4-trans-(4-trans-Propylcyclohexyl)-cyclohexancarbonic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

2002-02-12 to 2002-02-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2002

Report date:

2002

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

02-1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

07-1992

Deviations:

no

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

(1r,1's,4r,4'r)-4'-propyl-[1,1'-bi(cyclohexane)]-4-carboxylic acid

EC Number:

613-782-9

Cas Number:

65355-32-0

Molecular formula:

C16 H28 O2

IUPAC Name:

(1r,1's,4r,4'r)-4'-propyl-[1,1'-bi(cyclohexane)]-4-carboxylic acid

Test material form:

solid: particulate/powder

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Remarks:

SPF

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage Scientifique des Dombes, F-01400 Chatillon sur Chalaronne, France
- Age at study initiation: 11 weeks (male) and 8-9 weeks (female)
- Weight at study initiation: 2.21 - 2.47 kg
- Housing: Individually in stainless steel cages equipped with feed hoppers, drinking water bowls, with wood, and haysticks for gnawing
- Diet: ad libitum
- Water: ad libitum

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17 - 23
- Humidity (%): 30 - 70
- Photoperiod (hrs dark / hrs light): 12 / 12

IN-LIFE DATES: Days 1 to 7

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

A single application of 100 mg into the conjunctival sac of the left eye

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

7 days;

Viability/mortality: daily from delivery of the animals to the termination of the test;

Clinical signs: Daily from delivery of the animals to the termination of the test;

Body weights: At start of acclimatization, on the day of application and at termination of observation;

Irritation scores: 1, 24, 48, and 72 hours, as well as 7 days after treatment

Number of animals or in vitro replicates:

2 females and 1 male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: The treated eyes were not rinsed after instillation
- Time after start of exposure: 7 days

SCORING SYSTEM: The occular reaction was assessed according to the numerical scoring system listed in the EU Regulation (EC) No 1272/2008 (CLP), as amended for fifteenth time in Regulation (EU) No 2020/217, at approximately 1, 24, 48 and 72 hours as well as 7 days after application. When present, corrosion and/or staining of sclera and cornea by the test item were recorded and reported.

TOOL USED TO ASSESS SCORE: Eye examinations were made with a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel/ Switzerland)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

24 hours

Results 2

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

72 hours

Results 3

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

fully reversible within:

Remarks:

24 hours

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

0.33

Max. score:

4

Reversibility:

fully reversible within: 72 hours

Results 5

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

72 hours

Results 6

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

7 days

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

0.33

Max. score:

3

Reversibility:

fully reversible within:

Remarks:

48 hours

Results 8

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

0.67

Max. score:

3

Reversibility:

fully reversible within: 7 days

Results 9

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

4

Reversibility:

other: no effects observed

Remarks on result:

no indication of irritation

Results 10

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: no effects observed

Remarks on result:

no indication of irritation

Irritant / corrosive response data:

Application of the test item to healthy rabbit conjunctivae resulted in a primary eye irritation score of 1. No abnormal findings were observed in the cornea or iris of any animal at any of the measuring intervals (table 1). Slight to moderate reddening of the conjunctivae was observed in all animals 1 hour after treatment. Slight reddening continued to be observed in all animals but gradually diminished to clear at the 7-day reading (table 1). Swelling of the conjunctivae (slight with partial eversion of lids or with lids about half-closed) was apparent in all animals at the 1-hour reading. Swelling persisted in one animal up to 48 hours after treatment (table 1). Assessment of the sclera was not possible in one animal at the 1-hour reading due to swelling of the conjunctiva. Moderate reddening was, however, subsequently observed in this animal at the 24- and 48-hour readings but diminished to clear 7 days after treatment. Moderate reddening was similarly observed in the remaining two animals 1 hour after treatment but cleared in one animal at the 24-hour reading and in the other animal at the 48-hour reading (table 1). A slight to moderate waterly discharge was present in all animals 1 hour after treatment and a slight waterly discharge was still evident in one animal at the 24-hour reading. No abnormal findings were observed in the treated eye of any animal 7 days after treatment, the end of the observation period for all animals. No corrosion of the cornea was observed at any of the reading times.

