Iron sulphide

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 402 (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

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:

male/female

Details on test animals or test system and environmental conditions:

- Source: Toxicology, Department of Safety Assessment, Advinus Therapeutics Limited, Bangalore 560 058, India
- Age at treatment: 11 to 12 weeks
- Weight at treatment: Males: 254.39 to 273.81 g; Females: 203.10 to 210.6 g
- Fasting period before study: Not provided
- 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; water bottles were replenished once daily and changed once a week
- Acclimation period: Females: 5 days; Males: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-22°C
- Humidity (%): 64-66%
- Air changes (per hr): 12-15/hour
- Photoperiod (hrs dark / hrs light):12/12

IN-LIFE DATES: From: June 1, 2012 To: June 22, 2012

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

other: Milli-Q water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsolateral thorax
- % coverage: about 10% of body surface
- Type of wrap if used: cotton gauze secured in position by adhesive tape wound around torso

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with water and with Johnson’s Baby Soap and next with water
- Time after start of exposure: after 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg bw
- Constant volume or concentration used: Based on the individual body weight, the test item at the dose of 2000 mg/kg bw was weighed on an aluminum foil and made into a paste by adding sufficient volume of Milli-Q water.
- For solids, paste formed: yes

VEHICLE
- Amount(s) applied (volume or weight with unit): sufficient volume to make a paste

Duration of exposure:

24 hours

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: 4 times on day 1 and once daily during days 2-15; individual body weights on day 1 (pre-application), 8 (7 days post application) and 15 (14 days post application
- Necropsy of survivors performed: yes

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality

Clinical signs:

other: No clinical signs

Gross pathology:

There were no skin reactions observed at the site of application. There was no abnormality detected at necropsy.

Any other information on results incl. tables

Table 1  Body Weight, Body Weight Changes and Pre-Terminal Deaths

Group and Dose (mg/kg body weight)	Rat No.	S e x	Body weight (g)					No.dead / No.tested	Pre- terminal deaths (%)
			Initial	8^th  day	Weight change (day 8 – Initial)	15^thday	Weight change (day 15 – Initial)
G1 2000	Rm881	F	203.72	212.33	8.61	225.92	22.20	0/10	0
	Rm882	F	204.81	214.39	9.58	230.06	25.25
	Rm883	F	204.97	215.08	10.11	228.62	23.65
	Rm884	F	203.10	211.91	8.81	226.11	23.01
	Rm885	F	210.06	218.17	8.11	230.90	20.84
	Rm886	M	267.52	279.60	12.08	298.15	30.63
	Rm887	M	270.40	281.64	11.24	299.69	29.29
	Rm888	M	258.31	267.80	9.49	286.33	28.02
	Rm889	M	254.39	268.62	14.23	286.36	31.97
	Rm890	M	273.81	290.03	16.22	304.80	30.99

F: Female;       M: Male         

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

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

Executive summary:

An acute dermal toxicity test was conducted with Wistar rats (male and female) to determine the potential toxicity for iron sulfide (Tribotecc® - Ferrostar) to produce toxicity from a short term exposure via the dermal route. The test item at the dose of 2000 mg/kg body weight (based on the individual body weight of rats) was weighed on an aluminum foil and made into a paste by adding sufficient volume of Milli-Q water. The prepared paste was completely transferred on to the cotton gauze (size: males: 9 x 6 cm; Females: 8 x 5 cm of 6 ply) and was applied on to the clipped dorsolateral thoracic surface of the skin of the rats to cover about 10% of body surface of the animal and it was secured in position by adhesive tape wound around torso. The test item contact period with the skin was for 24 hours. After the 24 hour contact period, the dressing was removed and the applied area was washed with water and with Johnson’s Baby Soap (Johnson & Johnson U.S.A.®J&J*TM) and again with water. Washed animals were wiped dry with a cotton hand towel. The treatment was initiated in 5 female rats at the dose of 2000 mg/kg body weight. There were no clinical signs of toxicity, local skin reactions or mortality observed, hence 5 male rats were treated at the same dose of 2000 mg/kg body weight. All the rats were observed for clinical signs of toxicity, local skin reactions and mortality for 14 days post application. There were no clinical signs of toxicity, local skin reactions or mortality. At the end of observation period, all surviving animals were euthanized and subjected to necropsy. There were no abnormalities detected at the necropsy. Based on the present study results, the acute dermal LD₅₀ of Tribotecc®-Ferrostar is greater than 2000 mg/kg body weight in male and female Wistar rats.