Condensation products of oil shale alkylresorcinols and formaldehyde

Endpoint summary

Description of key information

The test material is not considered to be irritating to the skin or eyes of rabbits.

Key value for chemical safety assessment

Skin irritation / corrosion

Link to relevant study records

Reference

Endpoint:

skin irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

30 March 2004 and 13 April 2004

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Qualifier:

according to guideline

Guideline:

OECD Guideline 404 (Acute Dermal Irritation / Corrosion)

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): free access to certified rabbit diet
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: at least five days
- Other: The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

IN-LIFE DATES: From: 30 March 2004 To: 13 April 2004

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

water

Remarks:

Distilled

Controls:

no

Amount / concentration applied:

0.5 g

Duration of treatment / exposure:

3 minutes, 1 hour and 4 hours

Observation period:

Observations made at 1 hour, 24 hours, 48 hours, 72 hours and 7 days after removal of the patch.

Number of animals:

3

Details on study design:

TEST MATERIAL APPLICATION
One rabbit was initially treated. Three suitable sites were selected on the back of the rabbit. At each test site a quantity of 0.5 g of the test material, moistened with 0.5 mL of distilled water, was introduced under a 2.5 cm x 2.5 cm cotton gauze patch and placed in position on the shorn skin. Each patch was secured in position with a strip of surgical adhesive tape. To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset and the animal was returned to its cage for the duration of the exposure period.
After consideration of the skin reactions produced in the first animal, two additional animals were treated with 0.5 g of test material moistened with 0.5 mL of distilled water. One patch was applied to the back of each rabbit, and was allowed to remain in contact with the skin for a period of four hours.

REMOVAL OF TEST SUBSTANCE
- Washing (if done): Any residual test material was removed by gentle swabbing with cotton wool soaked in distilled water.
- Time after start of exposure: One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application.

SCORING SYSTEM: Draize J H (1959) "Dermal Toxicity" In: Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics. Association of Food and Drug Officials of the United States, Austin, Texas, p.47:

Irritation parameter:

erythema score

Basis:

animal #1

Time point:

other: mean of time points 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

erythema score

Basis:

animal #2

Time point:

other: mean of time points 24, 48 and 72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritation parameter:

erythema score

Basis:

animal #3

Time point:

other: mean of time points 24, 48 and 72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible within: 7 days

Irritation parameter:

edema score

Basis:

animal #1

Time point:

other: mean of time points 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: no edema observed

Irritation parameter:

edema score

Basis:

animal #2

Time point:

other: mean of time points 24, 48 and 72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 2 days

Irritation parameter:

edema score

Basis:

animal #3

Time point:

other: mean of time points 24, 48 and 72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within: 3 days

Irritant / corrosive response data:

4 hour exposure:
Very slight erythema was noted at two treated skin sites one hour after patch removal. Very slight to well-defined erythema was noted at all treated skin sites at the 24 and 48-hour observations with very slight erythema at two treated skin sites at the 72-hour observation.
Very slight oedema was noted at one treated skin site one hour after patch removal with very slight to slight oedema at two treated skin sites at the 24-hour observation and very slight oedema at one treated skin site at the 48-hour observation.
One treated skin site appeared normal at the 72-hour observation and the remaining two treated skin sites appeared normal at the 7-day observation.

1 hour exposure:
Very slight erythema was noted at the treated skin site at the 24 and 48-hour observations.
The treated skin site appeared normal at the 72-hour observation.

3 minutes exposure:
No evidence of skin irritation was noted during the study.

Other effects:

None

Table 1: Individual Skin Reactions Following 4-Hour Exposure

Skin Reaction	Observation Time	Individual Scores – Rabbit Number and Sex			Total
		Rabbit #1	Rabbit #2	Rabbit #3
Erythema/Eschar Formation	1 hour	0	1	1	2
	24 hours	1	1	2	4
	48 hours	1	1	2	4
	72 hours	1	0	1	2
	7 days	0	0	0	0
Oedema Formation	1 hour	0	0	1	1
	24 hours	0	1	2	3
	48 hours	0	0	1	1
	72 hours	0	0	0	0
	7 days	0	0	0	0

Sum of 24 and 72-hour Readings (S): 9

Primary Irritation Index (S/6): 9/6 = 1.5

Transcutaneous Electrical Resistance Assay

After a test material contact time of 24 hours, the mean electrical resistance was determined as 17.6 (± 7.3) kΩ. The test material was considered not to be corrosive to the skin in vivo.

