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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 May - 03 Jun 2011

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

National GLP Compliance Monitoring Authority, Department of Science & Technology, New Delhi, India

Test type:

standard acute method

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

Test material form:

solid

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: in-house bred (Outbred); Toxicology, Department of Safety Assessment, Advinus Therapeutics Limited, Bangalore, India
- Age at study initiation: 11-12 weeks
- Weight at study initiation: 264.9-285.8 g (males), 203.6-211.5 g (females)
- Housing: the rats were housed individually in standard polysulfone cages (approximately L 425 mm x B 266 mm x H 175 mm), with a stainless steel top grill. Steam sterilized corn cob bedding was used and changed with the cage twice per week. The water bottles were changed weekly.
- Diet: Ssniff rats / mice pellet food - maintenance meal (Ssniff Spezialdiäten GmbH., Soest, Germany), 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 (manufactured by Eureka Forbes Ltd., Mumbai, India), ad libitum
- Acclimation period: males were acclimatised for 7 days, females were acclimatised for 5 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: 18 May 2011 (females), 20 May 2011 (males) To: 03 Jun 2011

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Remarks:

water was added to the test substance to form a paste

Details on dermal exposure:

TEST SITE
- Area of exposure: approximately 8 cm x 10 cm on the dorsolateral (back and side) thoracic part of the rats
- % coverage: approximately 10
- Type of wrap if used: the test substance was spread onto a 6-ply cotton gauze patch (9 cm x 5 cm for males, 8 cm x 5 cm for females), which was applied to the shaved skin area of the rats. The gauze patch was held in place with non-allergenic surgical tape that was wound around the torso.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): the application sites were washed with water and wiped clean with a towel to remove any residual test substance
- Time after start of exposure: 24 h

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg bw
- Constant volume or concentration used: no, the dose was calculated based on body weight
- For solids, paste formed: yes

Duration of exposure:

24 h

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

not required

Details on study design:

- Duration of observation period following administration: at least 15 days
- Frequency of observations and weighing: the animals were observed for mortality and clinical signs of toxicity 4 times on day 1 (the day exposure started) and once daily thereafter. The body weights were recorded on day 1 (prior to exposure), 8 and 15. The treated skin sites were assesed for local skin irritation daily after exposure ended.
- Necropsy of survivors performed: yes, the external surface of the body, all orifices, tissues and organs of the thoracic and abdominal cavities of all animals were examined
- Other examinations performed: clinical signs, body weight, local skin irritation

Results and discussion

Effect levels

Key result

Sex:

male/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 signs of toxicity were observed during the study period.

Gross pathology:

The necropsy and gross pathological examination revealed no substance-related findings.

Other findings:

- Other observations: there were no local skin irritation reactions

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

CLP: not classified
DSD: not classified