3-diethylaminophenol

Repeated dose toxicity: dermal

Administrative data

Endpoint:

chronic toxicity: dermal

Type of information:

experimental study

Adequacy of study:

weight of evidence

Reliability:

2 (reliable with restrictions)

Data source

Reference

Reference Type:

publication

Title:

Lack of Toxicity and Carcinogenicity of Some Commonly Used Cutaneous Agents

Author:

FREJ STENBACK AND PHILIPPE SHUBIK

Year:

1974

Bibliographic source:

TOXICOLOGY AND APPLIED PHARMACCLOGY 30, 7-13

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

other:

Principles of method if other than guideline:

The potential carcinogenicity and toxicity of several commonly used cutaneous agents of which one is resocersinol were studied in female Swiss mice by administering repeated applications of the chemical on the skin for the life-span of the animals

GLP compliance:

not specified

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Resorcinol

Cas Number:

Resorcinol

Molecular formula:

C6H6O2

IUPAC Name:

Resorcinol

Constituent 2

Reference substance name:

1,3-Benzenediol

Cas Number:

108-46-3

Molecular formula:

C6H6O2

IUPAC Name:

1,3-Benzenediol

Constituent 3

Reference substance name:

Resorcinol

EC Number:

203-585-2

EC Name:

Resorcinol

Cas Number:

108-46-3

Molecular formula:

C6H6O2

IUPAC Name:

1,3 benzenediol

Details on test material:

- Name of test material (as cited in study report):resorcinol
- Substance type: Organic
- Physical state: Solid

Test animals

Species:

mouse

Strain:

Swiss

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Eppley colony
- Age at study initiation: Seven-week-old
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: plastic cages with commercial bedding
- Diet (e.g. ad libitum):commercial diet Wayne, Allied Mills, ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

IN-LIFE DATES: From: To:

Administration / exposure

Type of coverage:

open

Vehicle:

acetone

Details on exposure:

TEST SITE
- Area of exposure: dorsal skin between the flanks
- % coverage: l-inch square area
- Type of wrap if used: no data
- Time intervals for shavings or clipplings: shaved regularly.

REMOVAL OF TEST SUBSTANCE
- Washing (if done):no data
- Time after start of exposure:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.02 ml
- Concentration (if solution): 5, 25,50 %
- Constant volume or concentration used: no data
- For solids, paste formed: no data

Duration of treatment / exposure:

life time

Frequency of treatment:

twice a week

Doses / concentrations

Remarks:

Doses / Concentrations:
0,5,25,50% (8333.33, 41666.6, 83333.3 mg/kg bw/day)
Basis:
nominal per unit area

No. of animals per sex per dose:

50/dose group

Control animals:

yes, concurrent vehicle

Positive control:

7,12-dimethylbenzanthracene

Examinations

Sacrifice and pathology:

The animals were checked weekly, and all lesions, as well as tumors, were recorded. Animals were allowed to die spontaneously or were killed when moribund. Complete autopsies were performed on all animals. The skin from all animals, all grossly observed tumors and other lesions in the lungs, livers, kidneys, etc., from treated as well as control groups were studied histologically. Formalin-fixed paraffin-embedded specimens were cut and stained with hematoxylin-eosin and other stains when needed.

Statistics:

The statistical significance of the results was evaluated using the methods presented by Armitage

Results and discussion

Results of examinations

Clinical signs:

no effects observed

Dermal irritation:

effects observed, treatment-related

Mortality:

no mortality observed

Body weight and weight changes:

not examined

Food consumption and compound intake (if feeding study):

not examined

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

not examined

Clinical biochemistry findings:

not examined

Urinalysis findings:

not examined

Behaviour (functional findings):

not examined

Gross pathological findings:

not examined

Histopathological findings: non-neoplastic:

effects observed, treatment-related

Histopathological findings: neoplastic:

effects observed, treatment-related

Details on results:

Animals treated with resorcinol showed skin lesions with ulceration, inflammation and hyperplasia. Two skin tumors were seen, 1 on the back and 1 on the ear as well as 1 subcutaneous fibrosarcoma.

Effect levels

Dose descriptor:

LOAEL

Effect level:

8 333.33 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

female

Basis for effect level:

other: skin lesions with ulceration, inflammation and hyperplasia was observed

Target system / organ toxicity

Critical effects observed:

not specified

Applicant's summary and conclusion

Conclusions:

The LOAEL of resorcinol in female swiss mice in a life time study was observed at dose concentration of 8333.33 mg/kg bw/day

Executive summary:

50 female swiss mice were applied resorcinol at dose concentration of 0,5,25,50% (8333.33, 41666.6, 83333.3 mg/kg bw/day) (0.02 ml) were dropped on the dorsal skin between the flanks twice a week on a l-inch square area which was shaved regularly. The animals

were checked weekly, and all lesions, as well as tumors, were recorded. Animals treated with resorcinol showed skin lesions with ulceration, inflammation and hyperplasia. Two skin tumors were seen, 1 on the back and 1 on the ear as well as 1 subcutaneous fibrosarcoma. Hence the LOAEL was considered to be 8333.33 mg/kg bw/day.