Isooctadecanoic acid, reaction products with tetraethylenepentamine

Endpoint summary

Description of key information

Skin: 
The test material caused well defined to severe erythema with no to moderate edema 24 hours after dosing, decreasing slightly by the 72 hour scoring. Seven days after dosing, almost all sites had slight to well defined erythema with flaky, discolored, or slightly hardened skin. By the 14 day reading, slight erythema was observed at two sites. Flaky or thickened skin was seen at almost all sites. 
Histopathological examination of the skin sections taken at sacrifice showed trace to mild hyperkertosis, epidermal crusting, and dermal inflammation at almost all sites; trace to mild acanthosis was seen at two sites. 
The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 2.6 and 0.77, respectively. Therefore, EC 701-204-9 is classified as a Category 2 skin irritant in accordance with Regulation (EC) No 1272/2008.
Eye:
The test material produced corneal opacity at the 1 hour, 96 hour, and 7 day observation periods which cleared by Day 14,  when applied without rinsing to the eyes of six New Zealand White rabbits. Corneal opacity and iritis mean scores for the 24, 48 and 72 hour observation periods were 0. Conjunctival irritation and chemosis mean scores were 1.6 and 2, respectively. All findings were fully reversible after 7 days. Positive responses were exhibited by 6/6. 
Corneal opacity mean score for the 24, 48 and 72 hour observations was 0.1 for this test substance while iritis mean score was 0.2. Conjunctival irritation and chemosis mean scores were 1.9 and 2, respectively. All findings were fully reversible after 14 days. Positive responses were exhibited by 3/3. 
Under the conditions of this study, EC 701-204-9 is classified as a Category 2 eye irritant in accordance with Regulation (EC) No 1272/2008.

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:

6AUG1985 - 4NOV1985

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The GLP study was conducted in accordance with a recognised guideline and with sufficient detail to assess the quality of the data.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

yes

Remarks:

Animals were abraded

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: LIT Rabbitry, Whitehall, Montana
- Age at study initiation: 21-23 weeks
- Weight at study initiation: data not available
- Housing: individually
- Diet (e.g. ad libitum): Purina Laboratory Rabbit Chow - ad lib
- Water (e.g. ad libitum): ad lib
- Acclimation period: 13 weeks

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22.2 - 22.5 C
- Humidity (%): 36.3-45.3%
- Air changes (per hr): data not available
- Photoperiod (hrs dark / hrs light): 12 hour light/dark

Type of coverage:

occlusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

no

Amount / concentration applied:

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

VEHICLE
- no vehicle

Duration of treatment / exposure:

4 hour exposure period

Observation period:

Irritation was scored at 1, 24, 48, and 72 hours after removal of the test material and at 7 and 14 days.

Number of animals:

6 animals - female

Details on study design:

TEST SITE
- Area of exposure: 1 square inch
- % coverage: not data available
- Type of wrap if used: gauze patch secured with porous tape

REMOVAL OF TEST SUBSTANCE
- Washing (if done): gauze pads with mineral oil
- Time after start of exposure: 4 hours

SCORING SYSTEM: Draize

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2.6

Max. score:

2.8

Reversibility:

not fully reversible within: 14 days

Remarks on result:

other: Intact

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.77

Max. score:

0.9

Reversibility:

fully reversible

Remarks:

7 days

Remarks on result:

other: Intact

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

2.6

Max. score:

2.8

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Abraded

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

1.1

Max. score:

2.7

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Abraded

Interpretation of results:

Category 2 (irritant)

Conclusions:

Under the conditions of this study, EC 701-204-9 is classified as a Category 2 skin irritant in accordance with Regulation (EC) No 1272/2008.

Executive summary:

The primary irritation score for the test material in this study was 3.1

The test material caused light to moderate erythema with no to moderate edema at all sites one hour after unwrapping. All sites showed well defined to severe erythema with no to moderate edema 24 hours after dosing, decreasing slightly by the 72 hour scoring. Seven days after dosing, almost all sites had slight to well defined erythema with flaky, discolored, or slightly hardened skin. By the 14 day reading, slight erythema was observed at the two sites. Flaky or thickened skin was seen at almost all sites.

Histopathological examination of the skin sections taken at sacrifice showed trace to mild hyperkertosis, epidermal crusting, and dermal inflammation at almost all sites; trace to mild acanthosis was seen at two sites.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (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:

1994

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: The study was conducted according to an internationally approved guideline and followed Good Laboratory Practice standards.

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

Deviations to temperature and humidity were slight and did not compromise any aspect of this study.

GLP compliance:

yes

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Myrtle's Rabbitry Incorporated, Thompson Station, TN
- Housing: wire mesh suspension cage, 1 rabbit/ cage
- Diet (e.g. ad libitum): TEKLAB RABBIT DIET (or otehr comparable diet)
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: at least 7 days.

