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

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

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 undiluted test substance was applied to the clipped intact shaven skin of five male albino rabbits. The application sites were covered with impervious cuffs for a period of 24 h, after which the cuffs were removed. Clinical observations at 24 h 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: 24 h exposure on 5 animals
- Parameters analysed / observed: Mortality, and clinical observations, body weights and necropsy

GLP compliance:

no

Remarks:

The study has been conducted in 1976 before the implementation of the Good Laboratory Practice. 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. 0098

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Room temperature
- Stability under test conditions: Stable

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: No
- Final dilution of a dissolved solid, stock liquid or gel: Undiluted

OTHER SPECIFICS: Purity of test material was 13.2%

Test animals

Species:

rabbit

Strain:

other: Albino

Sex:

male

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Age at study initiation: Adult
- Weight at study initiation: Range of weight: 246-261 g

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: Clipped intact shaven skin, back of each animal
- Type of wrap if used: Occlusion with an impervious cuff

REMOVAL OF TEST SUBSTANCE
Not described in report

TEST MATERIAL
- Amount(s) applied: Kathon™ 886 was applied undiluted at doses of 313, 625, 1250 and 2500 mg/kg.

Duration of exposure:

24 hours

Doses:

313, 625, 1250 and 2500 mg/kg.

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: Clinical observations at 24 h after dosing and daily thereafter for 14 days. Body weights at 0 and 14 days.
- Necropsy of survivors performed: yes

Statistics:

n/a

Results and discussion

Preliminary study:

n/a

Effect levels

Effect levels 1

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

660 mg/kg bw

Based on:

test mat.

95% CL:

370 - 1 210

Effect levels 2

Key result

Sex:

male

Dose descriptor:

LD50

Effect level:

87.12 mg/kg bw

Based on:

act. ingr.

Mortality:

n/a

Clinical signs:

other: Clinical signs were observed in dose levels up to and including 1250 mg/kg. However, rabbits in the 2500 mg/kg dose group appeared to have died prior to the recording of the first clinical observations. Clinical signs observed included: lethargy, prostrat

Gross pathology:

Necropsy of the decedents and survivors revealed only subcutaneous tissue damage at the application site.

Other findings:

n/a

Any other information on results incl. tables

Dose (mg/kg)	Number of dead /number of investigated	Time of death (range)	Observations
313	0/5	no deaths
625	2/5	2 at 24 h
1250	5/5	4 at 24 h; 1 at 48 h
2500	5/5	5 at 24 h
LD50value	LD50was determined to be 660 mg/kg.

 

Applicant's summary and conclusion

Interpretation of results:

Category 2 based on GHS criteria

Conclusions:

Skin irritation consisted of severe erythema and edema followed by eschar formation. LD50 was determined to be 660 mg KathonTM 886/kg bw with 95% confidence limits of 370 and 1210 mg/kg. This corresponds to LD50 = 87.12 mg/kg a.i. (pure CMIT/MIT).

Executive summary:

The undiluted test substance was applied to the clipped intact shaven skin of five male albino rabbits. The application sites were covered with impervious cuffs for a period of 24 h, after which the cuffs were removed. Clinical signs were observed in dose levels up to and including 1250 mg/kg. However, rabbits in the 2500 mg/kg dose group appeared to have died prior to the recording of the first clinical observations. Clinical signs observed included: lethargy, prostration, ataxia, dilation of pupils, hypothermia, slow respiration and poor food consumption.Skin irritation consisted of severe erythema and edema followed by eschar formation.LD₅₀was determined to be 660 mg Kathon 886/kg bw with 95% confidence limits of 370 and 1210 mg/kg. This corresponds to LD₅₀= 87.12 mg/kg a.i. (pure CMIT/MIT).

According to Annex VI of Directive 67/548/EEC, CMIT/MIT should be classified as Toxic in contact with skin (R24) and assigned the symbol T by a single dermal administation (i.e., the acute dermal LD50is between 50 and 400 mg/kg bw in rats).

The technical grade Kathon 886F should be classified as harmful in contact with skin (R21) and assigned the symbol Xn by a single dermal administation (i.e., the acute oral LD50 is between 400 and 2000 mg/kg bw in rats)