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Repeated dose toxicity: inhalation

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Administrative data

Endpoint:
sub-chronic toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
March 1981 - June 1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study with acceptable restrictions
Cross-reference
Reason / purpose for cross-reference:
reference to same study

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
Unnamed
Year:
1989
Reference Type:
secondary source
Title:
Chloroethane CAS: 75-00-3
Author:
OECD SIDS
Year:
2006
Bibliographic source:
SIDS Initial Assessment Report for SIAM 22

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 413 (Subchronic Inhalation Toxicity: 90-Day Study)
Deviations:
yes
Remarks:
no clinical pathology performed; food and water consumption, organ weights (except liver) not determined; no monitoring of exposure conditions (e.g. test concentration)
GLP compliance:
yes
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Chloroethane
EC Number:
200-830-5
EC Name:
Chloroethane
Cas Number:
75-00-3
Molecular formula:
C2H5Cl
IUPAC Name:
chloroethane
Details on test material:
- Name of test material (as cited in study report): chloroethane
- Physical state: gas
- Analytical purity: >99.5% pure
- Lot No.: A082280 (Metheson Gas Products, East Rutherford, NJ, USA), A040181 and A042881 (Air Products, Inc., Tamaqua, PA, USA)

Test animals

Species:
mouse
Strain:
B6C3F1
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories (Portage, MI, USA)
- Age at study initiation: 8-9 weeks
- Weight at study initiation: males: 23.1 - 24.2 g; females: 18.5 - 20.7 g
- Housing: individually in stainless steel wire cages (Hazleton Systems, Inc., Aberdeen, MD, USA); no bedding
- Diet (e.g. ad libitum): NIH 07 Rat and Mouse Ration (Zeigler Bros., Inc., Gardners, PA, USA); available ad libitum during non-exposure periods
- Water (e.g. ad libitum): automatic watering system (Edstrom Industries, Waterford, WI, USA); available ad libitum
- Acclimation period: 21 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21.7 - 23.3
- Humidity (%): 40 - 65
- Air changes (per hr): 10 during exposure; 20 during non-exposure
- Photoperiod (hrs dark / hrs light): 12 / 12


IN-LIFE DATES: From: February 1981 To: June 1981

Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
air
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: vapour generation system; the liquid to be vaporized was forced under pressure, at a metered rate, directly from the shipping container into a stainless steel boiler that was maintained at about 32 °C by a controlled-temperature water bath. The vapour was routed through a gas metering valve and a purge/expose valve into a pipe at the chamber inlet, where the vapour was mixed with dilution air entering the chamber.
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
6 hours/day
Frequency of treatment:
5 days/week for 13 weeks
Doses / concentrationsopen allclose all
Dose / conc.:
2 500 ppm (nominal)
Remarks:
corresponding to 6596 mg/m³
Dose / conc.:
5 000 ppm (nominal)
Remarks:
corresponding to 13192 mg/m³
Dose / conc.:
10 000 ppm (nominal)
Remarks:
corresponding to 26384 mg/m³
Dose / conc.:
19 000 ppm (nominal)
Remarks:
corresponding to 50130 mg/m³
No. of animals per sex per dose:
10
Control animals:
yes, sham-exposed
Details on study design:
- Dose selection rationale: the absence of compound-induced mortality and toxic effects was the basis for selecting 19000 ppm as the highest exposure concentration in the 13-weeks studies.

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: 3 times per day during exposure

DETAILED CLINICAL OBSERVATIONS: No

BODY WEIGHT: Yes
- Time schedule for examinations: once per week

FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No

FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: No

WATER CONSUMPTION: No

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: No

CLINICAL CHEMISTRY: No

URINALYSIS: No

NEUROBEHAVIOURAL EXAMINATION: No

OTHER: liver weight at necropsy
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (performed on all control and high dose animals)

Tissues examined include: adrenal glands, bone marrow, brain, colon, oesophagus, gallbladder, heart, jejunum, kidneys, larynx, liver, lungs and bronchi, mammary gland, mandibular lymph nodes, nasal cavity, pancreas, parathyroid glands, pituitary gland, prostate/testes or ovaries/uterus, salivary glands, seminal vesicles, skin, spleen, stomach, thymus, thyroid gland, trachea and urinary bladder.
Statistics:
Survival analyses: estimated by the product-limit procedure of Kaplan and Meier (1985). Statistical analyses for a possible compound-related effect on survival used the method of Cox (1972). All reported P values for the survival analysis are two-sided.

Calculation of incidence: The incidence of neoplastic or non-neoplastic lesions is given as the ratio of the number of animals bearing such lesions at a specific anatomic site to the number of animals in which that site was examined.

Results and discussion

Results of examinations

Details on results:
CLINICAL SIGNS AND MORTALITY
One of 10 male mice exposed to 10000 ppm chloroethane died before the end of the study.
No compound related clinical signs were seen.

BODY WEIGHT AND WEIGHT GAIN
The final mean body weights of all exposed groups were generally higher than those of controls.

ORGAN WEIGHTS
The liver weight to body weight ratio for female mice exposed to 19000 ppm was significantly greater than that for controls (P < 0.01); however no microscopic liver changes were observed. The effects was considered to be adaptive.

GROSS PATHOLOGY/HISTOPATHOLOGY:
Nasal cavity haemorrhage of minimal severity was observed grossly in 3/10 male and 6/10 female mice exposed to 19000 ppm but was considered to be an artefact of necropsy and unrelated to exposure to chloroethane because no microscopic lesions associated with exposure to chloroethane were observed in the nasal mucosa of these animals.

Effect levels

Key result
Dose descriptor:
NOAEC
Effect level:
50 130 mg/m³ air (nominal)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: non-toxicologically relevant increased relative liver weights; decreased body weight

Target system / organ toxicity

Key result
Critical effects observed:
no

Applicant's summary and conclusion

Conclusions:
In a 13-week study, mice were exposed to 0, 2500, 5000, 10000, or 19000 ppm chloroethane. No compound-related deaths occurred. Final mean body weights of exposed mice were generally higher than those of controls. No compound-related clinical signs or gross or microscopic pathologic effects were seen. The liver weight to body weight ratios for female mice exposed to 19000 ppm were greater than those for controls.
Executive summary:

Male and female mice were exposed to 0, 2500 ppm, 5000 ppm, 10000 ppm, or 19000 ppm chloroethane for 6 hours/day, 5 days/week for 13 weeks (National Toxicology Program, 1989). All animals lived to the end of the study; except one male mouse of the 10000 ppm dose group, which died during the first week of exposure. The final mean body weights of all exposed mice were generally higher than those of controls. No compound-related clinical signs were seen. The liver weight to body weight ratio for female mice exposed to 19000 ppm was significantly greater than that for controls, but no microscopic liver changes were observed. In the 13-week study in mice (National Toxicology Program, 1989), the liver weights were 1557+46, 1604+35, 1580+40, 1540+39, and 1993+66 mg at 0, 2500, 5000, 10000 and 19000 ppm, respectively. A statistically significant increase in liver weight was noted only at 19000 ppm (P < 0.01). Nasal cavity hemorrhage of minimal severity was observed grossly in 3/10 male and 6/10 female mice exposed to 19000 ppm but was considered to be not related to chloroethane because no microscopic lesions were observed in the nasal mucosa of these animals. 

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