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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
10 February 1992 - 9 March 1992
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1992
Report date:
1992

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
EPA OPP 81-1 (Acute Oral Toxicity)
Version / remarks:
EPA Pesticide Assessment Guidelines, Subdivision F, Hazard Evaluation:Human and Domestic Animals 81-1 Acute oral toxicity study (November 1984)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
2-Ethylhexyl (R)-2-(2-methyl-4chlorophenoxy)propionate
EC Number:
630-324-3
Cas Number:
861229-15-4
Molecular formula:
C18H27ClO3
IUPAC Name:
2-Ethylhexyl (R)-2-(2-methyl-4chlorophenoxy)propionate
Specific details on test material used for the study:
SOURCE OF TEST MATERIAL
- batch No.of test material: 5007
- sample No.:1505E
- Expiration date of the lot/batch: March 1993

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 4°C in the dark




Test animals

Species:
rat
Strain:
other: CD
Remarks:
of Sprague-Dawley origin (Hsd/Ola:Sprague-Dawley(CD))
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Harlan Olac Ltd., Bicester,Oxon,England
- Age at study initiation: 6 weeks
- Weight at study initiation: 140 to 160 g
- Fasting period before study: yes
- Housing: in groups of 5 rats of the same sex in metal cages with wire mesh floors
- Diet: ad libitum, Standard laboratory diet (Biosure LAD 1)
- Water: ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23°C
- Humidity (%): mean 58%
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12 hours/12 hours

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Doses:
Preliminary study 800 mg/kg bw
Main study: 1000, 1260, 1600 mg/kg bw
No. of animals per sex per dose:
Preliminary study: 2/sex/dose
Main study: 5/sex/dose
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
body weight: recorded on Day 1 (prior dosing), 8 and 15 or at death
animals were observed for clinical signs soon after dosing and at frequent intervals for the remainder of Day 1 and subsequent twice a day
- Macroscopic examination; macroscopic appearance of all examined tissues recorded

Statistics:
The acute median lethal oral dose (LD50) to rats was calculated using the method of Finney [FINNEY, D.J. (1971) Probit Analysis, 3rd ed., Cambridge University Press, Cambridge]. Separate LD50 values for males and females were estimated by undertaking probit analysis on the mortality data from the main study by fitting two parallel lines to the data (males only and females only) using the technique described by Finney [Finney, D.J. (1978) Statistical Method in Biological Assay, 3rd ed., Charles Griffin, London]. A chi-square test was carried out to check that the data did not contain any evidence of non-parallelism.

Results and discussion

Preliminary study:
The results of the preliminary study indicated that the acute lethal oral dose to rats of MCPP-p 2EHE was greater than 0.8 g/kg bw.
Effect levelsopen allclose all
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
1 400 mg/kg bw
Based on:
test mat.
95% CL:
1.2 - 1.6
Sex:
male
Dose descriptor:
LD50
Effect level:
1 300 mg/kg bw
Based on:
test mat.
95% CL:
1.1 - 1.6
Sex:
female
Dose descriptor:
LD50
Effect level:
1 400 mg/kg bw
Based on:
test mat.
95% CL:
1.2 - 1.9
Mortality:
There were deaths following a single dose of MCPP-P 2-EHE among rats of both sexes dosed at 1260 mg/kg bw and above. Death occurred at intervals from Day 2 until Day 5.
Clinical signs:
Piloerection was observed in all rats within 5 minutes of dosing and throughout the remainder of Day 1. This sign persisted and was accompanied on Day 1 and/or later intervals by: abnormal body carriage (hunched posture), lethargy, decreased respiratory rate, ptosis, pallor of the extremities and ataxia for all rats dosedat 1000, 1260 and 1600 mg/kg bw; abnormal gait (waddling) for all rats dosed at 1000 and 1260 mg/kg bw and one male and one female dosed at 1600 mg/kg bw, prostration for two females dosed at 1000 mg/kg bw, four males and one female dosed at 1260 mg/kg bw and three males and three females dosed at 1600 mg/kg/bw. Recovery of surviving rats, as judged by external appearance and behavior, was complete by Day 4 (1260 mg/kg bw), Day 3 or 5 (1000 mg/kg bw) or Day 4 or 7 (1600 mg/kg bw).
Body weight:
Small bodyweight gains were recorded on Day 8 for one male and one female dosed at 1600 mg/kg bw and one female dosed at 1000 mg/kg bw. All other surviving rats achieved satisfactory bodyweight gains throughout the study.
Gross pathology:
No macroscopic abnormality was observed for animals killed on Day 15.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
The oral LD50 for MCPP-P 2-EHE was 1400 mg/kg bw.
Executive summary:

A GLP study according EPA Pesticide Assessment Guidelines, 81-1 acute oral toxicity (Revised Edition November 1984) on rats was performed to assess the acute oral toxicity of MCPP-P 2-EHE. Groups of 10 fasted rats (5 male/5 female) were administered a single oral dose by gavage of the test substance, as supplied, at dose levels of 1000, 1260 and 1600 mg/kg bw. There were deaths among male and female rats dosed at 1260 mg/kg bw and above from Day 2 until Day 5. Clinical signs of reaction to treatment included pilo-erection, abnormal body carriage (hunted posture), abnormal gait (waddling), lethargy, decreased respiratory rate, ptosis, pallor of the extremities, ataxia and prostration. Recovery of surviving rats, as judged by external appearance and behavior, was complete by Day 4 (1260 mg/kg bw), Day 3 or 5 (1000 mg/kg bw) or day 4 to 7 (1600 mg/kg bw). Small bodyweight gains were recorded on Day 8 for one male and one female dosed at 1600 mg/kg bw and one female dosed at 1000 mg/kg bw. All other surviving animals achieved satisfactory bodyweight gains throughout the study. No abnormalities were recorded at macroscopic examination at the end of the study. The LD50 (males/females) was 1400 mg/kg bw.