Octadecyl 3-mercaptopropionate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

11 Sep 2008 - 26 Nov 2008

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 434 (Acute Dermal Toxicity - Fixed Dose Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: First addendum to OECD Guidelines for Testing of Chemicals, Section 4, No. 404, "Acute Dermal Irritation/Corrosion" adopted 24th April, 2002.

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Remarks:

Bayerisches Landesamt für Arbeitsschutz, Arbeitsmedizin und Sicherheitstechnik

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Isooctyl 3-mercaptopropionate

EC Number:

250-157-6

EC Name:

Isooctyl 3-mercaptopropionate

Cas Number:

30374-01-7

Molecular formula:

C11H22O2S

IUPAC Name:

isooctyl 3-mercaptopropionate

Details on test material:

- Name of test material (as cited in study report): Isooctyl mercaptopropionate
- Analytical purity: 99.9 % area (GC)
- Purity test date: 2008-08-26
- Lot/batch No.: 24317
- Expiration date of the lot/batch: 2009-08-11
- Physical state: liquid at RT
- Storage: at room temperature
- Other: colorless

Test animals

Species:

rat

Strain:

Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Winkelmann GmbH, D-33178 Borchen
- Age at study initiation: 8 - 12 weeks
- Weight at study initiation: 190 - 200 g
- Housing: Semi-barrier condition in an air conditioned room; animals were kept in IVC cages, type III H, polysulphone cages on Altromin saw fiber bedding
- Diet (ad libitum): free access to Altromin 1324 maintenance diet for rats and mice
- Water (ad libitum): free access to tap water, sulphur acidified to a pH value of approximately 2.8 (drinking water, municipal residue control, micro biologically controlled at frequent intervals)
- Acclimation period: at least five days


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

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: no less than 10 %
- Type of wrap if used: The test article was held in contact with the skin by a dressing which consisted 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): At the end of the exposure, residual test item was removed by using aqua ad injectionem (B. Braun Melsungen; Lot 7494A191).
- Time after start of exposure: The test article was held in contact with the skin throughout a 24 hour period.


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

Duration of exposure:

24 hours

Doses:

2000 mg/kg

No. of animals per sex per dose:

A total of five animals was made up of one animal from the sighting study dosed at the selected dose level together with additional four animals.

Control animals:

not required

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: A careful clinical examination was made immediately after the dosing, at least once during the first 30 minutes, periodically during the first 24 hours, with special attention given during the first 4 hours, and daily thereafter. Primary skin irritation was assessed 1, 2 and 3 days after removal of the test substance.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight

Statistics:

Primary skin irritation was assessed using the scoring system laid down in OECD 404.

Results and discussion

Preliminary study:

A sighting study was performed to allow the selection of the appropriate starting dose for the main study. The test article was applied to one female at a dose of 2000 mg/kg body weight (oral LD50 rat >2000 mg/kg bw).
As the animal survived, the main test was performed with the same dose, with four additional animals.

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Mortality:

No mortality occured.

Clinical signs:

other: In the main study 1 out of 4 animals showed a bloody nose on day 9 after the application of the test item. This finding is considered to be incidental and not treatment related. No other clinical signs of toxicity were observed throughout the observation

Body weight:

other body weight observations

Remarks:

For animal no. 3, a minimal weight loss of 1 g during the first week was recorded. The body weight development of further animals was within the expected range.

Gross pathology:

At necropsy of the main study, 1 out of 4 animals showed a clearly visible prominence and light-colored deposits on the spleen as well as dark-colored spots on the right heart ventricle. In the absence of clinical signs, this isolated finding does not appear to be of toxicological significance or a resultof treatment. Except for acute injection of blood vessels in the abdominal region, which was caused by the euthanasia injection, no specific gross pathological changes were found in any of the other animals.

Other findings:

No signs of skin irritaion were noted.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The dermal LD50 was determined to be > 2000 mg/kg bw. Therefore, the test item Isooctyl mercaptopropionate is unclassified according to the criteria of Annex VI to Commission Directive 2001/59/EC. Judging from the absence of local skin effects after 24 hours of exposure to 2000 mg/kg bw, it is concluded that the test article is not a primary skin irritant.

Executive summary:

This study was conducted to assess the acute dermal toxicity of the test item iOMP after a single dermal administration to 5 female Wistar rats in accordance eith OECD TG 434.

The test item was applied as a single dose uniformly over an area which was approx. 10% of the total body surface.
The test item was held in contact with the skin by a dressing which consisted of a gauze-dressing and non-irritating tape, and was fixed with an additional dressing in a suitable manner. The starting dose was 2000 mg/kg body weight.

The test item was held in contact with the skin throughout a 24-hour period. At the end of the exposure, residual test item was removed by using aqua ad injectionem.

The dermal LD50 was determined to be > 2000 mg/kg bw.