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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
sept 29, 1989
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

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

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
other: 40 CFR Part 158 Subdivision F; Pesticide Assessment Guidelines Hazard Evaluation-Human and Domestic Animals NTIS:PB83-153916:section 81-1; pp. 34-39
Version / remarks:
PSL protocol No. 012/P321
Deviations:
no
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
yes

Test material

Constituent 1
Chemical structure
Reference substance name:
Cocamidopropyl PG-dimonium chloride
Cas Number:
136920-08-6
Molecular formula:
C20-30H43-63ClN2O2 range
IUPAC Name:
Cocamidopropyl PG-dimonium chloride
Test material form:
other: aqueous solution
Details on test material:
Lot# HH105P
Cocamidopropyl PG dimonium chloride
Lexquat AMG-WC

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
Healthy, Sprague-Dawley derived albino rats were recived from Hilltop Lab Animals, Scottdale, PA. Twenty males and twenty females were selected test based on body weight and health status

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
2.0 / 3.0 / 4.0 g/kg body weight
limit test 5.0 g/kg limit test
No. of animals per sex per dose:
5 males and 5 females per dose
Control animals:
no
Details on study design:
Preliminary acute oral limit test:
A preliminary single dose acute oral toxicity limit test was conducted between June 13-27, 1989. Five grams of test material per kg body weight was gavaged into the stomachs of 5 male and 5 female young adult healthy Sprague-Dawley albino rats after they had been fested for approximately 18 hours.

90% mortality occured within day 1 after dosing. Signs prior to death included lethargy, hunched posture, and diararhea. The detailed results of this study are presented in report T-9156. An LD50 study was recommended.

Defined LD50
After acclimating to the lab environment for 10 to 31 days, rats in the appropriate weight range were fasted on the fay before dosing for approximately 18 hrs by removing feed from their cages. During fasting, water was provided ab-libitum. After the 18 hr fast period, the rats were examined and wheighed again. Ten animals (5 males/ 5 females) were uniquely identified and were selected for each test group on the basis of their health and fasting weight. Individual doses were immediately calculated based on the fasting weight taking into account the specific gravity of the test material. Each rat was then individually and singly dosed by gavage using calibrated syringe and a stainless steel intubation needle.
The test material was adminitrated as received, undiluted. After dosing, each rat was returned to its designated cage. Feed was replaced approximately 1 hr after dosing. Feed and water were provided ab-libitum for the balance of the study. the rats were observed at 1, 2, and 4 hrs after dosing and at least once daily thereafter for signs of gross toxicity and mortality. Body weights were recorded initially, on day 7, at termination (day 14) or after death. Gross necropsis were performed on all decedents and all survivors at terminal sacrifice.

Results and discussion

Preliminary study:
A preliminary single dose acute oral toxicity limit test was conducted. Five grams of test material per kg body weight was gavaged into the stomachs of 5 male and 5 female young adult healthy Sprague-Dawley albino rats after they had been fested for approximately 18 hours.
90% mortality occured within day 1 after dosing. Signs prior to death included lethargy, hunched posture, and diararhea.
Effect levelsopen allclose all
Sex:
female
Dose descriptor:
LD50
Effect level:
3 other: g/kg body weight
Based on:
test mat.
95% CL:
>= 2.6 - <= 4
Sex:
male
Dose descriptor:
LD50
Effect level:
3.8 other: g/kg body weight
Based on:
test mat.
95% CL:
>= 2.6 - <= 4
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
3.2 other: g/kg bw
Based on:
test mat.
95% CL:
>= 2.6 - <= 4
Mortality:
The effects levels mentioned above are based on mortality
Body weight:
See the attached report for body weights and mortality based on dose levels
Gross pathology:
Active and healthy
Red facial staining
Hunched posture
Diarrhea
Lethargic
Soft feces
Tan ano-genital stain
Dead
See attached report for details
Other findings:
Necropsy observations:
Lunge: slightly red to mottled dark
Liver: dark around edges
Stomach: moderatley to extremely distended, gaseous to filled with yellow fluid

Applicant's summary and conclusion

Conclusions:
LD50 (14d) = 3.2 g/kg bw
Executive summary:

The test material was tested as received undiluted or as a 75 %w/w solution in distilled water to facilitate accurate dosing at the lowest level.

A preliminary Acute Oral limit test at a single dose level of 5 g/kg bw caused 90% mortality within 1 day of dosing. A defined acute oral LD50 test was performed at dose levels of 4.0, 3.0, 2.0 g/kg bw.

After acclimating to the laboratory, 5male and 5 female rats where assigned to each dose level. They were fasted to approximately 18 hrs, then dosed with the appropriate dose levels.

Dosage 2.0 g/kg bw

There was 10% mortality at day 1. Most rats exhibit toxic signs such as hunched posture, red facial staining, soft feces or diarrhea and lethargy but were fully recovered by day 4. All survivors gained weight.

Dosage 3.0 g/kg bw

There was 40% mortality at day 1. Signs prior to death included hunched posture, red facial staining, soft feces, diarrhea, lethargy and ano-genital staining. Survivors exhibit similar symptoms but had recover fully by day 5 and remain active and healthy. All survivors gained weight.

Dosage 4.0 g/kg bw

There was 60% mortality at day 1. Signs prior to death included hunched posture, red facial staining, diarrhea, lethargy, ano-genital staining, and irregular or shallow respiration. Survivors exhibit similar symptoms but had recover fully by day 8. All survivors gained weight.

The Acute Oral Single Dose LD50 calculated by Probit Analysis was 3.2 g/kg bw with 95% confidence limit of 4.0 (upper) and (2.6) lower. The data do not permit calculation of LD50 for each sex separately. Graphically the LD50 for male and female was estimated to be 3.8 g/kg bw and 3.0 g/kg bw respectively.