diethylmethoxyborane

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: in vitro GLP-study which was performed as a dose-finding screening study for the guinea pig maximization test

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Principles of method if other than guideline:

Assessment of physico-chemical and bioiogical reactions of different concentrations of DEMB when placed on non-living animal-skin.
The clipped, dorsal skin of three sacrificed female rats was removed, stretched and fixed on a flat, metal surface. Single samples of approximately 0.5 ml of a
10 mg/ml, a 200 mg/ml solution and the undiluted test substance were each placed on a different stretched, clipped skin (open application).
A sacrificed guinea pig was in situ treated as follows: intradermal injections were given in the clipped scapular region of the undiluted test substance and a 200 mg/ml and 10 mg/ml solution, mimicking the procedures of a sensitisation study. Moreover, the undiluted test substance and the 200 mg/ml solution were each occlusively, applied to a clipped flank. Two hours after application the dressing was removed.

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

-

EC Number:

425-380-9

EC Name:

-

Cas Number:

7397-46-8

Molecular formula:

C5H13BO

IUPAC Name:

methyl diethylborinate

Details on test material:

- Name of test material (as cited in study report): DEMB
- Physical state: Water-white liquid
- Analytical purity: 99.4 %
- Lot/batch No.: 183
- Expiration date of the lot/batch: August 01, 1997
- Stability under test conditions: in the vehicle dry propylene glycol stable for 16-20 h
- Storage condition of test material: At room temperature in the dark
- Other: Density 0.76 g/ml

Test animals

Species:

other: skin in vitro model

Strain:

other: Wistar rats strain Crl:(WI) BR; guinea pig: Himalayan strain

Details on test animals or test system and environmental conditions:

a skin in vitro model was used

Test system

Type of coverage:

other: open and occlusive

Preparation of test site:

other: not applicable

Vehicle:

other: Propylene glycol

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL
- Concentration (if solution): 10, 200 mg/ml and undiluted test substance

Duration of treatment / exposure:

rat-skin: 1, 5, 10, 30 min
guinea pig: 15 min and 2 hours

Observation period:

Rat-skin: The physico-chemical and biological reactions were continuously monitored during the exposure period. Findings were recorded approximately 1, 5, 10 and 30 minutes after application.
Guinea pig: The reactions in the dermal tissue were assessed and recorded 15 minutes (intradermal injection sites only) and 2 hours after treatment.

Number of animals:

rats: 3
guinea pig: 1

Details on study design:

Three female rats were sacrificed using a oxygen/carbon dioxide asphyxiation procedure. The dorsal fur was clipped using an electric clipper. The dorsal fur was removed, stretched and fixed on a flat, metal surface using sticking tape. The skin to be treated was intact and free from any abnormality. Single samples of approximately 0.5 ml of a 10 mg/ml, a 200 mg/ml solution and the undiluted test substance were each placed on a different stretched, clipped skin (open application).
At a later stage, a guinea pig was sacrificed in an identical manner. Subsequently, intradermal injections were given in the clipped scapular region of the undiluted test substance and a 200 mg/ml and 10 mg/ml solution (0.1 ml/injection in duplicate), mimicking the procedures of the sensitisation study. One of each pair of injections was on each side of the midline and from cranial (10 mg/ml) to caudal (undiluted). Moreover, the undiluted test substance and the 200 mg/ml solution (0.5 ml each) were each occlusively, applied to a clipped flank using Scotchpak-non-woven patches (2x3 cm) on Micropore tape and held in place by Coban elastic bandage. Two hours after application the dressing was removed.

Results and discussion

In vitro

Results

Remarks on result:

other: see "Any other information on results incl. tables"

Any other information on results incl. tables

Administration of undiluted DEMB or any of the dilutions (ie. 200 and/or 10 mg/ml in propylene glycol) on freshly prepared non-living animal skin via open or occlusive application, did not result in any physico-chemical reaction. After open application, no biological reactions in the rat-skin were observed in response to the three concentration used.

Occlusive administration of the undiluted test substance for 2 hours to a sacrificed, intact guinea pig, caused corrosion of the skin as observed after removal of the bandages. The skin-site treated with a 200 mg/ml solution caused no visible changes as assessed in situ. After excision of the treated skin, slight effects, a yellowish discolouration of the subcutis, were observed to a 200 mg/mL solution. The intradermal injections of different concentrations made in the guinea pig showed a dose response relation ship present as a gradual increase of the diameter of necrosis with increasing concentrations.

Applicant's summary and conclusion

Conclusions:

Rat: non-corrosive
Guinea pig: corrosive

Executive summary:

When administered under occlusive conditions the undiluted test substance should be regarded as corrosive to the skin. The absence of any significant biological effect after occluded administration of a 200 mg/ml concentration indicate that this (and lower) concentration is acceptable and well tolerated in vivo. The results of the intradermal injections indicate that concentrations lower than 10% may be acceptable for use in vivo, ie. a skin sensitization guinea pig maximization test. In view of the selection criteria for suitable concentrations to be used in a skin sensitization study, a maximum concentration of 5% is suggested for intradermal injection and a 20% for epidermal application.

According to Annex VI of EU Regulation (EC) N0. 1272/2008 (CLP) and Annex I of EU directive 67/548/EEC, DEMB is classified as corrosive Cat 1b and R34, respectively.