Methyl isothiocyanate

Endpoint summary

Description of key information

Methyl isothiocyanate is corrosive for the skin, highly irritating for the eyes and irritant for the respiratory tract.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

other:

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (corrosive)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP Guideline study (OECD 405)

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: EPA - Pesticide assessment guidelines

Deviations:

not specified

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG (Ch4414 Fuellinsdorf, Switzerland)
- Age at study initiation: 15-16 weeks
- Weight at study initiation: 2.1-2.2 weeks
- Housing: individually in stainless steel cages aquipped 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: 4 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22+/-2
- Humidity (%): 55+/-10
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12 (8h music/light period)

Vehicle:

unchanged (no vehicle)

Controls:

other: the right eye (untreated eye) of each animal

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml/animal
- Concentration (if solution): no data

VEHICLE : no

Duration of treatment / exposure:

a single dose was administered to the left eye of each animal.

Observation period (in vivo):

72 hours.
According to the results observed and due to ethical reasons the test was terminated after an observation period of 72 hours.

Number of animals or in vitro replicates:

3 = 2 females + 1 male

Details on study design:

REMOVAL OF TEST SUBSTANCE : NO
SCORING SYSTEM: the same in guideline of OECD (405)
TOOL USED TO ASSESS SCORE: a slit-lamp 30 SL and a Varta Cliptrix diagnostic-lamp.

Irritation parameter:

cornea opacity score

Remarks:

(opacity)

Basis:

mean

Remarks:

3 animals

Time point:

other: 24-72 hours

Score:

2.66

Max. score:

4

Reversibility:

other: not examined

Remarks on result:

other: Individual scores: 3, 2, 3.

Irritation parameter:

iris score

Basis:

mean

Remarks:

3 animals

Time point:

other: 24-72 hours

Score:

1.67

Max. score:

2

Reversibility:

other: not examined

Remarks on result:

other: Individual scores: 2, 1, 2.

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

mean

Remarks:

3 animals

Time point:

other: 24-72 hours

Score:

3

Max. score:

3

Reversibility:

other: not examined

Remarks on result:

other: Individual scores: 3, 3, 3.

Irritation parameter:

conjunctivae score

Remarks:

(chemosis)

Basis:

mean

Remarks:

3 animals

Time point:

other: 24-72 hours

Score:

3.47

Max. score:

4

Reversibility:

other: not examined

Remarks on result:

other: Individual scores: 3.7, 3, 3.7

Irritant / corrosive response data:

MITC to the eyes of rabbits produced severe inflammation including corneal opacity, iritis and conjunctival swelling. The mean value of the scores for each type of lesion, calculated for each animal separately, from 24 to 72 hours. See table.
Corrosion of the cornea and conjuntivae was observed at each of the measuring intervals.

Other effects:

Slight sedation was observed in all animals at day one of test. No other acute toxic symptoms were observed in the animal during the remaining test period, and no mortality occurred. The body weight gain of all rabbits was similar.
In the area of application, no discoloration of the cornea and conjunctivae which could be related to effects of MITC was observed.
Due to the results obtained, no macroscopic organ examination was indicated.

Table of results (MITC) :

Animal	Mean 24-72h
	Cornea opacity	Iris	Conjunctivae
			Redness	Chemosis
1 – male	3	2	3	3.7
2 – female	2	1	3	3
3 – female	3	2	3	3.7

Interpretation of results:

Category 1 (irreversible effects on the eye)

Remarks:

Migrated information Criteria used for interpretation of results: other: Regulation EC no.1272/2008

Conclusions:

MITC induced risk of serious damage to eyes, it was highly irritating.

Executive summary:

The purpose of this primary eye irritation study was to assess possible irritation potential when single doses of MITC are placed in the conjunctival sac of rabbit eyes.

MITC to the eyes of rabbits produced severe inflammation including corneal opacity, iritis and conjunctival swelling.