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21
- Humidity (%):30-60%
- Photoperiod (hrs dark / hrs light): 12 hour light/dark cycle

IN-LIFE DATES: 17 September, 1993 – 19 October 1993

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

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

Duration of treatment / exposure:

Test material was instilled into one eye of the test animal while the other eye remained untreated to serve as a control. Nine animal of either sex (Group 1 - six animals; Group 2 - three animals). The eyes of the six rabbit in Group 1 were not rinsed following instillation of the test material. The treated eyes of the three rabbits in Group 2 were rinsed after 30 seconds of test material contact for approximately one minute with approximately 200 mL of lukewarm tap water.

Observation period (in vivo):

The treated eyes of all animals were examined for ocular irritation at 1, 24, 48, 72, and 96 hours and on Days 7 and 14 after treatment. With the exception of the 1 hour scoring, all eyes were scored again for corneal opacity, intensity, and area usig sodium fluorescein. Irritation was graded and scored using the Driaze technique. All eye abnormalities were recorded. Apparent test material residue were adhered to the cornea of two nonrinsed animals in Group 1, animals 1-688 and 2-689. Following the 24 hour reading, an attempt was made to remove the residue using a cotton swab moisterened with saline and/or gentle rinsing of the eyes with saline. A definitive determination could not be made as to whether or not all residue had been removed. This situation was deemed to represent an unrealistic evaluation of the potential to cause eye irritation in humans. Therefore, these animals were considered compromised and subsequently euthanized. The data collected from these animals were not considered for classification and are not presented in this study. Two additonal animals were initiated in the nonrinsed group to serve as replacements for the compromised animals. Each animal was observed daily for any physiological or behavioral abnormalities.
All animals at termination of the experimental phase were euthanized according to laboratory SOPs and discarded.
No statisical analysis was conducted for the evaluation of data.

Number of animals or in vitro replicates:

Nine rabbits

Details on study design:

SCORING SYSTEM: Draize scoring

TOOL USED TO ASSESS SCORE: Sodium fluorescein

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: nonrinsed

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Remarks on result:

other: nonrinsed

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.6

Reversibility:

fully reversible within: 96 h

Remarks on result:

other: nonrinsed

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: nonrinsed

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.1

Reversibility:

fully reversible within: 72 h

Remarks on result:

other: rinsed

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0.2

Reversibility:

fully reversible within: 96 h

Remarks on result:

other: rinsed

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

1.9

Reversibility:

fully reversible within: 96 h

Remarks on result:

other: rinsed

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

2

Reversibility:

fully reversible within: 7 days

Remarks on result:

other: rinsed

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

Under the conditions of this study, EC701-204-9 is classified as a Category 2 eye irritant in accordance with Regulation (EC) No 1272/2008.

Executive summary:

The primary ocular irritancy of undiluted test material (C1234 -04 -01) was evaluated in compliance with conditions specified in the regulation for the enforcement of the Federal Insecticide, Fungicide, and Rodenticide Act (40 CFR), the Toxic Substances Control Act (40 CFR), and the OECD Guidelines.

The test material produced corneal opacity which had cleared by the Day 14 reading, and conjunctival irritation which had cleared by the Day 14 reading, when applied without rinsing to the eyes of six New Zealand White rabbits. Maximum total irritation scores for individual nonrinsed animals ranged from 12 to 19. the mean total irritation score at the 24 hour reading was 11.7 /110. Positive responses were exhibited by 6/6. No evidence of corrosion was noted. No physiological or behavioral abnormalities were noted.

The test material produced corneal opacity which had cleared by the 72 hour reading, iritis which had cleared by the 96 hour reading, and conjunctival irritation which had cleared by the Day 14 reading, when applied with rinsing to the eyes of three New Zealand White rabbits. Maximum total irritation scores for individual rinsed animals ranged from 14 to 20. The mean total irritation score at the 24 hour reading was 12.7/110. Positive responses were exhibited by 3/3. No evidence of corrosion was noted. No physicological or behavioral abnormalities were noted.

Rinsing appeared to have no significant effect on the severity or persistence of the ocular irritation produced in response to the test material.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin:

 

- In the key study, Korenga, 1985, test material was held in contact with the skin by occlusive means for 4 h followed by rinsing with a gauze pad soaked in mineral oil. The study design was comparable to the OECD Guideline 404 (Acute Dermal Irritation / Corrosion) and was conducted according to GLP. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997. This is considered the most reliable study available and of sufficient quality to use for classification.

The mean value of the scores for erythema and edema formation for 24, 48 and 72 hours was calculated to be 2.6 and 0.77, respectively and therefore meets the criteria for classification as irritating in accordance with Regulation (EC) No 1272/2008.

