Butane-1,2,3,4-tetracarboxylic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Data is from NTP and NTRL report.

Justification for type of information:

Data is from NTP and NTRL report.

Data source

Reference

Reference 1

Reference Type:

other: Authoritative database.

Title:

Acute oral toxicity test in rats.

Author:

Arthur D. Little, Inc.

Year:

1991

Bibliographic source:

EXECUTIVE SUMMARY OF SAFETY AND TOXICITY INFORMATION,NATIONAL TOXICOLOGY PROGRAM

Reference 2

Reference Type:

secondary source

Title:

Acute Oral Toxicity (LD50) test in rats

Author:

Mallinckrodt INC

Year:

1980

Bibliographic source:

NTIS Report, OTS – 02800059 - IN

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

Acute oral toxicity was access in rats using Butane-1,2,3,4-tetracarboxylic acid.

GLP compliance:

not specified

Test type:

other: not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Butane-1,2,3,4-tetracarboxylic acid

EC Number:

216-938-0

EC Name:

Butane-1,2,3,4-tetracarboxylic acid

Cas Number:

1703-58-8

Molecular formula:

C8H10O8

IUPAC Name:

butane-1,2,3,4-tetracarboxylic acid

Test material form:

solid

Details on test material:

- Name of the test chemical: Butane-1,2,3,4-tetracarboxylic acid- IUPAC name: Butane-1,2,3,4-tetracarboxylic acid - Molecular Formula: C8H10O8- Molecular Weight: 234.159 g/mol- Smile Notation: OC(=O)C[C@H]([C@H](CC(=O)O)C(=O)O)C(=O)O- InChI : 1S/C8H10O8/c9-5(10)1-3(7(13)14)4(8(15)16)2-6(11)12/h3-4H,1-2H2,(H,9,10)(H,11,12)(H,13,14)(H,15,16)/t3-,4+- Substance type: organic

Specific details on test material used for the study:

Name of the test chemical: Butane-1,2,3,4-tetracarboxylic acidMolecular Formula: C8H10O8Molecular Weight: 234.159 g/molSmile Notation: OC(=O)C[C@H]([C@H](CC(=O)O)C(=O)O)C(=O)OInChI : 1S/C8H10O8/c9-5(10)1-3(7(13)14)4(8(15)16)2-6(11)12/h3-4H,1-2H2,(H,9,10)(H,11,12)(H,13,14)(H,15,16)/t3-,4+Substance type: organic Physical state: Solid

Test animals

Species:

rat

Strain:

other: COX-SD

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALSWeight at study initiation:198-293gmFasting period before study: yes, overnight fasting Housing: Metal wire bottomed cagesDiet (e.g. ad libitum): Purina Rodent Laboratory Chow, ad libitiumWater (e.g. ad libitum):Tap water, ad libitium IN-LIFE DATES: From: To: one group was dosed at 21/8/79 and second group 17/10/79 and sacrificed on 31/10/79

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Distilled water

Details on oral exposure:

VEHICLEConcentration in vehicle: 10%(w/w)MAXIMUM DOSE VOLUME APPLIED: 3170g/kgbw Rationale for the selection of the starting dose: Prior to the actual LD50 determination, exploratory doses were administered to eight rats to estimate the order of toxicity of the test material. Based on the results of the preliminary assay, groups of ten rats (five males and five females) were dosed at intervals spaced so as to provide a suitable dosage mortality curve for quantitative assessment of oral LD50

Doses:

800, 1260, 1590, 2000 and 3170mg/kgbw

No. of animals per sex per dose:

5 animals

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days (or other?): 14 days- Frequency of observations and weighing: Observations for gross signs were performed at regular intervals on the day of dosage and 5 days per week and thereafter for fourteen days, Surviving animals were weighed seven days post-treatment.- Necropsy of survivors performed: Yes

Statistics:

LD50 with confidence limits and slope function with confidence limits (method of Litchfield and Wilcoxon)

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 720 mg/kg bw

Based on:

test mat.

95% CL:

> 1 420 - < 2 080

Mortality:

Cumulative Mortality dataDosage Level mg/kgbw% Mortality80001260101590202000803170100

Clinical signs:

other: Slight to severe hypoactivity,hypersalivation, diarrhea. unkempt pelage, piloerection, malaise and proneness were seen.

Gross pathology:

Moderate to severe congestion of the kidneys, adrenaIs , lungs, liver and intestines, scattered brownish lesions and/or erosion of the mucosa of the stomach (opaque portion), blanching of the mucosa of the stomach (opaque and translucent portions) and small intestine, paleness of the liver (underside of lobes) and brownish-gray coloration throughout the lungs.

Applicant's summary and conclusion

Interpretation of results:

Category 4 based on GHS criteria

Conclusions:

The acute oral LD50 of BTCA , when administered to 5 male COX-SD rats was considered to be 1740mg/kgbw, with a confidence interval of 1330 to 2280mg/kgbwThe acute oral LD50 of BTCA , when administered to 5 female COX-SD rats was considered to be 1620mg/kgbw.

Executive summary:

Acute oral toxicity test was performed in rats COX-SD strain for a period of 14 days. The rats have 198-293gm and metal wire bottomed cages were used for the housing of rats. The chemical was given orally in the form of gavage in distilled water. 5 animals per sex per dose were used in 800, 1260, 1590, 2000 and 3170 mg/kg bw concentrations. Observations for gross signs were performed at regular intervals on the day of dosage and 5 days per week and thereafter for fourteen days. Necropsy of survivors was also done at termination of the study.

Body weight were observed in animals some has constant weight and some has slight decrease in weight was observed.

Moderate to severe congestion of the kidneys, adrenaIs , lungs, liver and intestines, scattered brownish lesions and/or erosion of the mucosa of the stomach (opaque portion), blanching of the mucosa of the stomach (opaque and translucent portions) and small intestine, paleness of the liver (underside of lobes) and brownish-gray coloration throughout the lungs.

The acute oral LD50 of BTCA , when administered to 5 male COX-SD rats was considered to be  1740 mg/kgbw, with a confidence interval of 1330 to 2280 mg/kg bw.The acute oral LD50 of BTCA , when administered to 5 female COX-SD rats was considered to be 1620 mg/kgbw.