4-hydroxybenzoic acid

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

08.09.1980-08.10.1980

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Acceptable, well-documented study report which meets basic scientific principles.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1981

Report date:

1981

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: 40 CFR Part 163.81-2 EPA Pesticides Program

Deviations:

no

Principles of method if other than guideline:

equivalent or similar to 40 CFR Part 163.81-2 EPA Pesticides Program(Environmental Protection Agency, Pesticides Program, Proposed Guideline for Registering Pesticides in the U.S.; Hazard Evaluation: Humans and Domestic Animal, Acute Dermal Toxicity Study.de

GLP compliance:

no

Remarks:

Acceptable, well-documented study report which meets basic scientific principles.

Test type:

fixed dose procedure

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

4-HBA

IUPAC Name:

4-HBA

Details on test material:

Test material was labeled with C-194
-white powder
-storage: room temperature

Comment by the applicant:
Existing retained samples from batches of C-194 of 1980 were analytically rechecked. The identity was confirmed with a content of 4-HBA of approximately 100% (NMR analysis).

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
Supplier: Dutchland Laboratory Animals, Denver, Pennsylvania
Age at study initiation: young adults
males: 2.2-2.8 kg
females: 2.5-3.0 kg
Equilibration period: 16 days
Housing: individually
Food: Purina Rabbit Chow, ad libitum
Water: automatic watering system, ad libitum
ENVIRONMENTAL CONDITIONS
Temperature: 62 - 66°F
Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Type of coverage:

occlusive

Vehicle:

physiological saline

Details on dermal exposure:

On the day before dosing the hair of each rabbit was closely clipped from the trunk with an electric clipper. Just prior to dosing, the skin of all the animals was abraded longitudinally every 2 to 3 centimeters over the area of exposure, deep enough to penetrate the stratum corneum.
The dry material was placed directly onto an 8-ply, 4'' by 12'' piece of gauze (10.16 cm x 30.5 cm) and then moistened with a measured amount of physiological saline (approximately 15 ml). The gauze was then wrapped around the animal to cover the application site. The animal was then wrapped in an impervious plastic sleeve, designed to contain the test material without leakage or undue pressure. The sleeve was secured with masking tape and Elizabethan collars were placed on all animals.

Duration of exposure:

Following 24 hours of exposure, the wrappings were removed and the test site wiped free of excess test material. After 30 minutes, dermal observations were made.

Doses:

2000mg/kg bw., 1.6 mg/cm²

No. of animals per sex per dose:

5 per sex and dose, together 10

Control animals:

no

Details on study design:

Parameters: body weight, mortality, dermal observation, in-life observation,
necropsy: 13 days after application (day 14/ first day of application: day 1).
Dosing start: September 24, 1980
Dosing finish (24h): September 25, 1980
Termination/Sacrifice/Necropsy: October 8, 1980

Statistics:

no statistics performed

Results and discussion

Preliminary study:

A single dermal application of 2000mg/kg bw. for 24 hours in an occlusive way did not cause any mortality.
No clear signs of systemic toxicity werde observed. Dermal observations revealed only very slight erythema and/or slight edema.
Possible signs of systemic toxicity were: urinary staining, fecal staining, soft stool, left eye - red nictitating membrane, food consumption decrease. During the 24 hours test material application, signs exhibited sporadically in single animals included nasal and/or oral and/or ocular discharge, fecal staining, soft stool, unrinary staining, red eye - red nictitating membrane and hypoactivity. Decreased food consumption was exhibited in several animals from Day 2 through Day 11. During the 8-14 day interval, nasal discharge was exhibited by four males and four females.

Effect levels

Key result

Sex:

male/female

Dose descriptor:

discriminating dose

Effect level:

> 2 000 mg/kg bw

Mortality:

no mortality observed

Clinical signs:

other: During the 24 hours test material application, signs exhibited sporadically in single animals included nasal and/or oral and/or ocular discharge, fecal staining, soft stool, unrinary staining and hypoactivity, decreased food consumption

Gross pathology:

2 animals: no observable abnormalities,
5 animals: nasal discharge, lungs: mottled tan,
4 animals: kidneys: pale, ovaries: clear cysts,
3 animals: spleen: roughened,
2 animals: adrenals: red foci
1 animal: lung: all lobes - mottled brown periphery

Other findings:

Dermal observations: Very slight (barely perceptible) erythema was exhibited by eight of the ten animals and three animals exhibited very slight edema. Two animals exhibited no signs of dermal irritation.

Applicant's summary and conclusion

Interpretation of results:

practically nontoxic

Remarks:

Migrated information Criteria used for interpretation of results: OECD GHS

Conclusions:

The LD50 of the test substance is greater than 2000 mg/kg.
Therefore p-Hydroxybenzoic acid does not have to be classified according to OECD-GHS criteria. Acute dermal toxicity is greater than 2000 mg/kg bw.

Executive summary:

A single dermal application of 2000 mg/kg bw. for 24 hours in an occlusive way did not cause any mortality.

On the day before dosing the hair of each rabbit was closely clipped from the trunk with an electric clipper. Just prior to dosing, the skin of all the animals was abraded longitudinally every 2 to 3 centimeters over the area of exposure, deep enough to penetrate the stratum corneum. The dry material was placed directly onto an 8-ply, 4'' by 12'' piece of gauze (10.16 cm x 30.5 cm) and then moistened with a measured amount of physiological saline (approximately 15 ml). The gauze was then wrapped around the animal to cover the application site. The animal was then wrapped in an impervious plastic sleeve, designed to contain the test material without leakage or undue pressure. The sleeve was secured with masking tape and Elizabethan collars were placed on all animals. Following 24 hours of exposure, the wrappings were removed and the test site wiped free of excess test material. After 30 minutes, dermal observations were made.

No clear signs of local or systemic toxicity werde observed. Dermal observations revealed only very slight erythema and/or slight edema.

Possible signs of systemic toxicity were: urinary staining, fecal staining, soft stool, left eye - red nictitating membrane, food consumption decrease.

During the 24 hours test material application, signs exhibited sporadically in single animals included nasal and/or oral and/or ocular discharge, fecal staining, soft stool, unrinary staining, left eye - red nictitating membrane and hypoactivity. Decreased food consumption was exhibited in several animals from Day 2 through Day 11. During the 8-14 day interval, nasal discharge was exhibited by four males and four females.