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material is not considered to be irritating to the skin of rabbits.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. Three female rabbits were used. The test material was moisted with distilled water prior to application to the clipped flank of the rabbits.

Irritation was scored according to the method of Draize (1977). A semi-occlusive dressing was used. The study was performed in accordance with the OECD 404 and EU Method B.4 guidelines.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight to well-defined erythema and very slight to slight oedema. One treated skin site appeared normal at the 72-hour observation and the remaining two treated skin sites appeared normal at the 7-day observation. 3-minute and 1-hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects.

The test material is therefore not considered to be irritating to the skin of rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Eye irritation

Link to relevant study records

Reference

Endpoint:

eye irritation: in vitro / ex vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

07 April 2004 - 16 April 2004.

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results.

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)

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: David Percival Ltd, Moston, Sandbach, Cheshire, UK
- Age at study initiation: 12 - 20 weeks old
- Weight at study initiation: 2.0 - 3.5 kg
- Housing: individually housed in suspended metal cages
- Diet (e.g. ad libitum): free access to certified rabit diet
- Water (e.g. ad libitum): free access to mains drinking water
- Acclimation period: at least five days
- Other: The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 to 23 °C
- Humidity (%): 30 to 70 %
- Air changes (per hr): at least fifteen changes per hour
- Photoperiod (hrs dark / hrs light): twelve hours continuous light (06:00 to 18:00) and twelve hours darkness

IN-LIFE DATES: From: 07 April 2004 To: 16 April 2004.

Vehicle:

water

Remarks:

Distilled

Controls:

yes, concurrent no treatment

Amount / concentration applied:

0.1 mL (approx. 72 mg)

Duration of treatment / exposure:

The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released.

Observation period (in vivo):

Observations were made 1, 24, 48 and 72 hours after treatment.

Number of animals or in vitro replicates:

3

Details on study design:

ADIMINSTRATION OF TEST SUBSTANCE
Immediately before the start of the test, both eyes of the provisionally selected test rabbits were examined for evidence of ocular irritation or defect with the aid of a light source from a standard ophthalmoscope. Only animals free of ocular damage were used.
Initially, a single rabbit was treated. A volume of 0.1 mL of the test material, which was found to weigh approximately 72 mg (as measured by gently compacting the required volume into an adapted syringe) was placed into the conjunctival sac of the right eye, formed by gently pulling the lower lid away from the eyeball. The upper and lower eyelids were held together for about one second immediately after treatment, to prevent loss of the test material, and then released. The left eye remained untreated and was used for control purposes. Immediately after administration of the test material, an assessment of the initial pain reaction was made.
After consideration of the ocular responses produced in the first treated animal, two additional animals were treated.

SCORING SYSTEM: Draize JH (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.48 to 49). See Table 1.
Immediately after administration of the test material, an assessment of the initial pain reaction was made according to the six point scale shown in Table 2.

TOOL USED TO ASSESS SCORE: standard ophthalmoscope

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 h time points

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

other: mean of 24, 48 and 72 h time points

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

other: mean of 24, 48 and 72 h time points

Score:

0.3

Max. score:

3

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 h time points

Score:

0

Max. score:

4

Reversibility:

other: no chemosis observed

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

other: mean of 24, 48 and 72 h time points

Score:

0

Max. score:

4

Reversibility:

other: no chemosis observed

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

other: overall at 24, 48 and 72 h

Score:

0

Max. score:

4

Reversibility:

other: no chemosis observed

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 h time points

Score:

0

Max. score:

4

Reversibility:

other: no effect on the cornea observed

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

other: mean of 24, 48 and 72 h time points

Score:

0

Max. score:

4

Reversibility:

other: no effect on the cornea observed

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

other: mean of 24, 48 and 72 h time points

Score:

0

Max. score:

3

Reversibility:

other: no effect on the cornea observed

Irritation parameter:

iris score

Basis:

animal #1

Time point:

other: mean of 24, 48 and 72 h time points

Score:

