2-ethylhexyl 10-ethyl-4,4-dimethyl-7-oxo-8-oxa-3,5-dithia-4-stannatetradecanoate

Endpoint summary

Description of key information

Skin irritation: modified Primary Irritation Index 1.75; moderate irritant in rabbits
Eye irritation: conjunctival irritation produced which cleared by 24 hours in rabbits

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation / corrosion, other

Remarks:

in vivo study in the rabbit. The existing in vivo data is considered to fulfil the in vitro skin irritation/corrosion requirement.

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, Massachusetts, USA
- Age at study initiation: approx 14-18 weeks
- Weight at study initiation: 2.7-3.5 kg
- Housing: 1/cage in suspended wire cages
- Diet (e.g. ad libitum): PMI Rabbit Chow (Diet #5321) daily
- Water (e.g. ad libitum): ad libitum
- Acclimation period: at least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 deg C
- Humidity (%): 60-86%
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hour light / 12 hour dark


IN-LIFE DATES: From: June 20, 2006 To: June 27, 2006

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.5 mL/site
- Concentration (if solution): N/A


VEHICLE- no vehicle

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

2 males and 1 female

Details on study design:

TEST SITE
- Area of exposure: dorsal area of the trunk
- % coverage: 10 x 10 cm
- Type of wrap if used: piece of fabric (semi-occlusive) secured with adhesive tape


REMOVAL OF TEST SUBSTANCE
- Washing (if done): wiped with paper towels saturated with tap water and blotted dry with paper towels
- Time after start of exposure: after 4 hours of exposure


SCORING SYSTEM:scored according to Draize technique

Irritation parameter:

other: Modified Primary Irritation Index

Basis:

mean

Time point:

other: 4-hr

Score:

1.75

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: Edema was absent at 72 hours and on Day 7; Erythema was absent on Day 7

Irritant / corrosive response data:

Erythema was absent to well defined at 60 minutes, 24 hours and 48 hours following the 4 hour exposure. Erythema was absent to very slight at 72 hours and absent on day 7. Edema was absent to very slight at 60 minutes following the 4 hour exposure and absent to well defined at 24 and 48 hours. Edema was absent at 72 hours and on Day 7.

Other effects:

There were no abnormal physical signs noted during the observation period.
All body weight changes were normal.

Interpretation of results:

moderately irritating

Remarks:

Migrated information Criteria used for interpretation of results: other: USEPA Review Manual, Chapter 8: Precautionary Labeling (1997)

Conclusions:

The test substance is a dermal irritant with a modified Primary Irritation Index of 1.75.

Executive summary:

To determine the irritant or corrosive effects of the test substance when applied dermally. The study followed OECD test guideline 404. Since the test substance was not expected to produce severe irritation or corrosion, three healthy New Zealand White rabbits (2 males-1 female) were dosed dermally with the test substance. The substance (0.5 mL) was applied dermally to one intact site/rabbit. The test substance was kept in contact with the skin for 4 hours at which time the wrappings were removed. Dermal reactions were scored at 60 minutes after removal of the wrappings. Reactions were scored again at 24, 48 and 72 hours and on Day 7. The skin was also evaluated for ulceration and necrosis or any evidence of tissue destruction at these time periods. Body weights were recorded pretest, at 72 hours and at termination. A modified Primary Irritation Index was calculated using the 60 minute, 24, 48 and 72 hour scoring intervals.

Erythema was absent to well defined at 60 minutes, 24 hours and 48 hours following the 4 hour exposure. Erythema was absent to very slight at 72 hours and absent on day 7. Edema was absent to very slight at 60 minutes following the 4 hour exposure and absent to well defined at 24 and 48 hours. Edema was absent at 72 hours and on Day 7. There were no abnormal physical signs noted during the observation period. All body weight changes were normal. The test substance is a dermal irritant.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation, other

Remarks:

in vivo study in the rabbit. The existing in vivo data is considered to fulfil the in vitro eye irritation requirement.

