O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

26 October 2005 to 16 November 2005

Reliability:

1 (reliable without restriction)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 425 (Acute Oral Toxicity: Up-and-Down Procedure)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

up-and-down procedure

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate

EC Number:

255-255-2

EC Name:

O-(4-bromo-2-chlorophenyl) O-ethyl S-propyl phosphorothioate

Cas Number:

41198-08-7

Molecular formula:

C11H15BrClO3PS

IUPAC Name:

4-bromo-2-chlorophenyl ethyl (propylsulfanyl)phosphonate

Test material form:

liquid

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

female

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

unchanged (no vehicle)

Doses:

350, 1100 mg/kg

No. of animals per sex per dose:

5/gp

Control animals:

no

Results and discussion

Effect levels

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 620.5 mg/kg bw

Based on:

test mat.

95% CL:

ca. 350 - ca. 1 100

Any other information on results incl. tables

Individual bodyweights/weight gains and mortality are presented in Table 1, Individual cage-side observations and necropsy observations are presented in Tables 2 and 3, respectively.

 

350 mg/kg (3 animals)

All animals survived, appeared active and healthy and gained body weight over the 14-day observation period. There were no signs of gross toxicity, adverse pharmacologic effect or abnormal behavior. No gross abnormalities were noted for either animal when necropsied following the 14-day observation period.

 

1,100 mg/kg (3 animals)

All animals died within two days of test substance administration. Toxic signs noted prior to death included ocular discharge, hypoactivity, abnormal posture, piloerection, ano-genital staining and a reduced fecal volume. Gross necropsy of the decedents revealed discoloration of the intestines.

 

Table 7.2.1 -2: Individual body weights/weight gains doses and mortalities

Animal No.	Sex	Dose Level (mg/kg)	Body Weight (g)					Dose (mL)	Mortality
			Day 0 Weight	Day 7 Weight	Gain*	Day 14 Weight	Gain*		Day	Weight (g)
6099	F	350	200	218	18	247	47	0.048	E	-
6220	F		215	227	12	249	34	0.052	E	-
6372	F		223	234	11	282	59	0.054	E	-
6108	F	1,100	185	-	-	-	-	-	1	176
6261	F		219	-	-	-	-	0.16	2	201
6384	F		225	-	-	-	-	0.17	1	219

 

Table 7.2.1 -3: Individual cage side observations

Animal Number	Findings	Day of Occurrence
350 mg/kg
6099	Active and healthy	0-14
6220
6372
1100 mg/kg
6108	Active and healthy Hypoactive Ocular discharge (clear), hunched posture Dead	0 (1 hr) 0 (3-6 hrs) 0 (6 hrs) 1
6261	Active and healthy Hypoactive Ano-genital staining, reduced faecal volume Prone posture Dead	0 (1 hr) 0 (3 hrs)-1 1   1 2
6384	Active and healthy Hypoactive Hunched posture, piloerection) Dead	0 (1 hr) 0 (3-7 hrs) 0 (7 hrs) 1

 

Table 7.2.1 -4: Individual necropsy observations

Animal Number	Tissue	Findings
350 mg/kg
6099, 6220, 6372	All tissues and organs	No gross abnormalities
1100 mg/kg
6108, 6261, 6384	Intestines	Red

 

Applicant's summary and conclusion

Conclusions:

Under the conditions of this study, the acute oral LD50 of Profenofos Technical is estimated to be 620.5 mg/kg of body weight in female rats with an approximate 95% Confidence Interval of 350 mg/kg (lower) to 1,100 mg/kg (upper).

Executive summary:

An acute oral toxicity test (Up and Down Procedure) was conducted with rats to determine the potential for Profenofos Technical to produce toxicity from a single dose via the oral route.

 

Based on an estimate of the LD50 supplied by the Sponsor (1,100 mg/kg), an initial dose of 350 mg/kg was administered to one healthy female rat by oral gavage. Following the Up and Down procedure, five additional females were tested at levels of 350 or 1,100 mg/kg. Females were selected for the test because they are frequently more sensitive to the toxicity of test compounds than males. All animals were observed for mortality, signs of gross toxicity, and behavioral changes at least once daily for 14 days after dosing or until death occurred. Body weights were recorded prior to administration and again on Days 7 and 14 (termination) following dosing or after death. Necropsies were performed on all animals.

 

Under the conditions of this study, the acute oral LD₅₀ of Profenofos Technical is estimated to be 620.5 mg/kg of body weight in female rats with an approximate 95% Confidence Interval of 350 mg/kg (lower) to 1,100 mg/kg (upper).