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Acute Toxicity: oral

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acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
31 March 1987 to 15 April 1987
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: GLP study according to OECD guideline 401

Data source

Reference Type:
study report
Report date:

Materials and methods

Test guidelineopen allclose all
according to guideline
OECD Guideline 401 (Acute Oral Toxicity)
according to guideline
EPA OPP 81-1 (Acute Oral Toxicity)
GLP compliance:
yes (incl. QA statement)
Test type:
standard acute method
Limit test:

Test material

Constituent 1
Chemical structure
Reference substance name:
Bis(2,3-epoxypropyl) terephthalate
EC Number:
EC Name:
Bis(2,3-epoxypropyl) terephthalate
Cas Number:
Molecular formula:
1,4-bis[(oxiran-2-yl)methyl] benzene-1,4-dicarboxylate
Details on test material:
- Name of test material (as cited in study report): M-3200
- Physical state: white powder
- Lot/batch No.: P-123
- Storage condition of test material: room temperature

Test animals

Details on test animals or test system and environmental conditions:
Young adult male and female rats of the CD strain (remote Sprague-Dawley origin), supplied by Charles River (UK) Ltd., were
about 5-6 weeks old at arrival and were within the body weight range of 120-137 g. This strain has been widely used in toxicological testing since its establishment under SPF conditions in 1955.
The animals were housed in high density polypropylene GPR-1 cages measuring 56x38x18 cm, with stainless steel grid floors and tops
(North Kent Plastics Ltd., Dartford, Kent, England). The grid floor ensured rapid removal of waste material to undertrays, which
were cleaned out as necessary. A minimum floor area of 400 sq. cm per rat was provided by grouping no more than five animals of
the same sex in each cage. Mobile racks held up to eighteen suspended cages each.

All rooms in the limited access area were kept at slight positive pressure relative to the outside and each had its own filtered air
supply giving about 15 complete air changes per hour without recirculation. Maximum and minimum temperatures during the
preceding 24-hour period and relative humidity were recorded at the beginning of each working day. Target ranges for temperature and
relative humidity were 21° ± 2°C and 55 ± 15% RH. Electric time-switches regulated a lighting cycle of twelve hours artificial
light per day.
A commercially-available powdered rodent pelletted diet (Altromin 1321N) was fed without restriction except on the night before
Animals had free access to tap water supplied in two bottles per cage. The water was taken from the public supply after passing
through a water purifier (Tami-Tana, Israël, Ltd.) and meets the accceptable WHO Standard for quality of water.

On arrival each rat was inspected and only suitable animals were accepted for use. A sample of the delivery was weighed, and the
range of body weights recorded for each sex.
An acclimatisation period of seven days was allowed between arrival at the laboratory and administration of the test material.
A daily check on the general condition of the animals was recorded and this record was consulted before animals were put on study.
Ear-marks uniquely identifying each animal within the room were made before the start of this study. At the same time the sex of
each animal was confirmed.
Each cage was relabelled with details of the schedule number, unique cage reference, treatment level and route of
administration, ear-mark, numbers and sex of occupants, responsible personnel and date of dosing.
Food was removed from the hoppers at about 16:00 hours on the day before dosing. This ensured that the stomach was void of food at
the time of dosing.
Body weight the day before dosing was within the range 159-l83 g for male rats and 141-150 g for females. At the time of dosing
male rats were within the body weight range of l47"l67 g and females 125-133 S- The animals were about 7-8 weeks old at this

Administration / exposure

Route of administration:
oral: gavage
maize oil
Details on oral exposure:
The test material was prepared in maize oil at a constant volume-dosage of 20 ml/kg. The test material was homogenized and
then sonicated to achieve an homogeneous solution. Dosages were expressed gravimetrically (mg/kg) and were freshly prepared on the
morning of administration.
A single group of five male and five female rats was dosed at a dose level of 2500 mg/kg. This dose level was selected on the
basis of a range finding study, as it is the maximum practical dose that can be handled.

Dose volume was determined for each rat according to fasted body weight on the morning of dosing. The dose volume was divided into
two applications with approximately 1 hour between the applications . The dosing was performed with a feeding catheter introduced into the
oesophagus allowing instillation of the test material into the lumen of the stomach.
Food hoppers were returned to the cage immediately after dosing was completed.
A single group of five male and five female rats was dosed at a dose level of 2500 mg/kg. This dose level was selected on the
basis of a range finding study, as it is the maximum practical dose that can be handled.
No. of animals per sex per dose:
A single group of five male and five female rats was dosed at a dose level of 2500 mg/kg
Control animals:
Details on study design:
Animals were returned to their cages immediately after dosing.
Animals were inspected three times on the day of dosing and twice daily thereafter (once daily at weekends and holidays). The type, time of onset and duration of reactions to treatment were recorded.
Body weights were recorded on the day before dosing, on Day 1, and weekly thereafter. The test was terminated on Day 15.

Animals were killed at termination of the study by C02 inhalation and were examined at necropsy by the following procedure to detect
pathological changes caused by sublethal dosages of the test material. All body cavities were opened. Larger organs were
narrowly sectioned and the gastro-intestinal tract was opened at intervals for examination of the mucosal surfaces. All
abnormalities were described or normal appearance of major organs confirmed for each animal.

Results and discussion

Preliminary study:
A preliminary study was performed in the same way as the main study using 5 groups each of 2 male and 2 female rats treated with the test material at 50, 500, 1000, 1800 and 2500 mg/kg diluted in maize oil and applied at a volume of 10 mL/kg.
No death was noted during the course of the preliminary study.
Effect levels
Dose descriptor:
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
No death occurred during the course of the study.
Clinical signs:
other: No clinical signs or toxic reaction to treatment were seen in any of the any of the animals.
Gross pathology:
No macroscopic findings at necropsy.

Any other information on results incl. tables

Body weights (g):

 Sex / Animal Number  Day -1  Day 1  Day 8  Day 15

 male 141

183  165 220 279
 male 142 173  154 210  250
 male 143 181  157 199  259
 male 144 159 147 194   249
 male 145 182 167  245 313 
 female 146 141 128  164  186
 female 147  141 125   163  190
 female 148 142 128  169  200
 female 149 150  133  170  179 
female 150 149  133  171   183

Applicant's summary and conclusion

Interpretation of results:
not classified
Migrated information Criteria used for interpretation of results: EU
Under the conditions of this study, M-3200 was found to have an acute oral median lethal dose (LD50) greater than 2.5 g/kg.
Executive summary:

Five male rats and five female rats (CD) were treated by oral gavage administration at a dosage of 2500 mg/kg body weight. The test item was diluted in vehicle (Maize Oil) and administered at a dosing volume of 20 mL/kg. The animals were observed for 14 days.

No death occurred during the course of the study. No clinical signs were noted during the observation period in any of the treated animals.

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 2500 mg/kg