Chinomethionate

Endpoint summary

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin corrosion: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

29 to 31 August 2017

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 431 (In Vitro Skin Corrosion: Human Skin Model Test)

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Bx 160722-01
- Expiration date of the lot/batch: 22 July 2018
- Purity test date: no data

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: 15 - 25°C below 70% RH.
- Stability under test conditions: no data
- Solubility and stability of the test substance in the solvent/vehicle:
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
- Preliminary purification step (if any):
- Final dilution of a dissolved solid, stock liquid or gel:
- Final preparation of a solid:

FORM AS APPLIED IN THE TEST (if different from that of starting material)

TYPE OF BIOCIDE/PESTICIDE FORMULATION (if applicable)

OTHER SPECIFICS:

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Cell source:

other: Adult human-derived epidermal keratinocytes are seeded on a dermal substitute consisting of a collagen type I matrix coated with type IV collagen.

Justification for test system used:

The EPISKINTM(SM) model has been validated for corrosivity testing in an international trial (Fentem, 1998) and its use is recommended by the relevant OECD guideline for corrosivity testing (OECD No. 431); therefore, it was considered to be suitable for this study.

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used: Adult human derived epidermal keratinocytes
- Tissue batch number(s):
- Production date:
- Shipping date:
- Delivery date:
- Date of initiation of testing:

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure: 37°C
- Temperature of post-treatment incubation (if applicable):

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps:
- Observable damage in the tissue due to washing:
- Modifications to validated SOP:

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration:
- Incubation time:
- Spectrophotometer:
- Wavelength:
- Filter:
- Filter bandwidth:
- Linear OD range of spectrophotometer:

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability:
- Barrier function:
- Morphology:
- Contamination:
- Reproducibility:

NUMBER OF REPLICATE TISSUES:

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- Fresh tissues / killed tissues
- Procedure used to prepare the killed tissues (if applicable):
- N. of replicates :
- Method of calculation used:

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION:

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive to skin if [complete, e.g. the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15%.]
- The test substance is considered to be non-corrosive to skin if [complete, e.g. the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%.]
- Justification for the selection of the cut-off point(s) if different than recommended in TG 431 and 439:

Control samples:

yes, concurrent no treatment

Duration of treatment / exposure:

4 hours

Duration of post-treatment incubation (if applicable):

The viability of each disk was assessed by incubating the tissues for 3 hours with MTT solution.

Number of replicates:

6

Type of coverage:

occlusive

Irritation / corrosion parameter:

other: Optical density

Run / experiment:

Mean

Value:

0.727

Vehicle controls validity:

valid

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

no indication of irritation

Interpretation of results:

GHS criteria not met

Conclusions:

The results of this study indicate that chinomethionate is not corrosive to skin.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

13 September 2017

Reliability:

2 (reliable with restrictions)

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

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source and lot/batch No.of test material: Bx 160722-01
- Expiration date of the lot/batch: 22 July 2018
- Purity test date:

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Controlled room temperature (15-25 ºC, below 70 RH%) - Stability under test conditions:
- Solubility and stability of the test substance in the solvent/vehicle:
- Reactivity of the test substance with the solvent/vehicle of the cell culture medium:

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing:
- Preliminary purification step (if any):
- Final dilution of a dissolved solid, stock liquid or gel:
- Final preparation of a solid:

FORM AS APPLIED IN THE TEST (if different from that of starting material)

TYPE OF BIOCIDE/PESTICIDE FORMULATION (if applicable)

OTHER SPECIFICS:

Test system:

human skin model

Source species:

human

Cell type:

non-transformed keratinocytes

Source strain:

not specified

Vehicle:

unchanged (no vehicle)

Details on test system:

RECONSTRUCTED HUMAN EPIDERMIS (RHE) TISSUE
- Model used:
- Tissue batch number(s):
- Production date:
- Shipping date:
- Delivery date:
- Date of initiation of testing:

TEMPERATURE USED FOR TEST SYSTEM
- Temperature used during treatment / exposure:
- Temperature of post-treatment incubation (if applicable):

REMOVAL OF TEST MATERIAL AND CONTROLS
-Volume and number of washing steps:
- Observable damage in the tissue due to washing:
- Modifications to validated SOP:

MTT DYE USED TO MEASURE TISSUE VIABILITY AFTER TREATMENT / EXPOSURE
- MTT concentration:
- Incubation time:
- Spectrophotometer:
- Wavelength:
- Filter:
- Filter bandwidth:
- Linear OD range of spectrophotometer:

FUNCTIONAL MODEL CONDITIONS WITH REFERENCE TO HISTORICAL DATA
- Viability:
- Barrier function:
- Morphology:
- Contamination:
- Reproducibility:

NUMBER OF REPLICATE TISSUES:

CONTROL TISSUES USED IN CASE OF MTT DIRECT INTERFERENCE
- Fresh tissues / killed tissues
- Procedure used to prepare the killed tissues (if applicable):
- N. of replicates :
- Method of calculation used:

NUMBER OF INDEPENDENT TEST SEQUENCES / EXPERIMENTS TO DERIVE FINAL PREDICTION:

