Registration Dossier

Diss Factsheets

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:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1999
Report date:
1999

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Qualifier:
according to guideline
Guideline:
EU Method B.2 (Acute Toxicity (Inhalation))
Qualifier:
according to guideline
Guideline:
EPA OPP 81-3 (Acute inhalation toxicity)
Version / remarks:
- FIFRA Guideline
Qualifier:
according to guideline
Guideline:
EPA OTS 798.1150 (Acute inhalation toxicity)
Version / remarks:
- TSCA Guideline 40CFR
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
5-chlorovaleryl chloride
EC Number:
216-403-1
EC Name:
5-chlorovaleryl chloride
Cas Number:
1575-61-7
Molecular formula:
C5H8Cl2O
IUPAC Name:
5-chlorovaleryl chloride
Details on test material:
- Name of test material (as cited in study report): 5-Chloropentanoyl chloride
- Physical state: colourless liquid
- Storage conditions: room temperature

Test animals

Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Boehringer Ingelheim Pharma KG, FRG
- Age at study initiation: 8 - 9 weeks
- Weight at study initiation: Male 257.0 - 285.8 g, Female 162.1 - 206.7 g
- Housing: singly housing, in type DK III cages (Becker, Germany) without bedding
- Diet: ad libitum, KLIBA rat/mouse/hamster laboratory diet 10 mm pellets (Provimi Kliba SA, Kaiseraugst, Switzerland)
- Water: ad libitum
- Acclimation period: at least 1 week

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

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: IKA 02 (glass-steel construction)
- Exposure chamber volume: 200 L
- Method of holding animals in test chamber: animals were kept singly in compartmentalized wire cages, and were exposed in the chamber.
- Technical equipment, test group 1: continuous infusion pump Perfusor VII (B. Braun), vaporizer with thermostat (glass), aerosol mixing vessel (glass).
- Techinical equipment, test group 2: glass generator with sintered glass disk (pore - size 90-150 µm), glass tube with quartz wool plug to prevent aerosol transfer to the inhalation chamber.
- Procedure, test group 1: The vapor was generated by supplying 1.8 mL/h of the test substance to the heated vaporizer by means of the continuous infusion pump. The vapors that developed were taken up by the supply air and passed into the exposure system. During exposure no total evaporation of the test substance in the generator was achieved and the panes of the chamber steamed up.
- Procedure, test group 2: The test substance was introduced into a glass generator above a sintered glass disk and vapors were generated by bubbling air through the substance column. The mass of the generator was determined before and after exposure for calculation of the substance flow. During exposure the panes of the chamber steamed up.
- Exposure: the exposure system was located inside an exhaust cabin in an air-conditioned laboratory. The about 3 or 7% higher amounts of exhaust air, which were adjusted by means of a separate exhaust air system, achieved a slightly negative pressures inside the exposure systems. This ensured that no contamination of the laboratory occurred as result of possible leakage from the inhalation chambers. The supply and exhaust air flows were adjusted and continously measured with flowmeters (Rota).
- Rate of air: An air changes of 15 times per hour can be calculated by dividing the supply air flows by the volume of the inhalation system.
- Supply air: 3000 L/h
- The temperatures in the inhalation systems were measured continously with a digital thermometer.

TEST ATMOSPHERE
- Brief description of analytical method used: Samples were taken with a 4 mm sampling probe, 2 absorption vessels and a fritted glass flask connected in series and filled with sorption solvent (2-Propanole). Sampling was done with a flow of 1 L/min, velocity of 1.25 m/s. 4 samples per concentration group in about hourly invervals were taken. With a gas chromatographic method (GC HP 5840 A, Hewlett Packard) the concentration of the test atmoshpere was measured.
- Samples taken from breathing zone: yes
Analytical verification of test atmosphere concentrations:
yes
Remarks:
using a gas chromatographic method (GC HP 5840 A, Hewlett Packard)
Duration of exposure:
4 h
Remarks on duration:
plus 20 min of equilibration time
Concentrations:
Test group 1: 0.27 mg/L
Test group 2: 0.32 mg/L
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: The body weight of the animals was determined just prior to exposure, after 7 days 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 in the observation period.
- Necropsy of survivors performed: yes
Statistics:
The statistical evaluation of the concentration-response relationship was carried out using a computer program: Depending on the data of the concentration-response relationship obtained by way of experiment, this program is used to estimate the LC50 or to perform a Probit analysis. Estimation of the LC50 will produce types " LC50 greater than", " LC50 approx .", or " LC50 smaller than" . If the results are type "LC50 greater than" or "LC50 smaller than", an additional binomial test is carried out, in order to verify these statements statistically .

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 0.32 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Mortality:
No mortality was observed in all exposed animals.
Clinical signs:
other: - Irregular respiration was observed in 1 out of 5 male animals exposed to 0.27 mg/L, until 1 hour after start exposure. - No clinical signs were observed female animals exposed to 0.27 mg/L. - Irregular respiration, accelerated respiration, eyelid closur
Body weight:
Mean body weight start study
- 0.27 mg/L: Male 262 g; Female 194 g
- 0.32 mg/L: Male 274 g; Female 187 g

Mean body after 14 days
- 0.27 mg/L: Male 330 g; Female 223 g
- 0.32 mg/L: Male 335 g; Female 220 g
Gross pathology:
No gross pathological abnormalities were detected in all exposed animals.

Applicant's summary and conclusion

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