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Toxicological information

Acute Toxicity: dermal

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Administrative data

Endpoint:
acute 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: The study is comparable with OECD Guideline 402 with exceptable restrictions (post exposure observation period 7 days; only females [minor restriction]).

Data source

Reference
Reference Type:
publication
Title:
The dermal toxicity of phenol
Author:
Conning DM, Hayes MJ
Year:
1970
Bibliographic source:
Brit J Ind Med 27: 155-159

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
GLP compliance:
not specified
Test type:
standard acute method
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
reagent grade phenol
no further data

Test animals

Species:
rat
Strain:
other: Alderly Park
Sex:
female
Details on test animals and environmental conditions:
5 rats per cage
certified diet and water ad libitum
no further details

Administration / exposure

Type of coverage:
other: 1st trial occlusive and 2nd trial uncovered
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: shorn backs
- % coverage: no data
- Type of wrap if used: 1st trial: treated skin covered with polythene plus waterproofed adhesive dressing ; 2nd trial uncovered, collar prevented licking


REMOVAL OF TEST SUBSTANCE
- Washing: yes, in trial 1 & 2 with mild detergent (after removal of dressing in 1st trial)
- Time after start of exposure: 24 h
Duration of exposure:
24 h
Doses:
1st trial: 1.0, 0.5, 0.25 or 0.1 ml phenol/kg bw
2nd trial: 1.0, 0.75, 0.3 and 0.1 ml/kg bw
rats received single applications of molten phenol (warmed in a water-bath until melted and maintained in this state at approximately 40°C)
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
- Duration of observation period following administration: 7 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs and histopathology of kidney and skin
Statistics:
no data

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
0.625 mL/kg bw
Remarks on result:
other: in both trials (occlusive dressing or uncovered); corresponding to 660 mg/kg bw at 40°C
Mortality:
1st trial: all rats at a dose of 1 ml/kg bw and 2 rats at 0.5 ml/kg bw died within 4 h.
2nd trial: all rats at 1 or 0.75 ml/kg bw died within 24 h
Clinical signs:
Local effects
All animals showed severe skin lesions with immediate onset of oedema followed within 4 hours by necrosis associated at 24 hours with discoloration and surrounding erythema.

Systemic effects
All the animals behaved similarly: between 5-10 minutes after dosing they developed severe muscle tremors causing marked twitching which developed into generalised convulsions with loss of consciousness and prostration. At varying times between 45-90 minutes, depending upon the dose administered, the animals developed severe haemoglobinuria.
Body weight:
no data
Gross pathology:
At necropsy, those animals dying in the acute stage from phenol poisoning showed renal congestion, and the urinary bladders were distended with blood-stained fluid.
Other findings:
Histopathology
Kidneys showed haematin casts in the distal convoluted tubules and in the tubules of the medulla and papillae. The skin showed extensive epidermal necrosis characterised by a hyaline appearance of the cells, loss of intercellular processes, and deposition of eosinophilic debris in the intercellular spaces. There was extensive superficial necrosis of the dermis, which was stained a purple colour by haematoxylin and eosin suggesting a coagulative type necrosis.

Applicant's summary and conclusion

Conclusions:
The dermal LD50 in female rats was 660 mg/kg bw.
Executive summary:

The study is comparable with OECD Guideline 402 with acceptable restrictions (post exposure observation period 7 days; only females [minor restriction]).

Five female Alderly Park rats per dose received dermal application of molten phenol at dose levels of 1.0, 0.5, 0.25 or 0.1 ml phenol/kg bw (1st trial, occlusive) or in the 2nd trial (uncovered) of 1.0, 0.75, 0.3 and 0.1 ml/kg bw. Exposure was terminated after 24 h by washing with a mild detergens. The post exposure observation period was 7 days. Necropsy was performed as well as histopathology of skin and kidney. In the 1st trial all rats died at a dose of 1 ml/kg bw and 2 rats at 0.5 ml/kg bw within 4 h; in the 2nd trial all rats died at 1 or 0.75 ml/kg bw within 24 h. Local effects included severe skin lesions with immediate onset of oedema followed within 4 hours by necrosis associated at 24 hours with discoloration and surrounding erythema. Systemic effects: all the animals behaved similarly; between 5-10 minutes after dosing they developed severe muscle tremors causing marked twitching which developed into generalised convulsions with loss of consciousness and prostration. At varying times between 45-90 minutes, depending upon the dose administered, the animals developed severe haemoglobinuria. Necropsy revealed renal congestion and the urinary bladders were distended with blood-stained fluid. Kidneys showed in histopathology haematin casts in the distal convoluted tubules and in the tubules of the medulla and papillae. The skin showed extensive epidermal necrosis and desrcibed effects suggested a coagulative type necrosis.

Conclusion: The dermal LD50 in female rats was 660 mg/kg bw.