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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Study period:
19 Jul - 5 Aug 1983
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1983
Report date:
1983

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
adopted in 1981
Deviations:
no
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Version / remarks:
adopted in 2009
Deviations:
no
GLP compliance:
no
Test type:
traditional method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Clorofene
EC Number:
204-385-8
EC Name:
Clorofene
Cas Number:
120-32-1
Molecular formula:
C13H11ClO
IUPAC Name:
clorofene

Test animals

Species:
rat
Strain:
other: CD
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Charles River (U.K.) Limited
- Weight at study initiation: 182 - 224 g (males), 199 - 223 g (females)
- Housing: 5 animals of the same sex per cage in high density polypropylene cages (56 x 38 x 18 cm) with stainless steel grid floors and top
- Diet: Spratt´s Laboratory Diet No. 1, pelleted (K and K Greeff Chemicals Ltd.), ad libitum (except for the removal of food approximately 18 h before the test substance was administered)
- Water: tap water, ad libitum
- Acclimation period: 12 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 (18 - 25 acceptable limits)
- Humidity (%): 55 (40 - 65 acceptable limits)
- Air changes (per hr): approximately 17
- Photoperiod (hrs dark / hrs light): 12 / 12

Administration / exposure

Route of administration:
inhalation: aerosol
Type of inhalation exposure:
nose only
Vehicle:
other: isopropanol
Mass median aerodynamic diameter (MMAD):
>= 4 - <= 5.1 µm
Geometric standard deviation (GSD):
>= 2.5 - <= 2.8
Remark on MMAD/GSD:
The particle size analysis of the isopropanol aerosol (vehicle) proved impracticable because of excessive evaporation.
Details on inhalation exposure:
GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: exposure chamber with a 30 cm diameter aluminium alloy cylinder
- Exposure chamber volume: ca. 60 L
- Method of holding animals in test chamber: individual polycarbonate restraining holder
- Source and rate of air: Dry oil-free compressed air was pressed through the annular jet of the atomiser at a pressure of ca. 10 psi giving an air-flow of ca. 20 L/min.
- System of generating particulates/aerosols: Test atmospheres were generated using controlled fluid feed from a motorized syringe (Sage syringe pump, model 355, from Arnold R. Horwell Limited, London, England) to a glass concentric jet atomiser mounted into the top of the chamber.
- Method of particle size determination: The aerosol was characterised using a cascade impactor (Model MKIIa, from C.F. Casella and Company Limited, London) ahich was located into a vacant animal exposure port. The particle size distribution was determined using the ECD (Effective Cut-off Diameter) method of bulk estimation, the mass recovered at each stage being determined by the weight gain of the sampling discs.
- Treatment of exhaust air: Exhaust air was passed through mineral oil, a glass cyclone separator, an activitated carbon "scrubber" and a pair of absolute filters arranged in series before being vented to atmosphere via the pump.
- Temperature, humidity, pressure in air chamber: Target temperature and humidity in the exposure chamber were 22 ± 3 °C and 40 - 60%, respectively.

TEST ATMOSPHERE
- Brief description of analytical method used: The total aerosol concentration was determined by drawing a continous atmosphere sample through an absolute filter located in the chamber wall at a flow rate of 2 L/min. The fractional concentrations of chlorophen and isopropanol were subsequently determined by passing dry air through the absolute filters for a minimum of two hours to remove the isopropanol by evaporation. In addition, the vapour concentration of isopropanol was determined by further passing the above air samples through a trap containing approximately 10 g of activated charcoal to absorb isopropanol.

