Dodecane-1-thiol

Skin irritation / corrosion

Administrative data

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2009-12-30 to 2010-02-12

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: This study is classified as reliable without restrictions because reporting it was well documented and followed sound scientific guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2010

Report date:

2006

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

temperature and relative humidity exceeded the recommended values (23 C and 16%). These minor deviations were not considered to have compromised the validity or integrity of the study.

Test guideline 2

Qualifier:

according to guideline

Guideline:

other: Commission Regulation (EC) No. 440/2008, B.4, 30 May 2008

GLP compliance:

yes (incl. QA statement)

Remarks:

OECD Principles of Good Laboratory Practice

Test material

Test material information

Constituent 1

Reference substance name:

Dodecane-1-thiol (CAS # 112-55-0)

IUPAC Name:

Dodecane-1-thiol (CAS # 112-55-0)

Details on test material:

- Name of test material (as cited in study report): n-dodecyl mercaptan (dodecane-1-thiol)
- Substance type: colorless liquid
- Physical state: liquid
- pH: 5
- Analytical purity: 99.0%
- Lot/batch No.: 9500NDM09
- Supplier: Arkema Inc - Houston
- Expiration date: November 2010
- Storage condition of test material: glass flask, room temperature

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Laboratories
- Age at study initiation: 5 to 6 months old
- Weight at study initiation: 3.554 ± 0.090 kg
- Sex: Male
- Housing: individually in Pajon cages (50 cm x 57 cm x 75 cm)
- Diet (e.g. ad libitum): 110 pelleted diet, ad libitum; analyzed regularly by the supplier for composition and contaminant levels
- Water (e.g. ad libitum): water filtered by a FG Millipore membrane, ad libitum; bacteriological and chemical analyses of water are performed regularly by external laboratories
- Acclimation period: at least 5 days before the beginning of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 ± 3°C
- Humidity (%): 30 to 70%
- Air changes (per hr): 12 cycles/hour of filtered, non-recycled air
- Photoperiod (hrs dark / hrs light): 12 h/12 h (7:00 - 19:00)

Test system

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: The untreated skin served as control.

Amount / concentration applied:

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

Duration of treatment / exposure:

3 minutes, 1 hour, and 4 hours

Observation period:

1, 24, 48, and 72 hours after dressing removal

Number of animals:

1 for the 3-minute and 1-hour exposure and 2 for the 4-hour exposure

Details on study design:

TEST SITE
- Area of exposure: 6 cm2
- Type of wrap if used: adhesive hypoallergenic aerated semi-occlusive dressing and a restraining bandage

REMOVAL OF TEST SUBSTANCE
- Washing (if done): any residual test item was wiped off by means of a dry cotton pad
- Time after start of exposure: directly following end of exposure period

SCORING SYSTEM:
Erythema and eschar formation:
. no erythema........................................................................................................... 0
. very slight erythema (barely perceptible) ............................................................. 1
. well-defined erythema........................................................................................... 2
. moderate to severe erythema................................................................................. 3
. severe erythema (beet redness) to slight eschar formation (injuries in depth)...... 4

Edema formation
. no edema ............................................................................................................... 0
. very slight edema (barely perceptible).................................................................. 1
. slight edema (edges of area well-defined by definite raising) .............................. 2
. moderate edema (raised approximately 1 millimeter) .......................................... 3
. severe edema (raised more than 1 millimeter and extending beyond area
of exposure)........................................................................................................... 4

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48, 72 hours

Score:

2.3

Max. score:

4

Reversibility:

not reversible

Remarks:

on 15 days

Remarks on result:

other: 3-min exposure

Results 2

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: 24, 48, 72 hours

Score:

2.3

Max. score:

4

Reversibility:

not reversible

Remarks:

on day 15

Remarks on result:

other: 4-hour exposure

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: 24, 48, 72 hours

Score:

3

Max. score:

4

Reversibility:

not reversible

Remarks:

on day 8 (sacrificed on day 8)

Remarks on result:

other: 4-hour exposure

Results 4

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: D5 to D15

Score:

2.8

Max. score:

4

Reversibility:

not reversible

Remarks:

on day 15

Remarks on result:

other: 3-min exposure

Results 5

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: D5 to D15

Score:

2.8

Max. score:

4

Reversibility:

not reversible

Remarks:

on day 15

Remarks on result:

other: 1-h exposure

Results 6

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: D5 to D8

Score:

3.25

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: 4-hour exposure

Irritant / corrosive response data:

3-minute exposure:
A very slight to severe erythema (grades 1 to 4) was observed all over the observation period. A slight or moderate edema (grade 2 or 3) was noted from day 5 until the end of the observation period (day 15). A brownish area was noted from day 5 until day 13. Dryness of the skin was recorded from day 6 until day 15.

1-hour exposure:
A well-defined to severe erythema (grades 2 to 4) was observed all over the observation period. A slight or moderate edema (grade 2 or 3) was noted from day 5 until the end of the observation period (day 15). A brownish area was noted from day 7 until day 13 following by scabs (not further described) on days 14 and 15. Dryness of the skin was recorded from day 6 until day 15.

4-hour exposure:
Animal 1: A well-defined or moderate erythema (grade 2 or 3) was observed all over the observation period. A brownish area was noted from day 10 until day 13. Dryness of the skin was recorded from day 9 until the end of the observation period (day 15).

Animal 2: A well-defined to severe erythema (grades 2 to 4) and a very slight to severe edema (grades 1 to 4) were noted from day 1 until day 8. Brownish area, related to a tissular necrosis and tissue burn on days 7 and 8, was noted from day 5 until day 8, associated with dryness of the skin from day 6 until day 8. According to the severe cutaneous reactions observed, the animal was sacrificed on day 8 for ethical reasons.

Other effects:

no data

Applicant's summary and conclusion

Interpretation of results:

Category 1C (corrosive)

Remarks:

Migrated information Corrosive after 4-hour of exposure Criteria used for interpretation of results: EU

Conclusions:

In a primary dermal irritation study, male New Zealand white rabbits dermally exposed to dodecane-1-thiol for 4-hour showed the test substance to be corrosive under EU Category 1C.

Executive summary:

In a dermal irritation/corrosion study (OECD 404), a single male New Zealand white rabbit was dermally exposed to 0.5 mL of undiluted dodecane-1-thiol (CAS Number 112-55-0) for 3 minutes, 1 hour, and 4 hours. Since the test material was deemed a severe irritant but not corrosive during the 4-hour exposure on this first animal, a second animal was exposed to the test material for 4 hours. Animals were observed for 14 days and erythema and oedema scores were recorded at daily and at 24, 48, and 72 hours.  

The 3-minute exposure resulted in a slight to severe erythema and a slight or moderate oedema for the length of the observation period. The 1-hour exposure resulted in a well-defined to severe erythema and a slight or moderate oedma throughout the length of the observation period in addition to scabs by day 13. For the 4-hour exposure both animals exhibited well-defined, moderate, or severe erythema and in the second animal slight to severe oedema. According to the severe cutaneous reactions observed, the second animal was sacrificed on day 8 for ethical reasons. The 4-hour exposure mean scores over 24, 48 and 72 hours for each animal were 2.3 and 3.0 for erythema and 0.0 and 1.0 for oedema. None of the symptoms noted for any exposure period were reversible within 14 days.   

 

Dodecane-1-thiol was classified as corrosive under EU criteria Category 1C because signs of corrosion (erythema score of 3 or 4 and tissular necrosis and tissue burn on days 7 and 8) were noted for the 4 -hour exposure during the 14 -day observation period.