N-(dodecylphenyl)naphthalen-1-amine

Endpoint summary

Description of key information

Skin irritation/corrosion - in vivo

The test material produced a primary irritation index of 0.2 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme.

The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations.

Eye irritation - in vivo

The test material produced a maximum group mean score of 10.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

 

The test material did not meet the criteria for classification as irritant according to EU labelling regulations.

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:

29 April 1999 to 7 May 1999.

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:

OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 17 July 1992)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Method B4 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

No further details specified in the study report.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or test system and environmental conditions:

Three New Zealand White rabbits supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK were used. At the start of the study the animals weighed 2.68 to 3.01 kg and were twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK) was allowed throughout the study.
The temperature and relative humidity were controlled to remain within target ranges of 17 to 23 °C and 30 to 70% respectively. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Type of coverage:

semiocclusive

Preparation of test site:

clipped

Vehicle:

unchanged (no vehicle)

Controls:

not specified

Amount / concentration applied:

At each test site a quantity of 0.5 ml of the test material was introduced.

Duration of treatment / exposure:

One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application.

Observation period:

Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation.

Number of animals:

3

Details on study design:

On the day before the test each rabbit was clipped free of fur from the dorsal flank area using veterinary clippers. Only animals with a healthy intact epidermis by gross observation were selected for the study.
One rabbit was initially treated. Three suitable test sites were selected on the back of the rabbit. At each test site a quantity of 0.5 ml of the test material 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 (BLENDERM: approximate size 2.5 cm x 4.0 cm). To prevent the animal interfering with the patches, the trunk of the rabbit was wrapped in an elasticated corset (TUBIGRIP) and the animal was returned to its cage for the duration of the exposure period.
One patch was removed at each of three time points: 3 minutes, 1 hour and 4 hours after application. Any residual test material was removed by gentle swabbing with cotton wool soaked in 74% industrial Methylated Spirits.
After consideration of the skin reactions produced in the first animal, two additional animals were treated with 0.5 ml of test material. 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.
Approximately one hour following the removal of the patches, and 24, 48 and 72 hours later, the test sites were examined for evidence of primary irritation and scored.

Irritation parameter:

erythema score

Basis:

mean

Time point:

24/48/72 h

Score:

0.7

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Irritation parameter:

edema score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Irritant / corrosive response data:

4-Hour Exposure Period
Very slight erythema was noted at one treated skin site at the 24 and 48-hour observations. No other signs of dermal irritation were noted during the study.

1-Hour Exposure Period
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-Minute Exposure Period
No signs of dermal irritation were noted during the study.

Other effects:

No further effects detailed in the study report.

INDIVIDUAL SKIN REACTIONS FOLLOWING 4-HOUR EXPOSURE PERIOD

Skin Reaction	Observation Time	Individual Scores – Rabbit Number and Sex (Bodyweight kg)			Total
		184 Female (2.78)	170 Female (2.68)	215 Female (3.01)
Erythema/Eschar Formation	1 Hour 24 Hours 48 Hours 72 Hours	0 1 1 0	0 0 0 0	0 0 0 0	(0) 1 (1) 0
Oedema Formation	1 Hour 24 Hours 28 Hours 72 Hours	0 0 0 0	0 0 0 0	0 0 0 0	(0) 0 (0) 0
Sum of 24 and 72-hour Readings (S)	:	1
Primary Irritation Index (S/6)	:	1/6 – 0.2
Classification	:	MILD IRRITANT

( ) – Total values not used for calculation of primary irritation index

 

INDIVIDUAL DAILY AND MEAN SCORES FOR DERMAL IRRITATION FOLLOWING 4-HOUR EXPOSURE REQUIRED

FOR EU LABELLING REGULATIONS

Skin Reaction	Reading (Hours)	Individual Scores – Rabbit Number and Sex (Bodyweight kg)
		184 Female (2.78)	170 Female (2.68)	215 Female (3.01)
Erythema/Eschar Formation	24 48 72	1 1 0	0 0 0	0 0 0
Total		2	0	0
Mean Score		0.7	0.0	0.0
Oedema Formation	24 48 72	0 0 0	0 0 0	0 0 0
Total		0	0	0
Mean Score		0.0	0.0	0.0

 

