Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
7 February 1989 to 2 March 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study performed in accordance with US EPA test guidelines in compliance with GLP.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1989
Report Date:
1989

Materials and methods

Test guideline
Qualifier:
according to
Guideline:
other: "Acute Exposure Oral Toxicity," Health Effects Test Guidelines, U. S. Environmental Protection Agency Office of Pesticide and Toxic Substances, pp. 22-31, October 1984.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Test Material: HP-10 [Phosphorus acid, 2.2 methyiene bis-(4.6.di-t-butyl phenyl)2 ethyl hexyl ester]
Physical Description: White powder
Purity and Stability: Sponsor assumes responsibility for purity and stability determinations (including under test conditions).
Storage and Retention: The test material was stored at room temperature.
Any unused material will be discarded according to HLA Standard Operating Procedure.
Safety Precautions: Normal handling procedures were used according to HLA Standard Operating Procedure.

Test animals

Species:
rat
Strain:
other: Crl:CD®(SD)BR
Sex:
male/female
Details on test animals and environmental conditions:
Young adult male and female albino rats of the Crl:CD®(SD)BR strain (approximately 8 weeks of age) were procured, separated by sex, maintained in group cages in temperature- and humidity-controlled quarters, provided continuous access to Rodent Chow® 5001, Purina Mills, Inc., and water and held for an acclimation period of at least 7 days. Animal husbandry and housing at HLA comply with standards outlined in the "Guide for the Care and Use of Laboratory Animals". If variations from the prescribed environmental conditions existed, they were documented and considered to have no effect on the study outcome. No contaminants were expected to have been present in the feed or water which would have interfered with or affected the results of the study.

All animals were chosen at random, treated, and maintained during the observation period as specified for the acclimation period and were identified by animal number and corresponding ear tag. Food and water were available ad libitum throughout the study, except for an overnight period just before test material administration when food, but not water, was withheld.
Reason for Species Selection: Historically, rats have been used as a representative of a rodent species and are preferred by various regulatory agencies.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
Preparation and Administration of Test Material: For the range-finding study, the test material was mixed with corn oil to a uniform suspension at a specific concentration for each dose level. For the definitive study, the test material was mixed with corn oil to a uniform suspension at a concentration of 500 mg/ml. An individual dose was calculated for each animal based upon its fasted body weight and administered at a dose volume of 10 ml/kg by gavage. Each test material mixture was stirred with a stir plate and magnetic stir bar during dosing to maintain a uniform suspension.
Reason for Route of Administration: This is the method for administering a known quantity of test substance and has been the route of choice historically.
Doses:
Range-finding dose levels of 50, 100, 1,000, 2,500, and 5,000 mg/kg of body weight (one male and one female/dose level).
Based on the results of this range-finding study, in the definitive LD50 study animals were treated at a single level of 5,000 mg/kg of body weight.
No. of animals per sex per dose:
Range finding study - one male/one female per dose level.
Definitive study - five males & five females.
Control animals:
no
Details on study design:
Initially, five male and five female acclimated rats, weighing from 202 to 259 g, were used for five range-finding dose levels of 50, 100, 1000, 2500, and 5,000 mg/kg of body weight (one male and one female/dose level).
These range-finding animals were housed individually.
Based on the results of this range-finding study, five male and five female rats, weighing from 215 to 282 g, were used for the definitive LD50 study.
Animals were treated at a single level of 5,000 mg/kg of body weight. These definitive study animals were housed by sex in groups of five.
Observations: The range-finding study animals were observed for clinical signs and mortality at 1, 2, 4, 24, 48 and 72 hours after treatment. The definitive study animals were observed for clinical signs and mortality at 1, 2 and 4 hours after test material administration. These animals were observed daily thereafter for 14 days for clinical signs and twice daily for mortality.
All animals were weighed just before test material administration. Body weights of definitive study animals were taken again at 7 and 14 days.
Pathology: All range-finding study animals were sacrificed at termination and discarded. All definitive study animals, were sacrificed at termination, subjected to a gross necropsy examination and all abnormalities were recorded. After necropsy, animals were discarded and no tissues were saved.
Statistics:
Statistical Methods: No statistical method was performed.

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
There were no deaths during the study.
Clinical signs:
Diarrhoea was observed in three of the five female animals on the day of dosing.
Body weight:
There was no significant effect on body weight gain.
Gross pathology:
No visible lesions were recorded at the time of necropsy.

Any other information on results incl. tables

Range-Finding Mortality Summary

Dose Level (mg/kg)

Hours

0-4

24

48

72

Male

Female

Male

Female

Male

Female

Male

Female

50

0

0

0

0

0

0

0

0

100

0

0

0

0

0

0

0

0

1000

0

0

0

0

0

0

0

0

2500

0

0

0

0

0

0

0

0

5000

0

0

0

0

0

0

0

0

 

DEFINITIVE STUDY

Sex

Dose Level (mg/kg)

Average Body Weights (g)

Mortality (Number Dead/Number Dosed)

Initial

Day 7

Terminal

Male

5000

266

343

377

0/5

Female

5000

230

259

264

0/5

 

Clinical Signs (Number of Animals Affected)

Observation

Hours

Days

1.0

2.0

4.0

1

2

3

4

5

6

7

8

9

10

11

12

13

14

Males (5000 mg/kg)

Appeared normal

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

5

Females (5000 mg/kg)

Appeared normal

2

2

2

5

5

5

5

5

5

5

5

5

5

5

5

5

5

Diarrhoea

3

3

3

0

0

0

0

0

0

0

0

0

0

0

0

0

0

 

PATHOLOGY

Animal Number

Test Day

Sex

Died

Sacrificed

Necropsy Comment

Dose Level : 5000 mg/kg of Body Weight

C30518

M

-

14

No visible lesions

C30520

M

-

14

No visible lesions

C30517

M

-

14

No visible lesions

C30516

M

-

14

No visible lesions

C30547

M

-

14

No visible lesions

C30321

F

-

14

No visible lesions

C30322

F

-

14

No visible lesions

C30323

F

-

14

No visible lesions

C30324

F

-

14

No visible lesions

C30325

F

-

14

No visible lesions

 

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The estimated oral LD50 was determined to be >5,000 mg/kg of body weight for males, females and the combined sexes.
Executive summary:

The acute oral toxicity of HP-10 was evaluated in male and female rats.

This study was conducted in accordance with the Environmental Protection Agency's Good Laboratory Practice Standards, 40 CFR 792 and"Acute Exposure Oral Toxicity," Health Effects Test Guidelines, U. S.Environmental Protection Agency Office of Pesticide and ToxicSubstances, pp. 22-31, October 1984.

 

The estimated oral LD50was determined to be >5,000 mg/kg of body weight for males, femalesandthe combined sexes. Diarrhoea was observed in three of the five female animals on the day of dosing. There was no significant effect on body weight gain. No visible lesions were recorded at the time of necropsy.