2,2-bis(hydroxymethyl)butanoic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1996-11-04 to 1996-11-25

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: GLP study conducted without any deviation.

Cross-reference

Cross-reference 1

Reason / purpose for cross-reference:

reference to same study

Cross-reference 2

Reason / purpose for cross-reference:

reference to other study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1997

Report date:

1997

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

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

Deviations:

no

Principles of method if other than guideline:

Not applicable

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

2,2-bis(hydroxymethyl)butanoic acid

EC Number:

424-090-1

EC Name:

2,2-bis(hydroxymethyl)butanoic acid

Cas Number:

10097-02-6

Molecular formula:

C6H12O4

IUPAC Name:

2,2-bis(hydroxymethyl)butanoic acid

Test material form:

solid: particulate/powder

Remarks:

migrated information: powder

Details on test material:

- Name of test material (as cited in study report): DMBA
- Physical state: White powder
- Analytical purity: 99 %
- Lot/batch No.: 5J01
- Date of receipt: 1996-10-09
- Expiration date of the lot/batch: Six months from receipt
- Storage condition of test material: Room temperature in the dark

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Harlan Interfauna (UK) Ltd, Huntingdon, Cambridgeshire, England.
- Age at study initiation: Approximately 13 weeks
- Weight at study initiation: 3.0-3.2 kg
- Housing: Animals were individually housed in metal cages with perforated floors.
- Diet: Standard laboratory diet SDS Stanrab (P) Rabbit Diet, ad libitum
- Water: Drinking water, ad libitum
- Acclimation period: NA

ENVIRONMENTAL CONDITIONS
- Temperature: 17.5-22.5 °C
- Humidity: 40-73 %
- Air changes: Approximately 19 air changes/hour
- Photoperiod: 12 hours dark / 12 hours light

IN-LIFE DATES: From: 1996-11-04 To: 1996-11-25

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 60 mg (the weight occupying a volume of 0.1 mL)

Duration of treatment / exposure:

Eyes were not rinsed throughout study

Observation period (in vivo):

21 days

Number of animals or in vitro replicates:

3 females

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: No

SCORING SYSTEM: Draize method

TOOL USED TO ASSESS SCORE: Hand-held light

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

24/48/72 h

Score:

0.66

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: Not reversible in one rabbit

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

24/48/72 h

Score:

0

Max. score:

2

Reversibility:

fully reversible

Remarks on result:

other: No effect observed

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

24/48/72 h

Score:

2.2

Max. score:

3

Reversibility:

not reversible

Remarks on result:

other: Not reversible in one rabbit

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

24/48/72 h

Score:

1.89

Max. score:

4

Reversibility:

fully reversible within: 14 days

Remarks on result:

other: Fully reversible in two rabbits by 7 days

Irritant / corrosive response data:

- A single instillation of DMBA elicited corneal opacification and well defined to moderate conjunctival irritation in one rabbit: these effects persisted (without reduction, in the case of corneal opacity) until study termination, 21 days after treatment.
- However the other two rabbits showed markedly less reaction: no corneal effects were seen, and all conjunctival changes had resolved seven days after treatment.

Other effects:

There were no signs of toxicity or ill health in any rabbit during the observation period.

Any other information on results incl. tables

See attached document for information on tables of results

Applicant's summary and conclusion

Interpretation of results:

irritating

Remarks:

Migrated information Criteria used for interpretation of results: EU

Conclusions:

Under the test conditions, DMBA is classified as "Category 2 irritating to eyes" according to CLP Regulation (EC) N° (1272/2008).

Executive summary:

Test Guidance EU Method B.5 (Acute Toxicity: Eye Irritation / Corrosion) guideline and in compliance with GLP. Method 3 New Zealand White female rabbits were exposed to 60 mg of DMBA in one eye while the contralateral eye remained untreated and served as control. The eyelids were then gently held together for one second before releasing. The eyes were examined and the changes were observed at 1, 24, 48 and 72 hours and 4, 7 and up to 14 and 21 days after treatment and graded according to the Draize method. Result A single instillation of DMBA elicited corneal opacification and well defined to moderate conjunctival irritation in one rabbit, these effects persisted (without reduction, in the case of corneal opacity) until study termination, 21 days after treatment. However the other two rabbits showed markedly less reaction; no corneal effects were seen, and all conjunctival changes had resolved seven days after treatment. There were no signs of toxicity or ill health in any rabbit during the observation period. Mean individual scores at 24, 48 and 72 h after exposure for the 3 animals were 2.0, 0.0, 0.0 for cornea score; 0.0, 0.0, 0.0 for iris score; 2.7, 2.0, 2.0 for conjunctivae score and 2.3, 1.7, 1.7 for chemosis score. In this study, DMBA is an eye irritant on rabbits. Conclusion Under the test conditions, DMBA is classified as "Category 2 irritating to eyes" according to CLP Regulation (EC) N° (1272 /2008).