Ichthammol

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

January/February 1984

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

May 12, 1981

Deviations:

no

GLP compliance:

yes

Test type:

fixed dose procedure

Limit test:

no

Test material

Test material information

1

Reference substance name:

Ichthammol

EC Number:

232-439-0

EC Name:

Ichthammol

Cas Number:

8029-68-3

Molecular formula:

unspecified

IUPAC Name:

Ichthammol (UVCB substance)

Test material form:

liquid: viscous

Details on test material:

sample from a batch from regular production released for use as an active pharmaceutical ingredient in medicinal products.

Specific details on test material used for the study:

The test substance was taken from a regular production batch (CH.029213, 5/82) at the registrant's manufacturing site. At the time of conduct of the study the test substance in general has been used for treatment of skin disorders in human medicine for many decades.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

The experimental animals were male and female Sprague-Dawley rats (a crossbred from breeder "Lippische Versuchstierzucht, Hagemann GmbH & Co., D-4923 Extertal 1, Germany") weighing between 160 and 170 g. The initial age was 42 days for the males and 40 days for the females.
The animals were fed the commercial feed ALTROMIN 1324, manufacturer ALTROMIN GmbH, D-4937 Lage/Lippe, Germany. The animals were deprived of food 16 - 18 hours before the beginning of the study; subsequently, both food and water were available ad libitum (except on the day of treatment).
During the follow up observation period the animals were housed in pairs in MAKROLON cages (type III) at a room temperature of 21 +- 1.0°C and a relative humidity of 55 +- 5%. The colony room was illuminated (approx. 150 lux at 1.50 m above the floor) from 6 a.m. to 6 p.m. and kept dark from 6 p.m. - 6 a.m.

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

Principle: The test substance was applied to rats once for 24 hours on the shaved intact dorsal skin (5.0 x 6.0 cm, 1/10 of the body surface area).
The application site was shaved without injury with a hand shaver. The site was approximately 5.0 x 6.0 cm and was located between the front and rear extremities on the backs of the animals.
The test substance was applied undiluted on a 5-layered gauze pad, covered over with a piece of plastic foil of the same size and attached between the foreleges and hind legs using a rubberized bandage.

Duration of exposure:

24 hours

Doses:

2 doses (17800 and 21500 mg/kg K.G., corresponding to a volume of 17.1 and 20.7 ml/kg body weight) were tested on 2 animals with intact skin. The dose interval followed the factor 1.21.

No. of animals per sex per dose:

Two per sex per dose

Control animals:

no

Details on study design:

Principle: The test substance is applied to rats once for 24 hours on the shaved intact dorsal skin (5.0 x 6.0 cm, 1/10 of the body surface area). After the exposure the backs of the animals were washed off with lukewarm water (30°C) and then swabbed. The treatment phase is followed by a 14-day follow-up observation period in which the following criteria are checked: skin reaction, behaviour, general condition, food intake and development of body weight.
At the end of the observation period, all animals were sacrificed, dissected and macroscopically examined.

Statistics:

If applicable, the LD50 is calculated according to LITCHFIELD and WILCOXON. This is based on the mortality rates within 24 hours and 14 days.

Results and discussion

Preliminary study:

No special sighting study was carried out.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 21 500 mg/kg bw

Based on:

test mat.

Remarks on result:

not determinable due to absence of adverse toxic effects

Mortality:

No mortalities in the study

Clinical signs:

other: No clinical signs in the study

Gross pathology:

Postmortem examination without pathological findings

Other findings:

No developement of erythema. No development of edema. No intolerance reactions.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The acute dermal toxicity of Ichthammol was investigated in vivo in rats at a dose level up to 21500 mg/kg b.w. in a GLP guideline study. No local skin reactions and no specific clinical symptoms were evident in the dose groups applied (there were no signs of erythema or edema). No specific pathological findings were evident on macroscopical examination at the end of the post-observation period. No changes in body weight development and food intake was observable. The LD50 was estimated to be > 21500 mg/kg b.w. (males and females).
Based on the findings of this study there is no need to carry out a special study on skin irritation / corrosion.