INDIVIDUAL SKIN REACTIONS FOLLOWING 1-HOUR AND 3-MINUTE EXPOSURES

Skin Reaction	Observation Time	Individual Scores – Rabbit Number and Sex (Bodyweight kg)
		184 Female (2.78)
		1-Hour Exposure	3-Minute Exposure
Erythema/Eschar Formation	1 Hour 24 Hours 48 Hours 72 Hours	0 1 1 0	0 0 0 0
Oedema Formation	1 Hour 24 Hours 48 Hours 72 Hours	0 0 0 0	0 0 0 0

 

Interpretation of results:

GHS criteria not met

Conclusions:

The test material, APAN, produced a primary irritation index of 0.2 and was classified as a MILD IRRITANT to rabbit skin according to the Draize classification scheme. No corrosive effects were noted.
The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations. No symbol and risk phrase are required.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the skin of the New Zealand White rabbit. The method used followed the recommendations of the OECD Guidelines for Testing of Chemicals No. 404 "Acute Dermal Irritation/Corrosion" (adopted 1 7 July 1992) and Method B4 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

 

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

 

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight erythema. All treated skin sites appeared normal at the 72-hour observation. No corrosive effects were noted.

 

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 produced a primary irritation index of 0.2 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme.

 

The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations. No symbol and risk phrase are required.

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:

10 May 1999 to 16 May 1999.

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:

OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 February 1987)

Deviations:

not specified

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

Method B5 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

Deviations:

not specified

GLP compliance:

yes (incl. QA statement)

Specific details on test material used for the study:

No further details specified in the study report.

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Three New Zealand White rabbits, supplied by David Percival Ltd, Moston, Sandbach, Cheshire, UK, were used. At the start of the study the animals weighed 2.59 to 2.70 kg and were twelve to sixteen weeks old. After a minimum acclimatisation period of five days each animal was given a number unique within the study which was written with a black indelible marker-pen on the inner surface of the ear and on the cage label.
The animals were individually housed in suspended metal cages. Free access to mains drinking water and food (STANRAB SQC Rabbit Diet, Special Diets Services Ltd, Witham, Essex, UK) was allowed throughout the study.
The temperature and relative humidity were controlled to remain within target ranges of 17 to 23 °C and 30 to 70% respectively. The rate of air exchange was approximately fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light and twelve hours darkness.

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

A volume of 0.1 ml of the test material, was instilled into the conjunctival sac of the right eye.

Duration of treatment / exposure:

single instillation.

Observation period (in vivo):

Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.

Number of animals or in vitro replicates:

3 animals

Details on study design:

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. Animals showing evidence of ocular lesions were rejected and replaced.
One rabbit was initially treated. A volume of 0.1 ml of the test material, was instilled 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 instillation, 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.
Assessment of ocular damage/irritation was made approximately 1 hour and 24, 48 and 72 hours following treatment.
Any other ocular effects were also noted. Examination of the eye was facilitated by the use of the light source from a standard ophthalmoscope.

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

10

Max. score:

110

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

10

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

80

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

20

Reversibility:

fully reversible within: 48 hours

Irritation parameter:

conjunctivae score

Remarks:

redness

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

10

Reversibility:

fully reversible within: 48 hours

Irritant / corrosive response data:

No corneal or iridial effects were noted during the study.
Moderate conjunctival irritation was noted in all treated eyes at the 1-hour observation with minimal conjunctival irritation at the 24-hour observation.
No ocular effects were noted at the 48-hour observation.

Other effects:

Brown-coloured residual test material was noted in and around all treated eyes at the 1-hour observation. Red/brown staining of the fur around the treated eye was noted in two animals at the 24-hour and subsequent observations.

INDIVIDUAL SCORES AND INDIVIDUAL TOTAL SCORES FOR OCULAR IRRITATION

Rabbit Number and Sex (Bodyweight kg)	IPR – 2				IPR – 2				IPR – 2
	53 Female (2.70)				115 Male (2.59)				119 Male (2.60)
Time After Treatment	1 hr	24 hr	48 hr	72 hr	1 hr	24 hr	48 hr	72 hr	1 hr	24 hr	48 hr	72 hr
CORNEA E = Degree of Opacity F = Area of Opacity	0 0	0 0	0 0	0 0	0 0	0 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
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 B = Chemosis C = Discharge	2 1 2Re	1 0 1	0 0 0	0 0 0	2 1 2Re	1 1 1Sf	0 0 0Sf	0 0 0Sf	2 1 2Re	1 1 1Sf	0 0 0Sf	0 0 0Sf
Score (A + B + C) x 2	10	4	0	0	10	6	0	0	10	6	0	0
Total Score	10	4	0	0	10	6	0	0	10	6	0	0

