Trometamol

Acute Toxicity: oral

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 guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

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

Test material information

Constituent 1

Reference substance name:

Trometamol

EC Number:

201-064-4

EC Name:

Trometamol

Cas Number:

77-86-1

Molecular formula:

C4H11NO3

IUPAC Name:

2-amino-2-(hydroxymethyl)propane-1,3-diol

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 or test system 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:

other: No clinical signs were observed during the study period.

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