Tris(oxiranylmethyl) benzene-1,2,4-tricarboxylate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1992

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: OECD 401 guideline study performed according to GLP regulation

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.1 (Acute Toxicity (Oral))

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Tris(oxiranylmethyl) benzene-1,2,4-tricarboxylate

EC Number:

230-638-7

EC Name:

Tris(oxiranylmethyl) benzene-1,2,4-tricarboxylate

Cas Number:

7237-83-4

Molecular formula:

C18H18O9

IUPAC Name:

1,2,4-tris[(oxiran-2-yl)methyl] benzene-1,2,4-tricarboxylate

Details on test material:

- Name of test material (as cited in study report): TKK 30009
- Trade name: LMB 5196
- Physical state: viscous liquid
- Analytical purity: > 75%
- Lot/batch No.: Z 2178
- Expiration date of the lot/batch: March 1995
- Storage condition of test material: room temperature

Test animals

Species:

rat

Strain:

other: Tif:RAI f1

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CIBA-GEIGY Limited, Animal Production 4332 Stein / Switzerland
- Weight at study initiation: 184 to 207 g
- Fasting period before study: overnight
- Housing: Macrolon cages type 4 with 5 animals/sex/cage
- Diet (e.g. ad libitum): ad libitum except overnight prior dosing
- Water (e.g. ad libitum): ad libitum
- Acclimation period: not mentioned


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 2
- Humidity (%): 55 +/- 10
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: treatment day To: day 14

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

arachis oil

Details on oral exposure:

VEHICLE
- Oleum arachidis Ph.H.VI (Siegfried AG, Zofingen, Switzerland)
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg



MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

Doses:

2000 mg/kg body weight

No. of animals per sex per dose:

5 males and 5 females

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Mortality was recorded twice daily during the week and once daily during the week-end
- Clinical signs were recorded daily
- Body weights were recorded immediately before administration and on days 7 and 14

Statistics:

none

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No death occurred during the course of the study

Clinical signs:

other: Ruffled fur, hunched posture, exophthalmos and dyspnea were observed and considered to be common symptoms in acute tests. Additionally, reduced locomotor activity and ataxia were also noted in the animals. Respiratory sounds were recorded in the females.

Gross pathology:

No macroscopic findings at necropsy.

Any other information on results incl. tables

Table 1 Body weights (g):

Sex / Animal Number	Treatment day	Day 7	Day 14
male 1	203	249	304
male 2	207	255	302
male 3	199	256	307
male 4	204	248	292
male 5	207	257	298
female 1	184	202	224
female 2	195	218	242
female 3	184	219	236

female 4	186	215	236
female 5	185	214	224

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Oral LD50 rats (male and female) is greather than 2000 mg/kg body weight

Executive summary:

Five male rats and five female rats (Tif: RAI f1) were treated by oral gavage administration at a dosage of 2000 mg/kg body weight. The test item was diluted in vehicle (Oleum arachidis) at a concentration of 0.2 g/mL and administered at a dosing volume of 10 mL/kg. The animals were observed for 14 days.

No death occurred during the course of the study. Ruffled fur, hunched posture, exophthalmos and dyspnea were observed and considered to be common symptoms in acute tests. Additionally, reduced locomotor activity and ataxia were also noted in the animals. Respiratory sounds were recorded in the females. All animals recovered within 5 to 6 days after treatment.

Body weights considered to be within the common range for this strain.

No macroscopic findings were noted at necropsy.

The median lethal dose after single oral administration to female and male rats, observed over a period of 14 days is: Oral LD50 (rat) greather than 2000 mg/kg