O-isopropyl ethylthiocarbamate

Endpoint summary

Description of key information

Eye irritation 
-The eye irritation study indicates that Propan-2-ol (Isopropyl alcohol) as a main constituent of IPETC/O-isopropyl ethylthiocarbamate is a irritant to rabbit eyes. 
The eye irritation study indicates that Butan-1-ol (Butyl alcohol)  as a main constituent of IPETC/O-isopropyl ethylthiocarbamate is a irritant to rabbit eyes.
Based on the descriptions of the lesions it is considered that IPETC/ O-isopropyl ethylthiocarbamate is classifiable as  irritant according to EU criteria. 
Skin irritation 
The acute skin irritation study indicates that Butan-1-ol (Butyl alcohol) as a main constituent of IPETC/O-isopropyl ethylthiocarbamate caused moderate irritation.
Based on the descriptions of the lesions it is considered that Reaction mass of O-isopropyl ethylthiocarbamate  and n-butanol  and propan-2-ol  is classifiable as  moderately  irritant according to EU criteria. 
Respiratory irritation. 
There were no treatment-related changes in the haematological or urinalysis values in any of the animals. No signs of irritation of respiratory tract and Nasal effects were observe

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Butan-1-ol (Butyl alcohol) is both reagents used in the manufacture of IPETC/O-isopropyl ethylthiocarbamatel. Therefore Butan-1-ol (Butyl alcohol) need to be considered in the assessment of IPETC/ O-isopropyl ethylthiocarbamate .

Qualifier:

according to guideline

Guideline:

other: Code of Federal Regulations, Title 16, Section 1500.41

Principles of method if other than guideline:

Six rabbits were exposed to the test substance for 24 hours under occlusive conditions (Draize-Test). The animals were observed for 8 days.

GLP compliance:

not specified

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: W. Ostrop breeding facility, Germany
- Weight at study initiation: 2.7 kg
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 4-6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 16-18 °C
- Humidity (%): 40 %
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

occlusive

Preparation of test site:

other: shaved or abraded

Vehicle:

unchanged (no vehicle)

Controls:

other: untreated skin of the same animals

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 ml

Duration of treatment / exposure:

24 hours

Observation period:

8 days

Number of animals:

6

Details on study design:

TEST SITE
- Area of exposure: flanks on an area of 8 x 8 cm on both sides
- % coverage: 2.5 x 2.5 cm
- Type of wrap if used: occlusive dressing


SCORING SYSTEM: edema and erythema formation graded from 0 to 4 (according to Draize)

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

4

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: only readings on shaved skin taken into account

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

3.17

Reversibility:

not fully reversible within: 8 days

Remarks on result:

other: only readings on shaved skin taken into account

The mean value for erythema formation was 4, the mean value for edema formation was 3.17. As no full thickness necrosis was reported, the test substance is considered as irritating to the skin.

Interpretation of results:

other: moderately irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The mean value for erythema formation was 4, the mean value for edema formation was 3.17. As no full thickness necrosis was reported, the test substance is considered as irritating to the skin.The acute skin irritation study indicates that Butan-1-ol (Butyl alcohol) as a main constituent of IPETC/ O-isopropyl ethylthiocarbamate caused moderate irritation.

Executive summary:

The acute skin irritation study indicates that Butan-1-ol (Butyl alcohol) as a main constituent of IPETC/O-isopropyl ethylthiocarbamate caused moderate irritation.

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

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

study well documented, meets generally accepted scientific principles, acceptable for assessment

Justification for type of information:

Propan-2-ol (Isopropyl alcohol) is both reagents used in the manufacture ofI IPETC/ O-isopropyl ethylthiocarbamate Therefore, propan-2-ol (Isopropyl alcohol) need to be considered in the assessment of IPETC/O-isopropyl ethylthiocarbamate .

