Ammonium iron(III) citrate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 authoritative database.

Data source

Reference

Reference 1

Reference Type:

other: authoritative database

Title:

Acute Toxicity Study - Test chemical

Author:

National Toxicology Program

Year:

1999

Bibliographic source:

National Toxicology Program

Reference 2

Reference Type:

other: authoritative database

Title:

Acute Dermal toxicity - Test chemical

Author:

U.S. National Library of Medicine

Year:

2018

Bibliographic source:

ChemIDplus

Reference 3

Reference Type:

other: secondary source

Title:

Acute dermal toxicity (LD50) test in rabbits.

Author:

National Technical Reports Library

Year:

1980

Bibliographic source:

National Technical Reports Library

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 the given test chemical.

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

Test animals

Species:

rabbit

Strain:

other: New Zealand Albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: 2.30 to 2.86 kg
- Fasting period before study: Not fasted
- Housing: The animals were individually housed in metal cages elevated above the 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:

occlusive

Vehicle:

other: 50%(w/w) isotonic saline

Details on dermal exposure:

TEST SITE
- Area of exposure: intact and abraded skin of the trunk, free of hair
- % coverage: two or three centimeters longitudinally over the area of exposure.
- Type of wrap if used: A plastic binder was slipped onto each animal, which was then placed in a comfortable but immobilized position in a multiple animal holder. The binder was then fastened tightly to keep the preparation in close contact with the skin for 24 hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): At the end of the period of exposure, the binders were removed, the amount of unabsorbed material estimated, the skin reactions recorded, and the remaining test material wiped from the animals' bodies.
- Time after start of exposure:24 hours

Duration of exposure:

Single exposure for a period of 24 hours

Doses:

2000, 4000, 8000 mg/kg bw

No. of animals per sex per dose:

Twelve rabbits, 6 animals per sex

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: Yes, animals which succumbed were necropsied.
- Other examinations performed: The animals were observed for gross effects at regular intervals on the day of dosing and daily thereafter for 14 days.Following the observation period, all surviving animals were weighed, sacrificed and necropsied.

Statistics:

not specified

Results and discussion

Preliminary study:

not specified

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 8 000 mg/kg bw

Based on:

test mat.

Remarks on result:

other: no mortality was observed.

Mortality:

No mortality at highest dose level.

Clinical signs:

other: 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

Gross pathology:

Gross necropsy of animal which succumbed showed the skin to have severe erythema of sides and ventrum with severe congestion appearance of subcutaneous tissue. It has the appearance of chemical burns. The stomach was blanched with severe erosion of the mucosal surface. The small intestines showed severe scattered congestion.
Gross necropsy of the animals sacrificed at 14 days showed one animal at 8000 mg./kg with an approximate 90% loss of fat tissue. Other organs and tissues in all animals were not remarkable.

Other findings:

not specified

Applicant's summary and conclusion

Interpretation of results:

other: not classified

Conclusions:

The acute dermal toxicity dose (LD50) was considered to be >8000 mg/kg, when 12 New Zealand Albino rabbits, six males and six females, were treated with the given test chemical following dermal application by a single exposure for a period of 24 hours.

Executive summary:

The acute dermal toxicity study was conducted by using the given test chemical in 12 New Zealand Albino rabbits, six males and six females, were used to evaluate the potential toxicity following dermal application by a single exposure for a period of 24 hours at the concentrations of 2000, 4000, 8000 mg/kg bw.

Prior to exposure, the animals were prepared by clipping the skin of the trunk free of hair, and only those animals without observable skin defects or irritation were used. 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. Abrasions were sufficiently deep to penetrate the stratum corneum but not to disturb the derma. A plastic binder was slipped onto each animal, which was then placed in a comfortable but immobilized position in a multiple animal holder. Test chemical in the form of a 50% w/w suspension in isotonic saline, was introduced under the plastic binder; the binder was then fastened tightly to keep the preparation in close contact with the skin for 24 hours. At the end of the period of exposure, the binders were removed, the amount of unabsorbed material estimated, the skin reactions recorded, and the remaining test material wiped from the animals' bodies. The animals were housed in their respective cages. The animals were observed for gross effects at regular intervals on the day of dosing and daily thereafter for 14 days. Animals which succumbed were necropsied. Following the observation period, all surviving animals were weighed, sacrificed and necropsied.

No mortality at highest dose level. 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. At 2000 mg/kg bw, two animals exhibited a generalized weakness for 24 to 48 hours after dosing. At 8000 mg/kg bw, 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. Final body weight of surviving animals at termination showed two with intact skin and one with abraded skin at 2000 mg/kg bw to have significant (100% or greater) weight gains. At 4000 mg/kg bw, one (abraded skin) has a significant weight gain. Other surviving animals had weight gains or losses which were less than 10%. Gross necropsy of animal which succumbed showed the skin to have severe erythema of sides and ventrum with severe congestion appearance of subcutaneous tissue. It has the appearance of chemical burns. The stomach was blanched with severe erosion of the mucosal surface. The small intestines showed severe scattered congestion. Gross necropsy of the animals sacrificed at 14 days showed one animal at 8000 mg/kg with an approximate 90% loss of fat tissue. Other organs and tissues in all animals were not remarkable.

Under the condition of the study, the acute dermal toxicity dose (LD50) was considered to be >8000 mg/kg, when 12 New Zealand Albino rabbits, six males and six females, were treated with the given test chemical following dermal application by a single exposure for a period of 24 hours.