In the area of application no discoloration of the cornea and conjunctivae was observed which could be related to effects of MITC.

The mean value of the scores of 3 rabbits at 24/72 hours were: Score of cornea opacity =2.66/4, score of iritis = 1.67/2, redness score =3/3 and chemosis score =3.47/4.

Slight sedation was observed in all animals at day one of test. No other acute toxic symptoms were observed in the animal during the remaining test period, and no mortality occurred. The body weight gain of all rabbits was similar.

To sum up, MITC induced risk of serious damage to eyes, it was highly irritating.

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Additional information

Skin irritation

Ullmann (1985d) tested methylisothiocyanate in GLP Guideline study (OECD 404). The purpose of this primary study skin irritation study was to assess possible irritation potential when single doses of methylisothiocyanate are placed on the skin on rabbits. All animals died within the 4 -hour treatment phase, therefore no irritation index could be determined.

The acute dermal toxicity studies performed in rats (Ullmann, 1985b) and rabbits (Ullmann, 1985c) indicated skin necrosis at dose levels as low as 120 and 50 mg/kg bw.

Eye irritation

The purpose of this primary eye irritation study was to assess possible irritation potential when single doses of methyl isothiocyanate are placed in the conjunctival sac of rabbit eyes (Ullmann, 1985e). Methyl isothiocyanate to the eyes of rabbits produced severe inflammation including corneal opacity, iritis and conjunctival swelling. In the area of application no discoloration of the cornea and conjunctivae was observed which could be related to effects of methyl isothiocyanate. The mean value of the scores of 3 rabbits at 24/72 hours were: Score of cornea opacity =2.66/4, score of iritis = 1.67/2, redness score =3/3 and chemosis score =3.47/4. Slight sedation was observed in all animals at day one of test. No other acute toxic symptoms were observed in the animal during the remaining test period, and no mortality occurred. The body weight gain of all rabbits was similar. To sum up, methyl isothiocyanate induced risk of serious damage to eyes, it was highly irritating.

Respiratory irritation

A sensory irritation study with methyl isothiocyanate was carried out to provide data on the irritating properties of methylisothiocyanate and to discriminate between sensory (nasal) irritation and pulmonary irritation in rats (Arts, 1993). For sensory irritation: a post-inspiratory apnoea was frequently seen in rats exposed to the higher concentration levels, 121, 195 and 309 mg/m3, and occasionally seen in rats exposed to 67 mg/m3. From these results, it was concluded that the RD50 (exposure concentration producing a 50% respiratory rate decrease) value of methylisothiocyanate was 93 mg/m3 as determined according to Alarie (1973) and 95 ± 8 mg/m3 according to Bos et al. (1992). These RD50 values were not affected by the inhibitory effects if the solvent ethanol.

Justification for selection of skin irritation / corrosion endpoint:
Only one reliable study is available to evaluate the skin irritation potential of MITC (Ullmann 1985). However due to the strong toxicity of MITC, no score could be determined. As MITC already is classified as corrosive for skin, and toxic if in contact with skin, no further study is required.

Justification for selection of eye irritation endpoint:
Only one reliable study is available to evaluate the eye irritation potential of MITC (Ullmann 1985).

Effects on skin irritation/corrosion: corrosive

Effects on eye irritation: highly irritating

Effects on respiratory irritation: irritating

Justification for classification or non-classification

Mandatory classification:

- Regulation (EC) No 1272/2008 Annex VI Table 3.1

Skin Corr. 1B: H314, Causes severe skin burns and eye damage

- Regulation (EC) No 1272/2008 Annex VI Table 3.2

C, R34: Causes burns

Self classification:

- Regulation (EC) No 1272/2008

Skin Corr. 1B: H314, Causes severe skin burns and eye damage

Eye Irr. 1: H318, Causes serious eye damage

STOT single exposure: H335, May cause respiratory irritation

-Directive 67/548/EEC

Xi, R37: Irritant for the respiratory tract

C, R34: Causes burns