3,7,11,15-tetramethylhexadecane-1,2,3-triol

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

The study was conducted between 07 March 1991 and 16 May 1991

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

3,7,11,15-tetramethylhexadecane-1,2,3-triol

EC Number:

277-923-2

EC Name:

3,7,11,15-tetramethylhexadecane-1,2,3-triol

Cas Number:

74563-64-7

Molecular formula:

C20H42O3

IUPAC Name:

3,7,11,15-tetramethylhexadecane-1,2,3-triol

Test material form:

liquid: viscous

Details on test material:

Identification: Phytantriol RO 04-3724
Description: Pale yellow, translucent to clear, viscous liquid
Batch number: 804258
Stability of test article: Stable; expiration date January 1992.

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

Test system: Rabbit, ChbbIm: NZW (SPF)
Justification: Recognised by the international guidelines as the recommended test system.
Source: BRL, Biological Research Laboratories Ltd, Wolferstrasse 4, CH-4414 Fuellinsdorf
Age at start of treatment:
Males: 14 weeks
Females: 15 weeks
Bodyweight at start of treatment:
Males: 2.6 kg
Females 2.6 - 2.7 kg
IdentificationL By unique cage number and corresponding ear tags
Acclimatization: Four days under laboratory conditions after veterninary examination
Allocation:
Animal numbers:
Male Nos.: 24 - 26
Females Nos.: 37 - 39
Conditions:
Standard laboratory conditions. Air-conditioned with 10 - 15 cahnges per hour and hourly monitored environment with temperature 20 ± 3 °C, relative humidity 40 - 70 %, 12 hours artificial fluorescent light / 12 hours dark; music during the light period.
Accommodation:
Individually in stainless steel cages equipped with an automatic cleaning and drinking system.
Diet:
Pelleted standard Kliba 341, Batch 58/90 rabbit maintenance diet ad libitum.
Water:
Community tap water from Itingen, ad libitum.

Test system

Vehicle:

other: Neantine

Controls:

no

Amount / concentration applied:

0.1 mL / animal (100%, 23 %, 10 % and 3 %)

Duration of treatment / exposure:

A single dose was administered and was not removed.

Observation period (in vivo):

14 days

Number of animals or in vitro replicates:

Three males and three females

Details on study design:

Test article preparation
The test article was applied undiluted (100 % and diluted (23 %, 10 % and 3 %) in Neantine. The test article dilutions (10 %, 23 % and 3 %) were placed into a glass beaker on a tared Mettler PE 360 balance, and the vehicle (Neantine) was added. A weight by weight dilution was prepared using a homogenzer (Ultra-Turrax, Janke and Kunkel) Homogeneity of the test article in the vehicle was maintained during treatment using a magentic stirrer (Janke & Kunkel).


Treatment
The eyes of the animals were observed 1 day prior to test article administration.
Only those animals with no signs of cular injury or irritation were used in the test.
On test day 1, a single dose was administered to the left (undiluted) and right (23 %) eyes of males No. 34 - 36 and the 10 % and 3 % test article dilution of females No. 37 to 39 respectively. The individual dose volume was 0.1 mL per animal and test article concentration. After application the lids were gently held together for about 1 second to prevent loss of the test article.
In cases of equivocal results when comparing the findings of the eyes, the illustrated guide from Consumer Product Safety Commission, Washington D.C. 20207 was used.


Observations
Viability, mortality and clinical signs: Daily
Body weights: At acclimatization, at day 1 of test (application day) and at termination of observation.


Irritation scores
The eyes of each animal was examined 1, 24, 48 and 72 hours, 7 and 14 days after administration.The irritation was assessed according to the OECD guidelines for testing of Chemicals, section 4, number 405 "acute eye irritation / corrosion", adopted February 24, 1987.
The corrosive properties of the test article and the colour of the treated eye were described and recorded.

Eye examinations were made with a slit-lamp 30 SL/M (C. Zeiss AG, Zuerich) and a Varta Cliptrix diagnostic-lamp (A. Riegger, Basel).


Treatment of results
Data were summarised in tabular form, showing for each individual animal the irritation scores at the designated observation time, a description of the degree and nature of irritation, the presence of serrious lesions and non-ocular effects.

Pathology
Necropsy
The observation was terminated 14 days after administration of the test article.
No necropsy was performed in the animals euthanised at termination of observation.
All rabbits were euthanised by an intravenous injection of T61 (Hoechst/AG) into the ear vei nand discarded.


Data compilation
The primary irritation score was calculated by totalling the individual cumulative scores at 1, 24, 48 and 72 hours and then divided by the number of figures.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal: 34

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

undiluted substance

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal: 35

Time point:

24/48/72 h

Score:

0.67

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

undiluted substance

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal: 36

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

undiluted substance

Results 4

Irritation parameter:

iris score

Basis:

animal: 34

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible

Results 5

Irritation parameter:

iris score

Basis:

animal: 35

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

other: Not applicable

Results 6

Irritation parameter:

iris score

Basis:

animal: 36

Time point:

24/48/72 h

Score:

0.33

Max. score:

2

Reversibility:

fully reversible

Results 7

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: 34

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

undiluted substance

Results 8

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: 35

Time point:

24/48/72 h

Score:

1

Max. score:

3

Reversibility:

fully reversible

Results 9

Irritation parameter:

conjunctivae score

Remarks:

Redness

Basis:

animal: 36

Time point:

24/48/72 h

Score:

1.67

Max. score:

3

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

undiluted substance

Results 10

Irritation parameter:

chemosis score

Basis:

animal: 34

Time point:

24/48/72 h

Score:

1.33

Max. score:

4

Reversibility:

fully reversible

Results 11

Irritation parameter:

chemosis score

Basis:

animal: 35

Time point:

24/48/72 h

Score:

1

Max. score:

4

Reversibility:

fully reversible

Results 12

Irritation parameter:

chemosis score

Basis:

animal: 36

Time point:

24/48/72 h

Score:

1.67

Max. score:

4

Reversibility:

fully reversible

Remarks on result:

positive indication of irritation

Remarks:

undiluted substance

Irritant / corrosive response data:

The test susbtance showed primary irritation scores of 4.17 (100 %), 2.25 (23 %), 0.75 (10 %) and 0.42 (3 %) when applied to healthy eye mucosa.

Colouration
In the area of application, no staining of the cornea and sclera by pigment or colouring of the test article was observed during the entire study period after test article application.

Corrosion
Generally severe to slight corneal opacity was observed at 100 % in the left eye of the animals (34, 35 and 36) between 1 hour and 72 hours of observation and generally slight corneal opacity was observed in the right eye of all animals (23 % diluted) at 1 hour but it returned to generally slight diffuse corneal opacity between 24 and 72 hours after test article application.
No corrosive effect on the treated skin was oberved after treatment with the 10 % and 3 % test article dilution.

Other effects:

Viability / mortality and clinical signs
No acute toxic symptoms were observed in the animals during the test and obesrvation period, and no mortality recorded.

Body weights
The body weight gain of all rabbits was similar.

Applicant's summary and conclusion

Interpretation of results:

Category 2 (irritating to eyes) based on GHS criteria

Conclusions:

A single application of the neat test sample into the conjunctival sac of the rabbit eye caused short-lasting corneal opacity with conjunctival reactions which was reversed within two weeks.

Executive summary:

The test substance was assessed for eye irritation potential according to OECD Test Guideline 405 and EU Method B.5. A single application of the neat test sample into the conjunctival sac of the rabbit eye caused short-lasting corneal opacity with conjunctival reactions which were reversed within two weeks. The effects were sufficient for classification as an eye irritant based on the conjunctival opacity.