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

study terminated at 14 days instead of 21 with complete revisibility only seen in 3 of 6 animals

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazelton Research Products, Inc. Denver, Pennsylvania
- Age at study initiation: 12 weeks
- Weight at study initiation: 2.25 to 3.06 kg
- Housing: Individual in suspended stainless steel cages
- Diet (e.g. ad libitum): Purina certified rabbit chow ad libitum
- Water (e.g. ad libitum): Automatic watering system (Elizabethtown watering company) ad libitum
- Acclimation period: 13 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-21
- Humidity (%): 40-60
- Photoperiod (hrs dark / hrs light):12/12


IN-LIFE DATES: From: June/July 1986 To: September 29-1986

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): 100%

Duration of treatment / exposure:

Single treatment

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

3/sex/group

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): none


SCORING SYSTEM: Draize Scale

I. CONJUNCTIVAE

A. Redness (refers to palpebral and bulbar conjunctivae
excluding cornea and iris)
Vessels normal 0
Some vessels definitely injected 1
Diffuse, crimson red, individual vessels not easily discernible 2
Diffuse beefy red 3

Q. Chemosis
No swelling 0
Any swelling above normal (includes nictitating membrane) 1
Obvious swelling with partial eversion of lids 2
Swelling with lids about half closed 3
Swelling with lids more than half closed 4

C. Discharge
No discharge 0
Any amount different from normal (does not include small amounts observed in inner canthus of normal animals) 1
Discharge with moistening of the lids and hairs just adjacent to lids
Discharge with moistening of the lids and hairs, and considerable area around eye 3

D. Necrosis or ulceration of palpebral and bulbar
conjunctivae or nictitating membranes

Not present 0*
Necrosis present N*
Ulceration present U*
Conjunctivae Score: (A + B + C) X 2 (maximum = 20)
* - Not included in Draize grading system

II. IRIS
A. Values
Normal 0
Markedly deepened folds, congestion, swelling, circumcorneal injection (any of these), iris still reacting to light (sluggish reaction is positive).1
No reaction to light, hemorrhage, gross destruction (any of these) 2
Iris Score: A X 5 (maximum = 10)

III. CORNEA

A. Opacity-degree of density (area most dense)
No opacity 0
Slight dulling of the normal luster +*
Scattered or diffuse areas of opacity, details of iris clearly visible 1
Easily discernible translucent area, details of iris slightly obscured.. 2
Nacreous areas, no details of iris visible, size of pupil barely discernible 3
Complete corneal opacity, iris not discernible 4

B. Area of cornea involved
Up to one quarter 1
Greater than one quarter, less than half 2
Greater than half, less than three quarters 3
Greater than three quarters .4

C. Stippling-area of pinpoint roughening
No stippling 0*
Up to one quarter 1*
Greater than one quarter, less than half 2*
Greater than half, less than three quarters 3*
Greater than three quarters 4*

D. Ulceration-absence of area of corneal epithelium
No ulceration P*
Up to one quarter :, 1*
Greater than one quarter, less than half 2*
Greater than half, less than three quarters 3*
Greater than three quarters 4*
Corneal Score: A X B X 5 (maximum = 80)
* - Not included in Draize grading system


TOOL USED TO ASSESS SCORE: fluorescein

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.67

Max. score:

110

Reversibility:

not fully reversible within: 24 hours

Irritation parameter:

iris score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

110

Reversibility:

not fully reversible within: 24 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

110

Reversibility:

not fully reversible within: 24 hours

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3

Max. score:

110

Reversibility:

not fully reversible within: 24 hours

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #5

Time point:

24 h

Score:

ca. 23

Max. score:

110

Reversibility:

not fully reversible within: 24 hours

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #6

Time point:

24 h

Score:

ca. 25

Max. score:

110

Reversibility:

not fully reversible within: 24 hours

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #1

Time point:

14 d

Score:

ca. 2

Max. score:

110

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: study terminated at 14 days, however trend of reversibility was observed

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #2

Time point:

14 d

Score:

ca. 0

Max. score:

110

Reversibility:

fully reversible

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #3

Time point:

14 d

Score:

ca. 0

Max. score:

110

Reversibility:

fully reversible

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #4

Time point:

