Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
February 2005-May 2005
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline study under GLP

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2005
Report Date:
2005

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
GLP compliance:
yes (incl. certificate)
Test type:
up-and-down procedure
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Test material form:
solid: particulate/powder
Remarks:
migrated information: powder
Details on test material:
Test Substance Identification: Cetylpyridinium Chloride
Lot#: 00217966
Purity: 100.1% by assay
Test Substance Description: White powder
Date received: January 12, 2005
PSL Reference No: 050112-ID
Study Initiation Date: February 9, 2005

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
Housing: The animals were singly housed in suspended stainless steel caging with mesh floors. Litter paper was placed beneath the cage and was changed at least three times per week.
Animal Room Temperature Range: 20-23C
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 21-28 Days
Food: Purina Rodent Chow #5012
Water: Filtered tap water was supplied ad-libitum by an automatic water dispensing system.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The test substance was administered as a 40% w/w mixture in distilled water using a stainless steel ball-tippd gavage needle attached to an appropriate syringe. Following administration, each animal was returned to its designated cage. Feed was replaced approximately 2-4 hours after dosing.
Doses:
95, 300 and 950 mg/kg
No. of animals per sex per dose:
3 females (1 animal for the low dose exposure)
Control animals:
no
Details on study design:
An acute oral toxicity test (Up and Down Procedure) was conducted with rats to determine the potential for Cetylpyridinium Chloride to produce toxicity from a single dose via the oral route.
Based on an estimate of the LD50 supplied by the Sponsor (300 mg/kg), a Main Test was conducted using a default starting dose level of 95 mg/kg which was administered to one healthy female rat by oral gavage. Following the Up and Down procedure, six additional animals were dosed at levels of 300 or 950 mg/kg. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for up to 14 days after dosing. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) after dosing or after death. Necropsies were performed on all animals.

Results and discussion

Effect levels
Sex:
female
Dose descriptor:
LD50
Effect level:
560.3 mg/kg bw
Based on:
test mat.
95% CL:
>= 300 - <= 950
Mortality:
3 deaths among 3 animals at 950 mg/kg Dose Level. Deaths occurred withing two days of test substance administration.
No deaths among one animal at 95 mg/kg Dose level and 3 animals at the 300 mg/kg Dose Level.
Clinical signs:
95 mg/kg Dose Level (1 animal)
There were no signs of gross toxicity, adverse pharmacologic effects, or abnormal behavior
300 mg/kg Dose level (3 animals)
Following administration, two animals exhibited soft feces, reduced fecal volume, or piloerection.
950 mg/kg Dose Level (3 animals)
Toxic signs noted prior to death included diarrhea, ano-genital staining, piloerection, hypoactivity, hunched posture, and reduced fecal volume. Gross necropsy of the decedents revealed discoloration of the intestines and/or lungs and/or gaseous distention of the intestines.
Body weight:
206-237 grams at experimental start
Gross pathology:
95 mg/kg Dose level
No gross abnormalities were noted for this animal when necropsied
300 mg/kg Dose Level
No gross abnormalities were noted for any of the animals when necropsied
950 mg/kg Dose Level
Gross necropsy of the decedents revealed discoloration of the intestines and/or lungs and/or gaseous distention of the intestines.

Any other information on results incl. tables

Under the conditions of this study, the acute oral LD50 of the test substance is estimated to be 560.3 mg/kg of body weight in female rats with an approximate 95% confidence interval of 950 mg/kg (upper) and 300 mg/kg (lower).

Applicant's summary and conclusion

Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information LD50 = 560.3 mg/kg, which is between 300 and 2000 mg/kg bw. Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 of Cetylpyridinium Chloride is estimated to be 560.3 mg/kg of body weight in female rats, with an approximate 95% confidence interval of 950 mg/kg (upper) and 300 mg/kg (lower)