Mecoprop

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Study period:

04 August 1986 to 30 September 1986

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1986

Report date:

1986

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

1

Reference substance name:

Mecoprop

EC Number:

230-386-8

EC Name:

Mecoprop

Cas Number:

7085-19-0

Molecular formula:

C10H11ClO3

IUPAC Name:

2-(4-chloro-2-methylphenoxy)propanoic acid

Test material form:

solid: particulate/powder

Details on test material:

- Storage conditions: At room temperature.

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Approximately 8 - 9 weeks.
- Weight at study initiation (mean ± s.d.): Male: 284 ± 19.8 g, female: 189 ± 14.2 g.
- Housing: Animals were housed in groups of five (test groups 1 and 2 and the male rats animal number 1 - 5 of the test group 3); from day 2 onward the male animals, animal number 6 - 10 of the test group 3 were housed singly (indications of not substance related aggressivity) in cages type D III of Becker, without bedding.
- Diet: Ad libitum during the post-exposure observation period
- Water: Ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 24 °C
- Humidity: 30 to 70 % relative humidity
- Photoperiod: 12 hours light/ 12 hours dark

Administration / exposure

Route of administration:

inhalation: dust

Type of inhalation exposure:

nose/head only

Vehicle:

other: The test material was milled and mixed with 1 wt % of Aerosil to achieve a more uniform dust concentration in air.

Mass median aerodynamic diameter (MMAD):

5.6 µm

Geometric standard deviation (GSD):

2.3

Remark on MMAD/GSD:

Test group 1

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Head-nose inhalation system INA 20 (glass-steel construction, BASF. Aktiengesellschaft, volume V ~ 55 1) : the animals were restrained in tubes and their snouts projected into the inhalation chamber.
-Generation on inhalation atmosphere: A dust air mixture was generated by means of a vibration dust partitioning equipment (BASF). The test material was milled and mixed with 1 wt % of Aerosil in order to achieve a more uniform dust concentration in air. The concentration was adjusted by varying the apertural width and by varying the amplitude of oscillations of the metering beaker.
- The following air flows were set: 1500 l/h compressed air through the injector and 1500 l/h conditioned air as dilution air. The supply air was conditioned via a central air-conditioning system in such a way that there was a temperature of 19 - 25 °c in the exposure apparatus. Deviations from this specification which would have had any adverse effect on the results of the study did not occur.
-The inhalation mixture was offered to the animals for inhalation for 4 hours.
-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 material and air was not diluted with laboratory air in the breathing zones of the animals.

TEST ATMOSPHERE
- Nominal concentration: The nominal concentration was calculated from the amount of test material -1 wt % excipient and the air flow.
- Sampling apparatus:
Vacuum compressed air pump: (Millipore) XX 60 220 50
Filtration equipment with probe (Millipore) (internal diameter: 4 mm)
Filter: MN 85/90 Bf (d = 4.7 cm)
Sampling velocity: 1.25 m/s
Sampling amount: 11 - 21
Sampling position: immediately adjacent to the animals’ noses
Sampling frequency: 1 sample about hourly for test group 3, and 1 sample about every 30 minutes for the test groups 1 and 2.
- Analytical determination method: Gravimetric determination of the inhalation atmosphere concentration
Equipment: balance: Mettler HL 52
The 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.

- Particle size analysis:
Equipment:
- Andersen Stack Sampler Hark III
- Millipore Vacuum Compressed Air Pump XX 60 220 50
- Sampling probe (internal diameter 6.9 mm)
- Stopwatch
Procedure:
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, the 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 one sample (3 - 9 L) was taken. The impactor was taken apart, 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.


RESULTS OF ANALYTICAL MEASUREMENTS
Concentration measurements: Each individual sample was analysed. The following are summaries of the results per group:
-Test group 1:
Mean uncorrected: 12.6 mg/L
Mean corrected for excipient: 12.5 mg/L
Standard deviation of the mean: ± 2.32 mg/L
Nominal concentration: 42.9 mg/L

-Test group 2:
Mean uncorrected: 9.6 mg/L
Mean corrected for excipient: 9.5 mg/L
Standard deviation of the mean: ± 1.27 mg/L
Nominal concentration: 28.0 mg/L

-Test group 3:
Mean uncorrected: 5.5 mg/L
Mean corrected for excipient: 5.4 mg/L
Standard deviation of the mean: ± 1.36 mg/L
Nominal concentration: 10.5 mg/L


RESULTS OF PARTICLE SIZE ANALYSES
- Test group 1:
MMAD 50%: 5.6 µm (geometric standard deviation = 2.3)
Respirable dust fraction that might reach alveoli of: 83 %.

- Test group 2:
MMAD 50%: 6.2 µm (geometric standard deviation = 2.3)
Respirable dust fraction that might reach alveoli of: 77 %.