0

Max. score:

2

Reversibility:

other: not effect on the iris observed

Irritation parameter:

iris score

Basis:

animal #2

Time point:

other: mean of 24, 48 and 72 h time points

Score:

0

Max. score:

2

Reversibility:

other: no effect on the iris observed

Irritation parameter:

iris score

Basis:

animal #3

Time point:

other: mean of 24, 48 and 72 h time points

Score:

0

Max. score:

2

Reversibility:

other: no effect on the iris observed

Irritant / corrosive response data:

No corneal or iridial effects were noted during the study. Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation in all treated eyes at the 24-hour observation. All treated eyes appeared normal at the 48-hour observation.

Other effects:

None

Table 3: Individual Scores and Individual Total Scores for Ocular Irritation

Rabbit Number	Rabbit #1				Rabbit #2				Rabbit #3
	IPR = 2				IPR = 2				IPR = 2
Time After Treatment (hours)	1	24	72	72	1	24	72	72	1	24	72	72
CORNEA
E = Degree of Opacity	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
Score (E x F) x 5	0	0	0	0	0	0	0	0	0	0	0	0
IRIS
D	0	0	0	0	0	0	0	0	0	0	0	0
Score (D x 5)	0	0	0	0	0	0	0	0	0	0	0	0
CONJUNCTIVAE
A = Redness	2	1	0	0	1	1	0	0	1	1	0	0
B = Chemosis	1	0	0	0	1	0	0	0	1	0	0	0
C = Discharge	1	0	0	0	1	0	0	0	1	0	0	0
Score (A + B + C) x 2	8	2	0	0	6	2	0	0	6	2	0	0
Total Score	8	2	0	0	6	2	0	0	6	2	0	0

Interpretation of results:

not irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

The test material is not considered to be irritating to the eyes of rabbits.

Executive summary:

The study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. Three rabbits were used. 0.1 mL of the test material was placed into the conjunctival sac of the right eye. The left eye served as the control. The irritation was scored according to the method of Draize (1977). The study was conducted in accordance with the OECD 405 and EU Method B.5 guidelines and to GLP standard in a certified laboratory.

Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation in all treated eyes at the 24-hour observation. All treated eyes appeared normal at the 48-hour observation.

The test material is therefore not considered to be irritating to the eyes of rabbits.

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed (not irritating)

Respiratory irritation

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

SKIN

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. Three female rabbits were used. The test material was moistened with distilled water prior to application to the clipped flank of the rabbits.

Irritation was scored according to the method of Draize (1977). A semi-occlusive dressing was used. The study was performed in accordance with the OECD 404 and EU Method B.4 guidelines.

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight to well-defined erythema and very slight to slight oedema. One treated skin site appeared normal at the 72-hour observation and the remaining two treated skin sites appeared normal at the 7-day observation. 3-minute and 1-hour semi-occluded applications of the test material to the intact skin of one rabbit produced no corrosive effects.

The test material is therefore not considered to be irritating to the skin of rabbits.

EYE

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. Three rabbits were used. 0.1 mL of the test material was placed into the conjunctival sac of the right eye. The left eye served as the control. The irritation was scored according to the method of Draize (1977). The study was conducted in accordance with the OECD 405 and EU Method B.5 guidelines and to GLP standard in a certified laboratory.

Minimal to moderate conjunctival irritation was noted in all treated eyes one hour after treatment with minimal conjunctival irritation in all treated eyes at the 24-hour observation. All treated eyes appeared normal at the 48-hour observation.

The test material is therefore not considered to be irritating to the eyes of rabbits.

Justification for selection of skin irritation / corrosion endpoint:
Well reported study performed in accordance with a recognised OECD guideline and in line with GLP in a certified laboratory. The study is assigned a reliability score of one in accordance with Klimisch et. al. (1997).

Justification for selection of eye irritation endpoint:
Well reported study performed in accordance with a recognised OECD guideline and in line with GLP in a certified laboratory. The study is assigned a reliability score of one in accordance with Klimisch et. al. (1997).

Justification for classification or non-classification

From the results of the study data available for this substance, no irritation / corrosion classification is required in accordance with Regulation (EC) No. 1972/2008 or Directive 67/548/EEC.