Ametryn

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

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:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

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:

Name: Ametryn Tecimical (034162)
Source: Syngenta Crop Protection Inc.
Colour: White
Physical state: Powder
Batch reference number: FL041153
Purity (% w/w): 97.5%
Expiry date: August 2007

Test animals

Species:

rat

Strain:

other: Alpk:APfSD (Wistar-derived)

Sex:

male/female

Details on test animals or test system and environmental conditions:

Specification: Young adult (8-12 weeks)
Weight range at start of exposure: 442-488 g (males); 283-307 g (females)

The rats were housed 5 per cage, sexes separately, in multiple rat racks, which were suitable for animals of this strain and the weight range expected during the course of the study.
However, due to fighting the males were separated and housed singly from day 2 to the end of the study: Additional animals were housed 1 per cage, sexes separately.

The animal room was designed to give the environmental conditions shown as follows:
Temperature: 22±3°C
Relative humidity: 30-70%
Air: At least 15 changes/hour
Light cycle: Artificial giving 12 hours light, 12 hours dark

Both temperature and relative humidity were measured and recorded daily. The recorded values were within the specified ranges.
Diet (RM1) supplied by Special Diets Services Limited, Witham, Essex, UK and mains water, supplied by an automatic system were available ad libitum, except during exposure.
Each batch of diet is routinely analysed for composition and for the presence of contaminants. Water is also periodically analysed for the presence of contaminants.

Nylabones and cardboard tubes provided environmental enrichment during the study, except for during the exposure period. Paper in loose balls was supplied as nesting and bedding material.

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose only

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

The test atmosphere was generated using a Wrights dust fee& Clean, dry air (dried and filtered using equipment supplied by Atlas-Copco, Sweden) was passed through the dust feed at a nominal flow rate of 221/minute (at normal temperature and 20 psi) and carried the atmosphere to the exposure chamber, having an internal volume of 27.6 litres, in order to achieve a minimum of 12 air changes per hour. Since diluting air was not employed, the flow rate through the exposure chamber was the same as that employed in the generation of the test atmosphere. Air flows were monitored continuously and recorded at least 3 times using variable area flowmeters (KEG Flowmeters, Burgess Hill, Sussex, UK) and were altered as necessary to maintain the target concentration.

The particulate concentration of the test atmosphere, close to the animals breathing zone, was measured gravimetrically at least twice during exposure.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

2.22 mg/L (analytical concentration)

A maximum atmospheric concentration of 2 mg/L (corresponding to 2.22 mg/L of analytical concentration), as recommended by the EPA guidelines on toxicity testing was selected as the target exposure concentration

No. of animals per sex per dose:

5 males and 5 females, [plus 1/sex for trial exposure]

Control animals:

no

Details on study design:

Clinical observations
Prior to the start of the study, all rats were examined to ensure that they were physically normal and exhibited normal activity. During exposure, they were observed frequently arid, at the end of the 4-hour exposure period, each rat was given a detailed clinical examination. The animals were also subjected to detailed clinical observations, included the finding of no abnormalities detected, daily during the 14 day observation period.

Bodyweights
The bodyweight of each rat was recorded on day -1 (to ensure animals of one sex were within a similar weight range), 1, 8 and prior to termination on day 15.

Termination
All rats were killed by an over-dose of anesthetic (halothane Ph Eur vapour) followed by exsanguination.

Macroscopic examination
All animals were examined post mortem. This involved an external observation and a careful internal examination of all thoracic and abdominal viscera.

Statistics:

No data

Results and discussion

Preliminary study:

no data

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 2.22 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

There were no deaths daring the exposure or observation periods.

Clinical signs:

other: Observations during exposure: Abnormalities generally associated with restraint (wet fur and chromodacryorrhoea) were observed in all or sonic animals during exposure. Some animals were salivating during exposure. All animals had test substance around the

Body weight:

Most male and some female animals had gained weight by the end of the study.

Gross pathology:

There were no abnormalities detected at necropsy in any animal.

Other findings:

no data

Applicant's summary and conclusion

Interpretation of results:

not classified

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Not of concern at the highest tested concentration.