Isophthalic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1990-03-28 to 1990-04-11

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1990

Report date:

1990

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Principles of method if other than guideline:

Acute oral toxcity study in rats; limit test

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Isophthalic acid

EC Number:

204-506-4

EC Name:

Isophthalic acid

Cas Number:

121-91-5

Molecular formula:

C8H6O4

IUPAC Name:

isophthalic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): Isophthalic Acid
- Physical state: White Powder
- Lot/batch No.: 313B
- Storage condition of test material: Stored at room temperature approx. 22 °C

Specific details on test material used for the study:

- Name of test material (as cited in study report): Isophthalic Acid
- Physical state: White Powder
- Lot/batch No.: 313B
- Storage condition of test material: Stored at room temperature approx. 22 °C

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

Male and female Sprague-Dawley rats, approximately 6 weeks of age were purchased from Charles River Breeding Laboratories (MI). They weighed 120-165 g on arrival. They were quarantined for at least 3 weeks and examined to ensure their health and suitability as test subjects. Individuals were identified by metal ear tags.
Purina Rodent Chow 5001 and reverse-osmosis purified water was supplied ad libitum (food was not available during the pre-dosing fasting period).
The rats were individually housed in suspended stainless steel cages. The animal rooms were maintained at approximately 22°C and 40% humidity. Fluorescent lighting was provided on a 12 hour light dark/cycle.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

Isophthalic acid was mixed thoroughly with reverse osmosis-purified water to form a 33 % (w/v) homogenous suspension which was stirred continuously while being administered at a dosing volume of 15 ml/kg of body weight, using a stainless steel ball-tipped needle.
Food was removed from the rat cages approximately 28 hours prior to dosing, and fasting was continued for approximately 4 hours after dosing. Dosage calculations were based on fasted bodyweights.

Doses:

5000 mg/kg bw

No. of animals per sex per dose:

5 male and 5 female rats

Control animals:

no

Details on study design:

Rats were randomly selected for testing.
The study animals were observed for signs of toxicity and mortality at approximately 1, 2, 3 and 4 hours after dosing, and at least once per day for the remainder of the 14-day observation period. Bodyweights were recorded prior to fasting, and immediately prior to dosing. All surviving rats were weighed on days 7 and 14.
The rats were euthanised with CO2 at the end of the observation period, and a limited gross necropsy was performed on all animals.

Statistics:

A formal statistical analysis is not required

Results and discussion

Preliminary study:

No preliminary results available.

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: No mortality at the limit dose

Mortality:

No deaths occurred during the study.

Clinical signs:

other: Signs observed within 24 hours following test article administration included irritability, salivation, redness around the nose, discolouration around the mouth, diarrhoea, wet and/or discoloured inguinal fur and discoloured paws. Most rats appeared norma

Gross pathology:

Gross necropsy findings were within normal limits in all rats.

Other findings:

No other findings reported.

Any other information on results incl. tables

Summary of clinical observations (5 rats/sex)

Observation	Incidence
	Males	Females
Irritability	0	1
Salivation	1	0
Diarrhoea^a	5	5
Redness around nose	5	3
Discolouration around nose	3	0
Wet inguinal fur	2	0
Discoloured inguinal fur	5	1
Discoloured paws	2	0

a – or evidence of dried diarrhoea below cage

 

 

Summary of mean body weights

Time point	Mean body weight (g) ± SD
	Males	Females
Initial (non-fasted)	357 ± 26.9	208 ± 12.0
Initial (fasted)	322 ± 24.9	185 ± 12.6
Day 7	370 ± 18.2	211 ± 10.8
Day 14	400 ± 16.4	217 ± 10.8
Weight change (g) [Day 14-initial (non-fasted)	43	9

*SD = Standard Deviation

 

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the results of this study, the median acute lethal oral dose (LD50) of isophthalic acid was estimated to be greater than 5000 mg/kg of body weight in male and female rats.

Executive summary:

The acute oral toxicity of isophthalic acid was evaluated in 5 male and 5 female Sprague-Dawley rats. The test substance was administered as a homogenous suspension in water, by gavage, at a single limit dose of 5000 mg/kg bw. Rats were fasted prior to dosing, and dose calculations were based on fasted body weights. Rats were observed for 14 days after dosing, and subject to gross necropsy at study termination. All rats survived to the end of the study. Clinical signs observed within 24 hours following test article administration included irritability, salivation, redness around the nose, discolouration around the mouth, diarrhoea, wet and/or discoloured inguinal fur and discoloured paws. Most rats appeared normal 48 hours following administration. There were no abnormalities detected at necropsy. The acute oral LD50 of isophthalic acid was therefore estimated to be greater than 5000 mg/kg bw in male and female rats under the conditions of this study.