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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:
supporting study
Study period:
April - May 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed in accordance with OECD/EC guidelines and GLP principles.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
other: JMAFF, 12 Nohsan, Notification no 8147, November 2000, including the most recent partial revisions
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: 2.5% aqueous solution
Details on test material:
- Name of test material (as cited in study report): TMA248WA
- Physical state: clear colourless liquid
- Analytical purity: 2.5% (solution in water)
- Lot/batch No.: 05C14001B
- Expiration date of the lot/batch: 13 February 2007
- Storage condition of test material: at room temperature in the dark
- pH 13.21 (determined at test lab)

Test animals

Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: young adults (approx. 11 weeks old)
- Weight at study initiation: 195-258 g
- Fasting period before study: yes, overnight
- Housing: group housing of 3 animals per cage in Macrolon cages containing purified sawdust as bedding material and paper as cage enrichment
- Diet: free access to standard pelleted laboratory animal diet (Altromin (code VRF 1), Lage, Germany)
- Water: free access to tap-water
- Acclimation period: at least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19.6-22.6
- Humidity (%): 27-73; deviations from the minimum level of humidity occurred; based on laboratory historical data these deviations were considered not to have affected the study results
- Air changes (per hr): approx. 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: 15 April to 3 May 2005

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Remarks:
= 2.5% aqueous solution
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 2.02 ml/kg

CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: no rationale given
Doses:
two groups at 300 mg/kg bw followed by a group at 2000 mg/kg bw
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days

OBSERVATIONS:
- Mortality/viability: twice daily
- Clinical signs: at periodic intervals on day of dosing and once daily thereafter
- Body weights: pre-administration (day 1) and on day 8 and 15
- Necropsy of survivors performed: yes, all animals
Statistics:
Not applicable

Results and discussion

Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
300 - 2 000 mg/kg bw
Based on:
dissolved
Remarks:
(2.5% TMAH)
Sex:
female
Dose descriptor:
LD50
Effect level:
7.5 - 50 mg/kg bw
Based on:
other: (pure TMAH)
Mortality:
No mortality occurred in females dosed at 300 mg/kg bw. Two females at 2000 mg/kg bw were found dead and the remaining animal was sacrificed for humane reasons on day 1.
Clinical signs:
300 mg/kg bw: hunched posture on day 1
2000 mg/kg bw: hunched posture, lethargy, flat posture, slow breathing, laboured respiration and/or ptosis
Body weight:
Reduced body weight gain and body weight loss was noted among animals at 300 mg/kg bw.
Gross pathology:
No abnormalities were observed at macroscopy of surviving animals. Macroscopic examination of animals found dead revealed reddish discolouration of the glandular mucosa of the stomach in one female.

Applicant's summary and conclusion

Interpretation of results:
very toxic
Remarks:
Migrated information category 2 Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 of TMA248WA in Wistar rats was established to be within the range of 300-2000 mg/kg bw, which corresponds to an LD50 of 7.5-50 mg/kg bw for the pure substance.
According to EC Regulation 1272/2008, pure TMAH is classified in category 2.
Executive summary:

In an acute oral toxicity test performed according to OECD 423, no mortality occurred at 300 mg/kg bw, but all three animals died/were killed at 2000 mg/kg bw. Hunched posture was noted at 300 mg/kg bw on day 1. At 2000 mg/kg bw hunched posture, lethargy, flat posture, slow breathing, laboured respiration and/or ptosis were seen. Reduced body weight gain and body weight loss was noted at 2000 mg/kg bw. Macroscopic examination of animals that died revealed reddish discolouration of the glandular mucosa of the stomach in one female. The LD50 was determined to be within the range of 300 -2000 mg/kg bw, which corresponds to an LD50 of 7.5-50 mg/kg bw for the pure substance. According to EC Regulation 1272/2008 pure TMAH is classified in category 2.