14 d

Score:

ca. 2

Max. score:

110

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: study terminated at 14 days, however trend of reversibility was observed

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #5

Time point:

14 d

Score:

ca. 2

Max. score:

110

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: study terminated at 14 days, however trend of reversibility was observed

Irritation parameter:

maximum mean total score (MMTS)

Basis:

animal #6

Time point:

14 d

Score:

ca. 0

Max. score:

110

Reversibility:

fully reversible

Irritant / corrosive response data:

Ocular instillation of isopropyl alcohol (MRD-86-962) elicited conjunctival, corneal and iridial responses in all animals.
Conjunctival responses included redness, chemosis, clear/white discharge and conjunctival ulceration. Redness was noted in all animals from the 1 Hour observation through the Day 10 observation. The incidence of redness decreased after these observations and three animals were noted with redness at the Day 14 observation. Chemosis was noted in all animals from the 1 Hour observation through the 48 Hour observation. The incidence of chemosis declined after these observations and chemosis was not noted at the Day 14 observation. Clear and/or white discharge was noted in all animals at the 1 and 4 Hour observations. The incidence of discharge decreased after these observations and no discharge was noted by the Day 4 observation. Conjunctival ulceration was noted in five animals during the study.
Iridial responses were noted in all animals during the study with varying incidences at the different observation intervals. Iridial responses were not noted after the Day 7 observation.
Corneal responses included opacity, stippling and corneal ulceration. Corneal opacity was noted in five animals, stippling was noted in five animals and corneal ulceration was noted in all animals during the study. All animals were clear of corneal responses by Day 7.
Other observations noted during the study included dye retention of the nictitating membrane and conjunctiva, and conjunctival blistering.
Ocular irritation was most prominent from the 1 Hour through the Day 4 observations where the total Draize score ranged from 4 to 25.

Animal	Effect	24 hrs	48 hrs	72 hrs	24-72hr avg	4 days	7 days	10 days	14 days
1	Cornea	4	4	3	3.67	1	0	0	0
	Iris	1	1	1	1.00	0	0	0	0
	Redness	3	3	3	3.00	3	2	1	1
	Chemosis	3	3	3	3.00	1	1	1	0
2	Cornea	4	2	0	2.00	0	0	0	0
	Iris	1	1	0	0.67	0	0	0	0
	Redness	3	3	3	3.00	3	1	1	0
	Chemosis	3	3	2	2.67	1	1	0	0
3	Cornea	3	2	0	1.67	0	0	0	0
	Iris	1	1	1	1.00	0	0	0	0
	Redness	3	3	3	3.00	3	1	1	0
	Chemosis	2	1	1	1.33	1	1	0	0
4	Cornea	0	0	0	0.00	0	0	0	0
	Iris	1	1	0	0.67	0	0	0	0
	Redness	3	3	3	3.00	3	1	1	1
	Chemosis	1	1	0	0.67	1	0	0	0
5	Cornea	4	3	2	3.00	0	0	0	0
	Iris	1	1	1	1.00	1	1	0	0
	Redness	3	3	3	3.00	3	2	1	1
	Chemosis	3	2	1	2.00	1	1	0	0
6	Cornea	2	1	0	1.00	0	0	0	0
	Iris	1	0	0	0.33	0	0	0	0
	Redness	3	3	2	2.67	2	2	1	0
	Chemosis	4	2	1	2.33	0	0	0	0
6-animal averages:   Cornea Iris Redness Chemosis					1.89	6 animals not fully reversed	6 animals not fully reversed	6 animals not fully reversed	3 animals not fully reversed

Interpretation of results:

other: irritating

Remarks:

Criteria used for interpretation of results: EU

Conclusions:

The results demonstrate a trend in reversibility; however, the study was ended at the day 14 instead of day 21 and full reversibility may have been observed at day 21. The results of this study indicate that the substance is a irritant to rabbit eyes. Propan-2-ol (Isopropyl alcohol) is both reagents used in the manufacture of IPETC/ O-isopropyl ethylthiocarbamate. Therefore Propan-2-ol (Isopropyl alcohol) need to be considered in the assessment of IPETC/O-isopropyl ethylthiocarbamate

