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Toxicological information

Repeated dose toxicity: dermal

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Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

Data source

Referenceopen allclose all

Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993
Reference Type:
secondary source
Title:
O-Phenylphenol and its Sodium and Potassium Salts: A Toxicological Assessment
Author:
Bomhard, E. M. et al.
Year:
2002
Bibliographic source:
Crit. Rev. Toxicol. 32(6):551-626

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
Deviations:
yes
Remarks:
(adrenal weights not determined; clinical chemistry parameters suggested by OECD 410 but not evaluated: ornithine decarboxylase, gamma-glutamyl-transpeptidase)
Qualifier:
according to
Guideline:
EU Method B.9 (Repeated Dose (28 Days) Toxicity (Dermal))
Deviations:
yes
Remarks:
(study duration should be 28 days, adrenal weights not determined)
Qualifier:
according to
Guideline:
other: US-EPA FIFRA §82-2, November 1984
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese MAFF, Subchronic Dermal Toxicity Study, 1985
Deviations:
no
GLP compliance:
yes
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report):2-phenylphenol, DOWICIDE 1 Antimicrobial, ortho-phenylphenol, o-phenylphenol
- Molecular formula (if other than submission substance): C6H4(C6H5)OH
- Physical state: white to light pink solid
- Analytical purity: 99.82%

Test animals

Species:
rat
Strain:
Fischer 344
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Kingston, Kingston, NY
- Age at study initiation: approximately 8 weeks
- Weight at study initiation: males: 167-196 g, females: 121-144 g
- Housing: individually in stainless steel cages
- Diet: Purina Certified Rodent Chow #5002 (Purina Mills Inc., St. Louis, MO) in meal form, ad libitum (except prior to necropsy)
- Water: municipal drinking water (City of Lake Jackson, TX), ad libitum
- Acclimation period: at least 7 days

ENVIRONMENTAL CONDITIONS- adequate (not further specified)
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
unchanged (no vehicle)
Details on exposure:
TEST SITE
- Area of exposure: back
- area covered: 5 cm²

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Application site was wiped with a water-dampened disposable gauze pad.
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
21 days
Frequency of treatment:
once daily on 5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
100, 500, and 1000 mg/kg bw/day
Basis:
nominal per unit body weight
No. of animals per sex per dose:
5
Control animals:
yes, sham-exposed

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: once daily
- Parameters checked: morbidity and mortality, presence of urine and faeces, alterations in skin, fur, mucous membranes, respiration, central nervous system function and animal behaviour

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: daily after removal of test item

BODY WEIGHT: Yes
- Time schedule for examinations: pre-study and once weekly during the study period

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes

OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations: pre-exposure and at necropsy
- Dose groups that were examined: all animals

HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to necropsy
- How many animals: all surviving animals
- Parameters checked: haematocrit, haemoglobin concentration, erythrocyte count, total and differential leukocyte count, platelet count, erythrocyte, leukocyte and platelet morphology

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: prior to necropsy
- How many animals: all surviving animals
- Parameters checked: sodium, potassium, chloride, calcium, phosphorus, fasting glucose, total bilirubin, blood urea nitrogen, creatinine, total protein, albumin, globulin, alkaline phosphatase, alanine aminotransferase, aspartate aminotransferase

URINALYSIS: Yes
- Time schedule for collection of urine: on Day 19
- Parameters checked: specific gravity, pH, protein, glucose, ketones, blood, bilirubin, urobilinogen, microscopic observation of solids
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
ORGAN WEIGHTS: Yes (liver, kidneys, testes, brain, heart)
HISTOPATHOLOGY: Yes (Control and high dose group; treated and untreated skin, liver, kidneys and gross lesions; mid dose group; untreated and treated skin. Tissues having grossly observable lesions and any target tissues identified in high dose group animals were also examined from animals of the intermediate dose groups.)
Statistics:
Descriptive statistics were calculated for feed consumption. Statistical outliers were identified by a sequential test.
Continuous data: Evaluation of variance was done with Bartlett’s test. If homogenous, group means were analysed by ANOVA followed by Dunnett’s test.

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
Description (incidence and severity):
dose-dependent local dermal irritation at 500 and 1000 mg/kg bw/day
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
no effects observed
Food efficiency:
no effects observed
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
effects observed, treatment-related
Description (incidence and severity):
changes were noted in treated skin and were based on irritating properties of the test substance
Histopathological findings: non-neoplastic:
effects observed, treatment-related
Description (incidence and severity):
changes were noted in treated skin and were based on irritating properties of the test substance
Histopathological findings: neoplastic:
not examined
Details on results:
CLINICAL SIGNS AND MORTALITY
No mortalities occurred throughout the study period.
Local irritation (erythema and scaling) of the application site was noted at 500 mg/kg bw/day and above. Oedema formation was not observed in either sex at any dose level. The authors suggest a dose-response relationship and a higher sensitivity of females to local dermal irritation as compared to males.

BODY WEIGHT AND WEIGHT GAIN
There was no test material-related adverse effect noted.

FOOD CONSUMPTION
There was no test material-related effect noted.

FOOD EFFICIENCY
There was no test material-related effect noted.

OPHTHALMOSCOPIC EXAMINATION
There was no test material-related effect noted.

HAEMATOLOGY
There was no test material-related effect noted.

CLINICAL CHEMISTRY
There was no adverse test material-related effect noted. Decresed aspartate aminotransferase activity in both sexes at 100 mg/kg bw/day and creatinin concentration in males treated with 500 mg/kg bw/day were considered to be not treatment-related.

URINALYSIS
There was no test material-related effect noted.

ORGAN WEIGHTS
There was no test material-related effect noted.

GROSS PATHOLOGY
Findings were limited to local skin irritation at the application site in mid- and high-dose animals (500 and 1000 mg/kg bw/day).

HISTOPATHOLOGY: NON-NEOPLASTIC
Hyperkeratosis and acanthosis were found in the treated skin of the mid- and high-dose animals (500 and 1000 mg/kg bw/day). The effects noted contribute to test substance-induced irritation rather than dermal toxicity. No other treatment-related findings were noted in liver or kidney in either male or female rats at any dose level.

Effect levels

open allclose all
Dose descriptor:
NOAEL
Remarks:
systemic
Effect level:
>= 1 000 mg/kg bw/day
Based on:
test mat.
Sex:
male/female
Dose descriptor:
NOAEL
Remarks:
local
Effect level:
100 mg/kg bw/day
Based on:
test mat.
Sex:
male/female

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion