Chlorpyrifos

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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:

1996

Report date:

1996

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-2 (Acute Dermal Toxicity)

Deviations:

no

Test guideline 3

Qualifier:

according to guideline

Guideline:

EU Method B.3 (Acute Toxicity (Dermal))

Deviations:

no

Test guideline 4

Qualifier:

according to guideline

Guideline:

other: JMAFF (Acute Dermal Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

standard acute 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: TSN100759
Lot #: 7299412
Purity: 97.6%

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Inc., Kalamazoo, Michigan
- Age at study initiation: 4 to 5 months
- Weight at study initiation: 2.184 to 2.649 kg
- Diet: 4 ounces per day
- Water: ad libitum
- Acclimation period: Atleast 2 weeks

ENVIRONMENTAL CONDITIONS
- Temperature: 19±3°C
- Humidity: 39 - 61%
- Air changes: 15 per hr
- Photoperiod: 12 hrs dark/12 hrs light

Administration / exposure

Type of coverage:

other: gauze patch was held in place by an elastic rabbit jacket

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 10 by 14 cm
- % coverage: 10% of the surface area of the rabbits
- Type of wrap if used: Gauze patch was held in place by an elastic rabbit jacket

REMOVAL OF TEST SUBSTANCE
- Washing: Skin was wiped thoroughly with a water moistened soft disposable towel and dried with a soft disposable towel
- Time after start of exposure: Approximately after 24-hour exposure period

TEST MATERIAL
- For solids, paste formed: Yes, melted to liquid

Duration of exposure:

24 hours

Doses:

2000 mg/kg, 5000 mg/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations and weighing: The rabbits were weighed prestudy, the day of treatment and on test days 2, 8 and 15
- Necropsy of survivors performed: yes

Statistics:

Means and standard deviations were calculated for body weights. The data were evaluated for statistical outliers by a sequential test (Grubbs, 1969), however, outliers were not routinely excluded from statistical analysis.

Results and discussion

Effect levels

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 5 000 mg/kg bw

Based on:

test mat.

Mortality:

None

Clinical signs:

other: Two males and one female administered 5000 mg/kg had fecal soiling in the perineal area on test days 1 or 2. Treatment-related dermal alterations at the application site consisted of erythema, edema, fissures and scaling in animals administered 5000 mg/kg

Gross pathology:

There were no treatment-related gross pathologic observations.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Dermal LD50 (Rabbit): >5000 mg/kg

Executive summary:

The test substance was evaluated for dermal toxicity according to the guidelines OECD 402 and EPA OPPTS 81-2. Five New Zealand White rabbits per sex per dose level received a single, 24-hour, dermal exposure of 2000 or 5000 mg/kg. Parameters evaluated included body weights, in-life observations and gross pathologic evaluation.

All rabbits administered 2000 or 5000 mg/kg (the limit test established by the guidelines) survived. No substantial weight change was observed during the two-week observation period.

Two males and one female administered 5000 mg/kg had fecal soiling in the perineal area on test days 1 or 2. Treatment-related dermal alterations at the application site consisted of erythema, edema, fissures and scaling in animals administered 5000 mg/kg; erythema and scaling were observed in animals administered 2000 mg/kg. All dermal alterations had resolved in all animals by the end of the 14-day observation period, with the exception of scaling that persisted at the application site of one female administered 5000 mg/kg. There were no treatment-related gross pathologic observations.

Under the conditions of this study, the acute dermal LD50 of the test substance was greater than 5000 mg/kg, the limit dose tested, for male and female New Zealand White rabbits.