4,6-bis(octylthiomethyl)-o-cresol

Endpoint summary

Description of key information

In a skin irritation study conducted according to the OECD Guideline 404, the test item caused a slight irritation (mean erythema score 1 in 2/3 animals), completely reversible within 7 days after treatment. In an eye irritation study conducted according to the OECD Guideline 405, the test article also caused a very slight irritation reaction (mean conjunctivae score 0.67 in all 3 animals), completely reversible within 72 hours.

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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

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: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12-14 weeks
- Sex: male
- Weight at study initiation: 2070-2110 g (within ± 20% of mean value)
- Housing: individually in metal cages
- Diet: ad libitum; standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: ad libitum (The quality of the drinking water was according to the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972))
- Acclimation period: 5 days
- Rationale for choice: The albino rabbit is the recommended species for skin irritation/corrosion studies

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: contra-lateral flank covered with gauze patch

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.5 ml

Duration of treatment / exposure:

4 hours

Observation period:

The skin reactions were evaluated 1, 24, 48, and 72 hours and 7 days after removing the gauze patches.

Number of animals:

3

Details on study design:

TEST SITE
- Area of exposure: An area of approx. 6 cm2 was shaved on both flanks of the animals approximately 24 hours before treatment.
- % coverage: A gauze patch (20 cm2)
- Type of wrap if used: The patches were loosely covered with an aluminium foil (36 cm2 and held in place by an adhesive tape (Isoplast, Isoplast AG, CH-5200 Brugg)

SCORING SYSTEM: according to the OECD scoring system

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no skin irritation was observed

Remarks on result:

no indication of irritation

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema was observed

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Slight scaling at the application area was observed in all animals on day 7. On the control flanks, no skin irritation effects were observed in any animal.

Other effects:

A slight loss of weight was observed in one animal on day 3 (2090 g versus 2110 g at start of test)

Summary of results:

		Animal 1	Animal 2	Animal 3
erythema	1 h	0	0	0
	24 h	1	0	1
	48 h	1	0	1
	72 h	1	0	1
	7 days	0	0	0
edema	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	7 days	0	0	0

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not 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:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

(adopted May 12, 1981)

Deviations:

no

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Kleintierfarm Madoerin AG, CH-4414 Fuellinsdorf
- Age at study initiation: 12-14 weeks
- Sex: male
- Weight at study initiation: 2060-2170 g (within ± 20% of mean value)
- Housing: individually in metal cages
- Diet: ad libitum; standard rabbit pellet - Nafag No. 814, Gossau, Switzerland
- Water: ad libitum (quality of the drinking water met the specifications of the "Schweizerisches Lebensmittelbuch" (Edition 1972))
- Acclimation period: 5 days
- Rationale for choice: The albino rabbit is the recommended species for acute eye irritation/corrosion studies

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3
- Humidity (%): 30-70
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12/12

Vehicle:

unchanged (no vehicle)

Controls:

other: The left eye remained untreated and served as a control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied: 0.1 ml

The test substance was placed into the conjunctival sac of the right eye of each animal, after gently pulling away the lower lid from the eyeball. The lids were then held together for about one second to prevent loss of the test material.

Duration of treatment / exposure:

eyes were not washed after instillation

Observation period (in vivo):

The ocular reactions were evaluated 1, 24, 48, 72 hours and 7 days after instillation

Number of animals or in vitro replicates:

3

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: no

SCORING SYSTEM: according to the OECD scoring system

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within: 24 hours

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects

Irritant / corrosive response data:

Two animals showed minimal edema (score 1) one hour after instillation, reversible within 24 hours. All animals had minimal erythema (score 1) during evaluation time points 1h, 24h and 48 h, reversible within 72 hours. No signs of irritation was seen on the iris and cornea.

Other effects:

A slight loss of weight was observed in one animal on day 3 (2110 g versus 2130 g at start of test)

Overview of results:

		Animal 1	Animal 2	Animal 3
redness	1 h	1	1	1
	24 h	1	1	1
	48 h	1	1	1
	72 h	0	0	0
	7 days	0	0	0
chemosis	1 h	1	0	1
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	7 days	0	0	0
cornea	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	7 days	0	0	0
Iris	1 h	0	0	0
	24 h	0	0	0
	48 h	0	0	0
	72 h	0	0	0
	7 days	0	0	0

Interpretation of results:

GHS criteria not met

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation

In a dermal irritation study performed according to the OECD Guideline 404, 0.5 ml unchanged test substance was applied to the shaved skin site of 3 male New Zealand White rabbits for 4 hours under a secured semi-occlusive gauze patch (20 cm²). The untreated contra-lateral flank of the same animals, also covered with gauze patch, was used as control. The skin reaction was observed 1, 24, 48, and 72 hours and 7 days after removing the gauze patch and evaluated according to the OECD scoring system. The only sign of irritation was a slight erythema reaction (mean 24-48-72-hour erythema score 1) observed in 2/3 animals, but fully reversible within 7 days.

 

Eye irritation

In an ocular irritation study performed according to the OECD Guideline 405, 0.1 ml unchanged test substance was applied to the conjunctival sac of each one eye of 3 male New Zealand White rabbits (no wash out) while the remaining untreated one served as negative control. The ocular reactions were then evaluated 1, 24, 48, 72 hours and 7 days after instillation according to the OECD scoring system, and the body weight was recorded at start and on days 3 and 7 of the test. The animals were also checked daily for systemic symptoms and mortality. The only sign of ocular irritation was a slight conjunctival reaction (mean 24-48-72-hour conjunctiva score of 0.67) observed in all treated eyes, but was fully reversible within 72 hours after treatment.

 

Respiratory irritation

No data available

Justification for classification or non-classification

Based on the results of the valid skin and eye irritation studies, there is no need for classification of the test substance for skin or eye irritation according to the CLP Regulation (EU) 1272/2008.