Prometryn

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

10 Aug 2004 to 13 Aug 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

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)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.2500 (Acute Dermal Irritation)

Version / remarks:

1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: JMAFF 59 NohSan No. 4200

Version / remarks:

January 29, 1985

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Prometryn

EC Number:

230-711-3

EC Name:

Prometryn

Cas Number:

7287-19-6

Molecular formula:

C10H19N5S

IUPAC Name:

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

Test material form:

solid: particulate/powder

Test animals

Species:

rabbit

Strain:

New Zealand White

Remarks:

albino

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: young adult
- Housing: The animals were singly housed in suspended stainless steel caging with mesh floors which conform to the size recommendations in the most recent Guide for the Care and Use of Laboratory Animals DHEW (NIH). Litter paper was placed beneath the cage and was changed at least three times per week.
- Diet: Pelleted Rabbit Chow
Water: Filtered tap water was supplied ad-libitum by an automatic water dispensing system.
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 19-22
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 10 Aug 2004 To: 13 Aug 2004

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

not required

Amount / concentration applied:

Five-tenths of a gram of the test substance (1.11 g of the test mixture)

Duration of treatment / exposure:

4 hours

Observation period:

72 hours

Number of animals:

1 male and 2 females

Details on study design:

PREPARATION AND SELECTION OF ANIMALS
On the day before application, a group of animals was prepared by clipping the dorsal area and the trunk. On the day of dosing, but prior to application, the animals were examined for health and the skin checked for any abnormalities. Three healthy animals without pre-existing skin irritation were selected for test.

APPLICATION OF TEST SUBSTANCE
Prior to application, the test substance was moistened with distilled water to achieve a dry paste by preparing a 45% w/w mixture. Five-tenths of a gram of the test substance (1.11 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. After 4 hours of exposure to the test substance, the pads and collars were removed and the test sites were gently cleansed of any residual test substance.

EVALUATION OF TEST SITES
individual dose sites were scored according to the Draize scoring system (see Table 1 in 'Any other information on materials and methods incl. tables') at approximately 1, 24, 48, and 72 hours after patch removal.

CAGE SIDE OBSERVATIONS
The animals were observed for signs of gross toxicity and behavioural 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 behaviour pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhoea and coma.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Results 2

Irritation parameter:

edema score

Basis:

animal: #1, #2, #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

One hour after patch removal, very slight erythema was noted for all three treated sites. The overall incidence and severity of irritation decreased with time. All animals were free from dermal irritation within 24 hours.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of the study (OECD 404, GLP), the mean erythema and oedema scores of all three animals for the 24/48/72 hours time points were determined to be 0.

Executive summary:

A primary skin irritation test was conducted with rabbits, in accordance with GLP and OECD guideline 404, to determine the skin irritation potential of the substance after a single topical application. An aliquot of 0.5 g test substance was moistened with distilled water and applied to the skin of three healthy rabbits for 4 hours under semi-occlusive conditions. Following exposure, dermal irritation was evaluated by the method of Draize et al.

One hour after patch removal, very slight erythema was noted for all three treated sites. The overall incidence and severity of irritation decreased with time. All animals were free from dermal irritation within 24 hours. The mean erythema and oedema scores of all three animals for the time points after 24/48/72 hours were determined to be 0.

Under the conditions of this study, the substance was considered to be not irritating to the skin of rabbits.