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

, control eyes were not scored at 1 hour.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Millbrook Breeding Labs, Amherst, MA
- Age at study initiation: Approximately 4 months old
- Weight at study initiation: 2.2 – 2.6 kg
- Housing: The animals were housed 1/cage in suspended cages. Bedding was placed beneath the cages and changed at least three times /week.
- Diet (e.g. ad libitum): Fresh PMI Rabbit Chow (Diet #5321) was provided daily.
- Water (e.g. ad libitum): ad libitum
- Acclimation period: At least 5 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 - 21◦C
- Humidity (%): 64-86 %
- Air changes (per hr): No data
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle


IN-LIFE DATES: From: 2006-07-03 To: 2006-07-06

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

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



VEHICLE- none

Duration of treatment / exposure:

24 hours

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): The treated and control eyes of each rabbit were washed with saline following 24 hour observation interval for approximately one minute using a volume and velocity of flow which did not cause injury.
- Time after start of exposure: 24 hours


SCORING SYSTEM: Draize

TOOL USED TO ASSESS SCORE:
Observations were performed using a Mini-Maglite® flashlight equipped with a high intensity bulb.

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24-72 hour

Score:

0

Max. score:

80

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24-72 hours

Score:

0

Max. score:

10

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24-72 hours

Score:

0

Max. score:

12

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Conjunctival irritation, noted in 3/3 eyes at 1 hour, cleared by 24 hours

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24-72 hours

Score:

0

Max. score:

8

Reversibility:

fully reversible within: 24 hours

Remarks on result:

other: Conjunctival irritation, noted in 3/3 eyes at 1 hour, cleared by 24 hours

Irritant / corrosive response data:

There was no corneal opacity or iritis noted at any observation period. Conjunctival irritation, noted in 3/3 eyes, cleared by 24 hours.

Other effects:

There were no abnormal physical signs noted during the observation period

Interpretation of results:

other: Not classified according to EU criteria.

Conclusions:

Ocular administration produced conjunctival irritation which cleared by 24 hours.

Executive summary:

To determine the irritant and/or corrosive effects, if any, of the test substance when instilled into the rabbit eye. Three healthy New Zealand White rabbits (2 males; 1 female) free from evidence of ocular irritation and corneal abnormalities, were dosed with 0.1 mL placed into the conjunctival sac of one eye of each rabbit. The contralateral eye served as control. The treated eye of each rabbit was examined and scored by the Draize technique at 1, 24, 48 and 72 hours postdose and the untreated eye was scored at 24, 48 and 72 hours. Both eyes were washed with saline following the 24 hour observation interval for approximately one minute using a volume and velocity of flow which did not cause injury. The eye irritation score for each rabbit was calculated each day. Body weights were recorded pretest and at termination.

There was no corneal opacity or iritis noted at any observation period. Conjunctival irritation, noted in 3/3 eyes, cleared by 24 hours. All three control eyes appeared normal at each observation period. There were no abnormal physical signs noted during the observation period.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

GLP guideline studies were used to evaluate the irritation potential to the skin and eye of rabbits. Dermal reactions were scored at 60 minutes after wrap removal and again at 24, 48 and 72 hours and on Day 7. The treated eye of each rabbit was scored by the Draize technique at 1, 24, 48 and 72 hours postdose. The test substance was moderately irritating to the skin of rabbits, but not classified as an eye irritant.

In the skin irritation study, the test substance caused erythema and edema that was absent by 72 hours and Day 7, respectively. A modified Primary Irritation Index was calculated to be 1.75 and the test substance was determined to be a moderate irritant. In the eye irritation study, no corneal opacity or iritis was noted and conjunctival irritation, noted in 3/3 eyes, cleared by 24 hours. The test substance is not categorized as an ocular irritant.

Based on the available data for skin irritation, it is considered that although effects were seen on the skin of rabbits that these were not severe enough to warrant classification in accordance with the CLP criteria.

Justification for classification or non-classification

In accordance with the criteria for classification as defined in Annex I, Regulation (EC) No 1272/2008, the substance does not require classification with respect to skin and eye irritation.