Other effects:

- Lesions and clinical observations: no clinical signs of systemic toxicty were observed in the animals during the study and no mortality occured
- white remnants of the test item were observed in the eye or conjunctival sac of all animals 1 hour after treatment and continued to be observed in one animal up to the 24-hour reading

Any other information on results incl. tables

Table 1: Eye irritation scores – individual values

Animal Number	Sex	Evaluation Interval	Corneal Opacity	Iris	Conjunctivae		Cumulative		Sclera
					Redness	Chemosis	Score	Mean
4	M	1 hour	0	0	2	1	3	3.33	2
5	F		0	0	1	3	4		n.a.
6	F		0	0	1	2	3		2
4	M	24 hours	0	0	1	0	1	1.67	1
5	F		0	0	1	2	3		2
6	F		0	0	1	0	1		0
4	M	48 hours	0	0	1	0	1	1	0
5	F		0	0	1	1	2		2
6	F		0	0	0	0	0		0
4	M	72 hours	0	0	0	0	0	0.33	0
5	F		0	0	1	0	1		1
6	F		0	0	0	0	0		0
4	M	7 days	0	0	0	0	0	0.00	0
5	F		0	0	0	0	0		0
6	F		0	0	0	0	0		0

n.a.= not assessable due to swelling of the conjunctivae

F= female

M=male

 

 

Table 2. Eye irritation scores – mean values after 24, 48 and 72 hours

Animal Number	Sex	Corneal Opacity	n	iris	n	Conjunctivae				Primary Eye Irritation Score
						redness	n	chemosis	n
4	M	0	3	0	3	0.67	3	0	3	1
5	F	0	3	0	3	1	3	1	3
6	F	0	3	0	3	0.33	3	0	3
Mean score		0		0		0.67		0.33

n= number of available data points

 

 

Table 3. Eye irritation scores – assessment according to EEC guidelines

Evaluated intervals	Corneal Opacity	Iris	Conjunctivae
			redness	chemosis
24 hours	Not irritating	Not irritating	Not irritating
48 hours
72 hours

Applicant's summary and conclusion

Interpretation of results:

GHS criteria not met

Conclusions:

The test item did not induce significant or irreversible damage to the rabbit eye and is considered to be "not irritating" to the rabbit eye.

Executive summary:

The primary eye irritation of the test item was investigated by instillation of 0.1 g into one eye of each of three young adult New Zealand White rabbits. Scoring of irritation effects was performed approximately 1, 24, 48 and 72 hours, as well as 7 days after test item application. The scores of each animal at the following reading times (24, 48 and 72 hours) were used in calculating the respective mean values for each type of lesion. The primary eye irritation score was calculated by totaling the mean cumulative scores at 24, 48 and 73 hours and then dividing the resulting total by the number of data points. The primary eye irritation score was 1.00 (max 13). The eye reactions (mean values from 24 to 72 hours) consisted of grade 0.00 corneal opacity, grade 0.00 iris lesions, grade 0.67 redness of the conjunctivae and grade 0.33 chemosis of the conjunctivae. The instillation of the test item into the eye resulted in mild, early-onset and transient ocular changes, such as reddening of the conjunctivae and sclerae, discharge and swelling. These effects were reversible and were no longer evident 7 days after treatment, the end of the observation period for all animals. No abnormal findings were observed in the cornea or iris of any animal at any reading. No corrosion was observed at any of the measuring intervals. No staining of the treated eyes by the test item was observed. Thus, the test item did not induce significant or irreversible damage to the rabbit eye. Based upon the referred classification criteria (EU Regulation (EC) No 1272/2008 (CLP), as amended for fifteenth time in Regulation (EU) No 2020/217), the test item is considered to be "not irritating" to the rabbit eye.