SRC TR-09-215

HPV4 CHEMICAL DATA ADEQUACY REVIEW AND ROBUST SUMMARY ADEQUACY 

REQUIREMENTS 

PHOSPHONIC ACID, DIBUTYL ESTER

Prepared by:

Justine Von Runnen, Christopher Janson and Joan D. Garey

Environmental Science Center

Syracuse Research Corporation

7502 Round Pond Road

North Syracuse, NY 13212

Contract No. EP-W-04-019

Task FA411.4.409.009

Submitted to:

OPPT/RAD/HPVCB (7403M)

U.S. Environmental Protection Agency

1200 Pennsylvania Avenue

Washington, D.C. 20460

Kathleen C. Kennedy, Project Officer

David Brooks, Work Assignment Manager

July 16, 2009
ACUTE TOXICITY STUDIES

Summary of endpoint: Adequate

Title: Acute Oral LD50

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: Dibutyl phosphate (CAS No. 1809-19-4)

Remarks: Clear colorless liquid; purity not reported

METHOD

Method/guideline followed: This test procedure is in accordance with the Code of Federal Regulations 

(Part 191.1, Chap I, Title 21) for evaluating highly toxic substances.

Type: Acute oral LD50

GLP: Not stated

Year: circa 1974

Species/Strain: Rat / Sprague-Dawley

Sex: Male

No. of animals per sex per dose: 5 males per dose

Vehicle: None

Route of administration: Oral gavage

Method remarks: The test material was administered in single doses by means of a stomach tube. Five 

animals were used for each dose level. Dose levels were 1000, 2150, 4640 and 10,000 mg/kg-bw. The 

animals were fasted for 24 hours prior to treatment. The animals were observed for toxicity for 14 days 

after treatment for mortalities and signs of toxicity.

Animal weight range was 170-225 grams

The 10,000 mg/kg dose level was assumed.

RESULTS

LD50 value:

3690 mg/kg (2710 – 5010)
Number of deaths at each dose level: 0/5 at 1000 mg/kg; 0/5 at 2150 mg/kg; 4/5 at 4640 mg/kg; 5/5 at 

10,000 mg/kg

Remarks: Slight to moderate depression was noted at all dose levels.

CONCLUSIONS

None stated

RELIABILITY CODE

2

REFERENCES 

Study information taken from a TSCATS submission OTS0538481 (TSCA 8(e) submission 8EHQ-92-

8985; DCN No. 88920007348, pg. 6)
Title: Acute Dermal LD50

The study is: Adequate Not Adequate

TEST SUBSTANCE

Identity: Dibutyl phosphate (CAS No. 1809-19-4)

Remarks: Clear colorless liquid; purity not reported

METHOD

Method/guideline followed: The test procedure employed is in accordance with the procedure described 

in the Code of Federal Regulations (Part 191.1, Chap I, Title 21) for evaluating highly toxic substances.

Type: Acute dermal LD50

GLP: Not stated

Year: circa 1974

Species/Strain: Rabbit / New Zealand White albino

Sex: Both

No. of animals per sex per dose: 4 rabbits total; 2/sex

Vehicle: Not stated

Route of administration: Dermal

Method remarks:

New Zealand White albino rabbits, in the 1.8 – 2.3 weight range were used in this study. Two male and 

two female rabbits had the test material applied to the closely clipped, intact abdominal skin beneath a 

protective binder. After a 24-hour period, the binder material was removed, the abdominal skin was 

inspected for irritation, and the test site was washed with soap and water and rewrapped in a gauze binder. 

The test animals were observed for a 14-day period following the initial treatment.

The dose level administered was 4640 mg/kg

RESULTS

LD50 value: 

> 4640 mg/kg

Number of deaths at each dose level: No mortalities were observed.

