Slags, tin-smelting

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 December 2013 - 26 February 2014

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP conform study following OECD guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2014

Report date:

2014

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:

Slags, tin-smelting

EC Number:

273-736-5

EC Name:

Slags, tin-smelting

Cas Number:

69012-35-7

Molecular formula:

Since slags are characterised as inorganic UVCB substances, no exact molecular formula can be defined.

IUPAC Name:

bicyclo[1.1.1]diferroxane; oxo[(oxoalumanyl)oxy]alumane; oxocalcium; silanedione

Test material form:

other: solid

Details on test material:

Batch No.: 24012013
Colour: grey

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River, 97633 Sulzfeld, Germany
- Age at study initiation: males: 9 - 10 weeks old; females: 12 - 13 weeks old
- Weight at study initiation: males: 234 – 244 g; females: 208 – 235 g
- Housing: Full barrier in an air-conditioned room
- Diet (e.g. ad libitum): yes - free access to Altromin 1324 maintenance diet for rats and mice (lot no. 0801)
- Water (e.g. ad libitum): yes - free access to tap water
- Acclimation period: at least five days under laboratory conditions

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22  3 °C
- Humidity (%): 55  10%
- Air changes (per hr): 10 x / hour
- Photoperiod (hrs dark / hrs light): Artificial light, sequence being 12 hours light, 12 hours dark

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

water

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: approximately 10% of the total body surface
- Type of wrap if used: dressing, consisting of a gauze-dressing and non-irritating tape and was fixed with an additional dressing in a suitable manner

REMOVAL OF TEST SUBSTANCE
- Washing (if done): yes - with water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 2000 mg/kg body weight

VEHICLE
- Amount(s) applied (volume or weight with unit): water
- Lot/batch no. (if required): Aqua ad injectionem (AlleMan Pharma, lot no. 260813_1, expiry date: 31/07/2016)
- Purity: high

Duration of exposure:

24 hours

Doses:

The test item was applied at a single dose of 2000 mg/kg body weight to each animal.

No. of animals per sex per dose:

5 male and 5 female

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: animals were weighed on day 1 (prior to the application) and on days 8 and 15; careful clinical examination was made several times on the day of dosing (at least once during the first 30 minutes and with special attention given during the first 4 hours post-dose). Thereafter, the animals were observed for clinical signs once daily until the end of the observation period.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology, gross necropsy

Statistics:

Not applicable, no clinical signs of irritation or mortality.

Results and discussion

Preliminary study:

not applicable

Effect levels

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occured

Clinical signs:

other: Neither signs of toxicity nor signs of irritation have been observed.

Gross pathology:

With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.

Other findings:

No unusual findings observed.

Any other information on results incl. tables

Table 1: Clinical signs of systemic toxicity - individual data - males and females

Test Group	Animal Number	Dose (mg/kg bw)	Observations
Male	21	2000	nsf during the whole observation period
	22	2000	nsf during the whole observation period
	23	2000	nsf during the whole observation period
	24	2000	nsf during the whole observation period
	25	2000	nsf during the whole observation period
Female	26	2000	nsf during the whole observation period
	27	2000	nsf during the whole observation period
	28	2000	nsf during the whole observation period
	29	2000	nsf during the whole observation period
	30	2000	nsf during the whole observation period

bw = body weight, nsf = no specific findings

Table 2: Skin Irritation – Individual Data – Males and Females

Test Group	Timepoint	Animal number	Edema / Erythema	Local skin findings
Male	Day 2 – Day 15	21	00	nsf
		22	00	nsf
		23	00	nsf
		24	00	nsf
		25	00	nsf
Female	Day 2 – Day 15	26	00	nsf
		27	00	nsf
		28	00	nsf
		29	00	nsf
		30	00	nsf

nsf = no specific findings

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the conditions of the present study, single dermal application of the test item Slags, tin-smelting to rats at a dose of 2000 mg/kg body weight was associated with no mortality and neither signs of toxicity nor signs of irritation. The dermal LD50 was determined to be > 2000 mg Slags, tin-smelting / kg body weight. Slags, tin-smelting has no obligatory labelling requirement for percutaneous toxicity and is unclassified.

Executive summary:

In the course of an acute dermal toxicity assessment 5 rats of each sex were exposed to slags, tin-smelting for 24 hours.The test item was applied at a single dose of 2000 mg/kg body weight to each animal. After dosing the animals were observed for 14 day; observation included assessment of skin irritation (including recording of erythema and oedema), weight assessment, clinical examination and pathology.

The test item showed no signs of acute dermal toxicity and no signs of dermal irritation after a single dose application. The body weight development of all male and female animals was within the expected range.With the exception of acute injection of blood vessels in the abdominal region, which is due to the euthanasia injection, no specific gross pathological changes were recorded for any animal.

The dermal LD50was determined to be > 2000 mg Slags, tin-smelting / kg body weight. According to Annex I of Regulation (EC) 1272/2008 the test item Slags, tin-smelting has no obligatory labelling requirement for percutaneous toxicity and is unclassified.