Methyl isothiocyanate

Acute Toxicity: dermal

Administrative data

Endpoint:

acute toxicity: dermal

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guidelines study (OECD 402)

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1985

Report date:

1985

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 402 (Acute Dermal Toxicity)

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: EPA - Pesticide assessment guidelines.

GLP compliance:

yes

Test type:

standard acute method

Limit test:

no

Test material

Test material information

Constituent 1

Reference substance name:

Methyl isothiocyanate

EC Number:

209-132-5

EC Name:

Methyl isothiocyanate

Cas Number:

556-61-6

Molecular formula:

C2H3NS

IUPAC Name:

isothiocyanatomethane

Details on test material:

Test article name : METHYLSENFOEL (MITC)
Source: DEGUSSA AG
Purity: technical
Solid; above 35 degrees centigrade liquid.

Test animals

Species:

rabbit

Strain:

New Zealand White

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG (CH4414 Fuellinsdorf/ Switzerland)
- Age at study initiation: 15-16 weeks old
- Weight at study initiation: males = 1.8/3.2 kg, females = 2.6-3.4 kg
- Fasting period before study: no data
- Housing: individually in stainless steel cages equipped with an automatic cleaning and drinking system.
- Diet (e.g. ad libitum): pelleted standard kliba 341, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55+/-10
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 (music/light period)

Administration / exposure

Type of coverage:

occlusive

Vehicle:

unchanged (no vehicle)

Details on dermal exposure:

TEST SITE
- Area of exposure: backs of the animals
- % coverage: 40 square centimeters
- Type of wrap if used: after application, area was covered with an occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm water
- Time after start of exposure: 24 hours

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.05 ml (50 mg/kg), 0.15 ml (150 mg/kg), 0.30 ml (300 mg/kg)

Duration of exposure:

24 hours

Doses:

50, 150 and 300 mg/kg bw

No. of animals per sex per dose:

5 rabbits/ sexe/ dose

Control animals:

not specified

Details on study design:

- Duration of observation period following administration: 15 days
- Frequency of observations: four times during test day 1, and daily during days 2-15.
- Frequency of weighing: test day 1, 8 and 15.
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight, histopathology.

Statistics:

The LOGIT-Model was applied to estimate the LD50 value. Additionally, the 90, 95 and 99% confidence intervals for the LD50 for each sex and the slope of the concentration response line was estimated.

Results and discussion

Preliminary study:

no

Effect levels

Effect levels 1

Sex:

male/female

Dose descriptor:

LD50

Effect level:

174 mg/kg bw

95% CL:

> 123 - < 272

Effect levels 2

Sex:

male

Dose descriptor:

LD50

Effect level:

145 mg/kg bw

95% CL:

> 81 - < 293

Effect levels 3

Sex:

female

Dose descriptor:

LD50

Effect level:

202 mg/kg bw

95% CL:

> 106 - < 140

Mortality:

At 50 mg/kg : 0% of mortality. At 150 mg/kg = 30%, and at 300 mg/kg : 90 % of mortality.

Clinical signs:

other: -At 50 mg/kg : sedation, dyspnea, myosis, erythema, edema, necrosis, curved body position. -At 150 mg/kg : sedation, dyspnea, myosis, erythema, edema, necrosis + atawia (males), latero-abdominal position (males), salivation -At 300 mg/kg : sedation, dyspn

Gross pathology:

-At 50 mg/kg (killed animals, 10) : lung (mottled, slight) = 1, no pathologic changes = 9.
-At 150 mg/kg (dead animals, 3) : lung (mottled, slight) =1, liver (mottled, slight) =1, no pathologic changes =1.
-At 150 mg/kg (killed animals, 7) : lung (mottled, severe) = 3, dark-red = 2, no pathologic changes =4.
-At 300 mg/kg (dead animals,9) : lung (mottled, slight) =1, lung (mottled, severe) = 1, dark-red seveve = 4, liver pale = 4, mottled = 2; stomach (marginal area, spotted, dark-red)=1, mammary glands (discolored, dark-red) =1, no pathologic changes =1.
-At 300 mg/kg (killed animals, 1) : lung (mottled, slight) = 1.

Other findings:

no

Applicant's summary and conclusion

Interpretation of results:

Toxicity Category II

Remarks:

Migrated information Criteria used for interpretation of results: other: Guidance on the application of regulation(EC) No 1272/2008

Conclusions:

Based on the observations, the LOGIT-Estimation for the acute dermal LD50 of MITC in rabbits of both sexes over a period of 15 days is 174 mg/kg.

Executive summary:

MITC was applied to the skin of rabbits (5/dose/sex) of both sexes for 24 hours at 50, 150 and 300 mg/kg bw.

Animals were observed during 15 days, mortality, clinical signs and bodyweight were recorded.

No mortality were observed at 50 mg/kg bw. 30% of rabbits died at 150 mg/kg bw, and 90% at 300 mg/kg bw.

Clinical signs as sedation, dyspnea, miosis, erythema, edema, necrosis, curved body position were observed at 50 mg/kg bw and higher.

Based on the observations, the acute dermal LD50 of MITC in rabbits of both sexes over a period of 15 days is 174 mg/kg.