Bis(2,3-epoxypropyl) phthalate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2016

Report date:

2016

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Bis(2,3-epoxypropyl) phthalate

EC Number:

230-566-6

EC Name:

Bis(2,3-epoxypropyl) phthalate

Cas Number:

7195-45-1

Molecular formula:

C14H14O6

IUPAC Name:

bis(oxiran-2-ylmethyl) phthalate

Test material form:

liquid

Details on test material:

As defined in Section 1.2 and 1.4.

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

DMSO

Details on oral exposure:

A total of five animals were therefore treated at a dose level of300 mg/kg in the study. All animals were dosed once only by gavage, using a metal cannula attached to a graduated syringe. The volume administered to each animal was calculated according to the fasted body weight at the time of dosing. Treatment of animals was sequential. Sufficient time was allowed between each dose group to confirm the survival of the previously dosed animals.

Doses:

2000 mg/kg bw
300 mg/kg bw

No. of animals per sex per dose:

2000 mg/kg bw: 1 female
300 mg/kg bwL 5 females

Control animals:

no

Details on study design:

Clinical observations were made 30 minutes, 1, 2, and 4 hours after dosing and then daily for up to 14 days. Morbidity and mortality checks were made twice daily. Individual body weights were recorded on Day 0 (the day of dosing) and on Days 7 and 14. Due to a technician error the body weight at death was not performed on the animal treated at a dose level of 2000 mg/kg that was humanely killed 4 hours after dosing. At the end ofthe observation period the surviving animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.

Statistics:

The following computerized system was used in the study:
Delta Controls - ORCA view

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 300 - < 2 000 mg/kg bw

Based on:

test mat.

Mortality:

The animal treated at 2000 mg/kg bw was killed for humane reasons, 4 hours after dosing, due to the occurrence of clinical signs of toxicity that approached the severity limit set forth in the UK Home Office
Project Licence. There were no deaths at the 300 mg/kg dose level.

Clinical signs:

other: At the 2000 mg/kg dose level signs of systemic toxicity noted were hunched posture, pilo-erection, ataxia, ptosis, labored respiration, cyanosis, hypothermia, dehydration and prostration. No signs of systemic toxicity were noted during the observation per

Gross pathology:

At the 2000 mg/kg dose level, abnormalities noted at necropsy were dark liver, brown colored lumpy substance (feces) in the stomach and epithelial sloughing of the gastric mucosa and non-glandular epithelium of the stomach. No abnonnalities were noted at necropsy at the 300 mg/kg bw dose level.

Any other information on results incl. tables

Body weight

Dose Level mglkg	Animal Number    and Sex	Body Weight (g) at Day			Body Weight Gain (g) During Week
		0	7	14	1	2
300	1-0 Female	152	165	179	13	14
	3-0 Female	147	160	179	13	19
	3-1 Female	145	170	181	25	11
	3-2 Female	153	173	187	20	14
	3-3 Female	162	180	193	18	13

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral median lethal dose (LDso) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight (Globally Harmonized Classification System - Category 4).

Executive summary:

Introduction

The study was performed to assess the acute oral toxicity of the test item in the Wistar strain rat.

Methods

Following a sighting test at dose levels of 2000 mg/kg and 300 mg/kg, a further group of four fasted females was given a single oral dose of test item, as a solution in dimethyl sulphoxide, at a dose level of 300 mg/kg body weight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy.

Results

Mortality. The animal treated at a dose level of 2000 mg/kg was killed for humane reasons, 4 hours after dosing, due to the occurrence of clinical signs of toxicity that approached the severity limit set forth in the UK Home Office Project Licence. There were no deaths at a dose level of 300 mg/kg.

Clinical Observations. Signs of systemic toxicity noted in the animal treated at a dose level of 2000 mg/kg were hunched posture, pilo-erection, ataxia, ptosis, labored respiration, cyanosis, hypothermia, dehydration and prostration. There were no signs of systemic toxicity at a dose level of 300 mg/kg.

Body Weight. Surviving animals showed expected gains in body weight.

Necropsy. Abnormalities noted at necropsy of the animal treated at a dose level of 2000 mg/kg were dark liver, brown colored lumpy substance (feces) in the stomach and epithelial sloughing of the gastric mucosa and non-glandular epithelium of the stomach. No abnormalities were noted at necropsy of animals treated at a dose level of 300 mg/kg.

Conclusion

The acute oral median lethal dose (LD₅₀) of the test item in the female Wistar strain rat was estimated to be in the range of 300 - 2000 mg/kg body weight (Globally Harmonized Classification System - Category 4).