Prometryn

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

4 Aug 2004 to 25 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 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Version / remarks:

December 2001

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Version / remarks:

December 2002

Test guideline 3

Qualifier:

according to guideline

Guideline:

other: JMAFF 59 NohSan No. 4200

Version / remarks:

January 28, 1985

GLP compliance:

yes

Test type:

up-and-down procedure

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:

derived, albino

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Females nulliparous and non-pregnant: yes
- Age at study initiation: Yound adult (11-12 weeks)
- Weight at study initiation: 197-222 grams
- Fasting period before study: overnight
- Housing: The animals were single 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: 22-29 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 to 24
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 4 Aug 2004 To: 25 Aug 2004

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

CMC (carboxymethyl cellulose)

Remarks:

1% w/w in distilled water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 25% w/w

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 of the animals were recorded prior to test substance administration (initial-Day 0) and again on Days 7 and 14 (termination) following dosing
- Cage-side observations: The animals were observed for mortality, sign of gross toxicity, and behavioural changes within the first several hours post-dosing and at least once daily thereafter for up to 14 days after dosing or until death occurred. 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 at the end of the 14-day observation period. 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:

female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

All animals survived study.

Clinical signs:

other: Following test substance administration, three of the five rats exhibited facial staining, piloerection and/or a reduced faecal volume but recovered by Day 3 and appeared active and healthy for the remainder of the 14-day observation period.

Gross pathology:

No gross abnormalties were noted.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Under the conditions of this study (OECD 425, GLP), the acute oral LD50 of the test material is greated than 2000 mg/kg bw in female rats.

Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with rats according to GLP and OECD guideline 425, to determine the acute toxicity resulting from a single dose via the oral route. An initial limit dose of 2000 mg of the test material per kg bw was administered to one healthy female rat by oral gavage. Due to the absence of mortality in this animal, four additional females were dosed in sequence at the same dose level. Since all of the animals survived, no additional animals were tested. 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 behavioural changes at least once daily for 14 days after dosing. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) after dosing. Necropsies were performed on all animals at terminal sacrifice. 

All animals survived and gained body weight during the study. Following test material administration, three of the five rats exhibited facial staining, piloerection and/or a reduced faecal volume but recovered by Day 3 and appeared active and healthy for the remainder of the 14-day observation period. 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 acute oral LD50 of the test material was greater than 2000 mg/kg bw in female rats.