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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
September - December 2002
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Remarks:
No reference to GLP and Guideline in the report, however the described procedure and results reflect internationally accepted requirements.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2002
Report date:
2002

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
The study design and report reflect all information necessary on judging study reliability and were assessed to be in concordance with current requirements.
GLP compliance:
no
Test type:
other: acute oral defined LD50
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Phosphoric acid, mixed esters with alcohols, C7-9-iso-, C8-rich and alcohols, C11-14-iso-, C13-rich, ethoxylated, potassium salt
EC Number:
947-738-8
Molecular formula:
Molecular formulas of exemplary components: C33H68KO10P C49H100KO16P C24H49K2O10P C24H50KO10P C16H34KO4P C8H17K2O4P C8H18KO4P
IUPAC Name:
Phosphoric acid, mixed esters with alcohols, C7-9-iso-, C8-rich and alcohols, C11-14-iso-, C13-rich, ethoxylated, potassium salt
Test material form:
liquid

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
A group of Sprague-Dawley derived, albino rats was received from Ace Animals, Inc., Boyertown, PA, USA. The animals were singly housed in suspended stainless steel caging with mesh floors. Litter paper was placed beneath the cages and was changed at least three times per week. The animal room was temperature controlled and had a 12-hour light/dark cycle. The animals were fed Purina Rodent Chow #5012 and filtered tap water was supplied ad libitum by an automatic watering system.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Following acclimation to the laboratory, 20 healthy rats were selected for test. Prior to dosing, each group of animals was fasted overnight by removing the feed from their cages.
During the fasting period, the animals were examined for health and weighed (initial). Individual doses were calculated based on these bodyweights, taking into account the specific gravity of the test substance. Each animal received the appropriate amount of the test substance by intubation using a stainless steel ball-tipped gavage needle attached to an appropriate syringe. After administration, each animal was returned to its designated cage. Feed was replaced approximately 3 hours after dosing.
Doses:
Dose levels of 1,250, 2,500 and 5,000 mg/kg were selected for testing.
No. of animals per sex per dose:
5000 mg/kg b.w. - 5 males and 5 females
2500 mg/kg b.w. - 5 females
1250 mg/kg b.w. - 5 females
Control animals:
no
Details on study design:
The animals were observed for mortality, signs of gross toxicity and behavioral changes at approximately one hour post dosing and at least once daily for 14 days. Bodyweights were recorded prior to initiation and at termination (Day 14) or after death. Surviving animals were euthanized by C02 inhalation at termination. A gross necropsy was performed on all decedents as soon as possible after death.
Statistics:
The acute oral defined LD50 was calculated by Probit Analysis with indication of 95% confidence limits.

Results and discussion

Effect levelsopen allclose all
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
3 127 mg/kg bw
Based on:
test mat.
95% CL:
1 719 - 7 247
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
5000 mg/kg b.w. - four females died within three days of test substance administration, all males survived
2500 mg/kg b.w. - two females died within two days of test substance administration
1250 mg/kg b.w. - all females survived
Clinical signs:
5000 mg/kg b.w. - Toxic sings noted prior to death included diarrhea, ano-genital staining, facial staining, reduced fecal volume and hypoactivity. Surviving animals exhibited similar clinical sings but, recovered by Day 5 and appeared active and healthy for the remainder of the study, gaining body weight over the entire 14-day observation period.

2500 mg/kg b.w. - Toxic signs noted prior to death included ano-genital staining, diarrhea and hypoactivity. Surviving animals exhibited similar clinical signs but recovered by Day 2 and appeared active and healthy for the remainder of the study, gaining body weight over the entire 14-day observation period.

1250 mg/kg b.w. - two animals exhibited ano-genital staining and two exhibited soft feces, but all affected animals recovered by Day 2 and appeared active and healthy for the remainder of the 14-day observation period.
Body weight:
5000 mg/kg b.w. - surviving animals showed body weight gain
2500 mg/kg b.w. - surviving females shoed body weight gain
1250 mg/kg b.w. - all females showed body weight gain
Gross pathology:
5000 mg/kg b.w. - Gross necropsy of the decedents revealed discoloration of the lungs and intestines.
2500 mg/kg b.w. - Gross necropsy of the decedents revealed discoloration of the lungs and intestines.

Applicant's summary and conclusion

Interpretation of results:
Category 5 based on GHS criteria
Conclusions:
Under the conditions of this study, the acute oral defmed LD50 calculated by Probit Analysis was 3,127 milligrams of the test substance per kilogram of body weight in the female rats with 95% Confidence Limits of 7,247 mg/kg (upper) and 1,719 mg/kg (lower) and is greater than 5, 000 mg/kg in the male rats.

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