Gas oils (petroleum), steam-cracked

Dermal absorption

Administrative data

Endpoint:

dermal absorption in vivo

Type of information:

experimental study

Adequacy of study:

supporting study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Published in peer reviewed literature, non-guideline, animal experimental study, minor restrictions in design and/or reporting but otherwise adequate for assessment

Data source

Reference

Reference Type:

publication

Title:

In vivo percutaneous absorption studies of volatile organic solvents in hairless mice II. Toluene, ethylbenzene and aniline

Author:

Susten AS, Niemeier RW and Simon SD

Year:

1990

Bibliographic source:

J. Applied. Toxicol, Vol 10(3), 217-225

Materials and methods

Test guideline

Qualifier:

no guideline followed

Principles of method if other than guideline:

Percutaneous absorption was assessed in hairless mice using a direct method.

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Ethylbenzene

EC Number:

202-849-4

EC Name:

Ethylbenzene

Cas Number:

100-41-4

Molecular formula:

C8H10

IUPAC Name:

ethylbenzene

Details on test material:

- Name of test material (as cited in study report): [14C]-ethylbenzene
- Supplied by: Pathfinder Laboratories, St Louis, MO, USA
- Substance type: single-ring, radiolabelled aromatic solvent
- Radiochemical purity (if radiolabelling): >98%
- Specific activity (if radiolabelling): 33.47 mCi mmol^-1
- Locations of the label (if radiolabelling): 14C
- Reagent grade non-labelled ethylbenzene used for dilutions
- Amount of isotope: 2.48 µCi/nominal 5 µL dose (equivalent to approximately 100 µCi/kg bw)

Radiolabelling:

yes

Test animals

Species:

mouse

Strain:

other: albino hairless (HRS/J)

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Jackson Laboratories, Bar Harbor, ME, USA
- Age at study initiation: no data
- Weight at study initiation: 23-32 g
- Fasting period before study: no
- Housing: individually in shoe-box plastic cages with sawdust bedding (prior to dermal application)
- Individual metabolism cages: yes (within 5 seconds of dermal application for 4 hours)
- Diet: Purina Rodent Chow (Purina, St Louis, MO, USA) ad libitum (prior to dermal application)
- Water: ad libitum (prior to dermal application)
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature: 23±2.5°C
- Humidity: 55±15%
- Air changes (per hr): no data
- Photoperiod: 12hrs dark / 12hrs light

IN-LIFE DATES: no data

Administration / exposure

Type of coverage:

other:

Vehicle:

unchanged (no vehicle)

Duration of exposure:

4 hours after dermal application

Doses:

- Amount applied (mean ± SD): 4.75 ± 0.22 ± / 4.10 ± 0.19 mg
- Amount applied (range): 4.39-4.89 µL / 3.79-4.30 mg
- Amount of isotope in nominal 5 µL doses: 2.48 µCi
- Nominal radioactive dose/mouse: 100 µCi/kg bw

No. of animals per group:

2 mice/experiment for a total of 6 experiments (data excluded from one mouse due to technical problems)

Control animals:

no

Details on study design:

APPLICATION OF DOSE:
- Equipment: Stainless steel skin depot device - skin contact area approximately 0.8 cm2. This comprised an outer stainless steel casing with inner stainless steel wire mesh basket containing 100-150 mg solid sorbent (for collection of evaporated vapour)
- Solid sorbent: coconut-derived activated charcoal (20/40 mesh)
- Desorbing agent (to desorb radioactivity from charcoal): non-labelled toluene
- Procedure: 5-10 mins before application, skin depot device glued to backs (mid thoracic region) of anaesthetised mice. Approx 5 µL of treatment solution placed in the skin depot device so it was just above the skin surface but below the solid sorbent using blunted needle of a 10 µL microsyringe and a 21-gauge "guide needle".
- Determination of radioactivity: 5 µL test solution injected into three 10 mL flasks containing suitable solvent. 0.1 mL aliquots (in triplicate) removed and analysed to determine average total 14C/flask and mean of 3 flasks considered to be nominal radioactive dose. Radioactivity (compound) remained in the guide needle and was subtracted from the nominal dose.

REMOVAL OF TEST SUBSTANCE: not applicable, mice killed at end of 4 hour application

SAMPLE COLLECTION:
- Expired air: at intervals of 0-15, 15-30, 30-60, 60-120, 120-180 and 180-240 mins after start of application

After 4 hours application, the mice were killed and the following collected:
- Skin depot (evaporated test substance)
- Wipe of treated skin site (unabsorbed test substance)
- Skin application site (bound test substance)
- Carcass minus treated skin site
- Faeces
- Urine
- Cage wash

SAMPLE PREPARATION: Treated skin and carcass digested in sodium hydroxide and aliquots of the digests oxidised.

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:

- Expired air: 14.3 ± 6 % of absorbed dose
- Skin application site (bound test substance): 4.5 ± 1 % of absorbed dose
- Carcass minus treated skin site: 15.5 ± 2 % of absorbed dose
- Excreta (faeces and urine): 65.6 ± 5 % of absorbed dose

Total recovery:

- Total recovery:
- Recovery of applied dose acceptable: Yes (>90%)
- Distribution (% nominal dose recovered): 3.4 ± 1.0, 86.7 ± 1, 5.0 ± 1 and 95.2 ± 1 % for absorbed, skin depot, guide needle and total recovered, respectively

Percutaneous absorption

Dose:

4.75±0.22uL

Parameter:

percentage

Absorption:

3.61 %

Remarks on result:

other: 294±14 sec

Remarks:

absorption rate = 37±31 µg/cm2/min

Any other information on results incl. tables

Average amount applied to skin: 4.10 mg of which 148 µg (3.61%) absorbed. The % of absorbed dose collected in expired air was related to the vapour pressure of the compound. The cumulative % of absorbed dose found in expired air was 9.3% for 0-15 min. For most mice, breath excretion rate was highest during 0 -15 mins but for 5 mice was higher during 15 -30 or 30 -60 mins. A breath decay curve showed decreasing trend with time showing that absorption of ethylbenzene was complete 15 minutes after application. There was initial rapid decay followed by a more gradual decay indicative of a two-compartment model. Estimated contact time during which absorption could occur was 5 min and the percutaneous absorption rate was calculated as 37 µg/cm2/min.

Applicant's summary and conclusion

Conclusions:

In an in vivo percutaneous absorption study using hairless mice and a direct method for volatile chemicals, total absorption of ethylbenzene was 3.61% of the achieved dose. A breath decay curve indicated absorption was complete 15 minutes after application. Evaporation rates were used to derive an estimated contact time of 5 min and the percutaneous absorption rate was calculated to be 37 µg/cm2/min.