kresoxim-methyl (ISO);methyl (E)-2-methoxyimino-[2-(o-tolyloxymethyl)phenyl]acetate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

other information

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: guideline study (only two dose levels)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

Remarks:

2 dose levels

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

methyl (2E)-2-methoxyimino-2-[2-[(2-methylphenoxy)methyl]phenyl]acetate

EC Number:

604-351-6

Cas Number:

143390-89-0

Molecular formula:

C18 H19 N O4

IUPAC Name:

methyl (2E)-2-methoxyimino-2-[2-[(2-methylphenoxy)methyl]phenyl]acetate

Details on test material:

- Name of test material (as cited in study report): Reg. No. 242 009 (test substance number: 91/180)
- Lot/batch No.: N 30 (= IIIa2); date of manufacturing: 1991-06-17
- Physical state: solid (powder) / light brown
- Storage condition of test material: room temperature, exclusion of light
- Physical state: solid (powder) / light brown
- Analytical purity: 96.6% (Reversed-Phase - HPLC with UV-Detection; certificate of analysis is available)
- Stability under test conditions: the storage stability was guaranteed over the study period
- Other: the homogeneity of the test substance was confirmed by analysis (Reversed-Phase - HPLC with UV-Detection)

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: CHBB: Thom (SPF); from Dr. K. Thomae GmbH, D-W7950 Biberach, FRG
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: animals of comparable weight (means of 278±10.6 for male and 197±4.9 for male animals).
- Fasting period before study: 16 hours, but water was available ad libitum
- Housing: singly in stainless steel wire mesh cages, Type DK-III (Becker & Co., Castrop-Rauxel, FRG)
- Diet (e.g. ad libitum): Kliba rat/mouse/hamster laboratory diet 24-343-4 10 mm pellets, Klingentalmuehle AG, CH-4303 Kaiseraugst, Switzerland
- Water: tap water (e.g. ad libitum only during the post exposure observation period)
- Acclimation period: at leat one week

ENVIRONMENTAL CONDITIONS
The animals were housed in fully air-conditioned rooms. There were no deviations from these ranges which influenced the results of the study.
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12/12 (6:00 - 18:00 / 18:00 - 6:00 hours)

Administration / exposure

Route of administration:

other: inhalation: dust aerosol

Type of inhalation exposure:

nose/head only

Vehicle:

other: see below

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 20 (glass-steel construction;BASF AG)
- Exposure chamber volume: 55 l
- Method of holding animals in test chamber: the animals were restrained in tubes and their snouts projected into the inhalation chamber.
- Source and rate of air: By means of an exhaust air system the pressure ratios in the inhalation system were adjusted in such a way that the amount of exhaust air was about 10% lower (excess pressure). This ensured that the mixture of test substance and air was not diluted with laboratory air in the breathing zones of the animals. The inhalation atmosphere was offered to the animals for inhalation for 4 hours. Air flow was adjusted to 1500 l/hour
- Method of conditioning air: The exposure system was placed in an air-conditioned laboratory.
- System of generating particulates/aerosols: the test substance was mixed with 1 (w/w)% of Aerosil in order to achieve a more uniform dust concentration in air. The aerosol was produced with dust generator [dosing-wheel dust generator (Gericke/BASF)] and compressed air [glass cyclonic separator (BASF)]. A cyclonic separator was connected downstream with the generator. The concentration was adjusted by varying the rotation of the metering disc.
- Method of particle size determination: 30 minutes after the beginning of the test at the earliest, one sample was taken per test group for the particle size analysis. Before the sampling, an impactor was equipped with glass-fiber collecting discs and a backup particle filter. The impactor was connected to the pump and the test apparatus, and the samples (9 - 24 l) were taken. The impactor was taken apart and the collecting discs and the backup particle filter were weighed. The contents of the pre-impactor as well as the amounts of the material adsorbed on the walls of the impactor and in the sampling probe (wall losses) were also determined quantitatively.
- Treatment of exhaust air: not specified
- Temperature, humidity, pressure in air chamber: The humidity in the inhalation systems were not measured due to technical reasons. It is assumed that deviations of humidity values from the guideline requirements (especially low humidity in dust aerosol) did not influence the test results because of the relative short exposure time. The temperatures in the inhalation systems were measured continuously and recorded once. Only deviations from the temperature range (22±2°C) of the OECD Guideline will be reported in the result section.

TEST ATMOSPHERE
- Brief description of analytical method used: A pre-weighed filter was placed into the filtration equipment. By means of a vacuum compressed air pump a volume of the dust aerosol was drawn through the filter. The dust concentration in mg/l was calculated from the difference between the pre-weight of the filter and the weight of the filter after sampling, with reference to the sample volume of the inhalation atmosphere. The concentrations were corrected for the amount of the added excipient.
- Samples taken from breathing zone: yes; immediately adjacent to the animals noses

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: the generated aerosols were well inhalable
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 1.8 / 2.4 µm

Analytical verification of test atmosphere concentrations:

yes

Remarks:

see above (the nominal concentration was calculated from the amount of substance consumed and the air flow.)

Duration of exposure:

4 h

Concentrations:

2.04 and 5.6 mg/l (analytical concentrations)

No. of animals per sex per dose:

5

Control animals:

other: historical air control data included

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: the body weight of the animals was checked before the beginning of the test, after 7 days and at the end of the observation period. Clinical findings were recorded for each animal separately several times during exposure and at least once on each workday in the observation period. A check for dead animals was made daily.
- Necropsy of survivors performed: yes, at the end of the 14-day observation period the animals were sacrificed with CO2 and were subjected to gross-pathological examination.

Statistics:

The statistical evaluation of the dose-response relationship was carried out using FORTRAN program AKPROZ: Depending on the data of the dose-response relationship obtained by way of experiment, this program is used to estimate the LC50 or to perform a Probit analysis. Estimation of the LC50 will produce 3 types of LC50 (LC50 greater, LC50 about, or LC50 smaller). If the results are Type LC50 greater or LC50 smaller, an additional binominal test is carried out, in order to verify these statements statistically, if necessary.
The calculation of the particle size distribution was carried out in the Department of Toxicology of BASF AG on the basis of mathematical methods for evaluating particle measurements.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 5.6 mg/L air (analytical)

Exp. duration:

4 h

Remarks on result:

other: the statistical reliability is 99%; no deaths occurred but some clinical signs were observed on day 1 (see below).

Mortality:

no mortalities were observed

Clinical signs:

other: - In the low concentration clinical examination revealed attempts to escape, accelerated and intermittent respiration, urine smeared fur and fur contamination in all, as well as reddish nose and eye discharge and reddish eyelid crusts in single male anima

Body weight:

Body weight gain was not affected in both concentrations during the whole post-exposure period (see Table 1).

Gross pathology:

During necropsy no macroscopic pathologic findings were noted.

Any other information on results incl. tables

Table 1: Body weight development
 

Treatment group (mg/l)	Mean body weight (g) after
	0 day		7 days		14 days
	Males	Females	Males	Females	Males	Females
2.04	271	194	307	206	334	215
5.6	285	200	309	211	347	225
Historical air control weight	248	177	286	196	318	211