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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1993-07-12 - 1993-09-07
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Scientifically valid GLP study on the registered substance itself according to the EPA Federal Register, Vol. 50, No. 188, Friday, September 27, 1985.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report date:
1993

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: EPA Federal Register, Vol. 50, No. 188, Friday, September 27, 1985.
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Reaction Products of Diphosphorus Pentaoxide with n-Alcohols, C8-10 (even), salted with Amines, C12-14, Tert-alkyl
EC Number:
943-016-1
Molecular formula:
Too complex
IUPAC Name:
Reaction Products of Diphosphorus Pentaoxide with n-Alcohols, C8-10 (even), salted with Amines, C12-14, Tert-alkyl
Test material form:
other: liquid
Details on test material:
- Substance type: pure substance

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Laboratories, Inc., Wilmington, Massachusetts
- Age at study initiation: 6-10 weeks
- Weight at study initiation: 171-217 grams. The weight variation in animals per sex did not exceed ± 20%.
- Fasting period before study: Rats were fasted, period not stated.
- Housing: Rats were housed individually in stainless steel ½" wire mesh cages, sized in accordance with the "Guide for the Care and Use of Laboratory Animals" of the Institute of Laboratory Animal Resources, National Research Council. Waste material was removed twice weekly. Cages and feeders were sanitized every two weeks.
- Diet (e.g. ad libitum): Harlan Teklad Lab Blox®, ad libitum, checked daily and added or replaced as needed. Feeders are designed to reduce soiling, bridging and scattering.
- Acclimation period: Min. 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12h / 12h

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
other: none (5000 mg/kg), corn oil (2000 mg/kg)
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 400 mg/ml
- Amount of vehicle (if gavage): 5ml/kg
- Justification for choice of vehicle: specified by the Sponsor
- Lot/batch no. (if required): Lot #80H0835

MAXIMUM DOSE VOLUME APPLIED: 5 ml/kg
Doses:
2000 and 5000 mg/kg
No. of animals per sex per dose:
5 / sex / dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: The rats were observed at approximately 1, 4 and 24 hours after dosing and once daily through Day 14 for pharmacological and toxicological effects. Viability was checked daily. Body weights were recorded at study initiation and Days 7 and 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, gross necropsy
Statistics:
Not applicable

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
5 000 mg/kg bw
Based on:
test mat.
Mortality:
Five of ten animals died at 5000 mg/kg and none of the animals died at 2000 mg/kg.
Clinical signs:
Clinical signs observed at 5000 mg/kg included chromodacryorrhea, decreased activity, abnormal gait, abnormal stance, decreased muscle tone, tremors and poor grooming. Clinical signs observed at 2000 mg/kg included chromodacryorrhea, salivation, diarrhea, tremors and elevated gait.
Body weight:
There was an apparent increase in body weight for all surviving animals during the study.
Gross pathology:
Necropsy of the animals that died on study revealed distended stomach and fluid-filled intestines. Terminal necropsy revealed mottled kidneys in one animal at 5000 mg/kg and in three animals at 2000 mg/kg.

Any other information on results incl. tables

Table 1: Incidence of Clinical signs / Death

Dose Level (mg/kg)

2000

5000

2000

5000

Sex

male

male

female

female

Signs observed

Number of animals affected

Appears normal

5/5

5/5

5/5

5/5

Decreased activity

0/5

3/5

0/5

2/5

Abnormal gait

0/5

2/5

0/5

2/5

Abnormal stance

0/5

2/5

0/5

2/5

Chromodacryorrhea

0/5

0/5

1/5

1/5

Diarrhea

0/5

0/5

2/5

0/5

Salivation

3/5

0/5

1/5

0/5

Tremors

1/5

5/5

0/5

5/5

Elevated gait

0/5

0/5

1/5

0/5

Decreased muscle tone

0/5

2/5

0/5

1/5

Poor Grooming

0/5

1/5

0/5

2/5

Death

0/5

2/5

0/5

3/5

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information to practically non-toxic Criteria used for interpretation of results: EU
Conclusions:
The study is well-documented and was performed according to the EPA Federal Register, Vol. 50, No. 188, Friday, September 27, 1985, under GLP conditions. Hence, the information provided in the report can be considered reliable. In consequence, the results are suitable for the assessment of the acute toxicity of the test item. Based on the results from the Acute Exposure Oral Toxicity in rats, the estimated acute oral LD50 (combined sexes) for the test item was determined to be 5000 mg/kg.
Executive summary:

In a Limit Test according to the EPA Federal Register, Vol. 50, No. 188, Friday, September 27, 1985, the test item was orally administered to one group of ten fasted, 6-10 weeks old Sprague-Dawley rats (five males and five females), at a dose level of 5000 mg/kg as received with a post-observation period of 14 days. Due to the mortality observed, an additional group of ten animals (five males and five females) was administered the test article at 2000 mg/kg in corn oil.

Clinical signs observed at 5000 mg/kg included decreased activity, chromodacryorrhea, abnormal gait, abnormal stance, decreased muscle tone, tremors and poor grooming. Clinical signs observed at 2000 mg/kg included chromodacryorrhea, salivation, diarrhea, tremors and elevated gait. There was an apparent increase in body weight for all surviving animals during the study. Five of ten animals died at 5000 mg/kg and none of the animals died at 2000 mg/kg. Necropsy of the animals that died on study revealed distended stomach and fluid-filled intestines. Terminal necropsy revealed mottled kidneys in one animal at 5000 mg/kg and three animals at 2000 mg/kg.

Based on the results from the Acute Exposure Oral Toxicity in rats, the estimated acute oral LD50(combined sexes) for the test item was determined to be 5000 mg/kg.