Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
The study meets scientific standards with acceptable restrictions (partly limited documentation, low number of animals). Phenol is a constituent of the reaction mass and by its toxicity drives the hazard of the rection mass, so that phenol hazard data are applied in the hazard assessment.

Data source

Reference
Reference Type:
publication
Title:
Local and systemic effects following application of dilute solutions of phenol in water and in Camphor-liquid petrolatum on the skin of animals
Author:
Deichmann WB, Miller T, Roberts JB
Year:
1950
Bibliographic source:
Arch Ind Hyg Occ Med 2: 454-461

Materials and methods

Principles of method if other than guideline:
Local and systemic effects following repeated dermal application of aqueous solutions of phenol were studied in rabbits.
GLP compliance:
not specified
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Reagent grade.
No further data

Test animals

Species:
rabbit
Strain:
other: albino, no further data
Sex:
not specified
Details on test animals and environmental conditions:
No further details

Administration / exposure

Type of coverage:
other: open (n=2) and bandaged (n=2), no further data
Vehicle:
water
Details on exposure:
See details on study design.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
18 days
Frequency of treatment:
5 h per day, 5 days per week for totally 18 days
Doses / concentrationsopen allclose all
Remarks:
Doses / Concentrations:
1.18, 2.37, 3.56, 4.75, 5.93, and 7.12% phenol
Basis:
other: nominal concentration
Remarks:
Doses / Concentrations:
130, 260, 390, 520, 650, and 780 mg/kg bw/day
Basis:
other: based on an assumed body weight of 3 kg
No. of animals per sex per dose:
4 animals (unknown sex) per concentration
Control animals:
not specified
Details on study design:
Albino rabbits were immobilized in the supine position and the hair was c!ipped from the abdomen, (repeated once a week throughtout the experiment). Four rabbits were treated with each phenol concentration, 2 of which were bandaged (not at the 2 high dose levels); exposed skin area 10-15 cm2; to keep the area of the belly continuously moistened the initial dose (for each concentration) was 5 ml, followed by 2 ml every 20 min. Animals were treated for 5 h (total amount applied was 33 ml) on each of 5 consecutive days of a week for a total of 18 days. After a 5 hour period of skin contact, the bandage (n=2) was removed and materials were washed from the skin of bandaged and unbandaged animals with soap and water.
Positive control:
No

Examinations

Observations and examinations performed and frequency:
Local and systemic effects were recorded daily during and after each dermal exposure.
Sacrifice and pathology:
No data
Other examinations:
No data
Statistics:
No data

Results and discussion

Results of examinations

Clinical signs:
effects observed, treatment-related
Dermal irritation:
effects observed, treatment-related
Mortality:
mortality observed, treatment-related
Body weight and weight changes:
not specified
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
not specified
Clinical biochemistry findings:
not specified
Urinalysis findings:
not specified
Behaviour (functional findings):
not specified
Organ weight findings including organ / body weight ratios:
not specified
Gross pathological findings:
not specified
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
The 1.18 and 2.37 per cent phenol in aqueous solutions produced no signs of local irritation, while systemic effects were limited to occasional mild tremors in animals exposed to 2.37%. Eighteen applications of a 3.56% phenol in aqueous solution produced local and systemic effects: mild degree of hyperemia during each of the 5 hours exposures (particularly apparent in the bandaged animals disappeared after washing) and systemic effects like mild tremors noted from time to time during exposure. The 4.75% phenol induced more severe local and systemic effects: tremors became apparent in all rabhits about 1 h after the start of each exposure. Prominent hyperkeratosis was found in 1 out of 4 animals followed by breaking of the skin, with hemorrhages along the cracking edges. At 5.93 and 7.12 per cent phenol the rabbits showed impressive local changes and from moderate to severe signs uf systemic intoxication. One rabbit died after the sixth exposure to the high concentration.
No further data were documented.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Effect level:
130 mg/kg bw/day
Sex:
not specified
Basis for effect level:
other: systemic effects
Dose descriptor:
LOAEL
Effect level:
260 mg/kg bw/day
Sex:
not specified
Basis for effect level:
other: systemic effects (e.g. tremor)
Dose descriptor:
conc. level: NOAEC
Effect level:
2.37 other: % in vehicle
Sex:
not specified
Basis for effect level:
other: no local effects
Dose descriptor:
conc. level: LOAEC
Effect level:
3.56 other: % in vehicle
Sex:
not specified
Basis for effect level:
other: local effects (hyperemia)

Target system / organ toxicity

Critical effects observed:
not specified

Any other information on results incl. tables

Systemic effects: NOAEL 130 mg/kg bw/day (1.18%) and LOAEL 260 mg/kg bw/day (2.37%).

Local effects: NOAEC 2.37% (260 mg/kg bw/day) and LOAEC 3.56% (390 mg/kg bw/day).

Lethal effects at 780 mg/kg bw/day

Applicant's summary and conclusion

Conclusions:
In rabbits the repeated dermal application of 260 mg/kg bw/day resulted in systemic effects, the NOAEL was 130 mg/kg bw/day. The LOAEC for local effects was 3.56% aqueous solution and the NOAEC 2.37%.
Executive summary:

The study meets scientific standards with acceptable restrictions (partly limited documentation, low number of animals).

Four albino rabbits per dose level (n=2 at the 2 highest doses) received repeated dermal application 5 days per week for 18 days. The daily exposure duration was 5 hours. The phenol concentrations of test solutions were 1.18, 2.37, 3.56, 4.75, 5.93, and 7.12% in water corresponding to systemic dose levels of 130, 260, 390, 520, 650, and 780 mg/kg bw/day (totally 33 ml of the test substance applied within 5 h). Systemic effects like tremor were detected at 260 mg/kg bw/day, mild irritant effects at a concentration of 3.56% and severe local effects at 4.75%. Mortality (presumably due to systemic effects) was reported at 780 mg/kg bw/day.

Conclusion: In rabbits the repeated dermal application of 260 mg/kg bw/day resulted in systemic effects, the NOAEL was 130 mg/kg bw/day. The LOAEC for local effects was 3.56% aqueous solution and the NOAEC 2.37%.