Hexyl chloroformate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP and guideline study. Available as unpublished report. No restrictions, fully adequate for assessment.

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:

OECD Guideline 403 (Acute Inhalation Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

EU Method B.2 (Acute Toxicity (Inhalation))

Test guideline 3

Qualifier:

according to guideline

Guideline:

EPA OPPTS 870.1300 (Acute inhalation toxicity)

GLP compliance:

yes (incl. QA statement)

Remarks:

BASF Aktiengesellschaft, Experimental Toxicology and Ecology, 67056 Ludwigshafen/Rhein, Germany

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Hexyl chloroformate

EC Number:

228-036-4

EC Name:

Hexyl chloroformate

Cas Number:

6092-54-2

Molecular formula:

C7H13ClO2

IUPAC Name:

hexyl carbonochloridate

Details on test material:

- Name of the test substance used in the study report: n-Hexylchloroformate
- Physical state / appearance: Liquid / clear
- Homogeneity: homogeneous
- Storage conditions: room temperature, avoid temperature over 80° C
- Purity: 99.2 area %
- Expiry date: unlimited
- Batch No.: 18803836W0

Test animals

Species:

rat

Strain:

Wistar

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: RCC Ltd Laboratory Animal Services; Wölferstraße 4, 4414 Füllinsdorf, Switzerland
- Age at study initiation: approx. 8 - 10 weeks for males and approx. 11 - 13 weeks for females.
- Weight at study initiation: Males: 210.3 - 281.3 g; Females: 187.7 - 207.3 g
- Housing: Single houding in cages type DK III (Becker, Germany) without bedding
- Diet: KLIBA mouse / rat laboratory diet 10 mm pellets “GLP”, Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water: ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air changes (per hr): Fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12 ( 6 a.m. - 6 p.m. light on, 6 p.m. - 6 a.m. light off

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

air

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Continuous infusion pump Perfusor VII (B. Braun), vaporizer (glass, BASF) with thermostat (Fa. Haake), Glass tube to prevent aerosol transfer to the inhalation chamber, mixing vessel (glass, BASF).
- Exposure chamber volume: 200 liter
- Method of holding animals in test chamber: Whole-body inhalation systems: IKA 02 (glass-steel construction), BASF Aktiengesellschaft, the animals were kept singly in compartmentalized wire cages, and were exposed inside the chamber.
- Method of conditioning air: Vapor-air mixture was generated. For each test group the vapors were generated by supplying amounts of the test substance to a heated vaporizer by means of the pump. The vapors that developed were transferred into the inhalation system by the supply air.

TECHNICAL SETTINGS:
- The generator temperatures were set to 60°C.
- The exposure systems were located inside exhaust cabins in an air-conditioned laboratory.
- To prevent hydrolysis of the test substance in the air, dry compressed air was used as supply air.
- Supply air flows (compressed air) of 3.0 m³/h were used for the exposures. The exhaust airflows were set at 3.2 m³/h.
- The generator temperatures were set to 60°C.
- Air changes of about 15 times per hour can be calculated by dividing the supply air flows by the volume of the inhalation systems.
- The higher amounts of exhaust air, which were adjusted by means of a separate exhaust air system, achieved negative pressures inside the exposure system. This ensured that no contamination of the laboratory occurred as result of possible leakage from the inhalation chambers.

DETERMINATION OF THE INHALATION ATMOSPHERE CONCENTRATION
Sampling equipment and procedure:
- Air sampler GS 312 (DESAGA)
- Sampling probe (diameter: 4 mm) with 2 fritted glass flask and a fritted glass flask connected in series and filled with sorption solvent
- Sorption solvent: Acetonitrile Gradient grade f. HPLC
- Sampling position: immediately adjacent to the animals' noses
- Sampling flow: 1 L/min
- Sampling velocity: 1.25 m/s
- Sampling frequency: 4 samples per concentration group in about hourly intervals

Analytical verification of test atmosphere concentrations:

yes

Remarks:

gas chromatographic method

Duration of exposure:

4 h

Remarks on duration:

plus equilibration time of the inhalation systems (about 20 min.)

Concentrations:

0.53, 1.17, 2.08 mg/L

No. of animals per sex per dose:

5

Control animals:

no

Details on study design:

- After the exposures, the surviving animals were observed for 14 days.
- For each test group, the body weights of the animals were determined just prior to exposure (day 0), weekly thereafter and at the end of the observation period. A check for overt clinical signs of toxicity or mortality as well as a check for the presence of feed and drinking water was made twice a day on workdays and once daily on weekends and public holidays.
- Detailed clinical observations were recorded for each animal separately several times during exposure and at least once on each workday of the observation period. No comprehensive clinical examination was performed on public holidays or weekends.
- At the end of each observation period the surviving animals were sacrificed with CO2 and were subjected to gross-pathological examination, as were all other animals which had died before. To clarify the gross-pathological findings, selected organs of individual animals were examined histopathologically.

Statistics:

Probit analysis

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.17 mg/L air

Based on:

test mat.

Exp. duration:

4 h

Mortality:

No mortality occurred at 0.53 mg/L. Three of five males and two of five female animals died at 1.17 mg/L, as well as all male and female animals at 2.08 mg/L.

Clinical signs:

other: 0.53 mg/L: Increased respiration, salivation, apathy and urine smeared fur around anogenital region. Findings were observed from hour 0 of exposure to study day 2. 1.17 mg/L: Increased respiration, salivation, eyelid closure, squatting posture, abdominal

Body weight:

0.53 mg/L: The mean body weights of the male animals increased throughout the study period. The mean body weights of the female animals decreased slightly during the first post exposure observation week but increased during the second week.
1.17 mg/L: The mean body weights of the surviving male and female animals decreased during the first post exposure week but increased during the second week. At termination of the study, the body weights of the animals were higher than the initial body weight prior to exposure.
2.08 mg/L: An evaluation of the body weight development of the animals was not possible due to the early death of the animals.

Gross pathology:

0.53 mg/L: There were no gross pathological abnormalities noted during necropsy at termination of the study.
1.17 mg/L: During necropsy of the 2 male and 1 female animals that were found death after exposure, lung edema of all lung lobes was observed. In 2 male and 2 female animals that were found death focal dark red discoloration of all lung lobes, partly sunken tissue surface of the lung was observed. The three animals that were found death on study day 0 and 1 were processed histopatholgically and examined by light microscopy. Histopathology of the lungs of all animals showed multifocal necrotizing pneumonia, acute diffuse interstitial and alveolar edema of mild to moderate grade.
2.08 mg/L: Necropsy of these animals showed red or dark red discoloration of all lung lobes. The surface of lung tissue was partly sunken.

Applicant's summary and conclusion

Interpretation of results:

toxic

Remarks:

Migrated information