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

Acute Toxicity: oral

Administrative data

Endpoint:

acute toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Qualifier:

no guideline available

Principles of method if other than guideline:

- Principle of test: The test material was administered as a single dose by oral gavage to 10 animals/dose. Examinations: Clinical observations at 0-6 hr after dosing and daily thereafter for 14 days. Body weights at 0 and 14 days. Necropsy on found dead and on survivors at day 14.
- Short description of test conditions: Single dose, 10 animals/dose, post-examination up to 14 days
- Parameters analysed / observed: Mortality, and clinical observations, body weights and necropsy

GLP compliance:

no

Remarks:

The study was conducted in 1977 before implementation of the GLP. However, it follows the scientific procedures in force at that time, is well documented and raw data is available.

Test type:

standard acute 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™ 886 all magnesium formulation
- Physical state: Amber liquid
- Stability under test conditions: stable at room temperature

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. 76/0445 and 0098

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: 221, 313, 442, 625 or 883 mg/kg bw

OTHER SPECIFICS: Purity of test material was 14 % a.i. (Batch No. 76/0445) and 13.3 % a.i. (Batch No. 0098)

Test animals

Species:

rat

Strain:

other: Charles River CD

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: Adult
- Weight at study initiation: 209 to 211 g

Administration / exposure

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

VEHICLE
- Concentration in vehicle: Kathon™ 886 was prepared as a 10 % w/v aqueous dispersion

Doses:

221, 313, 442, 625 or 883 mg/kg b.w.

No. of animals per sex per dose:

10

Control animals:

no

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical observations at 0-6 hr after dosing and daily thereafter for 14 days. Body weights at 0 and 14 days. Necropsy on found dead and on survivors at day 14.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology

Results and discussion

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

457 mg/kg bw

Based on:

test mat.

95% CL:

>= 382 - <= 580

Remarks on result:

other: Lot 76/0445

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

64 mg/kg bw

Based on:

act. ingr.

Remarks on result:

other: Lot 76/0445

Effect levels 3

Sex:

male

Dose descriptor:

LD50

Effect level:

561 mg/kg bw

Based on:

test mat.

95% CL:

>= 482 - <= 654

Remarks on result:

other: Lot 0098

Mortality:

Lot 76/0445: The acute oral LD50 in male rats was 457 mg/kg with 95 % confidence limits of 382 and 580 mg/kg, whole product.
Lot 0098: The acute oral LD50 in male rats was 561 mg/kg with 95 % confidence limits of 482 and 654 mg/kg, whole product.

Clinical signs:

other: Clinical signs were observed in all dose levels of this study. Lot 76/0445: salivation, lethargy, ptosis, piloerection, lacrimation, ataxia, prostration, nasal discharge and diarrhea. Lot 0098: lethargy, ptosis, piloerection, lacrimation, ataxia, prostrat

Gross pathology:

Necropsy of the decedents and survivors revealed gross changes in all dose levels.
Lot 76/0445: decedents - reddening and irritation of the stomach and intestines and sloughing of the stomach mucosa; survivors – scar tissue of the stomach and reddening of the intestines.
Lot 0098: decedents - reddened intestines, reddening and edema of the stomach, sloughing of the stomach mucosa and gas distention of the intestines; survivors scar tissue of the stomach and reddening of the stomach and intestines.

Any other information on results incl. tables

.

Table A6.1.1/01-1.    Table for Acute Oral Toxicity in Rats
Dose (mg/kg)	Number of dead / number of investigated Lot 76/0445        Lot 0098		Time of death (range) Lot 76/0445  Lot 0098		Observations
221	1/10	0/10	day 6	no deaths
313	0/10	0/10	no deaths	no deaths
442	4/10	2/10	4 at 0-6 h	2 at 0-6 h
625	9/10	6/10	9 at 0-6 h	4 at 0-6 h;           1 at 24h ;             1 at 8-14 days
883	no animals dosed	10/10	no animals	8 at 0-6 h;           2 at 24h
LD50value	457 mg/kg in male rats

 

Applicant's summary and conclusion

Interpretation of results:

Category 3 based on GHS criteria

Conclusions:

The acute oral LD50 in male rats is based on the lowest value, 457 mg/kg [64 mg/kg a.i.].

Executive summary:

10 male rats per dose (221, 313, 442, 625 or 883 mg/kg b.w.) were tested. Clinical signs were observed in all dose levels of this study.

Lot 76/0445: salivation, lethargy, ptosis, piloerection, lacrimation, ataxia, prostration, nasal discharge and diarrhea.

Lot 0098: lethargy, ptosis, piloerection, lacrimation, ataxia, prostration, nasal discharge and diarrhea.

The acute oral LD₅₀in male rats is based on the lowest value, 457 mg/kg Kathon 886 corresponding to 64 mg/kg a.i. (pure CMIT/MIT).