Prometryn

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 Aug 2004 to 18 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 402 (Acute Dermal Toxicity)

Version / remarks:

1997

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: JMAFF 59 NohSan No. 4200

Version / remarks:

January 28, 1985

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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:

rat

Strain:

Sprague-Dawley

Remarks:

albino

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: 9-10 weeks
- Weight at study initiation: 282-336 grams (males), 201-225 grams (females)
- 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: Rodent Chow
- Water: Filtered tap water was supplied ad libitum by an automatic water dispensing system
- Acclimation period: 15 days

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

IN-LIFE DATES: From: 4 Aug 2004 To: 18 Aug 2004

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Remarks:

moistened with distilled water to achieve a dry paste

Details on dermal exposure:

PREPARATION AND SELECTION OF ANIMALS
On the day prior to application, a group of animals was prepared by clipping the dorsal area and the trunk. After clipping and prior to application, the animals were examined for health, weighed (initial) and the skin checked for any abnormalities. Ten healthy rats (five males and five females) 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. The test substance was then applied to a 2 inch x 3 inch, 4-ply gauze pad and placed on a dose area of approximately 2 inches x 3 inches (approximately 10% of the body surface). The gauze pad and entire trunk of each animal were then wrapped with 3-inch Durapore tape to avoid dislocation of the pad and to minimize loss of the test substance. The rats were then returned to their designated cages. The day of application was considered Day 0 of the study. After 24 hours of exposure to the test substance, the pads were removed and the test sites were gently cleansed of any residual test substance.

Duration of exposure:

24 hours

Doses:

2000 mg/kg bw

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Body weights: Individual body weights of the animals were recorded prior to test substance application (initial) and again on Days 7 and 14 (termination).
- Cage-side observations: The animals were observed for mortality, signs of gross toxicity, and behavioural changes during the first several hours after application and at least once daily thereafter for 14 days. 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.
- Necropsy of survivors performed: yes, all rats were euthanized via CO2 inhalation on Day 14. Gross necropsies were performed on all animals. Tissues and organs of the thoracic and abdominal cavities were examined.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived the study.

Clinical signs:

other: All animals appeared active an healthy during the study. There were no signs of gross toxicity, adverse pharmacologic effects or abnormal behaviour.

Gross pathology:

No gross abnormalities were noted for any of the animals when necrosied at the conclusion of the 14-day observation period.

Other findings:

There were no signs of dermal irritation.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study (OECD 402, GLP), the single dose acute dermal LD50 of the test substance is greater than 2000 mg/kg of body weight in male and female rats.

Executive summary:

An acute dermal toxicity test was conducted with rats according to GLP and OECD guideline 402, to determine the potential acute toxicity resulting from a single topical application. Two thousand milligrams per kilogram of body weight of the test substance was moistened with distilled water and applied under semi-occlusive conditions to the skin of ten healthy rats for 24 hours. The animals were observed for mortality, signs of gross toxicity, and behavioural changes at least once daily for 14 days. Body weights were recorded prior to application and again on Days 7 and 14 (termination). Necropsies were performed on all animals at terminal sacrifice. All animals survived, gained body weight and appeared active and healthy during the study. There were no signs of gross toxicity, dermal irritation, adverse pharmacologic effects or abnormal behaviour. No gross abnormalities were noted for any of the animals when examined at the conclusion of the 14-day observation period.

Under the conditions of this study, the single dose acute dermal LD50 of the test substance was greater than 2000 mg/kg of body weight in male and female rats.