Registration Dossier

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:
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 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1200 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Remarks:
National GLP Compliance Monitoring Authority, Department of Science & Technology, New Delhi, India
Test type:
standard acute method
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% (w/w) water
- Lot/batch No.: XK0731LA1C
- Storage condition of test material: at ambient temperature, 18-36 °C
- Recertification date: 22 Feb 2013
- pH: 10.4 (1% aqueous solution)
- Other: soluble in water

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals 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
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:
No signs of toxicity were observed during the study period.
Body weight:
The body weight gains were within the normal ranges in males and females 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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
CLP: not classified
DSD: not classified