Remarks: No signs of toxicity were observed. Local effects included severe necrosis, edema and 

subdermal hemorrhaging.
CONCLUSIONS

None stated

RELIABILITY CODE

3

REFERENCES 

Study information taken from a TSCATS submission OTS0538481 (TSCA 8(e) submission 8EHQ-92-

8985; DCN No. 88920007348, pg. 9)
SKIN IRRITATION STUDY

Title: Primary Skin Irritation, Dot Protocol

TEST SUBSTANCE

Identity: Dibutyl phosphate (CAS No. 1809-19-4)

Remarks: Clear, colorless liquid; purity not reported

METHOD

Method/guideline followed: Primary skin irritation was determined according to the proposed FDA 

revision of the test for primary skin irritants published in the Code of Federal Regulations (Part 191, 

Chapter 1, Title 21) for evaluating hazardous substances. 

GLP (Y/N): Not stated

Year: circa 1974

Species/strain: Rabbit / strain not stated

Sex (males/females/both): Not stated

Number of animals/sex/dose: 6 animals total

Volume administered: Not stated

Method remarks:

Substance was administered to intact skin of 6 rabbits (2 sites per rabbit) for 4 hours and observed for 

erythema-eschar and edema for 48 hours.

The proposed test differs from the procedure described in the Hazardous Substance Labeling Act, in that 

irritation is determined after a 4-hour exposure period. In the proposed test, readings are made 4-, 24- and 

48- hours after treatment. Animals are retained for observation for 96 hours after initial application. Any 

delayed necrosis is reported, but the data will not be used in determination of irritation indices. A 

corrosive substance is defined as a material that causes tissue destruction within 48 hours after application 

on any of the twelve intact sites.

RESULTS

Two rabbits developed subdermal hemorrhage. All animals except one showed eschar formation.

The primary irritation score was 5.8. Scores among the six rabbits ranged from 2.0 to 7.3.

CONCLUSIONS

The test substance is classified as corrosive.
RELIABILITY CODE

2

REFERENCES

The study summary is taken from a TSCATS submission OTS0538481 (TSCA 8(e) submission 8EHQ92-8985; DCN No. 88920007348, pg. 7, 10)
EYE IRRITATION STUDY

Title: Eye Irritation

TEST SUBSTANCE

Identity: Dibutyl phosphate (CAS No. 1809-19-4)

Remarks: Clear, colorless liquid; purity not reported

METHOD

Method/guideline followed: Procedure is in accordance with the test for eye irritants outlined in the code 

of Federal Regulations (Part 191.12, Chap. 1, Title 21) for evaluating hazardous substances.

GLP (Y/N): Not stated

Year: circa 1974

Species/strain: Rabbit / New Zealand White

Sex (males/females/both): Not stated

Number of animals/sex/dose: 6 animals total

Volume administered: 0.1 mL

Control: Untreated eye

Method remarks:

Six New Zealand White rabbits in the 1.6 – 2.1 kg weight range were used as the test animals. The test 

material was placed in one eye of each animal by gently pulling the lower lid away from the eyeball to 

form a cup into which the test material is dropped. The lids were gently held together for three seconds 

and the animal released. The other eye, remaining untreated, served as the control. The eyes were 

observed at 24-, 48-, and 72-hours following treatment and scored for irritation properties.

RESULTS

Corneal damage: Mild to moderate ocular opacity occurred at every test site.

Iritis: Some mild inflammation was noted at two test sites.

Conjunctivae:

a) erythema – little or no erythema was noted

b) chemosis – little or no edema was noted

c) discharge – little or not discharge was noted

Signs of remission: Five animals showed complete remission of all symptoms within 14 days, however, 

one animal showed only partial remission of the corneal opacity and complete remission of the other 

symptoms.
CONCLUSIONS

The test substance is classified as a severe irritant.

RELIABILITY CODE

2

REFERENCES

The study summary is taken from a TSCATS submission OTS0538481 (TSCA 8(e) submission 8EHQ92-8985; DCN No. 88920007348, pg. 8)
Summary of Endpoints

Endpoint Study Information 

Provided

Acceptable Data Gap

Aquatic Effects

Acute Toxicity to Fish No No Yes

Acute Toxicity to Daphnia No No Yes

Toxicity to Aquatic Plants No No Yes

Health Effects

Acute Toxicity Yes Yes No

Repeated-Dose Toxicity No No Yes

Genetic Mutation No No Yes

Chromosomal Aberrations No No Yes

Toxicity to Reproduction No No Yes

Developmental Toxicity No No Yes