2-(3-Chloro-2-pyridinyl)-5-oxo-3-pyrazolidinecarboxylic acid ethyl ester

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Study period:

June 2006 - September 2006

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2006

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1200 (Acute Dermal Toxicity)

Version / remarks:

1998

Test guideline 2

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Version / remarks:

1987

Test guideline 3

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

GLP compliance:

yes

Remarks:

The in-life portion of the study was conducted without a signed protocol and was not inspected by Quality Assurance. A Short-Term Study Protocol Sheet (STSPS) and a testing SOP was followed. These deviations did not affect the validity of the study.

Test type:

standard acute method

Limit test:

yes

Test material

Test material information

Constituent 1

Reference substance name:

ethyl 2-(3-chloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate

EC Number:

610-490-3

Cas Number:

500011-88-1

Molecular formula:

C11H12ClN3O3

IUPAC Name:

ethyl 2-(3-chloropyridin-2-yl)-5-oxopyrazolidine-3-carboxylate

Test material form:

solid

Test animals

Species:

rat

Strain:

other: Crl:CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories, Raleigh, NC
- Age at study initiation: Approximately 9 weeks old
- Weight at study initiation: 284.1–332.4 g for males; 218.5–246.8 g for females
- Housing: Animals were housed singly in stainless steel, wire-mesh cages suspended above cage boards.
- Diet: PMI Nutrition International, LLC Certified Rodent LabDiet (#5002), ad libitum
- Water: Tap water, ad libitum
- Acclimation period: At least 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26°C
- Humidity (%): 30-70%
- Air changes (per hr): Not recorded
- Photoperiod (hrs dark / hrs light): Alternating 12-hour light and dark cycles

IN-LIFE DATES: From 28 June 2006 to 25 September 2006

Administration / exposure

Type of coverage:

semiocclusive

Vehicle:

unchanged (no vehicle)

Remarks:

unchanged, test substance was applied moistened with deionized water

Details on dermal exposure:

TEST SITE
- Area of exposure: Approximately 5 cm × 7.4 cm (the back from the scapular to the lumbar region)
- % coverage: 10%
- Type of wrap if used: Semi-occlusive

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Excess test substance was washed from the dorsal skin of each animal with warm water and the skin was dried with a paper towel
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5000 mg/kg bw
- For solids, paste formed: yes, the aliquot of test substance designated for an animal was moistened with 0.9 mL (males) or 0.7 mL (females) of deionized water to form a thick paste.

Duration of exposure:

24 hours

Doses:

Male and female: 5000 mg/kg bw
The female group and male group were dosed a week apart.

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations: Animals were observed for mortality and signs of illness, injury, or abnormal behaviour daily. The animals were observed for clinical signs daily throughout study. Observations for dermal irritation were made daily (weekends excluded).
- Frequency of weighing: The rats were weighed prior to treatment (test day 0) and on test days 7 and 14.
- Necropsy of survivors performed: yes

Statistics:

No statistical analysis was performed

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:

No mortalities occurred

Clinical signs:

other: No clinical signs of systemic toxicity were observed.

Gross pathology:

No gross lesions were present in the rats at necropsy

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

Classification by the dermal route is not required based on the results of this study.
LD50 > 5000 mg/kg bw.

Executive summary:

In an acute dermal toxicity study conducted according to OECD Guideline 402, the median lethal dose (LD50) by skin absorption was investigated.

A single dose of the test item was applied to the shaved, intact skin of 5 male and 5 female rats at a dose of 5000 mg/kg of body weight. The female group and male group were dosed a week apart. The application site was covered with a semi occlusive dressing for 24 hours, after which the test substance was removed. The rats were observed for 14 days following application. The rats were necropsied to detect grossly observable evidence of organ or tissue damage or dysfunction at the end of the test period.

No deaths occurred. The rats exhibited no clinical signs of systemic toxicity, body weight loss, or dermal irritation. No gross lesions were present in the rats at necropsy.
Under the conditions of this study, the skin absorption LD50 for the test item was greater than 5000 mg/kg of body weight when applied to the skin of male and female rats for 24 hours. Classification by the dermal route is not required based on the results of this study.