Registration Dossier

Diss Factsheets

Toxicological information

Acute Toxicity: dermal

Currently viewing:

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 guidelineopen allclose all
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to guideline
Guideline:
other: EPA - Pesticide assessment guidelines.
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no

Test material

Constituent 1
Chemical structure
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 levelsopen allclose all
Sex:
male/female
Dose descriptor:
LD50
Effect level:
174 mg/kg bw
95% CL:
> 123 - < 272
Sex:
male
Dose descriptor:
LD50
Effect level:
145 mg/kg bw
95% CL:
> 81 - < 293
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.