Octadecanoic acid, reaction products with diethylenetriamine and urea, acetates

Endpoint summary

Description of key information

Two key studies, bothin vitro and in vivo were carried out to evaluate skin irritation/corrosion and eye irritation potency of the test substance following OECD guidelines and GLP.

In vitro key study performed in 2013 using the EPISKIN^(TM) reconstructed human epidermis model after a treatment period of 15 minutes followed by a post-exposure incubation period of 42 hours showed that FAT 93580 is non-irritant. To further substantiate the finding of key study a support primary irritation study performed on rabbit skin also did not show any observable response to treatment throughout the 72-hours observation period.

Similarly, a key study performed in 2013 to evaluate corrosivity potential of the test item using the EPISKIN^(TM) in vitro Reconstructed Human Epidermis (RHE) Model after treatment periods of 3, 60 and 240 minutes showed FAT 93580 is non-corrosive.

An in vivo key study was performed in 2013 to assess the irritancy potential of the test item following single 3 minute, 1 and 4 hour, semi-occluded applications to the intact rabbit skin. The study was conducted according to OECD guideline 404 and in accordance with GLP. The test item produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

A support study data from an in vivo study conducted in 1975 following US CFR guideline and classification performed according to EDTA subcommittee for toxicology showed the test item as non-irritating to rabbit skin.

Key in vitro eye irritation study was performed in 2013 to assess the ocular irritancy potential of the test item FAT 93580/A following application onto the cornea of the rabbit enucleated eye. Based on the irritation scores, test item FAT 93580/A was considered unlikely to have the potential to cause severe ocular irritancy in in vivo according to the results of the test.

An in vivo key study performed in 2013 to assess the irritancy potential of the test item to the eye of New Zealand White Rabbit. The study was conducted according to OECD guideline 405 and in accordance with GLP. The test item does not meet the criteria for classification as an eye irritant according to the Global Harmonized System of Classification and Labelling of Chemicals.

Added is another support study performed on Rabbit eye mucosa following the procedure prescribed by the Consumer Product Safety Commission of the USA mentioned in the code of Federal Regulations, also recorded ocular reactions after 24, 48 and 72 hrs. Based on the grade of ocular reaction the test substance is considered to be "non-irritant" to the rabbit eye.

Based on the data from all the in vitro and in vivo above studies a test item FAT 93580 is non-irritant and non–corrosive to the skin and also non–irritant to the rabbit eye.

Justification for selection of skin irritation / corrosion endpoint:
The study was conducted according to OECD guideline 404 and in accordance with GLP

Justification for selection of eye irritation endpoint:
The study was conducted according to OECD guideline 405 and in accordance with GLP

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

Study period:

2013

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

Qualifier:

according to guideline

Guideline:

EU Method B.4 (Acute Toxicity: Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Identification: Sapamine CSN
Batch: 0024141800
Purity: not supplied
Expiry date: not supplied
Storage Conditions: room temperature in the dark

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK
- Age at study initiation: 12 to 20 weeks old
- Weight at study initiation: 2.30 to 2.93 kg
- Housing: Individually housed in suspended cages
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-23 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 15/hr
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: To: 18th June 2013 - 28th June 2013

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Controls:

other: contralateral flank

Amount / concentration applied:

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

VEHICLE
- 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, 72 hrs

Number of animals:

3 male rabbits

Details on study design:

TEST SITE
- Area of exposure: 3 suitable sites on the back of the rabbit
- Type of wrap if used: 2.5 cm X 2.5 cm cotton gauze patch, secured with surgical adhesive tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Residual test item was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: 3 minutes, 1 hour and 4 hours

SCORING SYSTEM: Draize Scheme
Dermal irritation was graded in each animal according to the following scoring scale:
- Erythema and eschar formation:
0 no erythema
1 very slight erythema (barely perceptible)
2 well-defined erythema
3 moderate to severe erythema
4 severe erythema (beet redness) to slight eschar formation (injuries in depth).

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

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: all scores were zero at all time points.

Remarks on result:

no indication of irritation

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: all scores were zero at all time points

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Primary irritation index is "0"

Other effects:

All animals showed expected gain in body weight during the study.

Interpretation of results:

GHS criteria not met

Conclusions:

The test item produced a primary irritation index of 0.0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

Executive summary:

The study was performed on FAT 93580/A to assess the irritancy potential of the test item following single 3 minute, 1 and 4 hour, semi-occluded applications to the intact rabbit skin. The study was conducted according to OECD guideline 404 and in accordance with GLP.

