2,4-dichlorobenzyl alcohol

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1979

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Experimental study with details provided.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

The absorption and excrection of the 14C labeled test substance in rats was evaluated.

GLP compliance:

no

Test material

Test material information

Constituent 1

Reference substance name:

2,4-dichlorobenzyl alcohol

EC Number:

217-210-5

EC Name:

2,4-dichlorobenzyl alcohol

Cas Number:

1777-82-8

Molecular formula:

C7H6Cl2O

IUPAC Name:

(2,4-dichlorophenyl)methanol

Radiolabelling:

yes

Remarks:

14C

Test animals

Species:

rat

Strain:

other: Boots Wistar

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Weight at study initiation: approx. 150 g for dose vehicle test, approx. 100 g for all subsequent tests
- Housing: during experiment individually (Tissue distribution study 6 per group in cages), in all glass metabolism cage
- Individual metabolism cages: yes
- Diet: ad libitum
- Water: ad libitum

Administration / exposure

Type of coverage:

occlusive

Vehicle:

other: Analar acetone, acetone:water (90:10), dest. water

Duration of exposure:

- Dose vehicle test: 96 h
- 0 h recovery test: 3 min (as death occurred after 3 min)
- Expired CO2 balance study: 96 h
- Tissue distribution study: 6, 12, 24, 48 h

Doses:

- Dose vehicle test: 1) Acetone solution (analar acetone) 1.0 mg/mL, 2) Acteone:water solution 1.0 mg/mL, 3) Aqueous solution (destilled water) 1.0 mg/mL
- Subsequent tests: Analar acetone 2.0 mg/mL (1 mg/kg bw)

No. of animals per group:

- Dose vehicle test: 4 (total)
- 0 h recovery test: 4
- Expired CO2 balance study: 4
- Tissue distribution study: 6 per time

Control animals:

no

Details on study design:

VEHICLE
- Amount applied: 100 µL (dose vehicle test), 50 µL (subsequent tests)

TEST SITE
- Preparation of test site: clipped and wet shaved, 18 h before treatment
- Area of exposure: back, approx. 2.5 cm2
- Type of cover / wrap if used: thin plastic, aluminium foil, sleek adhesive dressing, 2 strips of adhesive tape wraped around the animals body

SITE PROTECTION / USE OF RESTRAINERS FOR PREVENTING INGESTION: yes, occlusive coverage

SAMPLE COLLECTION
- Collection of urine and faeces: Dose test: 0-6, 6-12, 12-24 h and afterwards daily; expired CO2 balance study: collected seperately, cooled by solid carbon dioxide, removed at 24, 48, 72, 96 h.
- Collection of expired air: Expired CO2 balance study: Air was drawn through the apparatus by means of a vacuum pump (Charles Austin) at a rate of 0.3 to 0.4 L/min. The air first passed through a column containing Drierite to dry the air and soda lime to remove carbon dioxide. After passing through the biochamber the air was drawn through 2 NILOX columns each containing 450 mL of a mixture (1:2 v/v) of ethanolamine:2-ethoxyethanol as a CO2 trapping agent.
- Terminal procedure: Dose vehicle test and expired CO2 balance study: metabowl washed with water; dressing, plastic discs, dosed areas of skin were stored seperately; aqueous homogenates of whole carcas and faecal samples were prepared and stored. 0 h recovery test: Dressing, plastic discs, dosed skin area, aqueous homogenates of whole carcas were pepared and processed within 1 h of dosing. Tissue distribution study: Dressing, plastic discs, dosed skin area removed and stored and tissues (whole blood, plasma, liver, kidney, stomach, pancreas, small intestine, large intestine, heart, spleen, urino-genital system, cerebellum, cerebrum, medulla, fat, muscle, eye, adrenal, thyroid, skin, hair, bone, thymus, lung, ovaries) were collected.

SAMPLE PREPARATION
- Storage procedure: -20 °C
- Preparation details: Plasma, urine, aqueous and methanol washes: Measured aliquots were added to 10 mL amounts of (1:1 v/v) Ria/Lipoluma Scintillator (LKB Wallac). Samples were shaken vigorously before counting. CO2 reagent: 5.0 mL amounts of reagent were added to 18 mL of toluene butyl P.B.D./ethoxyethanol scintillator. Sleek dressings: Dressinge were cut into pieces and placed in a 100 mL stoppered measuring cylinder. The material was then extracted with 50 mL of Analar methanol on a rotary mixer for 30 min. Methanol (0.5 mL) was then added to 10 mL of Ria/Lipoluma Scintillator for counting. Combustion of plastic discs, faeces and tissues: Plastic discs were compressed in a 5.5 cm diameter filter paper (Whatman No. 1) and combusted on a Packard 306 oxidiser. Homogenates of faeces and tissues were treated in a similar fashion. Aliquots of the homogenate were weighed into Combustocones, 200 µL of Combustaid was added and the sample burned in a Packard 306 oxidiser. Skin from the dose area was placed on a filter paper and cut into pieces. Each piece was then placed in a combustocone and combusted as for tissues and faeces. (Combustocones and Combustaid obtained from Packard Instruments Ltd.). Where possible all estimations of radioactive content were made on duplicate samples, counted by liquid scintillation using an Intertechnique 4220 counter.

ANALYSIS
- Method type(s) for identification: Liquid scintillation counting

Results and discussion

Signs and symptoms of toxicity:

not specified

Dermal irritation:

not specified

Absorption in different matrices:

- Urine: 0 to 24 h: 58.4 % (acteone), 43.4 % (acetone:water), 48.0 % (water)
- Faeces: 0 to 24 h: 3.1 % (acteone), 2.3 % (acetone:water), 1.7 % (water)
- Expired air: no radioactivity detected
- Plasma: 0.11 µg/mL (6 h), 0.025 µg/mL (12 h)
- Liver: 0.29 µg/g (6 h), 0.041 µg/g (12 h)
- Kidney: 0.34 µg/g (6 h), 0.06 µg/g (12 h)
- Hair: 0.15 µg/g (6 h), 0.238 µg/g (12 h)
- Stomach: 0.04 µg/g (12 h)
- Urino-genital system: 0.039 µg/g (12 h)
- Remaining tissues: < 0.11 µg/mL (6 h)

Total recovery:

- Total recovery: 79.1 % (0-96 h acteone), 66.4 % (0-96 h acetone:water), 70.0 % (0-96 h water), 94.1 % (0 h recovery: 1.9 % dressing, 5.0 % plastic, 85.2 % skin dose area, 2 % in carcass), 94.9 % (balance study: 88.4 % urine, 3.7 % faeces, 2.9 % others),

Percutaneous absorption

Dose:

1 mg/kg bw

Parameter:

percentage

Absorption:

94.9 %

Remarks on result:

other: 96 h

Remarks:

balance study