 

- The Gilman, 1982 study is non-GLP and conducted according to U.S. 16 CFR 1500.41. There are deviations affecting this study such as the test substance being left on for 24 hours rather than 4 hours as suggested in OECD guidelines and also scoring was only reported for the 24 and 72 hour observation periods. During the study, 0.5 mL aliquot of test material was applied to an abraded and an intact skin site on each rabbit and held in place by occlusive means. The Draize method of scoring was employed. Under the conditions of the study, the test material was determined to have a primary irritation score of 1.79 out of 8. With exclusion of a 48 hour score, the test material is not considered to be irritating to the intact and abraded skin of rabbits. The study was considered to have a reliability rating of 2, reliable with restrictions, according to the criteria of Klimisch, 1997.

 

Eye:

 

The Morris, 1994 study was chosen as the key study for eye irritation as it is the most recent and reliable study available. The study design was equivalent to OECD Guideline 405 (Acute Eye Irritation / Corrosion) and followed GLP principles. A reliability rating of 1 was assigned according to the criteria of Klimisch, 1997. Classification has been based on the results for this study. The 24, 48 and 72 hour scores were calculated as follows: corneal opacity = 0, iritis = 0, conjunctival irritation = 1.6, and chemosis = 2.0 when applied without rinsing. The 24, 48 and 72 hour scores were calculated as follows: corneal opacity = 0.1, iritis = 0.2, conjunctival irritation = 1.9, and chemosis = 2.0 when applied followed by rinsing with water. All findings were reversible in 14 days. Based on findings in this study, EC 701-204-9 meets the criteria for classification as a Category 2 Eye Irritant based on the criteria of Regulation (EC) 1272/2008.

 

The other supporting studies available are as follows:

 

- The Cushman, 1985 was performed similarly to an OECD 405 Guideline study and was GLP. This study was considered reliable but was not selected as the key study because a more recent study performed according to the Guideline was available. The 24, 48 and 72 hour scores were calculated as follows: corneal opacity = 1.6, iritis = 0.8, conjunctival irritation = 2.7, and chemosis = 2.2 when applied without rinsing. The 24, 48 and 72 hour scores were calculated as follows: corneal opacity = 1.3, iritis = 0.8, conjunctival irritation = 2.2, and chemosis = 1.4 when applied followed by rinsing with water. All findings were reversible in 21 days in rinsed eyes. Conjunctival irritation and chemosis was not fully reversed within 21 days in unrinsed eyes. This study supports the classification of EC 701-204-9.

 

- The Gilman, 1982 study is non-GLP and conducted according to U.S. 16 CFR 1500.42. The study was considered to have a

reliability rating of 2, according to the criteria of Klimisch, 1997 as observations were not carried out for long enough to enable reversibility of irritation (last observation at Day 7). One animal continued to show signs of chemosis through Day 7, however, at a decreased intensity (Draize score 1 vs 2 at the Day 2, 3, and 4 readings) and it is reasonable to believe reversibility would be obtained following 21 days. This deviation did not affect the ability to make a determination on classification as the test material only produced slight eye irritation in rabbits. The 24, 48 and 72 hour scores were calculated as follows: corneal opacity = 0, iritis = 0.2, conjunctival irritation = 0.9, and chemosis = 0.9 when applied without rinsing. Based on findings in this study, the test material did not meet the criteria for classification as an eye irritant based on the criteria of Regulation (EC) 1272/2008. Morris, 1992 is considered a supporting study with a Klimisch reliability rating of 1. During the study, 0.1mL of test material formulated as a 50% w/w solution in vehicle was instilled into one eye of each of six rabbits. Under the conditions of the test, no reaction was observed in the cornea or iris of treated eyes. Conjunctiva redness was observed in all animals persisting up to 72 hours in most animals. Slight conjunctiva chemosis was observed in 3/6 animals. The test material only elicited slight reactions in any of the animals during the course of the study and therefore would not require classification as an eye irritant as formulated.

Justification for selection of skin irritation / corrosion endpoint:
This is considered the most reliable study available and of sufficient quality to use for classification.

Justification for selection of eye irritation endpoint:
The Morris, 1994 study was chosen as the key study for eye irritation as it is the most recent and reliable study available.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: irritating

Justification for classification or non-classification

Skin:

 

The mean value (24, 48, 72h) of the Draize scores for erythema was calculated to be 2.6 and positive responses were seen in 6/6 animals. This meets the criteria of mean value ≥ 2.3 -≤4.0 for erythema in at least 2 of 3 test animals. Therefore, EC 701-204-9 is classified as a Category 2 skin irritant in accordance with Annex I, Regulation (EC) No 1272/2008.

 

Eye:

 

Chemosis mean scores with and without rinsing were 2. All findings were fully reversible after 14 days. Positive responses were exhibited by all animals. This meets the criteria of: At least in 2 of 3 tested animals a positive response of:conjunctival oedema (chemosis) ≥ 2 which fully reverses within an observation period of 21 days. Therefore, EC 701-204-9 is classified as a Category 2 eye irritant in accordance with Annex I, Regulation (EC) No 1272/2008.