3-minute and 1-hour semi-occluded applications of the test item to the intact skin of one rabbit produced no evidence of skin irritation. A single 4-hour, semi occluded application of the test item to the intact skin of three rabbits produced no evidence of skin irritation. All the scores at all time points tested were zero.

The test item produced a primary irritation index of 0 and was classified as non-irritant to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.

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

Study period:

2013

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:

EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

Identification: Sapamine CSN
Batch: 0024141800
Storage Conditions: room temperature in the dark

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Laboratories UK
- Age at study initiation: 12 to 20 weeks
- Weight at study initiation: 2.30 to 2.49 kg
- Housing: Individually housed in suspended cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): 15 air changes per hour
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 01st July 2013 To: 18th July 2013

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 ml (approximately 80 mg)

Duration of treatment / exposure:

72 hrs

Observation period (in vivo):

7 days

Number of animals or in vitro replicates:

3 male rabbits

Details on study design:

SCORING SYSTEM: Draize scale for scoring ocular irritation

TOOL USED TO ASSESS SCORE: hand-slit lamp

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: No scores at any time point.

Remarks on result:

no indication of irritation

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.11

Max. score:

2

Reversibility:

fully reversible within: 48h

Remarks on result:

no indication of irritation

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.66

Max. score:

3

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.77

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

All animals showed expected gain in body weight during the study.

Other effects:

Moderate conjuctival irritation was noted in all treated eyes one hour after treatment. Moderate conjuctival irritation was noted in one treated eye and minimal conjuctival irritation was noted in two treated eyes at the 24 and 48 hour observations. Minimum conjuctival irritation was noted in one treated eye at the 72 hour observation.

Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number and Sex	73300 Male					73339 Male				73340 Male
	IPR=O					IPR=O				IPR=O
Time After Treatment	1 Hour	24 Hours	48 Hours	72 Hours	7 Days	1 Hour	24 Hours	48 Hours	72 Hours	1 Hour	24 Hours	48 Hours	72 Hours
CORNEA
E = Degree of Opacity	0	0	0	0	0	0	0	0	0	0	0	0	0
F = Area of Cornea Involved	0	0	0	0	0	0	0	0	0	0	0	0	0
Score (E x F) x 5	0	0	0	0	0	0	0	0	0	0	0	0	0
IRIS
D	1	1	0	0	0	0	0	0	0	1	0	0	0
Score (D x 5)	5	5	0	0	0	0	0	0	0	5	0	0	0
CONJUNCTIVAE
A=Redness	2	2	2	1	0	2	2	1	0	2	1	1	0
B = Chemosis	2	1	1	1	0	2	1	1	0	2	1	1	0
C = Discharge	2	1	1	0	0	1	0	0	0	1	1	0	0
Score (A+ B +C)x 2	12	8	8	4	0	10	6	4	0	10	6	4	0
Total Score	17	13	8	4	0	10	6	4	0	15	6	4	0

IPR=    Initial pain reaction

Interpretation of results:

GHS criteria not met

Conclusions:

The test item does not meet the criteria for classification as an eye irritant according to the GHS of Classification and Labelling of Chemicals.

Executive summary:

The study was performed to assess the irritancy potential of the test item to the eye of New Zealand white Rabbit. The study was conducted according to OECD guideline 405 and B.5 Method of EC in accordance with GLP.

A single application of the test item to the non-irritated eyes of 3 male rabbits produced iridial inflammation and moderate conjunctival irritation. Two treated eyes appeared normal at the 72 hour observation and one treated eye appeared normal at the 7 day observation.

The mean 24/48/72 hr score was as follows;

Cornea opacity: 0

Iris: 0.11

Conjuctivae redness: 1.66

Chemosis: 0.77

Moderate conjuctival irritation was noted in all treated eyes one hour after treatment. Moderate conjuctival irritation was noted in one treated eye and minimal conjuctival irritation was noted in two treated eyes at the 24 and 48 hour observations. Minimum conjuctival irritation was noted in one treated eye at the 72 hour observation.

Based on the findings of the study, the test item does not meet the criteria for classification as an eye irritant according to the GHS of Classification and Labelling of Chemicals.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Justification for classification or non-classification

Test item FAT 93580 did not show any irritation/ corrosive effects in both in vitro and in vivo tests conducted to determine its potency to cause skin irritation/ corrosion. Similarly, no effects were noted in eye irritation tests. Hence, test substance can be classified as non- irritant and non – corrosive to the skin and also non – irritant to the eye.