Executive summary:

The eye irritation study indicates that Propan-2-ol (Isopropyl alcohol) as a main constituent of IPETC/O-isopropyl ethylthiocarbamate is a irritant to rabbit eyes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Additional information

Eye irritation

 

-The eye irritation study indicates that Propan-2-ol (Isopropyl alcohol) as a main constituent  IPETC/O-isopropyl ethylthiocarbamate is a irritant to rabbit eyes.

The eye irritation study indicates that Butan-1-ol (Butyl alcohol) as a main constituent of IPETC/O-isopropyl ethylthiocarbamate is a irritant to rabbit eyes.

 

Based on the descriptions of the lesions it is considered that IPETC/O-isopropyl ethylthiocarbamate l is classifiable as  irritant according to EU criteria.

 

Skin irritation

 

The acute skin irritation study indicates that Butan-1-ol (Butyl alcohol) as a main constituent of IPETC/ O-isopropyl ethylthiocarbamate caused moderate irritation.

 

Based on the descriptions of the lesions it is considered that IPETC/O-isopropyl ethylthiocarbamate l is classifiable as  moderately irritant according to EU criteria.

 

 

 

 

Respiratory irritation.

 

The results of the study (Burleigh-Flayer H, Garman R, Neptun D, Bevan C, Gardiner T, Kapp R, Tyler T & Wright G 1997) indicate that Propan-2-ol (Isopropyl alcohol) as a main constituent of IPETC/ O-isopropyl ethylthiocarbamate has not an adverse effect at concentration of 5000 ppm on kidneys in rats. Macroscopic changes such as granular kidney were noted in males and females of 2500 and 5000 ppm groups. A number of non-neoplastic histopathological changes were observed, with the most significant being in the kidney. The only neoplastic change observed was in male rats and was an increase in interstitial cell adenomas of the testis considered to represent marked hyperplasia and not autonomous growth.

There were no treatment-related changes in the haematological or urinalysis values in any of the animals. No signs of irritation of respiratory tract and Nasal effects were observe

Effects on skin irritation/corrosion: moderately irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Based on the hazard assessment of IPETC/ O-isopropyl ethylthiocarbamate

in section 2.1 and 2.2. in IUCLID 6., available data for the substance and following the “Guidance on Information Requirement and Chemical Safety Assessment R.8. Characterisation of dose [concentration]- response for human health” andaccording to the criteria described in Directive 67/548 and in the CLP Regulation:

 

Directive 67/548

Skin Corrosivity C R35 Causes severe burns R34 Causes burns Skin Irritation Xi R38 Irritating to skin R43 May cause sensitization by skin contact Eye Irritation (Ocular Lesions) Xi R36 Irritating to eyes R36/38 - Irritating to eyes and skin R37 irritating to respiratory system R41 Risk of serious damage to eyes

CLP

Skin Corrosivity  H314 Skin Corr 1A Causes severe skin burns and eye damage H314 Skin Corr 1B Causes severe skin burns and eye damage Skin Irritation  H315 Skin Irrit. 2 Causes skin irritation H317 Skin Sens. 1 May cause an allergic skin reaction Eye Irritation (Ocular Lesions) Xi H319 Eye Irrit. 2 Causes serious eye irritation H318 Eye Dam. 1 Causes serious eye damage H335 STOT SE 3 May cause respiratory irritation

 

It is concluded that the substance IPETC/O-isopropyl ethylthiocarbamate  meet the criteria to be classified for human health hazards for Dermal-local effect:  R36/38 - Irritating to eyes and skin, H315 Skin Irrit. 2 Causes skin irritation, H319 Eye Irrit. 2 Causes serious eye irritation

  

It is concluded that the substance IPETC/O-isopropyl ethylthiocarbamate  does not meet the criteria to be classified for human health hazards for respiratory irritation