- Test group 3:
MMAD 50%: 4.1 µm (geometric standard deviation = 2.3)
Respirable dust fraction that might reach alveoli of: 91 %.

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

5.4, 9.5 and 12.5 mg/L.
The selection of the concentration for test group 3 was based on the limit test, OECD Test Guidelin 403. The other concentrations were selected in order to achieve an estimation of the LD50.

No. of animals per sex per dose:

10 animals per sex per dose

Control animals:

not specified

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 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 surviving animals were sacrificed with CO2 and were subjected to gross-pathological examination like all other animals which had died before. To clarify the gross pathological findings selected organs of individual animals were examined histopathologically.

Statistics:

The statistical evaluation of the test was carried out in accordance with a probit analysis of D.J. Finney (0.J. Finney; Probit Analysis 1971, pp. 1 - 150. Published by the Syndics of the Cambridge University Press, Bentley House, 200 Euston Road, London N.W.1.).
The particle size was determined in the Department of Toxicology of BASF Aktiengesellschaft on the basis of mathematical methods for evaluating particle measurements (Silverman, L.: Particle Size Analysis in Industrial Hygiene, 1971, pp. 235 - 259).

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 12.5 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Remarks on result:

other: maximum achievable concentration tested.

Mortality:

Test group 1 (12.5 mg/L): 5/20 animals had died by day 14.
Test group 2 (9.5 mg/L): 4/20 animals had died by day 14.
Test group 3 (5.4 mg/L): 3/20 animals had died by day 14.

Clinical signs:

irregular respiration

Body weight:

A significant retarded body weight gain of female and male rats of all test groups compared with a historical control collective was observed.

Gross pathology:

Animals that died spontaneously (males and females):
5.4 mg/L: General congestion, Lung - slight oedematisation.
9.5 mg/L: General congestion
12.5 mg/L: Lung: some slightly sunken darker areas, with irregular margins.

Sacrificed animals (males and females):
- Organs: No abnormalities detected.
- Microscopic findings: 12.5 mg/L: One male animal that died - Beginning focal Bronchopneumonia.

Any other information on results incl. tables

Clinical Signs

- During exposure: single attempts to escape; irregular to jerky respiration; reddish nasal discharge (blood test positive).

- After exposure: irregular to jerky respiration; sounds of respiration; unsteady gait: noses partly with reddish smear or encrustations; reduced state of health: apathy; some male rats showed aggressivity (only test group 3).

- As of day 7 of the observation period, for the test group 1 and 3: day 12 for the test group 2 no abnormalities were detected in the animals.

 

Mortality in the Study

Cumulated Lethality on Day	Test Group (Concentration)
	1 (12.5 mg/L)		2 (9.5 mg/L)		3 (5.4 mg/L)
	M	F	M	F	M	F
0	2/10	0/10	2/10	2/10	2/10	1/10
1	3/10	2/10	-	-	-	-
2	-	-	-	-	-	-
7	-	-	-	-	-	-
14	-	-	-	-	-	-
Total at end of the study	5/20		4/20		3/20

M = Male, F = female

- = Lethality unchanged

0 = Day of exposure

 

Body Weight

Mean Body Weight		Before the Study		After 7 Days		After 14 Days
		Male	Female	Male	Female	Male	Female
Test group 1	Weight in g	300	203	313	213	337	217
	No. of animals	10	10	7	8	7	8
Test group 2	Weight in g	261	177	268	184	304	196
	No. of animals	10	10	8	8	8	8
Test group 3	Weight in g	292	187	291	195	328	206
	No. of animals	10	10	8	9	8	9
Historical (air) control	Weight in g	248	177	285	196	317	210

 

Applicant's summary and conclusion

Interpretation of results:

other: Not classified according to EU criteria

Conclusions:

Under the conditions of this study, the acute inhalation LC50 (4 h) of the test material was found to be >12.5 mg/L.

Executive summary:

The acute inhalation toxicity of the test material was investigated in a study design based on the OECD 403 guideline. The study was conducted under with GLP conditions.

10 male and 10 female Wistar rats per group were exposed to concentrations of 5.4, 9.5 and 12.5 mg/L of the active ingredient for a period of 4 hours.

During the exposure the following clinical signs were observed: single attempts to escape, irregular to jerky respiration, reddish nasal discharge. After the exposure irregular to jerky respiration, sounds of respiration, unsteady gait, noses partly with reddish smear or encrustations, reduced state of health and apathy were observed. In animals that died during the exposure period general congestion, slight oedematisation and some slightly sunken darker areas at the lung were found. In sacrificed animals no abnormalities were observed.

Under the conditions of this study, the acute inhalation LC50 (4 h) of the test material was found to be >12.5 mg/L.