sec-butyl chloroformate

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:

other: Comparable to Guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1984

Report date:

1984

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 401 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

sec-butyl chloroformate

EC Number:

241-475-6

EC Name:

sec-butyl chloroformate

Cas Number:

17462-58-7

Molecular formula:

C5H9ClO2

IUPAC Name:

butan-2-yl carbonochloridate

Constituent 2

Reference substance name:

sec. Butylchloroformate

IUPAC Name:

sec. Butylchloroformate

Constituent 3

Reference substance name:

83/282

IUPAC Name:

83/282

Details on test material:

- Name of test material (as cited in study report): sec.-Butylchlorformiat (butyl carbonochloridic acid ester)- Physical state: clear liquid- Analytical purity: ca. 99%- Impurities (identity and concentrations): traces of phosgen, di-sec.-butylcarbonate, 2-chlorbutane, HCl- Expiration date of the lot/batch: end of march 1984- Stability under test conditions: max. 24 h- Storage condition of test material: < 5°C

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS- Source: Dr. Thomae, Biberach, D- Mean weight per group at study initiation: males 177 - 187 g, females 178 - 187 g - Fasting period before study: 16 h- Diet (e.g. ad libitum): Kliba Labordiaet, Klingentalmuehle AG, Kaiseraugst, CH- Water (e.g. ad libitum): tap water- Acclimation period: at least 7 dENVIRONMENTAL CONDITIONS- Temperature (°C): 20 - 24- Humidity (%): 30 - 70- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

olive oil

Details on oral exposure:

MAXIMUM DOSE VOLUME APPLIED: 5 mL/kg

Doses:

562, 1000 and 1780 mg/kg

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 and weighing: Weighing was performed at the beginning and on d4, d7 and d14. Observations were performed several times on the day of application and at least once per workday- Necropsy of survivors performed: yes

Statistics:

not performed

Results and discussion

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

1 000 - 1 780 mg/kg bw

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

ca. 1 527 mg/kg bw

Remarks on result:

other: value extrapolated

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

ca. 1 527 mg/kg bw

Remarks on result:

other: value extrapolated

Mortality:

No mortality observed in the 562 and 1000 mg/kg dose groups. In the 1780 mg/kg dose group, 4/5 males and 4/5 females, respectively, died at least within 2 d

Clinical signs:

562 mg/kg: diarrhea; reversible within 2 h1000 mg/kg: staggering, diarrhea and imbalance; reversible within at least 8 d1780 mg/kg: dyspnea, apathy, staggering, piloerection, diarrhea and poor general state; reversible within at least 5 d

Body weight:

The mean body weight gain of the 1000 and 1780 mg/kg dose groups in males (36-30 g) was slightly reduced if compared with the 562 mg/kg dose group in the first week (53 g), while the mean body weight gain of the females over the whole observation period and of the males in the second week was comparable between all dose groups.

Gross pathology:

Animals that died: General congestive hyperemia; stomach: haemorrhagic gastritis in glandular stomach.Sacrificed animals: Gastric wall of the forestomach thickened.

Applicant's summary and conclusion

Executive summary:

The study is conducted similar to OECD 401 and is reliable without restrictions. Male and female Wistar rats were treated with 562, 1000 or 1780 mg/kg test substance by gavage. No mortality was observed in doses up to 1000 mg/kg. The acute LD50 of sec.-Butylchloroformate in rats lies between 1000 - 1780 mg/kg after oral application. Haemorrhagic gastritis in glandular stomach was found in animals found dead and thickened gastric wall of the forestomach in sacrificed animals at necropsy.

Conclusion

According to the results of the present study the test substance, sec-Butylchloroformate has to be regarded as harmful after single oral application (R 22 according to EU classification criteria; acute oral Cat. 4 according to GHS criteria).