Chlorpyrifos

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2015

Report date:

2015

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF Acute Oral Toxicity 2-1-1

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Chlorpyrifos

EC Number:

220-864-4

EC Name:

Chlorpyrifos

Cas Number:

2921-88-2

Molecular formula:

C9H11Cl3NO3PS

IUPAC Name:

O,O-diethyl O-3,5,6-trichloropyridin-2-yl phosphorothioate

Test material form:

solid

Specific details on test material used for the study:

Substance ID: TSN308540
Batch #: 2K04161692
Purity: 98.0%

Test animals

Species:

rat

Strain:

Wistar

Remarks:

RCCHan:WIST

Sex:

female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Animal Breeding Facility, Jai Research Foundation
- Females nulliparous and non-pregnant: Yes
- Age at study initiation: 10 to 11 weeks
- Weight at study initiation: 183.1 to 215.5 g
- Fasting period before study: Yes, overnight
- Housing: Three rats/cage (Solid bottomed, polypropylene rat cages covered with stainless steel grid tops were used)
- Diet: ad libitum (with the exception of overnight fasting prior to dosing and three hours post-dosing)
- Water: ad libitum
- Acclimation period: 6 to 13 days

ENVIRONMENTAL CONDITIONS
- Temperature: 20 to 23 °C
- Humidity: 65 to 67%
- Air changes: Minimum 15/hour
- Photoperiod: 12 hrs dark/ 12 hrs light

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

corn oil

Details on oral exposure:

The test item was solid so it was mixed in corn oil and the dose concentration (200, 30 and 5 mg/mL) was adjusted according to the body weight to permit constant dose volume (10 mL/kg body weight). Individual dose volume was adjusted according to body weight. All rats were dosed by gavage (day 0) using a metal cannula attached to a 1 mL disposable syringe which was graduated up to 1 mL.

Doses:

Set I: 2000 mg/kg
Set II: 300 mg/kg
Set III & IV: 50 mg/kg

No. of animals per sex per dose:

3 females per set

Control animals:

no

Details on study design:

- Duration of observation period following administration: The rats from set I, II, III and set IV were observed for signs of toxicity and mortality at 0.5, 1, 2, 3, 4 and 6 hours post-administration on the day of dosing. Subsequently, the rats were observed twice a day for morbidity and mortality for a period of 14 days following oral dosing.
- Frequency of observations and weighing: Individual body weight was recorded prior to dosing on day 0 and after dosing, on days 7 and 14 and at death.
- Necropsy of survivors performed: Yes

Results and discussion

Effect levels

Key result

Sex:

female

Dose descriptor:

LD50

Effect level:

200 mg/kg bw

Based on:

test mat.

Mortality:

All animals treated with 2000 and 300 mg/kg body weight were found dead. No mortality was observed in rats with 50 mg/kg body weight.

Clinical signs:

other: Clinical signs like lethargy, tremors, abdominal breathing and chromodacryorrhea were observed in rats at dose levels of 2000 and 300 mg/kg body weight. No signs of toxicity were observed in rats at the dose level of 50 mg/kg body weight.

Gross pathology:

External: External examination did not reveal any abnormality of pathological significance in any animal treated at 2000, 300 and 50 mg/kg body weight.
Internal: Visceral examination of animals found dead revealed liver congestion (Animal N° 1, 2, 3, 4, 5 and 6) and lung congestion (Animal N° 2, 3 and 5) respectively whereas the terminally sacrificed animals did not reveal any lesion. Lesions observed in the rats found dead could be correlated with the test item used in the present study.

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

Oral LD50 (Female Rat): 200 mg/Kg body weight

Executive summary:

The acute oral toxicity study was performed according to the acute toxic class method (OECD 423, OCSPP 870.1100, EC B.1 and JMAFF 2-1-1). The test substance was administered to fasted Wistar rats at dose levels of 2000 (for set I), 300 (for set II) and 50 (III and IV) mg/kg body weight. Observations included daily clinical signs and weekly body weight recordings over a 14 day observation period. Necropsy examination was performed in all animals.

Rats from set I and II were given a single dose of 2000 and 300 mg/kg body weight, respectively. Clinical signs like lethargy, tremors, abdominal breathing and chromodacryorrhea were observed after dosing and all animals were found dead. Visceral examination revealed congestion of the liver and lungs with no external abnormalities.

Hence, another two sets (set III and IV) of fasted Wistar rats (3 females per set) were given a single oral dose of the test substance at 50 mg/kg body weight.

No signs of toxicity, including clinical signs and body weight, were observed in any rat treated at the dose level of 50 mg/kg body weight during the whole observation period.

External and visceral examination of the terminally sacrificed rats did not reveal any lesion of pathological significance.

The acute oral median lethal dose (LD50 cut-off value) of the test substance in Wistar rats was found to be 200 mg/kg body weight.