5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, polymer with 1,2-propanediol

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Oct 10 2014 - Dec 2 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was performed according to OECD Guideline and EU Method on testing and assessment in compliance with GLP.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Principles of method if other than guideline:

same as guideline

GLP compliance:

yes (incl. QA statement)

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, reaction products with 1,2-propanediol

EC Number:

613-407-9

Cas Number:

63948-88-9

Molecular formula:

not applicable

IUPAC Name:

5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-, reaction products with 1,2-propanediol

Test material form:

solid: particulate/powder

Details on test material:

Product name: ZAN 573
Chemical name: 5-Isobenzofurancarboxylic acid, 1,3-dihydro-1,3-dioxo-,
polymer with 1,2-propanediol (85%) and Trimellitic anhydride (15%)
CAS numbers : 63948-88-9: 85% and 552-30-7: 15%
Batch number: 130072591
Appearance: Yellow to brown solid, coarse powder
Purity: treated as 100% (for more details see above)
Manufacturing date: 24 January 2014
Expiry date: 24 January 2016
Storage conditions: Controlled room temperature (15-25°C, below 70 RH%)

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

STUDY SCHEDULE
Reception of Animals 25 September 2014
Experimental Starting Date 14 October 2014
Experimental Completion Date 29 October 2014
Treatment 14 October 2014 (females no. 108, 109, 110)
15 October 2014 (females no. 111, 112, 113)
Observation 14 - 28 October 2014 (females no. 108, 109, 110)
15 - 29 October 2014 (females no. 111, 112, 113)
Necropsy: 28 October 2014 (females no. 108, 109, 110)
29 October 2014 (females no. 111, 112, 113)

EXPERIMENTAL ANIMALS
Species and strain: CRL: (WI) Wistar rats
Source: Charles River Laboratories, Research Models and Services, Germany GmbH, Sanhofer Weg 7, D-97633 Sulzfeld
Hygienic level at arrival: SPF
Hygienic level during the study: Standard housing conditions
Number of animals: 6 animals
Sex: Female, nulliparous and non-pregnant
Age of animals at dosing: Young healthy adult rats, 9-10 weeks old
Date of receipt: 25 September 2014
Body weight at treatment: 217 – 249 g
Acclimation period: At least 20 days

Husbandry
Animal health: Only healthy animals were used for the test. The veterinarian certified health status.
Number of animal room: 522/11
Housing: 3 animals / group
Cage type: Type II polypropylene/polycarbonate
Bedding: Lignocel Bedding for Laboratory Animals was available to animals during the study.
A copy of the Certificate of Analysis is retained in the archive at CiToxLAB Hungary Ltd.
Lighting period: 12 hours daily, from 6.00 a.m. to 6.00 p.m.
Temperature: 22 ± 3 °C
Relative humidity: 30 - 70 %
Ventilation: 15-20 air exchanges/hour
Enrichment: Animals were housed by group to allow social interaction and with deep wood sawdust bedding to allow digging and other normal rodent activities.
The temperature and relative humidity were recorded twice daily during the study.

Food and Water Supply
Animals received ssniff® SM R/M "Autoclavable complete diet for rats and mice – breeding and maintenance" produced by ssniff Spezialdiäten GmbH, D-59494 Soest Germany ad libitum, and tap water from the municipal supply, as for human consumption from 500 ml bottle ad libitum. The food is considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.

The batch of feed employed in the study were as follows: 190 1786, expiry date: January 2015
The supplier provided an analytical certificate for the batch used. Copy of the certificates will be archived with the raw data.
Water quality control analysis is performed once every three months and microbiological assessment is performed monthly, by Veszprém County Institute of State Public Health and Medical Officer Service (ÁNTSZ, H-8201 Veszprém, József A.u.36., Hungary). The quality control results are retained in the archives at CiToxLAB Hungary Ltd.

Animal Identification
Animals were individually identified using numbers written on the tail with an indelible marker pen. The numbers were given on the basis of CiToxLAB Hungary Ltd.' s Master File, for each animal allocated to the treatment groups. The cages were identified by cards, with information about study code, sex, dose group, cage number and individual animal numbers.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: methyl cellulose

Details on oral exposure:

Justification of the dose:
Initially, three female assigned to (Group 1) were treated at a dose level of
2000 mg/kg bw. As no mortality was observed, a confirmatory group (Group 2) was treated at the same dose level. The test item did not cause mortality in the confirmatory group, so no further testing was required according to OECD 423 and Commission Regulation (EC) NO 440/2008 of 30 May 2008, B.1.Tris.

Procedure
A single oral gavage administration was followed by a fourteen-day observation period. On the day before treatment, the animals were fasted. The food but not water was withheld during an overnight period. Animals were weighed just before treatment. The test item was administered by oral gavage in the morning. The food was returned 3 hours after the treatment.

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

3 + 3

Control animals:

no

Details on study design:

OBSERVATIONS
Clinical observations were performed on the animals at 30 minutes, 1, 2, 3, 4 and 6 hours after dosing and daily for 14 days thereafter. Individual observations were performed on the skin, fur, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous system, somatomotor activity and behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea, lethargy, sleep and coma.
The body weight was recorded on the day before treatment (Day -1), on the day of the treatment (Day 0) and weekly after.

NECROPSY
Macroscopic examination was performed on all animals. The surviving animals were sacrificed by exsanguination under pentobarbital anaesthesia (Euthasol® 40 %; details are presented in 3.1.3.). After examination of the external appearance, the cranial, thoracic and the abdominal cavities were opened and the organs and the tissues were observed. Macroscopic abnormalities were recorded.

Statistics:

The method used was not intended to allow the calculation of a precise LD50 value.
The test item was ranked into categories of Globally Harmonized Classification System (GHS) described in the OECD Guideline No. 423.

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

ZAN 573 did not caused mortality at the dose level of 2000 mg/kg bw.

Clinical signs:

other: Treatment with ZAN 573 at a dose level 2000 mg/kg bw did not cause any test item related effects on the animals.

Gross pathology:

A single oral gavage of ZAN 573 to the CRL: (WI) female rat at a dose level of 2000 mg/kg bw was not associated with any gross changes.

Applicant's summary and conclusion

Interpretation of results:

study cannot be used for classification

Remarks:

Migrated information

Conclusions:

The acute oral LD50 value of the test item ZAN 573 was above 2000 mg/kg bw in female CRL: (WI) Wistar rats.

Executive summary:

The single-dose oral toxicity of ZAN 573 was performed according to the acute toxic class method (OECD 423 and Commission Regulation (EC) No 440/2008 of 30 May 2008) in CRL: (WI) Wistar rats.

ZAN 573 was administered in Methyl cellulose 1% at concentrations of 200 mg/mL with a dosing volume of 10 mL/kg bw.

Initially, three fasted female assigned to (Group 1) were treated at a dose level of 2000 mg/kg bw. The test item did not cause test item-related effects or mortality in this group; therefore a confirmatory group (Group 2) was treated at the same dose level. The test item did not cause observable adverse effects or mortality in the confirmatory group, so no further testing was required according to OECD 423 and Commission Regulation (EC) No 440/2008. The substance is not classified according to Regulation EC No. 1272/2008.