Acid Catalysed Reaction Products of 3,7-dimethyl-2,6-octadienal in the presence of ethanol

Endpoint summary

Description of key information

Based on an in vivo skin irritation test, conducted according to OECD 404 and GLP principles, it was concluded that the substance is not irritating to the skin. Based on an in vivo eye irritation study, conducted in accordance with OECD 405 and according to GLP principles, it was concluded that the substance is also not irritating to the eyes. In addition, under the conditions of a human repeated insult (occlusive) patch test procedure, a 3% solution of the substance did not induce clinically significant skin irritation in human subjects.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Reference 1

Endpoint:

skin irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 7, 2001 - May 29, 2001

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Version / remarks:

(1992)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(1992)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Name of test material (as cited in study report): CITRATHAL R
- Description: Colourless to pale yellow liquid
- Analytical purity: not applicable (as it is an UVCB substance)
- Composition of test material, percentage of components: as defined in section 1.2
- Lot/batch No.: 9000416199
- Expiration date of the lot/batch: August 27, 2001
- Storage condition of test material: In the original container, at room temperature (range of 17-23 'C), away from direct sunlight

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

- Source: Centre Lago, F-01540 Vonnas, France
- Age at study initiation: 33-34 weeks (male) and 30-31 weeks (females)
- Weight at study initiation: 3.7-4.2 kg
- Housing: Animals were housed individually in stainless steel cages
- Diet: Free access to pelleted diet for rabbits (Provimi Kliba 3418). Haysticks were abailable during the study period.
- Water: Free access to tap water
- Acclimation period: 6 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 – 23
- Humidity (%): 30 - 70
- Air changes (per hr): approx 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: May 14, 2001 to May 29, 2001

Type of coverage:

semiocclusive

Preparation of test site:

shaved

Vehicle:

unchanged (no vehicle)

Controls:

other: Adjacent areas of the untreated skin of each animal served as controls

Amount / concentration applied:

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

Duration of treatment / exposure:

4 hours

Observation period:

15 days

Number of animals:

1 male and 2 females

Details on study design:

TEST SUBSTANCE PREPARATION
The substance was applied as such.

TEST SITE
Four days before treatment, the left flank was clipped with an electric clipper, exposing an area of approximately 100 square centimeters (10x10 cm). The skin of the animals was examined one day before treatment and regrown fur of all animals was again clipped.

APPLICATION
The test substance was placed on a surgical gauze patch (ca. 2.5 x 2.5 cm). This gauze patch was applied to approx. 6 square centimeters of 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.

REMOVAL OF TEST SUBSTANCE
Yes, at the end of the exposure period, using lukewarm tap water.

OBSERVATIONS
- Mortality/Viability: Daily
- Toxicity: Daily
- Body Weight: At start of acclimatization, on the day of application and at termination
- Necropsy: Not applicable
- Irritation:
The skin reactions were assessed at approximately 1, 24, 48 and 72 hours and 7, 10, 14 and 15 days after the removal of the dressings and test substance.

SCORING SYSTEM:
The irritation was assessed according to the numerical scoring system according to OECD 404

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2

Max. score:

4

Reversibility:

fully reversible within: 15 days

Remarks on result:

no indication of irritation

Remarks:

Mean value of score at 24, 48 and 72h after patch removal

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Remarks:

Mean value of score at 24, 48 and 72h after patch removal.

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Remarks on result:

no indication of irritation

Remarks:

Mean value of score at 24, 48 and 72h after patch removal.

Irritation parameter:

edema score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 48 hours (in all animals)

Remarks on result:

no indication of irritation

Remarks:

Mean value of score at 24, 48 and 72h after patch removal.

Irritant / corrosive response data:

See section "Any other information on results incl. tables"

Other effects:

- Scaling was present at the test site of the male from 7 to 10 days after treatment and in both females from 72 hours to 7 days after treatment
- No staining by the test material was observed
- No clinical signs of systemic toxicity were observed
- No mortality occurred
- No irreversible alterations of the treated skin were observed nor were corrosive effects evident on the skin
- Body weights were within the normal range of variability

Animal number	Sex	Evaluation Interval; time after patch removal	Erythema	Oedema	Scaling?
58	M	1 hour	2	1	No
59	F		2	1	No
60	F		2	1	No
58	M	24 hours	2	1	No
59	F		2	1	No
60	F		2	1	No
58	M	48 hours	2	0	No
59	F		1	0	No
60	F		2	0	No
58	M	72 hours	2	0	No
59	F		1	0	Yes
60	F		1	0	Yes
58	M	7 days	1	0	Yes
59	F		0	0	Yes
60	F		0	0	Yes
58	M	10 days	1	0	Yes
59	F		0	0	No
60	F		0	0	No
58	M	14 days	1	0	No
59	F		0	0	No
60	F		0	0	No
58	M	15 days	0	0	No
59	F		0	0	No
60	F		0	0	No

 

Interpretation of results:

GHS criteria not met

Conclusions:

In a skin irritation study with rabbits, performed in accordance with OECD 404 (1992) and according to GLP principles, irritation was observed; not sufficent to classify the substance in accordance with the CLP Regulation.

