mecoprop-P (ISO); (R)-2-(4-chloro-2-methylphenoxy)propionic acid

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 March 1994 to 29 April 1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1994

Report date:

1994

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-1 (Acute Oral Toxicity)

Version / remarks:

1984

Deviations:

no

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

(R)-2-(4-chloro-2-methylphenoxy)propionic acid

EC Number:

240-539-0

EC Name:

(R)-2-(4-chloro-2-methylphenoxy)propionic acid

Cas Number:

16484-77-8

Molecular formula:

C10H11ClO3

IUPAC Name:

(R)-2-(4-chloro-2-methylphenoxy)propionic acid

Test material form:

solid: particulate/powder

Remarks:

Beige powder

Details on test material:

- Storage conditions: The test material was stored in an air-tight, light-resistant container at room temperature.

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: 7 weeks old on arrival.
- Weight at study initiation: Selected animals were in a weight range from 306 to 365 g for the males and 185 to 226 g for the females on the day of treatment (i.e. within ± 20 % of the mean body weight).
- Fasting period before study: All animals were fasted overnight before test substance administration.
- Housing: Rats were housed individually in suspended stainless steel, wire mesh cages.
- Diet: Certified Rodent Pellet diet ad libitum.
- Water: Tap water from the municipal water supply, filtered and softened, ad libitum.
- Acclimation period: 13 days
- Method of randomisation in assigning animals to test and control groups: On the day before treatment, animals were assigned permanent identification numbers within groups using a randomisation procedure that ensures a similar body weight distribution among groups for each sex.

ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 2 °C
- Humidity: 55 ± 15 %
- Air changes: 15 air changes per hour (average, not monitored).
- Photoperiod: 12-hour light, 12-hour dark cycles.

IN-LIFE DATES:
From: 16 March 1994
To: 20 April 1994

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

other: 0.5 % methylcellulose in distilled water

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg

DOSAGE PREPARATION: The dosing formulation was prepared by suspending the test material in 0.5 % methylcellulose in distilled water to produce the required dosing concentration (w/w). The formulation was used as quickly as practicable after preparation.

Doses:

100, 180, 320 and 580 mg/kg

No. of animals per sex per dose:

5 animals per sex per dose

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: All animals were checked for clinical signs, moribundity and mortality approximately one hour after dosing and at least once more on Day 1. Thereafter, observed clinical signs were recorded at least once daily. The nature, onset, severity, reversibility and duration of clinical signs were recorded. Cages and cage-trays were inspected daily for evidence of ill-health, such as blood or loose faeces. In addition, animals were checked daily a second time for moribundity and mortality, except on weekends when they were checked once daily.
Each animal was weighed once during the acclimatisation period, on the day of test material administration then on Days 8 and 15.
- Necropsy of survivors performed: Yes. All animals were autopsied. At final sacrifice, surviving animals were anaesthetised by intraperitoneal injection of pentobarbital, then exsanguinated under deep anaesthesia before necropsy. Necropsy included macroscopic examination of abdominal and thoracic cavities, major organs and tissues. Significant macroscopic abnormalities were recorded.

Statistics:

LD50 values were calculated separately for each sex and for combined sexes from total mortality data using the method of Dragstedt-Lang.
For body weights and body weight gains, means and standard deviations were calculated.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

431 mg/kg bw

Based on:

test mat.

Mortality:

No deaths occurred at the 100, 180 and 320 mg/kg dose levels. All animals died at the 580 mg/kg dose level. All animals were found dead on Day 3 except one male which died on Day 8 and one female on Day 4.

Clinical signs:

other: There were no clinical signs in animals which received 100 mg/kg body weight. At 180 and 320 mg/kg, piloerection, reduced motor activity and hunched posture were observed on Days 1 and 2. From Day 3 all animals recovered and no clinical signs were observe

Gross pathology:

No treatment-related changes were observed at necropsy.

Any other information on results incl. tables

Mortality Levels

Dose Levels (mg/kg)	Number of Animals
	Males Dead / tested	Females Dead / tested	Combined Dead / tested
100	0 / 5	0 / 5	0 / 10
180	0 / 5	0 / 5	0 / 10
320	0 / 5	0 / 5	0 / 10
580	5 / 5	5 / 5	10 / 10

 

Applicant's summary and conclusion

Interpretation of results:

other: Classified according to EU criteria Category 4

Conclusions:

Under the conditions of this study, the acute oral LD50 of the test material was determined to be 431 mg/kg bw in male and female Sprague-Dawley rats.

Executive summary:

The potential for the test material to cause acute toxicity via the oral route was investigated in a study conducted in accordance with the standardised guidelines OECD 401 and US EPA OPP 81-1 and in compliance with GLP.

The acute oral toxicity was assessed after a single oral administration of the test material at 100, 180, 320 and 580 mg/kg body weight in groups of five male and five female Sprague Dawley rats. All animals were observed daily tor fifteen days and their body weight measured weekly. At termination of the study period or when found dead, animals were subjected to a necropsy.

No animal died at 100, 180 and 320 mg/kg body weight. All animals died at 580 mg/kg. No clinical signs were noted at 100 mg/kg body weight. At 180 and 320 mg/kg body weight, piloerection, hunched posture and reduced motor activity were observed only during Days 1 and 2. At 580 mg/kg body weight, piloerection, dyspnoea, prostration, absence of traction and of grasping reflex, muscular atony, reduced motor activity and unconsciousness were the major clinical signs observed before the death of the animals. The body weight evolution of the animals which survived the study period was unaffected by treatment. No treatment-related changes were observed at necropsy.

Under the conditions of this study, the acute oral LD50 of the test material was determined to be 431 mg/kg bw in male and female Sprague-Dawley rats.