reaction mass of 5-chloro-2-methyl-4-isothiazolin-3-one and 2-methyl-2H -isothiazol-3-one

Acute Toxicity: inhalation

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 1

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Reference 2

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Reference 3

Reference Type:

study report

Title:

Unnamed

Year:

1992

Report date:

1992

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

EPA OPP 81-3 (Acute inhalation toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Test material

Test material information

Constituent 1

Test material form:

other: Amber liquid

Details on test material:

- Name of test material (as cited in study report):Kathon(TM) 886F biocide

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Rohm and Haas, Batch No. J59098 and 60047

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Stable
- Solubility and stability of the test substance in the solvent/vehicle: Soluble and stable
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium: No

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: Dilution in water
- Final dilution of a dissolved solid, stock liquid or gel: 0.19, 0.32, 0.50, 1.26, 2.24, and 3.02 mg/L

FORM AS APPLIED IN THE TEST (if different from that of starting material)
Aerosol

OTHER SPECIFICS: 13.71 % a.i. (Batch No. J59098) and 13.99 % a.i. (Batch No. 60047)

Test animals

Species:

rat

Strain:

other: Crl:CD BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Kingston, Stone Ridge, New York, USA
- Age at study initiation: Not reported
- Weight at study initiation: Body weights were 184 to 230 grams for males and 193 to 230 grams for females.

Administration / exposure

Route of administration:

inhalation: aerosol

Type of inhalation exposure:

nose only

Vehicle:

air

Mass median aerodynamic diameter (MMAD):

2.7 µm

Geometric standard deviation (GSD):

3.8

Remark on MMAD/GSD:

Mean respirable fraction = 57 + 9 %
The fraction of aerosol <= 1 micrometer averaged 26 % for the 0.19, 0.32 and 0.50 mg/L concentrations and averaged 18 % for the 1.26, 2.24 and 3.02 mg/L concentrations

Details on inhalation exposure:

GENERATION OF TEST ATMOSPHERE / CHAMBER DESCRIPTION
- Exposure apparatus: Plexiglas® and stainless steel chamber with up to 3 nebulizers
- Exposure chamber volume: 240 L
- Method of holding animals in test chamber: Not described
- Source and rate of air: Conditioned air
- Method of conditioning air: Air was drawn through an absolute filter
- System of generating particulates/aerosols: Nebulizer
- Method of particle size determination: Gravimetrically, by drawing samples of the chamber atmosphere through a QCM Cascade Impactor
- Treatment of exhaust air: Not described
- Temperature, humidity, pressure in air chamber: The mean chamber atmospheric temperature was 67 ± 2 °F (circa 19 °C) and the mean chamber humidity was 74 ± 5 %.

TEST ATMOSPHERE
- Brief description of analytical method used:
- Samples taken from breathing zone: no

VEHICLE
- Composition of vehicle (if applicable):
- Concentration of test material in vehicle (if applicable):

TEST ATMOSPHERE (if not tabulated)
- Particle size distribution: Mean respirable fraction = 57 + 9 %. The fraction of aerosol <= 1 micrometer averaged 26 % for the 0.19, 0.32 and 0.50 mg/L concentrations and averaged 18 % for the 1.26, 2.24 and 3.02 mg/L concentrations.
- MMAD (Mass median aerodynamic diameter) / GSD (Geometric st. dev.): 2.7 micrometer / 3.8

Analytical verification of test atmosphere concentrations:

yes

Duration of exposure:

4 h

Concentrations:

Analytical concentration: 0.19, 0.32, 0.50, 1.26, 2.24, and 3.02 mg/L

No. of animals per sex per dose:

6

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations during exposure and twice per day for 14 days after exposure (except holidays and weekends). Body weights recorded at days 0, 1, 7 and 14. Necropsy on found dead and on survivors at day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Statistics:

A SAS probit regression analysis program was used to calculate LC50, slope and confidence limits.

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

2.36 mg/L air

Based on:

test mat.

95% CL:

>= 1.6 - <= 4.82

Exp. duration:

4 h

Effect levels 2

Key result

Sex:

male/female

Dose descriptor:

LC50

Effect level:

0.33 mg/L air

Based on:

act. ingr.

95% CL:

>= 0.22 - <= 0.67

Exp. duration:

4 h

Mortality:

n/a

Clinical signs:

other: Signs of respiratory irritation, including gasping, rales, hyperpnea, dyspnea and vocalization, were seen in some animals in all groups immediately post-exposure. The number of animals showing these signs and the severity of the respiratory irritation cor

Body weight:

n/a

Gross pathology:

Animals in groups 4, 5 and 6 showed stomachs and/or intestines filled with gas which correlated with the concentration of the test material to which the animals were exposed, the greater response was seen in
animals exposed to the greater concentration of the test material. This was judged to be the result of swallowing air in an attempt to breathe. No other treatment-related necropsy observations were seen in any animal.

Any other information on results incl. tables

Dose (mg/L)	Number of dead / number of investigated	Time of death (range)
0.19	0/12	No deaths
0.32	1/12	1 died within 3 h after removal from chamber
0.50	0/12	No deaths
1.26	3/12	1 died within 3 h after removal from chamber, 2 died within 24 h
2.24	4/12	3 died within 3 h after removal from chamber, 1 died within 24 h
3.02	9/12	8 died within 3 h after removal from chamber, 1 died within 24 h
LC50value	Combined male and female LC50= 2.36 mg Kathon™ 886F per liter of air.     Combined male and female LC50= 0.33 mg a.i. per liter of air.

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

Combined male and female LC50 = 2.36 mg Kathon™ 886F per liter of air. Combined male and female LC50 = 0.33 mg a.i. per liter of air.

Executive summary:

Six male and 6 female rats per group were exposed to 0.19, 0.32, 0.50, 1.26, 2.24, and 3.02 mg test material/L.

Clinical observations during exposure and twice per day for 14 days after exposure (except holidays and weekends). Body weights recorded at days 0, 1, 7 and 14. Necropsy on found dead and on survivors at day 14. Signs of respiratory irritation, including gasping, rales, hyperpnea, dyspnea and vocalization, were seen in some animals in all groups immediately post-exposure. The number of animals showing these signs and the severity of the respiratory irritation correlated with the concentration of the test material to which the animals were exposed in the report. The signs of respiratory irritation disappeared in all surviving animals, taking from two to twelve days. Small red droplets were seen on the drop sheets in Groups 3, 4, 5, and 6. This sign disappeared in all surviving animals taking from 6 to 12 days. This was judged to be expired nasal exudates and the result of nasal irritation due to exposure of the test substance. Other treatment related signs, including scant feces, thriftlessness and black or crusty material on the muzzle were also seen in several of the groups. The crusty material on the muzzle was judged to be the result of direct contact with the test material. These and all other signs disappeared in all surviving animals by Day 12.

Combined male and female LC₅₀= 2.36 mg Kathon™ 886F per liter of air.

Combined male and female LC₅₀= 0.33 mg a.i. per liter of air.