Bis(2,3-epoxypropyl) terephthalate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 Dec - 29 Dec 2010

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2011

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

2009 - Bayrisches Landesamt für Gesundheit und Lebensmittelsicherheit

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2,3-epoxypropyl) terephthalate

EC Number:

230-565-0

EC Name:

Bis(2,3-epoxypropyl) terephthalate

Cas Number:

7195-44-0

Molecular formula:

C14H14O6

IUPAC Name:

1,4-bis[(oxiran-2-yl)methyl] benzene-1,4-dicarboxylate

Constituent 2

Reference substance name:

bis(2,3-epoxypropyl)terephthalate

IUPAC Name:

bis(2,3-epoxypropyl)terephthalate

Constituent 3

Reference substance name:

bis(oxiran-2-ylmethyl)terephthalate

IUPAC Name:

bis(oxiran-2-ylmethyl)terephthalate

Details on test material:

- Name of test material (as cited in study report): bis(2,3-epoxypropyl)terephthalate
- Physical state: white solid
- Analytical purity: 94.3%
- Lot/batch No.: 29669168
- Expiration date of the lot/batch: August 31, 2012
- Storage condition of test material: at RT in the dark

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: males: 7 - 8 weeks old, females: 14 weeks old
- Weight at study initiation: males: 247 - 251 g, females: 225 - 233 g.
- Housing: individually in IVC cages, type lll H, polysulphone cages on Altromin saw fibre bedding (lot no. 150910)
- Diet (e.g. ad libitum): ad libitum Altromin 1324 maintenance diet for rats and mice (lot no. 1013)
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C):22 ± 3
- Humidity (%): 55 ± 10
- Air changes (per hr): 10
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

cotton seed oil

Details on dermal exposure:

TEST SITE
- Area of exposure: Dorsal trunk area
- % coverage: approximately 10 % of the body surface
- Type of wrap if used: gauze dressing with non-irritating tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with aqua injectionem
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg
- Concentration (if solution): undiluted moistened in cottonseed oil
- For solids, paste formed: yes, the test item was ground to a fine powder in a mortar with the help of a pestle. In order to ensure good skin contact, it was moistened sufficiently with cottonseed oil.

VEHICLE
Cottonseed oil (Sigma, lot no. MKBB7604, expiry date: 01/2011). This vehicle was chosen due to its non-irritating characteristics.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

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
- Frequency of observations and weighing: 30 minutes, 1h, 2h, 3h and 4h after the start of dosing and then once daily. The animals were weighed on day 1 (prior to the application) and on days 8 and 15.
- Necropsy of survivors performed: yes/no
- Other examinations performed: skin irritation: Signs of erythema amd oedema were assessed using the scoring system according to Draize daily during the observation period.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortalities occured

Clinical signs:

other: All animals had nasal discharge for 4h post dosing. Only very slight erythema of treated skin sites occurred in 5 out of 10 animals, which was fully reversible within 48 hours.

Gross pathology:

No abnormal findings

Any other information on results incl. tables

Table 1: Skin irritation scores of the individual animals

Animal number	Edema score after			Erythema score after
	24 hours	48 hours	72 hours	24 hours	48 hours	72 hours
Male 1	0	0	0	1	0	0
Male 2	0	0	0	0	0	0
Male 3	0	0	0	0	0	0
Male 4	0	0	0	0	0	0
Male 5	0	0	0	0	0	0
Female 1	0	0	0	1	0	0
Female 2	0	0	0	1	0	0
Female 3	0	0	0	0	0	0
Female 4	0	0	0	1	0	0
Feamle 5	0	0	0	1	0	0

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present study, single dermal application of the test item bis (2,3-epoxypropyl)terephthalate to rats at a dose of 2000 mg/kg body weight was associated with no mortality and very slight signs of toxicity as well as very slight signs of irritation.

Executive summary:

Male and female rats (WISTAR) were treated dermally by semi-occlusive application during 24 hours at a dosage of 2000 mg/kg body weight. The test item was applied undiluted (only moistened with cottonseed oil to ensure good contact). The animals were observed 30 minutes, 1h, 2h, 3h and 4h after the start of dosing and then once daily for 14 days. The animals were weighed on day 1 (prior to the application) and on days 8 and 15.

No deaths occurred during the course of the study.Very slight signs of toxicity as well as very slight signs of irritation were observed during the course of the study.

No abnormal body weight changes were noted.

At necropsy, no changes were noted.

The acute dermal median lethal dose (LD50) of bis(2,3 -epoxypropyl)terephthalate in rats is greather than 2000 mg/kg body weight.