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

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

data from handbook or collection of data

Justification for type of information:

data is from safety assessment reports

Data source

Reference

Reference Type:

review article or handbook

Title:

EXECUTIVE SUMMARY OF SAFETY AND TOXICITY INFORMATION: 1,2,3,4- BUTANETETRACARBOXYLIC ACID , CAS Number 1703-58-8

Author:

NATIONAL TOXICOLOGY PROGRAM

Year:

1991

Bibliographic source:

EXECUTIVE SUMMARY OF SAFETY AND TOXICITY INFORMATION, NATIONAL TOXICOLOGY PROGRAM, last updated 1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other: as mentioned below

Principles of method if other than guideline:

The dermal irritation potential of Butane-1,2,3,4-tetracarboxylic acid was assessed in rabbits as a part of acute dermal study

GLP compliance:

not specified

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:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

sex: male and female

Test system

Type of coverage:

occlusive

Preparation of test site:

clipped

Remarks:

intact and abradded skin

Vehicle:

physiological saline

Controls:

not specified

Amount / concentration applied:

2.0 g/kg (n=4), 4.0 g/kg (n=4), and 8.0 g/kg (n=4), each as a 50% w/w suspension in isotonic saline

Duration of treatment / exposure:

24 hours

Observation period:

daliy for 14 days

Number of animals:

12 (6 males and 6 females)

Details on study design:

TEST SITE- Area of exposure: trunk - % coverage: no data available- Type of wrap if used: no dataREMOVAL OF TEST SUBSTANCE- Washing (if done): yes- Time after start of exposure: after 24 hours of exposureSCORING SYSTEM: no data

Results and discussion

In vitro

Other effects / acceptance of results:

no data available

In vivo

Results

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

14 d

Reversibility:

fully reversible within: 14 days

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

At all dose levels, the rabbits exhibited moderate to severe erythema with chemical burns and/or blanching, especially along the abrasions. The intensity of the reactions increased with the dose level. On days 7 and 14, desquamation and drying were also observed.

Other effects:

At each dose level, the signs of systemic toxicity were limited. At the highest level (8.00 g/kg body weight), one animal exhibited generalized weakness for 72 hours, and three animals were observed to be thin after 72 hours and until day 10 of the study. Wry neck was seen in two animals at the 2.00 g/kg body weight dose level. Two animals in this dose group also exhibited a generalized weakness for 24-48 hours. No other signs of systemic toxicity were observed. Final body weight data of surviving animals at day 14 revealed that three animals (two with intact skin, one with abraded skin) in the 2.00 g/kg dose group had significant (10% or greater) weight gains. At 4.00 g/kg, one (abraded skin) had a significant weight gain. Other surviving animals had weight gains or losses that were less than 10%.

Applicant's summary and conclusion

Interpretation of results:

other: not irritating

Conclusions:

At all dose levels, the rabbits exhibited moderate to severe erythema with chemical burns and/or blanching, especially along the abrasions. The intensity of the reactions increased with the dose level. On days 7 and 14, desquamation and drying were also observed. Gross necropsy of the animals sacrificed at day 14 showed no remarkable abnormalities.According to the Federal Hazardous Substances Act (FHSA) Guidelines for classification, Butane-1,2,3,4-tetracarboxylic acid was not determined to be a toxic substance via dermal route.Hence, Butane-1,2,3,4-tetracarboxylic acid can be considered to be not a dermal irritant to rabbit skin.

Executive summary:

The dermal irritation potential of Butane-1,2,3,4-tetracarboxylic acid was assessed in rabbits as a part of acute dermal study.The concentrations for dermal application were 2.0 g/kg (n=4), 4.0 g/kg (n=4), and 8.0 g/kg (n=4), each as a 50% w/w suspension in isotonic saline. Prior to exposure, 12 New Zealand albino(6 male and 6 female) rabbits were prepared by clipping the skin of the trunk free of hair. One-half of the animals in each group (n=2) were further prepared by making epidermal abrasions over the area of exposure sufficiently deep enough to penetrate the stratum corneum, but not to disturb the derma. The test suspensions of BTCA were administered under binders fastened to each animal for a period of 24 hours. After 24 hours, the binders were removed, the amount of unabsorbed material was estimated, and the remaining suspension was wiped from the skin. The animals were observed for gross effects at regular intervals on the day of dosing and daily for 14 days, and any animals that perished were necropsied. When the observation period was completed, all surviving animals were weighed, sacrificed, and necropsied. At all dose levels, the rabbits exhibited moderate to severe erythema with chemical burns and/or blanching, especially along the abrasions. The intensity of the reactions increased with the dose level. On days 7 and 14, desquamation and drying were also observed. At each dose level, the signs of systemic toxicity were limited. At the highest level (8.00 g/kg body weight), one animal exhibited generalized weakness for 72 hours, and three animals were observed to be thin after 72 hours and until day 10 of the study. Wry neck was seen in two animals at the 2.00 g/kg body weight dose level. Two animals in this dose group also exhibited a generalized weakness for 24-48 hours. No other signs of systemic toxicity were observed. Final body weight data of surviving animals at day 14 revealed that three animals (two with intact skin, one with abraded skin) in the 2.00 g/kg dose group had significant (10% or greater) weight gains. At 4.00 g/kg, one (abraded skin) had a significant weight gain. Other surviving animals had weight gains or losses that were less than 10%.

According to the Federal Hazardous Substances Act (FHSA) Guidelines for classification,Butane-1,2,3,4-tetracarboxylic acid was not determined to be a toxic substance via dermal route.

Hence, Butane-1,2,3,4-tetracarboxylic acid can be considered to be not a dermal irritant to rabbit skin.