai, India), ad libitum
- Acclimation period: 5-10 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22-24
- Humidity (%): 58-68
- Air changes (per hr): 12-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 13 May 2011 To: 1, 3 and 6 June 2011

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Amount of vehicle (if gavage): 20 mL/kg bw
- Justification for choice of vehicle: the test substance forms a visibly homogenous solution in water

MAXIMUM DOSE VOLUME APPLIED: 20 mL/kg bw (3.5-3.6 mL absolute volume)
Doses:
5000 mg/kg bw
No. of animals per sex per dose:
3, dosed stepwise with a 2-day interval, according to the up-and-down procedure
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the animals were observed for mortality and clinical signs 1/2, 1, 2, 3 and 4 hours after administration on Day 1, and daily thereafter throughout the study period; the animals were weighed on Day 1 (prior to administration), 8 and 15
- Necropsy of survivors performed: yes, external surfaces of the body, all orifices, tissues and organs of the thoracic and abdominal cavities were examined, and all gross findings were recorded

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There was no mortality during the study period.
Clinical signs:
No clinical signs were observed during the study period.
Body weight:
No effect on body weight was noted.
Gross pathology:
Necropsy and histopathological examination revealed no substance-related findings.

Any other information on results incl. tables

Table 1: Mortality and clinical signs during the study period

 

Dose
[mg/kg bw]

Toxicological results*

Duration of clinical signs

Time of death

Mortality (%)

Females

5000

0/0/3

---

---

0

LD50 > 5000 mg/kg bw

                                                                                           

* first number = number of dead animals                                 

 second number = number of animals with clinical signs         

 third number = number of animals used                               

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified