Octanoyl chloride

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 guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Octanoyl chloride

EC Number:

203-891-6

EC Name:

Octanoyl chloride

Cas Number:

111-64-8

Molecular formula:

C8H15ClO

IUPAC Name:

octanoyl chloride

Details on test material:

- Name of test material (as cited in study report): Octanoic acid chloride
- Physical state: liquid, yellowish
- Analytical purity: 99.7% following analytical report
- Lot/batch No.: B090
- Stability under test conditions: The stability under storage conditions over the study period was guaranteed by the sponsor, and the sponsor holds this responsibility
- Storage condition of test material: Room temperature, under N2, protect against moisture

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, Woelferstrasse 4, CH-4414 Fuellinsdorf, Switzerland; Rat / Wistar / HanRcc:WIST(SPF); the female animals were nulliparous and non-pregnant
- Age at study initiation: male animals approx. 7 - 8 weeks, female animals approx. 10 – 11 weeks
- Weight at study initiation: Animals of comparable weight (± 20% of the mean weight): mean males 234 g ; females 198 g
- Housing: single in H-Temp (PSU) cages
- Diet (e.g. ad libitum): Kliba-Labordiaet (Maus / Ratte Haltung “GLP”), Provimi Kliba SA, Kaiseraugst, Basel, Switzerland, ad libitum
- Water (e.g. ad libitum): Tap water ad libitum
- Acclimation period: at least 5 days before exposure


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark / hrs light): 12/12

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: unchanged (no vehicle)

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Whole-body inhalation system: IKA 02 (glass-steel construction), BASF SE
- Exposure chamber volume: 200 L
- Method of holding animals in test chamber: the animals were kept singly in compartmentalized wire cages, and were exposed inside the chamber. The homogenous distribution of test substance atmospheres in this inhalation system has been verified with model vapors.
- Equipment: Vaporizer (glasses with thermostat and mixing vessel); continuous infusion pump Perfusor (B. Braun)
- Generation technique: Vapor atmospheres were 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 taken up by the supply air and passed into the exposure system.
- Generator temperature: 40°C (low concentration); 80°C (mid and high concentration)
- Supply air flows (compressed air): 3.0 m³/h; the flows were adjusted and continuously measured with a flowmeter (rota).
- Exhaust air flows: 3.2 m³/h (low conc.); 3.1 m³/h (mid and high dose); the flows were adjusted by a separate exhaust air system and continuously measured with a flow meter (rota).


TEST ATMOSPHERE
- Brief description of analytical method used:
Sampling equipment and procedure: The sample volumes were adjusted to achieve suitable amounts of the test substance in the samples of the test groups in reference to the calibration of the analytical method.
Air sampler GS 312 (DESAGA)
- Sampling frequency: 4 samples at about hourly intervals
For the quantitative determination of the vapor concentration, a gas chromatographic method was used.
- Samples taken from breathing zone: yes

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

0.34, 0.68 and 1.10 mg/L (analytical)

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: A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on 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. Individual body weights shortly before exposure (day 0), weekly thereafter and at the end of the study. Additionally, body weight was measured in animals that died from study day 1 onward.
- Necropsy of survivors performed: yes
- Other examinations performed: To clarify the gross-pathological findings, selected organs of individual animals were examined histopathologically. The scope of the examination can be seen from the results.

Statistics:

The LC50 was calculated by Probit analysis (FINNEY, D.J. (1971): "Probit Analysis" Cambridge University Press) by means of a computer program.

Results and discussion

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.63 mg/L air (analytical)

Exp. duration:

4 h

Mortality:

No mortality occurred at 0.34 mg/L. All the males and two of the five females died at 0.68 mg/L. At 1.1 mg/L, all the male animals and four of the five female animals died prematurely. Lethality was observed within the first two days after the exposure.

Clinical signs:

other: Clinical signs of toxicity in animals exposed to 0.34 mg/L comprised abdominal respiration, respiration in stretched position, eyelid closure, red crust formation of the nose, piloerection, squatting posture, apathy as well as poor general condition. Find

Body weight:

0.34 mg/L: The mean body weights of the male animals increased throughout the study period. The mean body weights of the female animals decreased during the first post exposure observation week but increased during the second week. This effect is observed at times in the rat strain used, because in the required age range the female animals have already reached the phase of slow growth.
0.68 mg/L: The mean body weights of the surviving female animals did not increase adequately during the first post exposure observation week but increased during the second week.
1.10 mg/L: The body weight of the surviving female animal did not increase adequately during the first post exposure observation week but increased during the second week.

Gross pathology:

0.34 mg/L: No gross pathological abnormalities were noted during necropsy at termination of the study.
0.68 mg/L: During necropsy of the male and female animals that died, focal dark red discoloration, partly sunken surface of the lung as well as lung edema was noted. At termination of the study, focal dark red discoloration of all lung lobes was noted in one female animal. No gross pathological
abnormalities were observed in the other two female animals sacrificed at termination of the study.
1.10 mg/L: During necropsy of the male and female animals that died either during exposure or shortly after the exposure, diffuse dark-red discoloration of all lung lobes as well as partly sunken surface of the lung were observed. Additionally, severe lung edema was noted in all the males and two female. No gross pathological abnormality was noted in the female animal underwent gross necropsy at termination of the post exposure observation period.

Other findings:

0.68 mg/L: Histological examination of the female animal with focal dark red discoloration of all lung lobes revealed moderate multifocal alveolar histiocytosis (foam cells) and mild multifocal interstitial fibrosis.
1.10 mg/L: To further evaluate the macroscopic findings, histopathological examination was carried out in representative animals (one male and one female animal). Histopathological findings of the lung comprised moderate multifocal acute alveolar emphysema and edema, minimal multifocal acute necrosis of alveolar walls as well as severe diffuse total loss of bronchiolar respiratory epithelium. Histopathological examination of the stomach showed no abnormalities.