PREDICTION MODEL / DECISION CRITERIA (choose relevant statement)
- The test substance is considered to be corrosive to skin if [complete, e.g. the viability after 3 minutes exposure is less than 50%, or if the viability after 3 minutes exposure is greater than or equal to 50 % and the viability after 1 hour exposure is less than 15%.]
- The test substance is considered to be non-corrosive to skin if [complete, e.g. the viability after 3 minutes exposure is greater than or equal to 50% and the viability after 1 hour exposure is greater than or equal to 15%.]
- Justification for the selection of the cut-off point(s) if different than recommended in TG 431 and 439:

Control samples:

yes, concurrent no treatment

Amount/concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 10mg
- Concentration (if solution):

VEHICLE
- Amount(s) applied (volume or weight with unit):
- Concentration (if solution):
- Lot/batch no. (if required):
- Purity:

NEGATIVE CONTROL
- Amount(s) applied (volume or weight): 50µL
- Concentration (if solution):

POSITIVE CONTROL
- Amount(s) applied (volume or weight): 50µL
- Concentration (if solution): 5% w/v

Duration of treatment / exposure:

42hr

Duration of post-treatment incubation (if applicable):

After the 42 hours incubation, all EPISKINTM (SM) units (except the two living colour control units in Experiment I) were transferred into the MTT working solution filled wells (2 mL of 0.3 mg/mL MTT per well). Then, all transferred EPISKINTM (SM) units were incubated for 3 hours (± 5 min) at 37°C in an incubator with 5% CO2 protected from light, in a >95% humidified atmosphere.

Number of replicates:

3

Irritation / corrosion parameter:

other: Optical density

Run / experiment:

mean

Value:

0.312

Vehicle controls validity:

not applicable

Negative controls validity:

valid

Positive controls validity:

valid

Remarks on result:

positive indication of irritation

Interpretation of results:

Category 2 (irritant) based on GHS criteria

Conclusions:

In conclusion, in this in vitro EPISKINTM (SM) model test with Chinomethionate (Batch number: 160722-01), the results indicate that the test item is irritant to skin, UN GHS Classification: Category 2 (since the test item is known not to be corrosive).

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:

12 September 1994 - 26September 1994

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:

EPA OPP 81-4 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EPA OTS 798.4500 (Acute Eye Irritation)

Deviations:

no

Qualifier:

according to guideline

Guideline:

other: JMAFF, Guidence on Toxicology Study Data for Application of Agricultural Chemical Registration, 59 NohSan No. 4200, January 1985.

Deviations:

no

GLP compliance:

yes

Specific details on test material used for the study:

SOURCE OF TEST MATERIAL
- Source of test material: MILES INC, Agricultural Division, Box 4913, Hawthorn Road, Kansas City, Missouri 64120-0013
- Test substance: MORESTAN Technical
- CAS Registry No. 2439-01-2
- Appearence: Light yellow crystals
- Batch No. of test material: 203930103
- Purity: 93.1% (Purity test date not detailed)

STABILITY AND STORAGE CONDITIONS OF TEST MATERIAL
- Storage condition of test material: Freezer
- Stability under test conditions: Assured for the duration of use
- Solubility and stability of the test substance in the solvent/vehicle: Assumed stable for the duration of the study
- Reactivity of the test substance with the vehicle: None

TREATMENT OF TEST MATERIAL PRIOR TO TESTING
- Treatment of test material prior to testing: None

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Small Stock Industries, Pea Ridge, Arkansas
- Age at study initiation: 11 weeks
- Weight at study initiation: Not reported
- Housing: Individually in stainless steel cages with flat rod floors suspended over ALPHA-Dri bedding material. Bedding changes three times a week and and animals transferred to new cages every two weeks.Room disinfected once every three weeks.
- Diet: Provided with 125g of maintance diet
- Water ad libitum
- Acclimation period: Six weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 -24
- Humidity (%): 40-70
- Air changes (per hr): No reported
- Photoperiod (hrs dark / hrs light): 12

IN-LIFE DATES: From: To: 12 September 1994 (Experimental start) to 26 September 1994 (Experimental Ternination date)

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.63 mg (weight-equavalent to 0.1 mL)

Duration of treatment / exposure:

14 Days

Observation period (in vivo):

Each treated animal eye was evaluated at 1, 24 48 and 72 hours in accordence with the criteria for evaluation of ocular reactions. At 7 and 14 days animals were evaluated to further charactorise the time-course and reversibility of lesions.

