Butyl chloroformate

Endpoint summary

Description of key information

In an acute oral toxicity study was the LD50 was determined to be 1325 mg/kg bw.
In an acute inhalation toxicity study the LC50 was determined to be more than 200 ppm for 1 hour exposure.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Reference

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP non-guideline, available as unpublished report, limitations in design and/or reporting but otherwise adequate for assessment.

Principles of method if other than guideline:

According to BASF-internal standard: Five Gassner rats per sex per dose were exposed to the test substance dissolved in an aqueous solution with Tragacanth gum. After an exposure period of 14 days animals were necropsied.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

other: Gassner rats

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Weight at study initiation: Males: 170 - 220g; Females 150 - 196 g

Route of administration:

oral: gavage

Vehicle:

other: Aqueous emulsion with Tragacanth

Details on oral exposure:

VEHICLE
- Concentration in vehicle: 10 and 20% (v/v)

Doses:

- 10% test concentration: 1000, 1250 mm3/kg
- 20% test concentration: 1600, 2000, 2500 mm3/kg

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 1 325 mg/kg bw

Based on:

other: test material as 10% test substance preparation

Remarks on result:

other: original value: 1250 mm3/kg

Sex:

male/female

Dose descriptor:

LD50

Effect level:

ca. 2 120 mg/kg bw

Based on:

other: test material as 20% test substance preparation

Remarks on result:

other: original value: 2000 mm3/kg

Mortality:

- 1000 mm3/kg: 1/10 after 14 days
- 1250 mm3/kg: 5/10 after 14 days
- 1600 mm3/kg: 2/10 after 14 days
- 2000 mm3/kg: 5/10 after 14 days
- 2500 mm3/kg: 10/10 after 14 days

Clinical signs:

other: Immediately after application all animals showed dyspnea, aqueous secretion from the oral cavity, ruffled fur, and apathy. During the observation period, hunched posture, intermittent breathing, and apathy were observed. No effects were observed after 6 d

Gross pathology:

Corrosion of the gastrointestinal tract, adhesive inflammatory processes in the stomach wall.

Interpretation of results:

moderately toxic

Remarks:

Migrated information

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

LD50

Value:

1 325 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records

Reference

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Non-GLP non-guideline, available as unpublished report, limitations in design and/or reporting but otherwise adequate for assessment.

Principles of method if other than guideline:

Ten rats were exposed to the test substance for 1 hour via inhalation. After an exposure period of 14 days animals were necropsied.

GLP compliance:

no

Test type:

standard acute method

Limit test:

no

Species:

rat

Strain:

not specified

Sex:

male/female

Details on test animals or test system and environmental conditions:

- Weight at study initiation (mean): Males: 158 g; Females 136 g

Route of administration:

inhalation

Type of inhalation exposure:

not specified

Vehicle:

not specified

Details on inhalation exposure:

4185 L/h

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

1 h

Concentrations:

about 200 ppm

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs

Sex:

male/female

Dose descriptor:

LC50

Effect level:

> 200 ppm

Based on:

test mat.

Exp. duration:

1 h

Mortality:

4 out of 10 animals exposed to 200 ppm died.

Clinical signs:

other: Eyelid closure, after a few minutes forced breathing, and partially thoracic breathing was observed. In the first days after exposure no abnormal signs were observed. However, on the sixth day of the observation period 3 animals died. One animal showed ga

Body weight:

- Weight at start study: Males: 158 g; Females 136 g
- Weight at end study: Males: 201.7 g; Females 178.3 g

Gross pathology:

- Animals that died: Pulmonary emphysema
- Sacrificed animals: no effects observed

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Acute oral toxicity

Five Gassner rats per sex per dose were exposed to butyl chloroformate, dissolved in an aqueous solution with Tragacanth, via oral gavage (BASF 1970). The animals received 1000 and 1250 mm3/kg using a 10% test substance preparation, and 1600, 2000 and 2500 mm3/kg using a 20% test substance preparation. Immediately after application all animals showed dyspnea, aqueous secretion from the oral cavity, ruffled fur, and apathy. During the observation period, hunched posture, intermittent breathing, and apathy were observed. No effects were observed after 6 days. Upon necropsy, corrosion of the gastrointestinal tract and adhesive inflammation processes of the stomach wall were observed. The LD50 was determined to be 1325 and 2120 mg/kg bw for 10% and 20% test substance preparation, respectively.

In a second study five Sprague-Dawley rats per sex per dose were exposed to the test substance, dissolved in olive oil, via oral gavage (BASF 1981). Animals received 1000, 1470, 2150, 2610 and 2160 mg/kg bw. After an observation period of 14 days animals were necropsied. Dyspnea, apathy, abnormal position, staggering, spastic gait, ruffled fur, diarrhea, cyanosis and a poor general state were observed in exposed animals. Acute dilatation of the atrium, acute congestive hyperemia, acute flatulence of the lung, bloody sloughing in the glandular stomach and forestomach (corrosive gastritis), and white intestinal mucosa (necrosis) were observed in animals that died. A thickened wall of the forestomach, margo plicatus padded thickened, and crusty removable mucosa were observed in sacrificed animals exposed to 2160 mg/kg. Indurated wall of the forestomach with scattered buttons was observed in sacrificed animals exposed to 1000 and 1470 mg/kg. The LD50 was determined to be ca. 2600 mg/kg bw.

Acute inhalation toxicity

In one study (BASF 1970) ten rats were exposed to 200 ppm (= ca. 1.12 mg/L) of the test substance for 1 hour via inhalation. After an observation period of 14 days animals were necropsied. Dyspnea was observed in exposed animals. Four animals died, and pulmonary emphysema was observed in these animals. No pathological findings were observed in sacrificed animals.

In a second study (BASF 1970, IHT) six and twelve rats were exposed for 10 and 3 minutes, respectively, to the saturated vapour. Vigorous attempts to escape, severe irritation to the mucosa and gasping breathing were observed. All exposed animals died. Upon necropsy considerable congestion and edema of the lungs with hydrothorax were observed. Based on a vapour pressure of 7.2 hPa at 20°C, the concentration in air is 7214 ppm (40 mg/L).

Justification for selection of acute toxicity – oral endpoint
Two acute oral toxicity studies are available. The study with the more severe results was chosen.

Justification for selection of acute toxicity – inhalation endpoint
Two acute inhalation studies are available. The study with the longest exposure period and a clear tested concentration was chosen.

Justification for classification or non-classification

Based on the lowest oral LD50 of 1325 mg/kg bw the substance will be classified as Acute Tox. 4: H302 according to CLP (EC/1272/2008).

An inhalation LC50 of >1.12 mg/L was determined after 1 hour of exposure. At that level 4 out of 10 animals died. Therefore, the substance will be classified as Acute Tox. 2: H:330: Fatal if inhaled in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008. This classification is in agreement with the harmonized classification in EC/1272/2008 Annex VI.

According to EC/1272/2008, Annex I: 3.1.2.3.3. the substance shall also be labelled as “corrosive to the respiratory tract” (EUH071), as the substance is corrosive to skin and eyes (H314), indicating that the mode of action for the acute toxicity is corrosivity.