Ametryn

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

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 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

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:

rat

Strain:

Sprague-Dawley

Sex:

female

Details on test animals or test system and environmental conditions:

Sex: Females, nulliparous and non-pregnant.
Species/Strain: Rat/Sprague-Dawley derived, albino.
Age/Body weight: Young adult (9-11 weeks)/172-233 grams at experimental start.
Source: Received from Ace Animals, Inc., Boyertown, PA on August 24 and September 7, 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: 19-25ºC
Photoperiod: 12-hour light/dark cycle
Acclimation Period: 7-20 days
Food: Purina Rodent Chow #5012
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 rat on receipt and a stainless steel ear tag bearing this number was attached to the rat. This number constituted unique identification.

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: solution of carboxymethylcellulose (CMC) in distilled water

Details on oral exposure:

The test substance was administered as a 23% w/w suspension in a 1% w/w solution of CMC in distilled water using a stainless steel ball-tipped gavage needle attached to an appropriate syringe. Following administration, each animal was returned to its designated cage. Feed was replaced approximately 3-4 hours after test substance administration.

The test substance was administered in sequence to the animals. The decision to proceed with the next animal was based on the survival of the previous animal following dosing. Dose progressions and stopping criteria were determined using a statistical program.

Doses:

430, 1,360 or 2,000 mg/kg.

No. of animals per sex per dose:

430 mg/kg (3 animals)
1,360 mg/kg (4 animals)
2,000 mg/kg (2 animals)

Control animals:

no

Details on study design:

Individual body weights of the animals were recorded prior to test substance administration (initial-Day 0) and again on Days 7 and 14 (termination) following dosing or after death.

The animals were observed for mortality, signs of gross toxicity, and behavioral changes within the first several hours post-dosing and at least once daily thereafter for up to14 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 behavior pattern. Particular attention was directed to observation of tremors, convulsions, salivation, diarrhea and coma.

Surviving rats were euthanized via CO2 inhalation at the end of the 14-day observation period. Gross necropsies were performed on all decedents and euthanized animals. Tissues and organs of the thoracic and abdominal cavities were examined.

Statistics:

The Acute Oral Toxicity (Guideline 425) Statistical Program (Weststat, version 1.0, May 2001) was used for all data analyses including: dose progression selections, stopping criteria determinations and/or LD50 and confidence limit calculations.

Results and discussion

Preliminary study:

not applicable

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

1 360 mg/kg bw

95% CL:

716 - 2 140

Mortality:

see remarks on results

Clinical signs:

other: see remarks on results

Gross pathology:

see remarks on results

Other findings:

see remarks on results

Any other information on results incl. tables

430 mg/kg (3 animals)

All animals survived and gained body weight over the 14-day observation period. Following test substance administration, all three animals were hypoactive or exhibited reduced fecal volume. However, all recovered by Day 3 and appeared active and healthy for the remainder of the study. No gross abnormalities were noted for any of the animals when necropsied following the 14-day observation period.

 

1,360 mg/kg (4 animals)

Two animals died within one day of test substance administration. Toxic signs noted prior to death included hypoactivity, hunched posture and piloerection. The two surviving rats exhibited clinical signs including hypoactivity, hunched posture and a reduced fecal volume, but recovered by Day 3 and appeared active and healthy for the remainder of the study. Both survivors gained body weight over the 14-day observation period. Gross necropsy of the decedents revealed discoloration of the intestines and/or liver. No gross abnormalities were noted for either of the euthanized animals necropsied following the 14-day observation period.

 

2,000 mg/kg (2 animals)

Both animals died within one day of test substance administration. Toxic signs noted prior to death included hypoactivity, hunched posture and facial staining. Gross necropsy of the decedents revealed discoloration of the intestines.

Applicant's summary and conclusion

Interpretation of results:

harmful

Remarks:

Migrated information Criteria used for interpretation of results: EU