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Acute Toxicity: inhalation

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Administrative data

Endpoint:
acute toxicity: inhalation
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Deficiencies: max. duration of treatment only 0.5 hour, no batch number indicated.Although some aspects of the study do not meet up-to-date standards, the results are reliable and allow a scientific valid evaluation of this toxicological endpoint. New studies are therefore not required and should not be conducted due to animal welfare considerations.
Cross-reference
Reason / purpose for cross-reference:
reference to other study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1987
Report date:
1987

Materials and methods

Test guideline
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 403 (Acute Inhalation Toxicity)
Deviations:
yes
Remarks:
Short exposure time (max. 30 min.)
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
Reference substance name:
Chlorine
EC Number:
231-959-5
EC Name:
Chlorine
Cas Number:
7782-50-5
Molecular formula:
Cl2
IUPAC Name:
Active chlorine generated from chloride of ambient water by electrolysis
Details on test material:
- Name of test material (as cited in study report): Chlorine - Analytical purity: 99.9 %- Impurities (identity and concentrations): Traces of Fe2(SO4)3- Lot/batch No.: Not stated - Stability under test conditions: Not stated- Traces of Fe2(SO4)3

Test animals

Species:
mouse
Strain:
Swiss
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS- Source: Charles River France SA, Saint Aubin les Elboeuf, France- Age at study initiation: Not stated- Weight at study initiation: mean weight 31.2 g (males); 25.3 g (females).

Administration / exposure

Route of administration:
inhalation: gas
Type of inhalation exposure:
whole body
Vehicle:
other: air
Details on inhalation exposure:
Duration of exposure:Group B, H, J, N, V and T: 10 min.Group R, E, K, C and Z: 30 min.
Duration of exposure:
>= 10 - <= 30 min
Concentrations:
Group B: 1680 mg/m3 (1.68 mg/L)Group C: 1757 ± 35 mg/m3 (1.757 mg/L)Group E: 1586 ± 47 mg/m3 (1.586 mg/L)Group H: 2186 ± 81 mg/m3 (2.186 mg/L)Group J: 2363 ± 81 mg/m3 (2.363 mg/L)Group K: 1665 ± 32 mg/m3 (1.665 mg/L)Group N: 3485 mg/m3 (3.485 mg/L)Group R: 1328 ± 55 mg/m3 (1.328 mg/L)Group T: 4798 mg/m3 (4798 mg/L)Group V: 3826 ± 38 mg/m3 (3.826 mg/L)Group Z: 1870 ± 21 mg/m3 (1.87 mg/L)
No. of animals per sex per dose:
5 per sex and group
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days- Frequency of observations and weighing: performed on days 1, 2, 4, 7 and 14- Necropsy of survivors performed: yes- Other examinations performed: clinical signs, Mortalities, gross autopsy, body weights, weight of kidneys, liver, and lungs, lung and conductive airways were preserved for microscopic examination
Statistics:
Method of determination of LD50:Response-concentration-time relationship was used to estimate the LC50 values

Results and discussion

Effect levelsopen allclose all
Sex:
male/female
Dose descriptor:
LC50
Effect level:
3 064 mg/m³ air
95% CL:
2 560 - 3 657
Exp. duration:
10 min
Sex:
male/female
Dose descriptor:
LC50
Effect level:
1 462 mg/m³ air
95% CL:
1 198 - 1 671
Exp. duration:
30 min
Mortality:
For mortalities please refer to table below.
Clinical signs:
other: Wet nares, bubble formation and nasal discharge (mainly in the highest concentration group)
Body weight:
Both male and female mice lost body weight during the first 2 days after exposure which is a common finding in this type of experiment. After day 4 most animals gained body weight again but weight gain was generally low.
Gross pathology:
Not stated
Other findings:
Organ weights:Relative lung weights were generally increased. For kidneys and liver no dose related effects were seen.

Any other information on results incl. tables

Mortality rates

Group

Concentration
(mg/L)±SDa

Exposure time (min.)

Mortality rate (%)

Day of death (number)

B

1.680±0

10

0

-

H

2.186±81

10

0

-

J

2.363±81

10

30

6(1); 13(2)

N

3.485±0

10

40

0(2); 10(1); 13(1)

V

3.826±38

10

100

0(8); 1(2)

T

4.798±0

10

100

0(10)

R

1.328±55

30

40

0(1); 8(2); 13(1)

E

1.586±47

30

70

0(4); 8(1); 9(1); 11(1)

K

1.665±32

30

60

0(2); 1(2); 9(1); 11(1)

C

1.757±35

30

90

0(5); 10(3); 13(1)

Z

1870±21

30

70

0(3); 1(2); 8(2)

a      SD: Standard deviation

Applicant's summary and conclusion

Interpretation of results:
Category 3 based on GHS criteria
Remarks:
Migrated information
Conclusions:
Most of the effects of chlorine occurred in the alveoli. Exposure to chlorine resulted additionally in changes in the conductive airways in some animals.The LC50 value for 30 min. exposure was derived at 1.462 mg/L.
Executive summary:

MATERIALS AND METHODS

11 groups of 5 male and 5 female mice were exposed to different concentrations of chlorine for 10, or 30 min. After exposure the animals were observed for 14 days (signs of intoxication, mortalities, and body weights on days 1,2,4,7 and 14). After the observation period they were killed and subjected to a gross post mortem examination. The lung and conductive airways from selected animals were preserved for microscopic examination. Weight of kidneys, liver, and lungs was determined.

RESULTS AND DISCUSSION

The clinical observation of nasal discharge with bubble formation indicates an increase in discharge of mucus from the respiratory tract. This can be explained by the irritative nature of Cl2. Foamy discharges usually indicate lung oedema. Swollen lungs possibly indicative of oedema were observed in animals which were examined closely after spontaneous death and after the scheduled kill in the satellite groups. However, for appraisal of acute oedema the lungs have to be cut to show the superfluous fluid which was not done since it is incompatible with fixation of the lungs for microscopic examination. With reference to the LC50 derivation no sex difference was observed. For pathological examinations please refer to 4.2. The loss of body weight is a common finding in this type of experiment. After day 4 most animals gained body weight again but weight gain was low. Relative organ weights were generally increased. The increase was positively correlated with the concentration level and the duration of exposure. For kidneys and liver no dose related effects were seen.

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