Phenol

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: see 'Remark'

Remarks:

The study is comparable to OECD Guideline 427 with acceptable restrictions (72 h exposure; partly limited documentation; no data about radioactivity in exhaled air [but only minor elimination route, see Section 7.1.1]; low dose [typically 1-5 mg/cm² applied] ).

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference Type:

publication

Title:

Disposition of phenol in rat after oral, dermal, intravenous, and intratracheal administration

Author:

Hughes MF, Hall LL

Year:

1995

Bibliographic source:

Xenobiotica 25: 873-883

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 427 (Skin Absorption: In Vivo Method)

Deviations:

not specified

GLP compliance:

not specified

Test material

Test material information

Constituent 1

Reference substance name:

Phenol

EC Number:

203-632-7

EC Name:

Phenol

Cas Number:

108-95-2

Molecular formula:

C6H6O

IUPAC Name:

phenol

Details on test material:

Uniformly 14C-ring labelled phenol (specific activity 100 μCi/μmol)
Radiochemical purity > 98% determined by radiochromatography
Source: Moravek Biochemicals (Brea, CA, USA)
No further data

Radiolabelling:

yes

Remarks:

14C-phenol

Test animals

Species:

rat

Strain:

Fischer 344

Sex:

female

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Duration of exposure:

72 h

Doses:

0.033 mg/kg bw

No. of animals per group:

3-4 animals (no further details)

Control animals:

no

Details on study design:

Rats used for dermal exposure were anaesthetized 24 h before treatment and hair on the dorsal skin surface removed with an electric clipper; animals received then a collar (for acclimatization). Animals were dosed with 0.033 mg 14C-phenol/kg bw.
dermal: rats anaesthetized by ether and phenol applied on a marked skin area of 2.57 cm²; plastic blister glued over the treated skin with cyanoacrylate adhesive. After dosing rats returned to the metabolism cages; urine collected at 4, 8, 12, 24, 48 and 72 h and faeces at 24, 48 and 72 h; samples weighed after collection and stored at - 70°C until analysed. Urine (0,1 ml) analysed for radioactivity in the scintillation counter. Faeces air-dried, weighed, pulverized, and 200-300 mg of the pulverized faeces combusted in the oxidizer and also analysed for radioactivity. Aliquots of the 4 and 8-h urine were directly analysed by HPLC methods (metabolites measured).
At 72 h post-exposure, the orally, intravenously, and intratracheally treated animals sacrificed (cardiac puncture) and tissues removed [liver, kidney, trachea, Iung, skin, muscle (vastus lateralis), epididymal fat, stomach, small intestine, large intestine (including caecum) and the contents of the last three tissues]. Tissues weighed, combusted and analysed for radioactivity; carcasses homogenized, combusted and also analysed for radioactivity.
Dermally treated animals anaesthetized and a piece of untreated skin removed (dorsal side); plastic blister cut with a razor blade and the treated skin washed with 3x1 ml of soap/water mixture, followed by 1x 1 ml water and dried; wash samples analysed for radioactivity; the treated skin was then removed from the animal and rat sacrificed (cardiac puncture), tissues collected as described above. Radioactivity detected in the skin washes and treated skin added to the recovered dose; radioactivity in blisters 2.5% (not in recovered dose).

Results and discussion

Signs and symptoms of toxicity:

not specified

Remarks:

not expected

Dermal irritation:

not specified

Absorption in different matrices:

Dermal exposure: 40% of the recovered dose was excreted in urine by 4 h and 70% by 12 h; urinary elimination of radioactivity after dermal exposure was essentially complete by 24 h; after 72 h totally 75% of applied radioactivity was detected in urine and 3% in faeces; washing the dermal site 72 h post-exposure removed 14% of the dose, 2% of the dose were detected in the skin. In carcass ca. 1% of recovered dose was detected.
In comparison to excretion via urine faecal elimination was considerably lower.

Total recovery:

Skin absorption of phenol in the rat was ca. 80%, although 15-20% lower compared with oral and intratracheal administration. The difference in absorption was found in the skin wash (14%) and treated skin (2%).

Percutaneous absorption

Dose:

0.033 mg/kg bw

Parameter:

percentage

Absorption:

ca. 80 %

Remarks on result:

other: 72 h

Any other information on results incl. tables

Absorption and elimination was rapid and extensive after dermal application. In comparison to excretion via urine faecal elimination was considerably lower.

Applicant's summary and conclusion

Conclusions:

In the rats 80% of the dermally applied dose was absorbed.

Executive summary:

The study is comparable to OECD Guideline 427 with acceptable restrictions (72 h exposure; partly limited documentation; no data about radioactivity in exhaled air [but only minor elimination route, see Section 7.1.1]; low dose [typically 1-5 mg/cm² applied]).

Female F344 rats (n=3 -4 per group) received 0.033 mg/kg bw 14C-labelled phenol via the dermal route (occlusive, exposure duration 72 h). Radioactivity in urine and faeces was analysed after sampling in metabolism cages; the animals were sacrificed 72 h after application and radioactivity in skin, carcass and washings determined. after 72 h totally 75% of applied radioactivity was detected in urine and 3% in faeces; washing the dermal site 72 h post-exposure removed 14% of the dose, 2% of the dose were detected in the skin. In carcass ca. 1% of recovered dose was detected. Skin absorption of phenol in the rat was ca. 80%, although 15-20% lower compared with oral and intratracheal administration. The difference in absorption was found in the skin wash (14%) and treated skin (2%).

Conclusion: In the rats 80% of the dermally applied dose was absorbed.