Bromochloromethane

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: No guideline was followed but well documented scientifically defensible approach was used to conduct the study.

Data source

Reference

Reference Type:

publication

Title:

Unnamed

Year:

1990

Materials and methods

Principles of method if other than guideline:

To asses the potential of bromochloromethane to penetrate the skin and be absorbed via this route, male rats were dermally exposed to the test substance to neat, saturated, two-thirds saturated and one-third saturated aqueous solutions. Blood samples were obtained and analysed for bromochloromethane content by GC.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

Bromochloromethane

EC Number:

200-826-3

EC Name:

Bromochloromethane

Cas Number:

74-97-5

Molecular formula:

CH2BrCl

IUPAC Name:

bromo(chloro)methane

Details on test material:

- Name of test material (as cited in study report): bromochloromethane
- Analytical purity: ≥ 99%

Radiolabelling:

no

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Breeding Laboratories (Raleigh, NC)
- Weight at study initiation: 215-300 g
- Fasting period before study: no
- Housing: in polycarbonate cages with hardwood Betachip beeding.
- Diet (e.g. ad libitum): ad libitum (Purina certified rodent chow #5002) , before and during exposure.
- Water (e.g. ad libitum): ad libitum, before and during exposure.
- Acclimation period: 7 days

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: unchanged and dissolved in water.

Duration of exposure:

24 hours.

Doses:

Animals were exposed to 2 ml of pure substance, 27.64 mg in water (saturated solution), 17.85 mg in water (two-thirds saturated solution) and 9.72 mg in water (one-third saturated solution).

No. of animals per group:

7 animals (pure substance group), 8 animals (saturated solution group), 9 animals (two-thirds saturated solution group), 8 animals (one-third saturated solution group).

Control animals:

yes

Remarks:

(vehicle)

Details on study design:

DOSE PREPARATION
- Method for preparation of dose suspensions: saturated aqueous solutions were prepared by mixing 10-20 ml of neat chemical with 200 ml HPLC-grade water in flasks with pressure-venting stoppers. Solutions were stirred for 7-21 days at room temperature using glass-covered stir bars. The excess immiscible organic was decanted, and the saturated aqueous solution filtered through a large capacity teflon filter (0.45 µm pore size) to remove any suspended immiscible chemical in the solution. Saturated solutions were diluted with HPLC-grade water to obtain one-third and two-thirds saturated solutions.
- Method of storage: samples of the saturated solution were transferred to zero head-space vials, sealed and refrigerated (5-10 ºC) 24-48 h until use in dermal exposures.

APPLICATION OF DOSE: two ml of test chemical were added to each exposure cell. The exposure cells were sealed with screw-caps containing Teflon-coated silicon septa.

VEHICLE
- Amount(s) applied (volume or weight with unit): 2 ml

TEST SITE
- Preparation of test site: the day before exposure, rats were anesthetized with a ketamine/xylazine mixture. The hair was carefully shaved from the lower back to avoid abrasion, and a 2-ml glass exposure cell (20 mm diameter) attached to the shaved area with cyanoacrylate adhesive.
- Area of exposure: 3.1 cm2

SAMPLE COLLECTION
- Collection of blood: blood samples (50 or 100 µl) were obtained from each rat via indwelling jugular catheters just prior to adding the test chemical (control samples), and after exposure for 0.5, 1, 2, 4, 8, 12 and 24 h.

ANALYSIS
- Method type(s) for identification: chemical concentrations in blood were determined by gas chromatography using headspace analysis.

Results and discussion

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Absorption in different matrices:

- Blood: The peak blood level during exposure to neat bromochloromethane was 113.3 µg/ml. The maximum blood level was attained after 4 -8 h exposure. Appearance in the blood of bromochloromethane from aqueous solutions was rapid; peak blood concentrations were attained within 2 h. Concentrations of bromochloromethane in the blood after dermal exposures to the aqueous solutions were highest after exposure to saturated aqueous solution, followed by the two-third and one-third saturated solution. The peak blood levels were reached at approximately the same time for the saturated, one-third and two-thirds saturated aqueous solutions. Levels of bromochloromethane in blood rapidly decreased to near control levels by 24 h, probably due to depletion of chemical from the exposure cell. The aqueous solution remaining in the exposure cell after exposure of rats for 24 h contained less than 1% (< 1ppm) of the initial bromochloromethane concentration.

Applicant's summary and conclusion

Conclusions:

Bromochloromethane showed a rapid dermal absorption from the aqueous solutions.

Executive summary:

The potential of bromochloromethane to penetrate the skin and be absorbed via this route was tested in male Fischer 344 rats by application of pure bromochloromethane and at different concentrations in water: 27.64 mg in 2 ml (saturated solution), 17.85 mg in 2 ml (two-thirds saturated solution) and 9.72 mg in 2 ml (one-third saturated solution). For the application, an occlusive reservoir glued to the shaved skin and closed by a screw cap containing a Teflon-coated silicon septum, covered the skin area. Blood samples (50 or 100 µl) were obtained from each rat just prior to adding the test chemical (control samples), and after exposure for 0.5, 1, 2, 4, 8, 12 and 24 h. The peak blood level during exposure to neat bromochloromethane was 113.3 µg/ml, which was attained after 4 -8 h exposure. Appearance in the blood of bromochloromethane from aqueous solutions was rapid (peak blood concentrations were attained within 2 h). Besides, the aqueous solution remaining in the exposure cells after exposure of rats for 24 h contained less than 1% (< 1ppm) of the initial bromochloromethane concentration, indicating that bromochloromethane was rapidly absorbed. Based on these results, it can be concluded that bromochloromethane has a rapid dermal absorption.