O-isopropyl ethylthiocarbamate

Endpoint summary

Description of key information

Eye irritation: OECD 405; rabbits; 24h; not irritant

Skin irritation/corrosion: OECD 439; Human skin model; 20min; irritant

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 439 (In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test system:

human skin model

Source species:

human

Cell type:

other: EST-1000 (CellSystems® Biotechnology GmbH)

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 30 µL IPETC were applied to the skin model with a surface area of 0.6 cm²
- Concentration (if solution): 95.7

VEHICLE
- Amount(s) applied (volume or weight with unit): no vehicle used

Duration of treatment / exposure:

20 minutes

Observation period:

n/a

Number of animals:

n/a

Details on study design:

Negative control: phosphate buffered saline (D-PBS)
Positive control: 5% aqueous sodium dodecyl sulphate (SDS)

Irritation / corrosion parameter:

% tissue viability

Value:

ca. 10.2

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

other: Mean of tissue sample responses in percentage. Time point: 20 minutes. Reversibility not tested. Indication of a positive result.

Other effects / acceptance of results:

Summarized results (Mean±SD):

Optical density 20 minutes
Extinction# (n=3 tissues) % Extinction compared to control

Negative control(D-PBS) 0.459±0.008
IPETC (test substance) 0.047±0.039 10.2
Positive control(SDS) 0.014±0.007 3.1

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Remarks:

Based on EU GHS criteria

Conclusions:

Under the present test conditions IPETC , tested at an exposure time of 20 minutes, was cytotoxic and, hence, irritant to skin in an experiment employing an artificial three-dimensional model of human skin.

Executive summary:

An In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method was performed with the test substance in accordance with OECD Guideline 439 (employing an epidermal human Skin Test 1000 (EST-1000) cell tissue system). Under the test conditions, the test substance tested at an exposure time of 20 minutes, in an artificial three-dimensional model of human skin, was cytotoxic and, hence, irritant to skin in an experiment employing an artificial three-dimensional model of human skin.  

 

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2012

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: LPT Laboratory of Pharmacology and Toxicology GmbH & Co. KG branch Löhndorf, 24601 Löhndorf/Post Wankendorf, Germany
- Age at study initiation: 6.5-7.5 months
- Weight at study initiation: At dosing
Animal no. 1: 2.8 kg
Animal no. 2: 2.5 kg
Animal no. 3: 2.5 kg
At Termination of test
Animal no. 1: 2.8 kg
Animal no. 2: 2.6 kg
Animal no. 3: 2.5 kg

- Housing: Singly in 380mm*425mm*600mm cages
- Diet (e.g. ad libitum): ssniff ® K-H V2333 ad libitum
- Water (e.g. ad libitum): tap water ad libitum
- Acclimation period: minimum 20 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20
- Photoperiod (hrs dark / hrs light): 12 h light / 12 h dark

IN-LIFE DATES: From: July 12, 2012 To: July 21, 2012

Vehicle:

unchanged (no vehicle)

Controls:

other: left eye served as control, right eye as test eye

Amount / concentration applied:

0.1 mL of the test item was administered into one eye each of three animals.

Duration of treatment / exposure:

24 hours after instillation the eyes were rinsed with 20 mL NaCl solution. For 8 hours following test item application, the animals were kept singly in restrain¬ers which allowed free movement of the head but prevented a complete body turn, wiping of the eyes with the paws and excluded irritation of the eye by excre¬ments and urine.

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with NaCl solution
- Time after start of exposure: 24

SCORING SYSTEM:

TOOL USED TO ASSESS SCORE: hand-slit lamp / fluorescein

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 1h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: (swelling, refers to lids and/or nictitating membrane)

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 1h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Remarks on result:

other: (redness, palpebra/bulbar conjunctivae; excl. cornea/iris)

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Remarks on result:

not measured/tested

Irritation parameter:

iris score

Basis:

mean

Time point:

24 h

Score:

0.33

Max. score:

1

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

iris score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

iris score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24 h

Score:

0.67

Max. score:

1

Reversibility:

fully reversible within: 72 Hours

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

48 h

Remarks on result:

not measured/tested

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

72 h

Remarks on result:

not measured/tested

Irritant / corrosive response data:

Under the present test conditions, a single instillation of 0.1 mL IPETC per animal into the conjunctival sac of the right eye of three rabbits caused the following changes:
Corneal opacity (grade 1) was observed in animal nos. one and three 24 and 48 hours after instillation.
The fluorescein test performed 24 hours after instillation revealed corneal staining in animal nos. 1 and 3 (up to 1/4 of the surface).
Irritation of the iris (grade 1) was observed in animal no. one 24 hours after instillation.
Conjunctival redness (grade 1) was observed in all animals 60 minutes and in animal nos. 1 and 3 up to 24 hours after instillation.
Chemosis (grade 1) was observed in all animals 60 minutes after instillation.
There were no systemic intolerance reactions.
All symtoms were fully reversible within 72 hours after exposure.

Interpretation of results:

GHS criteria not met

Remarks:

EU GHS criteria not met

Conclusions:

Under the present test conditions, under the criteria set up in EC-Commission directive 67/548/EEC and EC-Regulation 1272/2008, the test item is concluded to be non-irritating to eyes

Executive summary:

An in vivo eye irritation/corrosion test with the test substance was performed in 3 rabbits in accordance with OECD Guideline 405. Based on the obtained test results and in accordance with the criteria of Classification, Labelling and Packaging of Substances and Mixtures Regulation (EC) No 1272/2008 (CLP Regulation), the test substance is not classified for eye irritation.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

eye irritation/ corrosion endpoint:

An in vivo eye irritation/corrosion test with the test substance was performed in 3 rabbits in accordance with OECD Guideline 405. Based on the obtained test results and in accordance with the criteria of Classification, Labelling and Packaging of Substances and Mixtures Regulation (EC) No 1272/2008 (CLP Regulation), the test substance is not classified for eye irritation.

skin irritation / corrosion endpoint:

An In Vitro Skin Irritation: Reconstructed Human Epidermis Test Method was performed with the test substance in accordance with OECD Guideline 439 (employing an epidermal human Skin Test 1000 (EST-1000) cell tissue system). Under the test conditions, the test substance tested at an exposure time of 20 minutes, in an artificial three-dimensional model of human skin, was cytotoxic and, hence, irritant to skin in an experiment employing an artificial three-dimensional model of human skin.  

 

Justification for classification or non-classification

According to the Regulation (EC) No 1272/2008 (CLP), eye irritation test does not meet criteria of classification. Skin irritation test shows sufficient effects equivalent to the classification criteria as irritating to skin in Category 2.