Executive summary:

In a skin irritation study in rabbits, conducted in accordance with OECD 404 (1992), EU Method B.4 (1992) and according to GLP principles, 1 male and 2 female rabbits were semi-occlusively exposed for 4 hours to 0.5 mL of the substance. Well-defined erythema was observed in all animals 1 hour after treatment and persisted in the male up to the 72-hour reading, in one female up to the 24-hour reading and in the other female up to the 48-hour reading. Very slight erythema was evident in the male up to 14 days after treatment and in both females up to 72 hours after treatment. Very slight swelling was noted in all animals from 1 to 24 hours after treatment. Scaling was present at the test site of the male from 7 to 10 days after treatment and in both females from 72 hours to 7 days after treatment. No significant clinical signs of systemic toxicity nor mortalities were observed. Based on the results of this study, the substance does not need to be classified for skin irritation/corrosion in accordance with the CLP Regulation.

Reference 2

Endpoint:

skin irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro skin irritation study does not need to be conducted because adequate data from an in vivo skin irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Reference 1

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

May 29, 2001 - June 11, 2001

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:

(1987)

Deviations:

no

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

(1992)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

- Name of test material (as cited in study report): CITRATHAL R
- Description: Colourless to pale yellow liquid
- Analytical purity: not applicable (as it is an UVCB substance)
- Composition of test material, percentage of components: as defined in section 1.2
- Lot/batch No.: 9000416199
- Expiration date of the lot/batch: August 27, 2001
- Storage condition of test material: In the original container, at room temperature (range of 17-23 'C), away from direct sunlight

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne, France
- Age at study initiation: 10-11 weeks
- Weight at study initiation: 2.1-2.4 kg
- Housing: Animals were housed individually in stainless steel cages
- Diet: Free access to pelleted diet for rabbits (Provimi Kliba 3418). Haysticks were available during the study period.
- Water: Free access to tap water (ad libitum)
- Acclimation period: 6 days (1 female) and 7 days (other 2 animals)

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 – 23
- Humidity (%): 30 - 70
- Air changes (per hr): approx 10-15
- Photoperiod (hrs dark / hrs light): 12/12

TREATMENT DATES: June 5, 2001 (1 female) and June 6, 2001 (other 2 animals)

Vehicle:

unchanged (no vehicle)

Controls:

other: The right eye remained untreated and served as the reference control.

Amount / concentration applied:

TEST MATERIAL
- Amount applied: 0.1 mL

Duration of treatment / exposure:

Not applicable (as the eyes were not rinsed)

Observation period (in vivo):

72 hours

Number of animals or in vitro replicates:

1 female and subsequently 1 male and 1 female

Details on study design:

STUDY DESIGN
As it was suspected that the test substance might produce irritancy (based on the earlier performed skin irritation study in rabbits), one female was treated first. As neither a corrosive effect nor a severe irritant effect was observed, the test was completed using 2 additional animals the following day.

TREATMENT
On the day of treatment, the test substance was placed in the conjunctival sac of the left eye of each animal after gently pulling the lower lid away from the eyeball. The lids were then gently held together for about one second to prevent loss of the test substance.

REMOVAL OF TEST SUBSTANCE
The treated eyes were not rinsed.

OBSERVATIONS (beschrijf beperkt)
- Mortality/Viability: Daily
- Clinical signs: Daily
- Body Weight: At start of acclimatization, on the day of application and at termination
- Necropsy: not performed
- Irritation:
The eyes of each animal were examined approximately 1, 24, 48 and 72 hours after instillation of the test substance.
The irritation was assessed according to OECD 405.
Also staining of sclera and cornea by the test substance was examined. Eye examinations were made with a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel, Switzerland).

