Sodium 2-biphenylate

Repeated dose toxicity: dermal

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

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Reference 2

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 guideline

Test guideline 1

Qualifier:

according to guideline

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)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.9 (Repeated Dose (28 Days) Toxicity (Dermal))

Deviations:

yes

Remarks:

(study duration should be 28 days, adrenal weights not determined)

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: US-EPA FIFRA §82-2, November 1984

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: Japanese MAFF, Subchronic Dermal Toxicity Study, 1985

Deviations:

no

GLP compliance:

yes

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Biphenyl-2-ol

EC Number:

201-993-5

EC Name:

Biphenyl-2-ol

Cas Number:

90-43-7

Molecular formula:

C12H10O

IUPAC Name:

2-phenylphenol

Test material form:

solid

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 or test system 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

1

Key result

Dose descriptor:

NOAEL

Remarks:

systemic

Effect level:

>= 1 000 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: No adverse and treatment-related effects were observed up to and including the highest tested dose level.

2

Key result

Dose descriptor:

NOAEL

Remarks:

local

Effect level:

100 mg/kg bw/day

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: Local irritation (erythema and scaling) of the application site was noted at 500 mg/kg bw/day and above

Target system / organ toxicity

Critical effects observed:

not specified