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Administrative data

Endpoint:
acute toxicity: dermal
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

Referenceopen allclose all

Reference Type:
other: Authoritative database
Title:
Acute Dermal Toxicity (LD50) test in rabbits
Author:
Arthur D. Little, Inc.
Year:
1991
Bibliographic source:
NATIONAL TOXICOLOGY PROGRAM, EXECUTIVE SUMMARY OF SAFETY AND TOXICITY INFORMATION,1991
Reference Type:
secondary source
Title:
Acute Dermal Toxicity (LD50) test in rabbits
Author:
Mallinckrodt INC
Year:
1990
Bibliographic source:
NTIS – OTS02800059

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: as mentioned below
Principles of method if other than guideline:
Acute dermal toxicity test was access in rabbits using Butane-1,2,3,4-tetracarboxylic acid.
GLP compliance:
no
Test type:
other: not specified
Limit test:
no

Test material

Constituent 1
Chemical structure
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:
other: New Zealand Albino
Sex:
male/female
Details on test animals or test system and environmental conditions:
- Weight at study initiation: 2.30 to 2.86 kg - Fasting period before study: Not fasted- Housing: Metal cages elevated above droppings- Diet (e.g. ad libitum): Purina Rabbit Chow, ad libitium- Water (e.g. ad libitum): Tap water, ad libitum

Administration / exposure

Type of coverage:
other: intact and abraded skin
Vehicle:
other: 50%(w/w) isotonic saline
Details on dermal exposure:
No data available
Duration of exposure:
Single exposure for a period of 24 hours
Doses:
2000, 4000,8000 mg/kgbw
No. of animals per sex per dose:
Twelve rabbits, 6 animals per sexGroup NumberNumber of AnimalsSkin Preparation12Intact12Abraded22Intact22Abraded32Intact32Abraded
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days (or other?): 14 days- Necropsy of survivors performed: Yes- Other examinations performed: clinical signs, body weight, organ weights, histopathology, other: body weight, clinical signs

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 8 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 50 % mortality was observed
Mortality:
No mortality at highest dose level
Clinical signs:
Few systemic signs of toxicity were observed at any dose level.
Body weight:
Final body weight of surviving animals at termination (14 days) for intact skin, two animals showed significant weight gain (10% or greater) at 2000 mg/kg.Final body weight of surviving animals at termination (14 days) for abraded skin, one animal showed significant weight gain (10% or greater) at 2000 mg/kgbw. At 4000mg/kgbw one animal had significant weight gain.
Gross pathology:
Gross necropsy of animal which succumbed showed the skin to have severe erythema of sides and ventrum with severe congestion appearance of chemical burns. The stomach was blanched with the mucosal surface. The small intestines showed severe scattered congestion.
Other findings:
At all dose levels there was moderate to severe erythema with chemical burns and/or blanching especially along abrasions The intensity increased with the dose level.This was followed at 7 and 14 days with desquamation and drying.

Applicant's summary and conclusion

Interpretation of results:
other: not classified
Conclusions:
The lethal dose concentration causing 50% mortality skin exposure of 1,2,3,4 butane tetracarboxylic acid to New Zealand Albino rabbits was considered to be 8000mg/kgbw.
Executive summary:

Acute dermal toxicity test was performed in New Zealand Albino rabbits. Twelve New Zealand Albino rabbits, six males and six females were used and treated for 24 hrs. The rabbits weight was 2.30 to 2.86 kg were housed in metal cages elevated above droppings. Rabbits were given Purina Rabbit Chow and water ad libitium. Those animals which were without observable skin defects or irritation were used for experiment. One-half of the animals in each group were further prepared by making epidermal abrasions every two or three centimeters longitudinally over the area of exposure. A plastic binder was used onto each animal and 50% w/w suspension in isotonic saline, was introduced under the plastic binder. After the experiment the binder was removed and skin reactions were observed.

No mortality at highest dose level was observed. Few systemic signs of toxicity were observed at any dose level. At all dose levels there was moderate to severe erythema with chemical burns and/or blanching especially along abrasions. The intensity increased with the dose level. This was followed at 7 and 14 days with desquamation and drying. Gross necropsy of animal which succumbed showed the skin to have severe erythema of sides and ventrum with severe congestion appearance of chemical burns. The stomach was blanched with the mucosal surface. The small intestines showed severe scattered congestion.

As per the all observation, the LD 50 value for acute dermal toxicity for Butane-1,2,3,4-tetracarboxylic acid was considered to be 8000mg/kg bw. Based on that, Butane-1, 2, 3, 4-tetracarboxylic acid was considered to be non-toxic to rabbits and classified as “not classified “as per the CLP regulations.

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