VEHICLE
- Concentration of test material in vehicle: 75% (w/w)

TEST ATMOSPHERE
Please refer to Table 1 under "Any other information on materials and methods incl. tables".
Analytical verification of test atmosphere concentrations:
yes
Remarks:
gravimetric
Duration of exposure:
4 h
Concentrations:
15.5, 20.4 and 24.5 mg/L (nominal concentration for the test material)
11.6, 15.3 and 18.4 mg/L (nominal concentration for the active ingredient)
2.07, 2.40 and 3.13 mg/L (actual concentration for the active ingredient)
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: During exposure, animals were observed in 15 min intervals for the first hour and at 30 min intervals for the remainder of the exposure period. After exposure, animals were observed at 30 min intervals for the first 3 hours. Subsequently, animals were observed twice daily until study termination. Animals were weighed daily on the first 5 days and on Days 8, 11, and 15 (day of termination).
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, organ weights (liver, kidneys and lungs)

Results and discussion

Effect levelsopen allclose all
Sex:
male
Dose descriptor:
LC50
Effect level:
2.6 mg/L air
Based on:
act. ingr.
95% CL:
>= 1.92 - <= 3.52
Exp. duration:
4 h
Sex:
female
Dose descriptor:
LC50
Effect level:
2.43 mg/L air
Based on:
act. ingr.
95% CL:
>= 2.03 - <= 2.9
Exp. duration:
4 h
Sex:
male/female
Dose descriptor:
LC50
Effect level:
2.5 mg/L air
Based on:
act. ingr.
95% CL:
>= 2.13 - <= 2.93
Exp. duration:
4 h
Mortality:
2.07 mg/L: 1/5 male died during exposure and 1/5 female died on Day 2 after exposure
2.40 mg/L: 3/5 males and 3/5 females died during exposure
3.13 mg/L: 2/5 males and 3/5 females died during exposure, 1/5 male died 30 min after exposure and 1/5 female died on Day 2 after exposure
Clinical signs:
other: 2.07, 2.40 and 3.13 mg/L: displayed bradypnoea and hyperpnoea during exposure in all animals (apparent within 45 min of commencement of treatment until death or throughout the whole exposure period); decreased motor activity, ataxia, bradypnoea, gasping,
Body weight:
2.07, 2.40 and 3.13 mg/L: Body weight gains of surviving rats were considerably below expectation and were considered to reflect a clear effect of treatment with the test compound. There was, however, a trend to partial recovery towards the end of the recovery period.
Gross pathology:
2.07, 2.40 and 3.13 mg/L: externally localised or general surface staining of the coat in all decedents; incomplete collapse and congestion of the lungs, firm lungs and aerated fluid in the trachea together with gaseous and fluid stomach and intestinal content in decedents; three cases of hydronephrosis, four cases of enlarged cervical lymph nodes and a single hepatic nodule in decedents; distention of the stomach and intestinal tract and enlarged mesenteric lymph nodes in one surviving female of the highest exposure group; isolated hydronephrosis, pulmonary congestion or petechiae and a liver nodule in single surviving animals (not clearly treatment-related).
Other findings:
- Organ weights: increased lung weights consistent with pulmonary irritation and oedema in decedents (indication of acute respiratory failure due to oedema).

Any other information on results incl. tables

Table 2: Results of acute inhalation toxicity testing

chlorophene concentration [mg/L air]

Toxicological results*

Onset of clinical signs

Time of death

Mortality
[%]

Males

0.0

0/2/5

180 min

0

0

2.07

1/5/5

30 min

2.7 h during exposure

20

2.40

3/5/5

30 min

2.6-4.0 h during exposure

60

3.13

3/5/5

10 min

2.2 h during exposure– 0.5 h after exposure

60

LC50= 2.60 mg/L air

 

Females

0.0

0/1/5

210 min

0

0

2.07

1/5/5

45 min

Day 2 after exposure

20

2.40

3/5/5

30 min

1.8-3.7 h during exposure

60

3.13

4/5/5

15 min

1.7 h during exposure–
Day 2 after exposure

60

LC50= 2.43 mg/L air

 

* number of dead animals/number of animals with signs of toxicity/total number of animals tested

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
CLP: Acute Tox. 4, H332

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