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Description of key information

The acute oral LD50 (EC Guideline B1, GLP) was determined to be more than 500 mg/kg bw and less than or equal to 2000 mg/kg bw. In an acute inhalation toxicity study (OECD 403, GLP), the LC50 was determined to be more than 0.32 mg/L air.

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Dr. K. Thomae GmbH, Biberach, FRG
- Age at study initiation: young adults
- Weight at study initiation: Males: 168 - 187 g; Females: 173 - 181 g
- Fasting period before study: at least 16 hours, but water remained available
- Housing: single housing, in stainless steel wire mesh cages, type DK-III (Becker & Co., Castrop-Rauxel, FRG); no bedding in cages, sawdust in the waste trays.
- Diet: ad libitum, Kliba-labordiaet 343, Klingentalmuehle AG Kaiseraugst, Switzerland
- Water: ad libitum, tap water
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 24
- Humidity (%): 30 - 70
- Air: fully air-conditioned rooms
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
olive oil
Remarks:
DAB 10
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 4, 10 and 40 g/100 mL
- Administration volume: 5 mL/kg
- Justification for choice of vehicle: test substance is sensitive to hydrolysis

CLASS METHOD
- Rationale for the selection of the starting dose: A starting dose of 200 mg/kg bw was chosen based on the physical and chemical characteristics of the test substance and the composition.
Doses:
Group 1: 200 mg/kg bw
Group 2: 500 mg/kg bw
Group 3: 2000 mg/kg bw
No. of animals per sex per dose:
Group 1: 3 males & 3 females
Group 2: 3 males & 3 females
Group 3: 3 males
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days for group 1 and 2, 1 hour for group 3
- Frequency of observations and weighing: Recordings of signs and symptoms several times on the day of administration, at least once each workday for the individual animals. Individual body weights shortly before application (day 0), weekly thereafter and at the end of the study (before fasting period). A check for any dead or moribund animal was made twice each workday and once on Saturdays, Sundays and on public holidays.
- Necropsy of survivors performed: yes
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 500 - <= 2 000 mg/kg bw
Based on:
test mat.
Mortality:
- No mortality was observed in animals exposed to 200 or 500 mg/kg bw.
- All animals exposed to 2000 mg/kg died.
Clinical signs:
- No clinical signs were observed in female animals exposed to 200 mg/kg bw.
- An impaired general state, dypnoea, staggering and piloerection were observed in all female animals exposed to 500 mg/kg bw, between 0 and 5 hours after exposure.
- A poor general state, dypnoea, apathy, staggering and piloerection were observed in all male animals exposed to 200 mg/kg bw, between 1 and 5 hours after exposure.
- An impaired general state, dypsnoea and piloerection were observed in all male animals exposed to 500 mg/kg bw, between 1 and 5 hours after exposure. In 1 male animal exposed to 500 mg/kg bw staggering was also observed, between 1 and 2 hours after exposure.
- A poor general state, dyspnoea and apathy were observed in all male animals exposed to 2000 mg/kg bw. Twitching was observed in 2 male animals, and lying in an abdominal position, staggering and rolling convulsion were observed in 1 male animal exposed to 2000 mg/kg bw. All of these effects were observed directly after exposure.
Body weight:
Mean body weight start study
- 200 mg/kg bw: Male 173 g; Female 174 g
- 500 mg/kg bw: Male 186 g; Female 180 g
- 2000 mg/kg bw: Male: 171 g

Mean body weight after 13 days
- 200 mg/kg bw: Male 254 g; Female 214 g
- 500 mg/kg bw: Male 279 g; Female 218 g
Gross pathology:
- Animals that died: A bad postmortal state was observed.
- Sacrificed animals: no pathologic findings were noted.
Interpretation of results:
harmful
Remarks:
Migrated information
Endpoint conclusion
Endpoint conclusion:
adverse effect observed

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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
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
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
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 .
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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Acute toxicity: oral

In an acute toxic class method study (EU Method B1, GLP compliant), the test substance was administered to male and female Wistar rats by oral gavage (BASF 1997). Three fasted males were exposed to the test substance in olive oil DAB 10 at a dose level of 2000 mg/kg bw. Another two groups of six fasted animals (3 males and 3 females) were treated with dose levels of 200 and 500 mg/kg bw. After an observation period of 14 days surviving animals were necropsied. Clinical observations in the 2000 mg/kg bw group revealed a poor general state, dyspnoea, apathy, twitching, lying in an abdominal position, staggering and rolling convulsion. An impaired general state, dypnoea, staggering and piloerection were observed in male and female animals exposed to 500 mg/kg bw. A poor general state, dypnoea, apathy, staggering and piloerection were observed in all male animals exposed to 200 mg/kg bw. No clinical signs were observed in female animals exposed to 200 mg/kg bw. The mean body weight of the surviving animals increased throughout the study period within the normal range. No mortality was observed in animals exposed to 200 or 500 mg/kg bw. All animals exposed to 2000 mg/kg died. A bad postmortal state was observed in animals that died. No pathological findings were observed in surviving animals. The LD50 was therefore determined to be more than 500 mg/kg bw and less than or equal to 2000 mg/kg bw.  

Acute toxicity: inhalation

In a GLP compliant acute inhalation study (BASF 1999), performed according to OECD guideline 403, five Wistar rats per sex were exposed to the maximal attainable vapour concentration of the test substance for 4 hours. Using two different vapour generation methods, this concentration was found to be about 0.3 mg/L air (0.32 mg/L via one method and 0.27 mg/L via the other method). No mortality or pathological findings were observed in animals exposed to this concentration, via either method. Clinical examination did reveal some signs of discomfort during exposure, body weight was not influenced. The LC50 was therefore determined to be more than 0.32 mg/L air.


Justification for selection of acute toxicity – oral endpoint
One oral acute toxicity test available.

Justification for selection of acute toxicity – inhalation endpoint
One inhalation acute toxicity test available.

Justification for classification or non-classification

Because the oral LD50 is between 500 and 2000 mg/kg bw 5-chloropentanoyl chloride has to be classified as Acute toxicity Cat 4: H302: Harmful if swallowed in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and Xn: R22: Harmful if swallowed in accordance with EU Directive 67/548 (DSD).

Because the inhalation LC50 of 5-chloropentanoyl chloride was determined to be higher than 0.32 mg/L air, classification for acute inhalation toxicity is not warranted in accordance with EU Classification, Labeling and Packaging of Substances and Mixtures (CLP) Regulation No. 1272/2008 and EU Directive 67/548 (DSD).

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