Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study with acceptable restrictions

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1982
Report date:
1982

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
yes
Remarks:
no body weight determination
Principles of method if other than guideline:
No reference to OECD guideline is made in the report.
GLP compliance:
no
Remarks:
study performed prior to implementation of GLP
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: males 44 - 49 days, females 57 - 63 days
- Weight at study initiation: males 127 - 147 g, females 128 - 148 g
- Fasting period before study: 16 h
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21°C +/-2°C
- Humidity (%): 50-60%
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The following dose volumes of the test substance were applied: 4.64, 6.81 and 10 mL/kg bw
MAXIMUM DOSE VOLUME APPLIED: 10.0 mL/kg bw
Doses:
5197, 7627, 11200 mg/kg bw (related to product TMT 15)
equivalent to
780, 1144 and 1680 mg anhydrous TMT/kg bw
1418, 2080, 3055 mg TMT55/kg bw

No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations: at 0.5, 1, 2, 4, 8, 24 h, 2 days after dosing and once daily thereafter
- Frequency of weighing: day 0 (prior to dosing)
- Necropsy of survivors performed: yes
- Other examinations performed: gross examination of organs at necropsy
Statistics:
The LD50 value was calculated using the Probit Analysis.

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LD50
Effect level:
7 878 mg/kg bw
Based on:
test mat.
Remarks:
TMT 15
95% CL:
6 364 - 9 752
Remarks on result:
other: Probit analysis
Sex:
male
Dose descriptor:
LD50
Effect level:
1 182 mg/kg bw
Based on:
other: anhydrous form
Remarks on result:
other: recalculated value based on 15% TMT
Sex:
male
Dose descriptor:
LD50
Effect level:
2 149 mg/kg bw
Based on:
other: hydrated form (TMT 55)
Remarks on result:
other: calculated value for TMT 55
Sex:
female
Dose descriptor:
LD50
Effect level:
> 11 200 mg/kg bw
Based on:
test mat.
Remarks:
TMT 15
Sex:
female
Dose descriptor:
LD50
Effect level:
> 1 680 mg/kg bw
Based on:
other: anhydrous form
Remarks on result:
other: recalculated value based on 15% TMT
Sex:
female
Dose descriptor:
LD50
Effect level:
> 3 055 mg/kg bw
Based on:
other: hydrated form (TMT 55)
Remarks on result:
other: calculated value for TMT 55
Mortality:
All mortalities occurred between 4 h and 2 days after administration.
males: 0/5 at 5197 mg TMT 15/kg bw, 2/5 at 7627 mg TMT 15/kg bw, 5/5 at 11200 mg TMT 15/kg bw
females: 0/5 at 5197 mg TMT 15/kg bw, 1/5 at 7627 mg TMT 15/kg bw, 2/5 at 11200 mg TMT 15/kg bw
Clinical signs:
No clinical signs were noted in animals receiving the lowest dose. Piloerection, laboured respiration, increased pain perception, stilted gait and clonic convulsions were observed in rats administered the mid and high dose.
Gross pathology:
Accumulation of reddish-brown fluid in the stomach was observed in animals that died as well as in animals that were sacrificed at the end of the study. No further effects were noted in any of the organs at necropsy.

Applicant's summary and conclusion

Interpretation of results:
other: not classified for the test substance TMT 15, Toxicity Category V (OECD GHS) for TMT 55, Toxicity Category IV for anhydrous TMT
Remarks:
Criteria used for interpretation of results: OECD GHS
Conclusions:
In this acute oral toxicity study with TMT 15 the obtained LD50 values were 7878 mg/kg bw (corresponding to 1182 mg anhydrous TMT/kg bw) for male rats and >11200 mg/kg bw (corresponding to > 1680 mg anhydrous TMT/kg bw) for female rats.