Iron sulphide

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to GLP and valid methods, therefore it is considered relevant, reliable and adequate for classification.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2012

Report date:

2012

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

up-and-down procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Iron sulphide

EC Number:

215-268-6

EC Name:

Iron sulphide

Cas Number:

1317-37-9

Molecular formula:

FeS

IUPAC Name:

sulfanylideneiron

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Test animals

Species:

rat

Strain:

other: Wistar –HsdCpd: WU

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Toxicology, Department of Safety Assessment, Advinus Therapeutics Limited, Bangalore 560 058, India
- Age at treatment: 9-11 weeks
- Weight at treatment: 191.8-195.4g
- Fasting period before study: 16 - 18 hours (acces to water was not interrupted)
- Housing: Individually in standard polysulfone cages (Size approximately L 425 x B 266 x H 175 mm), with stainless steel top grill having facilities for pelletted food and drinking water; bedding: steam sterilized clean corn cob was used and changed along with the cage at least twice a week.
- Diet (e.g. ad libitum): Teklad Certified (2014C) Global 14% Protein Rodent Maintenance Diet-Pellet (Certified) manufactured by Harlan Laboratories B.V., Maasheseweg 87c PO Box 553, 5800, AN Venray, The Netherlands; ad libitum
- Water (e.g. ad libitum): Deep bore-well water passed through activated charcoal filter and exposed to UV rays in Aquaguard on-line water filter-cum-purifier manufactured by Eureka Forbes Ltd., Mumbai 400 001, India, in polycarbonate bottles with stainless steel sipper tubes; ad libitum
- Acclimation period: 5-15 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23°C
- Humidity (%): 65-66%
- Air changes (per hr): 12-15/hour
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: 28 June 2012 To: 27 July 2012

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: Milli-Q water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 100 mg/mL

MAXIMUM DOSE VOLUME APPLIED: 3.9 mL

DOSAGE PREPARATION (if unusual):
The test item suspension was prepared on each day of the test item administration.
Steps 1-5: A quantity of 4.0 g of the test item was weighed to a precalibrated beaker *(previously calibrated to a 40 mL volume) and the volume was made up to the mark with Milli-Q water (vehicle) to get the desired concentration of 100 mg/mL. The preparations were stirred using a homogenizer for at least 10 minutes before dosing.
Homogeneity of the test item in the vehicle was maintained during treatment by constant stirring by using homogenizer. Preparations were made prior (within one hour) to dosing.
*Pre-calibration of the beaker to desired volume: 40 mL Milli-Q water was measured in a graduated cylinder. The measured water was transferred into a clean beaker (to be pre-calibrated) and upper and lower meniscus of water was marked on the beaker using a glass marker. Once line has been marked, the water was discarded and the beaker was dried. This line is used to make up to the upper line volume when preparing the dose formulations
CLASS METHOD (if applicable)

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: observations: 5x on test day 1 and once daily during days 2-15; individual body weights: on test day 1 (pre-administration), day 8 (7 days post administration) and day 15 (14 days post administration)
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: No clinical signs of toxicity

Gross pathology:

There were no abnormalities detected at necropsy.

Any other information on results incl. tables

Table 1. Body weight, Body weight change and Pre-terminal deaths

Step and Dose (mg/kg Body weight)	Rat No.	Sex	Body weight (g)
			Initial (Day 1)	Day 8	Weight change (Day 8 – Initial)	Day 15	Weight change (Day 15 – Initial)
Step 1 (2000)	Rm921	F	193.7	209.7	16.0	215.0	21.3
Step 2 (2000)	Rm922	F	191.8	217.5	24.7	223.8	31.0
Step 3 (2000)	Rm923	F	192.3	210.0	17.7	216.3	24.0
Step 4 (2000)	Rm924	F	192.5	210.6	18.1	217.2	24.7
Step 5 (2000)	Rm925	F	195.4	206.8	11.4	215.4	20.0

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Based on the present study results, the estimated acute oral LD50 of Tribotecc® - Ferrostar is greater than 2000 mg/kg body weight in female rats.

Executive summary:

An acute oral toxicity test (Up-and-Down Procedure) was conducted with female Wistar rats to determine the potential of Tribotecc® - Ferrostar to produce toxicity from a single dose via the oral route. The test item was suspended in Milli-Q water and was administered as a single oral dose to fasted (16 - 18 hours) rats. A limit test at 2000 mg/kg was initiated with one female rat. The first animal survived, and four additional animals were tested sequentially with the same dose. Those four animals survived, and the test was concluded. All animals were active, showed no clinical observations and gained body weight during 14 days observation period. All animals were subjected to necropsy at sacrifice and there were no abnormalities observed in any of the rats. Based on the present study results, the estimated acute oral LD₅₀of Tribotecc® - Ferrostar is greater than 2000 mg/kg body weight in female rats.