Reaction mass of 1-Propanaminium, 2,3-dihydroxy-N,N-dimethyl-N-[3-[(1-oxododecyl)amino]propyl]-, chloride and 1-Propanaminium, 2,3-dihydroxy-N,N-dimethyl-N-[3-[(1-oxotetradecyl)amino]propyl]- , chloride

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

Sept 22, 1989

Reliability:

2 (reliable with restrictions)

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:

EPA OTS 798.4500 (Acute Eye Irritation)

Version / remarks:

Primary eye irritation Federal guidelines 40 CFR 798.4500

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

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 / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

albino

Details on test animals or tissues and environmental conditions:

Healthy, USDA certified nine New zealand Albino Rabbits from Davidson's MILL farm.
4 male and 5 females.
Rabbits were selected based on their eye condition and health status.
Acclimatation period: 10 or 25 days
Caging- individually in suspended stainless steel caging with mesh floors.
Room temperature 19-23C
Food: pelleted Purina Rabbit Chow ad-libitum
Water: tap-water supplied by automatic water system
identification: a number was allocated to each rabbit on receipt.
application day: on august 16, 1989, the test substance was instilled into the left or right eye of each individual rabbit.

Test system

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.10mL

Duration of treatment / exposure:

not applicable

Observation period (in vivo):

24, 48, and 72 hrs then at 4, 7, 10, 14, 17, and 21 days

Number of animals or in vitro replicates:

nine (4males / 5 females)

Details on study design:

Approximately 4.5 hrs before test, the eyes of a number of healthy, young rabbits were examined using fluorescein dye procedure. One drop of 2% ophthalmic fluorescein sodium was instilled into each eye of each rabbit. The eyes were irrigated with 30mL of physiological saline (0.9% NaCl) 30 seconds after instillation of the fluorescein. Using a black-ray lamp (compact 4 watt UV lamp), the eyes were checked for gross anomalies according to the "Scale for Scoring Ocular Lesions" Rabbits with score greater than zero (showing eye irritation, ocular defects or pre-existing corneal injury) were eliminated. Nine rabbits were selected for test using this pre-screening procedure.
0.10mL of the test material was placed in the conjunctival sac of the left or right eye of each rabbot by pulling the lower lid away from the eyeball. The upper and lower lids were then gently held together for about 1 second before releasing, to prevent loss of test material. The other eye of each rabbit remained intreated and served as control. The treated eyes of three rabbits were irrigated with 30 mL of physiological saline (0,9% NaCl) approximately 20-30 seconds after instillation of the test material. The eyes of the remaining six rabbits were not irrigated. The rabbits were returned to their cages and restrained with neck collars for 24 hrs. After initial introduction of the test material, ocular lesions were evaluated in accordance with Draize et al. at 24, 48, 72 hrs and at 4, 7, 10, 14, 17, 21 days. The eye scores were further classified by the system of Kay and Calandra. Special care was taken to look for and notate any unusual effects, such as pannus, blistering of the conjunctivae, ulceration and other indicators of corrosive action.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

24 h

Score:

40.7

Remarks on result:

other: unwashed eye

Results 2

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

24 h

Score:

34

Remarks on result:

other: washed eye

Irritant / corrosive response data:

Based on the 24 hr maximum mean total score, the test material is classified as severely irritating to the washed and unwashed eyes, respectively, when adminitered as received, undiluted.

Other effects:

One rabbit died on day 21 prior scoring. No toxic signs were noted prior to death. All other animals appeared active and healthy. Apart from the eye irritation noted below, there were no sign of gross toxicity, adverse pharmacologic effects or abnormal behavior.

Applicant's summary and conclusion

Conclusions:

Based on the 24 hr maximum mean total score, the test material is classified as severely irritating to the washed and unwashed eyes, respectively, when administered as received, undiluted.

Executive summary:

A sample of cocamidopropyl betaine was instilled as received, undiluted.

After acclimatation to the laboratory, nine healthy New Zealand white rabbits free of ocular lesions were selected for test. 0.10mL of test material was placed into the conjunctival sac of the left or right eye of each rabbit. The other eye remained untreated, and served as a control. The treated eyes of 3 rabbits were irrigaed with 30mL physilogical saline approximately 20-30 seconds after installation of the test material. The eyes of the remaining 6 rabbits were not irrigated. Ocular lesions were evaluated at 1, 24, 48, and 72 hrs and at 4, 7, 10, 14, 17, and 21 days by the methode of Draize and al.. The eye scores were further classified by the system of Kay and Calandra.

Based on the 24 hr maximum mean total score, the test material is classified as severely irritating to the washed and unwashed eyes, respectively, when administered as received, undiluted.

The incidence, severity and reversibility of irritation are detailed in the attached study report.