Number of animals or in vitro replicates:

Six young-adult male New Zealand White rabbits

Details on study design:

Rabbits were examined with 24 hours of study initiation and classified as free from eye irritation and corneal or iridal injury. 63 mg (weight-equivalent to 0.1 mL) of test item was then placed in the conjunctival sac of the left eye and the eyelids held closed for approx one second. The right eye received no test item and acted as the untreated control.
No washing of the eye is reported after test substance exposure

SCORING SYSTEM (Starred (*) figures indicate positive effect)

Criteria for Evaluation of Ocular Reactions

Cornea:
Opacity - degree of density (area most dense taken for reading)

No ulceration or opacity 0
Scattered or diffuse areas of opacity (other than a slight dulling of the normal luster), details of iris clearly visible 1*
Easily discernible translucent area, details of iris slightly obscured 2*
Nacreous area, no details of iris visible, size of pupil barely discernible 3*
Opaque cornea, iris not discernible through the opacity 4*

Iris

Normal 0
Folds markedly deepened, congestion, swelling, circumcorneal injection (any/all of these or combination of any thereof), iris still reacting to light (sluggish reaction is positive) 1*
No reaction to light, hemorrhage, gross destruction (any or all of these) 2*

Conjunctiva
Redness (refers to palpebral and bulbar conjunctivae, cornea and iris)

Vessels normal 0
Some vessels definitely injected above normal 1
Diffuse, deeper crimson red, individual vessels not easily discernible 2*
Diffuse beefy red 3*

Chemosis (lids and/or nictitating membranes)

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 about closed to completely closed 4*

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 2
Discharge with moistening of the lids and hairs and considerable area around the eye 3


TOOL USED TO ASSESS SCORE: Penlight to facilitate evalauation

Irritation parameter:

cornea opacity score

Basis:

animal: 62

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Irritation parameter:

iris score

Basis:

animal: 62

Time point:

24/48/72 h

Score:

1

Max. score:

1

Irritation parameter:

conjunctivae score

Basis:

animal: 62

Time point:

24/48/72 h

Score:

2.6

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal: 62

Time point:

24/48/72 h

Score:

2

Max. score:

3

Irritation parameter:

cornea opacity score

Basis:

animal: 63

Time point:

24/48/72 h

Score:

0.6

Max. score:

1

Irritation parameter:

iris score

Basis:

animal: 63

Time point:

24/48/72 h

Score:

1

Max. score:

1

Irritation parameter:

conjunctivae score

Basis:

animal: 63

Time point:

24/48/72 h

Score:

2

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal: 63

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 64

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Irritation parameter:

iris score

Basis:

animal: 64

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal: 64

Time point:

24/48/72 h

Score:

3

Max. score:

3

Irritation parameter:

chemosis score

Basis:

animal: 64

Time point:

24/48/72 h

Score:

3

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 65

Time point:

24/48/72 h

Score:

0.6

Max. score:

1

Irritation parameter:

iris score

Basis:

animal: 65

Time point:

24/48/72 h

Score:

0.6

Max. score:

1

Irritation parameter:

conjunctivae score

Basis:

animal: 65

Time point:

24/48/72 h

Score:

1.6

Max. score:

2

Irritation parameter:

chemosis score

Basis:

animal: 65

Time point:

24/48/72 h

Score:

1.6

Max. score:

3

Irritation parameter:

cornea opacity score

Basis:

animal: 66

Time point:

24/48/72 h

Score:

0.6

Max. score:

1

Irritation parameter:

iris score

Basis:

animal: 66

Time point:

24/48/72 h

Score:

0.6

Max. score:

1

Irritation parameter:

conjunctivae score

Basis:

animal: 66

Time point:

24/48/72 h

Score:

1.6

Max. score:

2

Irritation parameter:

chemosis score

Basis:

animal: 66

Time point:

24/48/72 h

Score:

2

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 67

Time point:

24/48/72 h

Score:

0.6

Max. score:

1

Irritation parameter:

iris score

Basis:

animal: 67

Time point:

24/48/72 h

Score:

0.6

Max. score:

1

Irritation parameter:

conjunctivae score

Basis:

animal: 67

Time point:

24/48/72 h

Score:

1.6

Max. score:

2

Irritation parameter:

chemosis score

Basis:

animal: 67

Time point:

24/48/72 h

Score:

2

Max. score:

4

Irritation parameter:

cornea opacity score

Basis:

animal: 68

Time point:

24/48/72 h

Score:

4

Max. score:

4

Irritation parameter:

iris score

Basis:

animal: 68

Time point:

24/48/72 h

Score:

1.3

Max. score:

2

Irritation parameter:

conjunctivae score

Basis:

animal: 68

Time point:

24/48/72 h

Score:

3

Max. score:

4

Irritation parameter:

chemosis score

Basis:

animal: 968

Time point:

24/48/72 h

Score:

4

Max. score:

3

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Six young-adult male New Zealand White rabbits were used to determine the potential for technical grade MORESTAN to cause primary eye irritation. Corneal and iridal irritation (grades 2 and 1, respectively) persisted in two animals to study termination. Conjunctiva! redness and chemosis (grades 1-3 and 1-4, respectively) were first observed at one hour and were present in all animals by 24 hours after dosing. These signs resolved by study termination (day 14) in five of six animals. Discharge (grades 1-3) was observed in all six animals at one hour post-dosing and was resolved in all animals by day 7 post-dosing. All positive signs of conjuctival irritation were resolved by day 14 after exposure.

Based on these results, technical grade MORESTAN was judged to be a severe irritant to the eye of the rabbit.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

The results indicate that the test item is irritant to skin, UN GHS Classification: Category 2 (since the test item is known not to be corrosive).