Key:        hr = hour(s)            IPR = initial pain reaction      

Re = brown-coloured residual test material in and around treated eye              Sf = red/brown-coloured staining of the fur

 

INDIVIDUAL TOTAL SCORES AND GROUP MEAN SCORES FOR OCULAR IRRITATION

Rabbit Number and Sex	Individual Total Scores At:
	1 Hour	24 Hours	48 Hours	72 Hours
53 Female 115 Male 119 Male	10 10 10	4 6 6	0 0 0	0 0 0
Group Total	30	16	0	0
Group Mean Score	10.0	5.3	0.0	0.0

 

INDIVIDUAL AND MEAN SCORES FOR CORNEA, IRIS AND CONJUNCTIVAE REQUIRED FOR EU LABELLING REGULATIONS

Rabbit Number and Sex (Bodyweight kg)	Time After Treatment	Corneal Opacity	Iridial Inflammation	Conjunctival Redness	Conjunctival Chemosis
53 Female (2.70)	24 Hours 28 Hours 72 Hours	0 0 0	0 0 0	1 0 0	0 0 0
Total		0	0	1	0
Mean		0.0	0.0	0.3	0.0
115 Male (2.59)	24 Hours 48 Hours 72 Hours	0 0 0	0 0 0	1 0 0	1 0 0
Total		0	0	1	1
Mean		0.0	0.0	0.3	0.3
119 Male (2.60)	24 Hours 48 Hours 72 Hours	0 0 0	0 0 0	1 0 0	1 0 0
Total		0	0	1	1
Mean		0.0	0.0	0.3	0.3

 

Interpretation of results:

GHS criteria not met

Conclusions:

The test material, APAN, produced a maximum group mean score of 10.0 and was classified as a MINIMAL IRRITANT (CLASS 3 ON A 1 TO 8 SCALE) to the rabbit eye
according to a modified Kay and Calandra classification system.
The test material did not produce positive criteria in any rabbit according to the EU labelling regulations. No symbol and risk phrase are therefore required.

Executive summary:

A study was performed to assess the irritancy potential of the test material to the eye of the New Zealand White rabbit. The method used followed that described in the OECD Guidelines for Testing of Chemicals No. 405 "Acute Eye Irritation/Corrosion" (adopted 24 February 1987) and Method B5 of Commission Directive 92/69/EEC (which constitutes Annex V of Council Directive 67/548/EEC).

 

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

 

A single instillation of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. No ocular effects were noted at the 48- hour observation.

 

The test material produced a maximum group mean score of 10.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

 

The test material did not meet the criteria for classification as irritant according to EU labelling regulations. No symbol and risk phrase are required.

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 vivo

A single 4-hour, semi-occluded application of the test material to the intact skin of three rabbits produced very slight erythema. All treated skin sites appeared normal at the 72-hour observation. No corrosive effects were noted.

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 produced a primary irritation index of 0.2 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme.

The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations.

Eye irritation - in vivo 

A single instillation of the test material to the non-irrigated eye of three rabbits produced moderate conjunctival irritation. No ocular effects were noted at the 48- hour observation.

The test material produced a maximum group mean score of 10.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not meet the criteria for classification as irritant according to EU labelling regulations.

Justification for classification or non-classification

Skin irritation/corrosion - in vivo

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

The test material produced a primary irritation index of 0.2 and was classified as a mild irritant to rabbit skin according to the Draize classification scheme.

The test material did not meet the criteria for classification as irritant or corrosive according to EU labelling regulations. No symbol and risk phrase are required.

Eye irritation - in vivo

The results may be used as a basis for classification and labelling under Annex VI of Council Directive 67/548/EEC (as adapted to technical progress by Commission Directive 93/21/EEC) relating to the classification, packaging and labelling of dangerous substances.

The test material produced a maximum group mean score of 10.0 and was classified as a minimal irritant (Class 3 on a 1 to 8 scale) to the rabbit eye according to a modified Kay and Calandra classification system.

The test material did not meet the criteria for classification as irritant according to EU labelling regulations. No symbol and risk phrase are required.