Irritation parameter:

cornea opacity score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

Mean score following grading at 24, 48 and 72 hours after installation

Irritation parameter:

iris score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

2

Remarks on result:

other:

Remarks:

Mean score following grading at 24, 48 and 72 hours after installation

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal: #1 and #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Remarks:

(redness)

Basis:

animal #2

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 72 hours

Remarks on result:

no indication of irritation

Remarks:

Mean score following grading at 24, 48 and 72 hours after installation

Irritation parameter:

chemosis score

Basis:

animal: #1, #2 and #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Remarks on result:

no indication of irritation

Remarks:

Mean score following grading at 24, 48 and 72 hours after installation

Irritant / corrosive response data:

- Slight reddening of the conjunctivae was noted in all animals from 1 to 24 hours and was still evident in one female at the 48-hour reading

Other effects:

- A slight watery discharge was observed in 2 animals at the 1-hour reading and a slight mucus discharge was evident in the other animal at this reading
- Moderate reddening of the sclera was observed in all animals 1 hour after treatment and slight reddening persisted in 2 animals up to and including the 48-hour reading
- At the 72 hour reading nothing was observed anymore

- No clinical signs of systemic toxicity were observed and no mortality occurred

- Body weights were within the normal range of variability

- No staining of the treated eyes by the test substance was observed

- No corrosion of the cornea was observed at any of the reading times

Interpretation of results:

GHS criteria not met

Conclusions:

In an eye irritation study with rabbits, performed in accordance with OECD 405 (1987) and according to GLP principles, limited irritation was observed.

Executive summary:

In an eye irritation study in rabbits, conducted in accordance with OECD 405 (1987), EU Method B.5 (1992) and according to GLP principles, 0.1 mL of the substance was placed in the conjunctival sac of the left eye of 1 female rabbit and subsequently of 1 male and 1 female rabbit the following day. The eyes were not rinsed and were examined approximately 1, 24, 48 and 72 hours after instillation. Slight reddening of the conjunctivae was noted in all animals from 1 to 24 hours and was still evident in one female at the 48-hour reading. No abnormal findings were observed in the cornea or iris of any animal at any reading. A slight watery discharge was observed in 2 animals at the 1-hour reading and a slight mucus discharge was evident in the other animal at this reading. Moderate reddening of the sclera was observed in all animals 1 hour after treatment and slight reddening persisted in 2 animals up to the 48-hour reading. No clinical signs of systemic toxicity nor mortalities were observed. Based on the results of this study, the substance does not need to be classified for eye irritation/corrosion in accordance with the CLP Regulation.

Reference 2

Endpoint:

eye irritation: in vitro / ex vivo

Data waiving:

study scientifically not necessary / other information available

Justification for data waiving:

an in vitro eye irritation study does not need to be conducted because adequate data from an in vivo eye irritation study are available

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Skin irritation / corrosion

In a skin irritation study in rabbits, conducted in accordance with OECD 404 (1992), EU Method B.4 (1992) and according to GLP principles, 1 male and 2 female rabbits were semi-occlusively exposed for 4 hours to 0.5 mL of the substance. Well-defined erythema was observed in all animals 1 hour after treatment and persisted in the male up to the 72-hour reading, in one female up to the 24-hour reading and in the other female up to the 48-hour reading. Very slight erythema was evident in the male up to 14 days after treatment and in both females up to 72 hours after treatment. Very slight swelling was noted in all animals from 1 to 24 hours after treatment. Scaling was present at the test site of the male from 7 to 10 days after treatment and in both females from 72 hours to 7 days after treatment. No significant clinical signs of systemic toxicity nor mortalities were observed.

Under the conditions of a human repeated insult (occlusive) patch test procedure, a 3% solution of the substance did not induce clinically significant skin irritation in human subjects.

Eye irritation / corrosion

In an eye irritation study in rabbits, conducted in accordance with OECD 405 (1987), EU Method B.5 (1992) and according to GLP principles, 0.1 mL of the substance was placed in the conjunctival sac of the left eye of 1 female rabbit and subsequently of 1 male and 1 female rabbit the following day. The eyes were not rinsed and were examined approximately 1, 24, 48 and 72 hours after instillation. Slight reddening of the conjunctivae was noted in all animals from 1 to 24 hours and was still evident in one female at the 48-hour reading. No abnormal findings were observed in the cornea or iris of any animal at any reading. A slight watery discharge was observed in 2 animals at the 1-hour reading and a slight mucus discharge was evident in the other animal at this reading. Moderate reddening of the sclera was observed in all animals 1 hour after treatment and slight reddening persisted in 2 animals up to the 48-hour reading. No clinical signs of systemic toxicity nor mortalities were observed.

Justification for selection of skin irritation / corrosion endpoint:
The only study with a reliability of 1 that is available.

Justification for selection of eye irritation endpoint:
The only study with a reliability of 1 that is available.

Justification for classification or non-classification

Based on the results of the skin and eye irritation study in rabbits, the substance does not need to be classified for skin and eye irritation/corrosion in accordance with the CLP Regulation.