Chlorinated Fatty Acid Methyl Ester

Skin irritation / corrosion

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2008

Report date:

2008

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

adopted April 24, 2002

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

methyl tetradecanoate, chloro

Molecular formula:

C13H26Cl4COOCH3 and C13H25Cl5COOCH3 (primary isomers based on product weight of 35-40% Cl by weight)

IUPAC Name:

methyl tetradecanoate, chloro

Constituent 2

Reference substance name:

Methyl octadecanoate, chloro

Molecular formula:

C17H30Cl4COOCH3, C17H29Cl5COOCH3 , and C17H28Cl6COOCH3 (primary isomers based on 35-40% Cl by weight)

IUPAC Name:

Methyl octadecanoate, chloro

Constituent 3

Reference substance name:

Methyl hexadecanoate, chloro

Molecular formula:

C15H28Cl4COOCH3 and C15H27Cl5COOCH3 (primary isomers based on 35-40% Cl by weight)

IUPAC Name:

Methyl hexadecanoate, chloro

Test material form:

liquid

Details on test material:

This is a UVCB substance developed from the chlorination of fatty acid methyl esters.

Specific details on test material used for the study:

Batch A070806

Test animals

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Animal source: Harlan Netherlands BV
Animal ages: 13-14 weeks at start of study

Accommodation
Air-conditioned with ranges for room temperature 17-23 °C, relative humidity 30-70 % and approximately 10-15 air changes per hour. Room temperature and humidity were monitored continuously and values outside of these ranges
may have occasionally occurred, usually following room cleaning. These transient variations are considered not to have any influence on the study and, therefore, these data are not reported but are retained at RCC. The animals were provided with an automatically controlled light cycle of 12 hours light and 12 hours dark. Music was played during the daytime light period.

Housing:
Individually in stainless steel cages equipped with feed hoppers and drinking water bowls. Wood blocks and haysticks were provided for gnawing.

Diet:
Pelleted standard Provimi Kliba 3418 rabbit maintenance diet ad libitum (batch no. 83/06) provided by Provimi KlibaAG, CH-4303 Kaiseraugst.

Water:
Community tap water from Follinsdorf, ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at RCC Ltd.

Test system

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Amount / concentration applied:

0.5 mL (~0.5 g) on 2.5x2.5 cm area.

Duration of treatment / exposure:

4 hours

Observation period:

7 days

Number of animals:

3 total; 1 male and 2 female

Details on study design:

Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 cm2 (10 cm x 10 cm). The skin of the animals was examined one day before treatment, and regrown fur of all animals was clipped again.

On the day of treatment, 0.5 ml of test material was placed on a surgical gauze patch (ca.2.5 cm x 2.5 cm). This gauze patch was applied to the intact skin of the clipped area. The patch was covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and anchored with tape.

The duration of treatment was 4 hours. Then the dressing was removed and the skin was flushed with lukewarm tap water to clean the application site so that any reactions (erythema) were clearly visible at that time.

As it was suspected that the test item might produce irritancy, a single animal (one female) was treated first. As neither a corrosive effect nor a severe irritant effect was observed after the 4-hour exposure, the test was completed using the two remaining animals for an exposure period of four hours.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 7 days

Results 2

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 3 days

Results 3

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 3 days

Results 4

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48 h

Score:

1

Max. score:

1

Reversibility:

fully reversible within: 3 days

Results 5

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

72 h

Score:

0

Max. score:

1

Reversibility:

fully reversible within: 3 days

Results 6

Irritation parameter:

edema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 7

Irritation parameter:

edema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

0

Max. score:

0

Results 8

Irritation parameter:

edema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

0

Irritant / corrosive response data:

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The mean erythema/eschar score of the three animals was 1.00, 0.67 and 0.67, respectively and the mean oedema score was 0.00 for each of the three animals. All three animals showed a very erythema at the 1-hour reading. The erythema persisted as very slight until the 48- or 72-hour reading, respectively. No abnormal findings were observed on the treated skin of any animal 7 days after treatment, the end of the observation time.

Other effects:

No clinical signs of systemic toxicity were observed in the animals during the study and no mortality occurred.

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The mean erythema/eschar score of the three animals was 1.00, 0.67 and 0.67, respectively and the mean oedema score was 0.00 for each of the three animals. All three animals showed a very erythema at the 1-hour reading. The erythema persisted as very slight until the 48- or 72-hour reading, respectively. No abnormal findings were observed on the treated skin of any animal 7 days after treatment, the end of the observation time.

Based on these finding C16 and C18 chlorinated methyl esters are not expected to be primary skin irritants.

Executive summary:

The skin irritancy of C16 and C18 chlorinated methyl esters was tested in three New Zealand white rabbits (one male and two female) based on the OECD 404 test guideline. Neat test material,0.5 mL, was applied directly to the skin for 4 hours using a semi-occluded patch.

The mean score was calculated across 3 scoring times (24, 48 and 72 hours after patch removal) for each animal for erythema/eschar grades and for oedema grades, separately. The mean erythema/eschar score of the three animals was 1.00, 0.67 and 0.67, respectively and the mean oedema score was 0.00 for each of the three animals. All three animals showed a very erythema at the 1-hour reading. The erythema persisted as very slight until the 48- or 72-hour reading, respectively. No abnormal findings were observed on the treated skin of any animal 7 days after treatment, the end of the observation time.

Based on these finding C16 and C18 chlorinated methyl esters are not expected to be primary skin irritants.