Ametryn

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

November 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study in compliance with guidelines

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2004

Report date:

2004

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Ametryn

EC Number:

212-634-7

EC Name:

Ametryn

Cas Number:

834-12-8

Molecular formula:

C9H17N5S

IUPAC Name:

N2-ethyl-6-(methylsulfanyl)-N4-(propan-2-yl)-1,3,5-triazine-2,4-diamine

Details on test material:

Batch Identification: FLC41 050
Product design Code: G34162
Product Common Name: Ametryn
Purity: 97.7% (wt/wt)
Appearance: white powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Age: Young adult.
Source: Received from Robinson Services, Inc. Clemmons, NC on August 18, 2004.


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: 20-21°C
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 13 days
Food: Pelleted Purina Rabbit Chow #5326
Water: Filtered tap water was supplied ad-libitum by an automatic water dispensing system.
Contaminants: There were no known contaminants reasonably expected to be found in the food or water at levels which would have interfered with the results of this study. Analyses of the food and water are conducted at least once a year and the records are kept on file at Product Safety Laboratories.


Cage: Each cage was identified with a cage card indicating at least the study number and identification and sex of the animal.
Animal: A number was allocated to each rabbit on receipt and a stainless steel ear tag bearing this number was attached to the animal. This number constituted unique identification.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

water

Controls:

no

Amount / concentration applied:

Prior to application, the test substance was moistened with distilled water to achieve a dry paste by preparing a 60% w/w mixture. Five-tenths of a gram of the test substance (0.83 g of the test mixture) was placed on a 1 inch x 1 inch, 4-ply gauze pad and applied to one 6 cm2 intact dose site on each animal. The pad and entire trunk of each animal were then wrapped with semi-occlusive 3 inch Micropore tape to avoid dislocation of the pad. Elizabethan collars were placed on each rabbit and they were returned to their designated cages.

Duration of treatment / exposure:

4 hours

Observation period:

1, 24, 48, and 72 hours after patch removal.

Number of animals:

3 (1 male, 2 females)

Details on study design:

The resulting Primary Dermal frritation Index (PDII) ranges were used to describe the level of irritation.

The animals were observed for signs of gross toxicity and behavioral changes at least once daily during the test period. Observations included gross evaluation of skin and fur, eyes and mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

other: 1, 24, 48, 72 hrs

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hrs

Results 2

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 1 hr

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 3

Irritation parameter:

erythema score

Basis:

mean

Time point:

other: 24, 48, 72 hrs

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 4

Irritation parameter:

edema score

Basis:

mean

Time point:

other: 1, 24, 48, 72 hrs

Score:

0

Max. score:

4

Reversibility:

other: not applicable

Results 5

Irritation parameter:

primary dermal irritation index (PDII)

Basis:

mean

Time point:

other: 1, 24, 48, 72 hrs

Score:

0.3

Max. score:

4

Reversibility:

fully reversible

Remarks:

24 hrs

Irritant / corrosive response data:

All animals appeared active and healthy. Apart from the skin irritation noted, there were no other signs of gross toxicity, adverse pharmacologic effects or abnormal behavior.

One hour after patch removal, very slight erythema was noted for all three treated sites. All animals were free from dermal irritation within 24 hours.

The Primary Dermal irritation Index for Ametryn Technical is 0.3.

Applicant's summary and conclusion

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU