N-(dodecylphenyl)naphthalen-1-amine

Eye irritation

Administrative data

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

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1999

Report date:

1999

Materials and methods

Test guideline

Test guideline 1

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

Test guideline 2

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)

Test material

Test material information

1

Reference substance name:

-

EC Number:

437-450-6

EC Name:

-

Cas Number:

64654-05-3

Molecular formula:

Hill formula: C28 H37 N

IUPAC Name:

N-(dodecylphenyl)naphthalen-1-amine

Test material form:

liquid: viscous

Details on test material:

Sponsor's identification: APAN
Description: redbrown viscous liquid
Lot number: EL01010B01/KZ8911.5
Storage conditions: room temperature in the dark

Specific details on test material used for the study:

No further details specified in the study report.

Test animals / tissue source

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.

Test system

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.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

mean

Time point:

24/48/72 h

Score:

10

Max. score:

110

Reversibility:

fully reversible within: 48 hours

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

10

Results 3

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

80

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.3

Max. score:

20

Reversibility:

fully reversible within: 48 hours

Results 5

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.

Any other information on results incl. tables

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

 

Applicant's summary and conclusion

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.