Methyl isothiocyanate

Acute Toxicity: inhalation

Administrative data

Endpoint:

acute toxicity: inhalation

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: Comparable to guideline study [OECD 403]

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

1977

Report date:

1977

Reference 2

Reference Type:

publication

Title:

Summary of toxicity data on methyl isothiocyanate (MITC)

Author:

Anonymous

Year:

1990

Bibliographic source:

Nippon Noyaku Gakkai (J. Pesticide Sci.), 15(2), 297-304.

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 403 (Acute Inhalation Toxicity)

Deviations:

yes

GLP compliance:

not specified

Test type:

standard acute method

Limit test:

yes

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 : METHYLISOTHIOCYANATE (MITC)
Purity: no data
A BROWNISH CRYSTALLINE SOLID

Test animals

Species:

rat

Strain:

Sprague-Dawley

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Anglia Laboratory animals (Alconbury, Cambridgeshire).
- Age at study initiation: no data
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: in polyprolylene wire bottomed cages which were suspended on movable racks. Each cage held 5 rats of the same sex.
- Diet (e.g. ad libitum): Spratt's laboratory Diet 1, ad libitum
- Water (e.g. ad libitum): tap water, ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55-70%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Administration / exposure

Route of administration:

inhalation: vapour

Type of inhalation exposure:

whole body

Vehicle:

other: no data

Details on inhalation exposure:

A stainless steel chamber with infernal dimensions 0.37 x 0.37 x 0.37 m and a nominal capacity of 50 L was used for the exposures. The chamber was divided horizontally into two sections by stainless steel mesh. The male and female animals were held in separate sections of the chamber during the exposure and the position of the sexes was changed for each exposure.
The total sample of methylisothiocyanate (1 kg) was melted by heating the container in a water bath at 400C and about 60 g of the Iiquid sample was transferred to the generator flask. The vapour from the generator flask passed through a distillation column packed loosely with glass wool into a second flask where it was diluted with air before entering the exposure chamber. The glass wool packing prevented the particulate rnaterial, formed as the vapour cooled, from reaching the dilution flask.

Analytical verification of test atmosphere concentrations:

not specified

Duration of exposure:

1 h

Concentrations:

0.6, 1.5, 2.2, 2.5 and 3.1 g per cubic metre of chamber air

No. of animals per sex per dose:

5 rats/ sexe / dose

Control animals:

yes

Details on study design:

- Duration of observation period following administration: 14 days
- Frequency of observations : twice daily
- Frequency of weighing : on days 1, 3, 7, 10, 14
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs, body weight,organ weights, histopathology

Statistics:

no

Results and discussion

Preliminary study:

no

Effect levels

Sex:

male/female

Dose descriptor:

LC50

Effect level:

1.9 mg/L air

Exp. duration:

1 h

Mortality:

yes see table.

Clinical signs:

other: A period of hyperactivity lasting for approximately 5 minutes was observed in all test groups on first contact with MITC vapour. Eye irritation, laboured breathing, hypoactivity convulsion and death were observed subsequently during the exposures. The rap

Body weight:

Groups exposed to concentrations of MITC between 1.5 and 2.5 g/m3 showed a temporary decrease in group mean bodyweight. The surviving animals had resumed a normal rate of body weight gain after 1-3 days.

Gross pathology:

Abnormalities seen in animals that died as a result of exposure were limited to slight to moderate lung congestion, areas of lung haemorrhage and hepatisation and distended gas filled stomachs and small intestine. Macroscopic pathology was considered to be within normal limits for animals that survived the 14 day observation period.

Other findings:

Organ weight : Lung to bodyweight ratios of animals that died following exposure to concentration of MITC between 1.5 and 2.5 g/m3 were considered to be high.

Any other information on results incl. tables

Table : Results of mortality

Concentration of MITC (g/m3)	No. dead/ No. exposed
3.1	10/10
2.5	5/10
2.2	4/10
1.5	3/10
0.6	0/10
0	0/10

Applicant's summary and conclusion

Interpretation of results:

other: Fatal if inhaled

Remarks:

Criteria used for interpretation of results: other: REGULATION (EC) No 1272/2008

Conclusions:

The LC50 (1h) for MITC is estimated at 1.9 g/m3 of air. Generic concentration limits for classification for inhalation toxicity are based on 4 hour testing exposures. According to the guidance to Regulation (EC) No 1272-2008 on classification, labelling and packaging (CLP) of substances and mixtures, conversion of existing inhalation toxicity data which have been generated using a 1 hour exposure can be carried out by dividing by a factor of 2 for gases and vapours. Accordingly the equivalent 4-hour LC50 for MITC is 0.85 mg/l for labelling purpose.

Executive summary:

Five groups (5 male + 5 female rats) were exposed continuously for 1 hour to the vapour generated from the sample of MITC. Rats were exposed at 0, 0.6, 1.5, 2.2, 2.5 or 3.1 g MITC/m3. Animals were observed during 14 days. Mortality, clinical signs, bodyweight, gross pathology were recorded.

No mortalities were observed at 0 and 0.6 g/m3. Respectively, 3, 4, 5 and 10 rats died at 1.5, 2.2, 2.5 and 3.1 g/m3 air.

A period of hyperactivity lasting for approximately 5 minutes was observed in all test groups on first contact with MITC vapour. Eye irritation, laboured breathing, hypoactivity convulsion and death were observed subsequently during the exposures. The rapidity of onset and the severity of these effects appeared to be dose related. The behaviour of animals in the control group was normal throughout the exposure period.

The LC50 (1h) for MITC is estimated at 1.9 g/m3 of air.