6-aminopenicillanic acid

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

other: A well documented GLP study which is comparable to current accepted guidelines.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1993

Report date:

1993

Materials and methods

Test guideline

Test guideline 1

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Test guideline 2

Qualifier:

equivalent or similar to guideline

Guideline:

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

GLP compliance:

yes (incl. QA statement)

Test material

Test material information

Constituent 1

Reference substance name:

6-Aminopenicillinic Acid

IUPAC Name:

6-Aminopenicillinic Acid

Constituent 2

Reference substance name:

6-aminopenicillanic acid

EC Number:

208-993-4

EC Name:

6-aminopenicillanic acid

Cas Number:

551-16-6

Molecular formula:

C8H12N2O3S

IUPAC Name:

6-amino-3,3-dimethyl-7-oxo-4-thia-1-azabicyclo[3.2.0]heptane-2-carboxylic acid

Details on test material:

- Name of test material (as cited in study report): 6-APA (6-Aminopenicillinic Acid)
- Substance type: White powder
- Physical state: Solid
- Analytical purity: No data
- Lot/batch No.: WCD3823

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Hazleton Research Products, Denver, PA
- Sex : Male
- Weight at study initiation: 2.618-2.849 kg
- Housing:Rabbits are housed in cages sized in accordance
- Diet : Purina Lab Rabbit Chow (HF), checked daily and added or replaced as needed according to Standard Operating Procedure PH-113. Feeders were designed to reduce soiling, bridging and scattering.
- Water : Fresh tap water was available ad libitum.
- Acclimation period: At least 5 days.


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 30-70 %
- Photoperiod (hrs dark / hrs light): 12 hour light cycle.

Test system

Vehicle:

unchanged (no vehicle)

Controls:

yes, concurrent no treatment

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied : 0.1 mL packed volume. Test material was ground to a fine powder and dosed as received.

Duration of treatment / exposure:

Up to 72 hours

Observation period (in vivo):

Eyes were examined at 1, 24, 48 and 72 hours post treatment.

Number of animals or in vitro replicates:

3 animals were included in the study.

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): No washing was performed


SCORING SYSTEM: Draize scores for primary eye irritation, and assessed using the modified Kay and Calandra system


TOOL USED TO ASSESS SCORE: Pen light

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 1 hour

Score:

12.7

Max. score:

14

Reversibility:

fully reversible within: 72 hours

Results 2

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 24 hours

Score:

0.7

Max. score:

2

Reversibility:

fully reversible within: 72 hours

Results 3

Irritation parameter:

maximum mean total score (MMTS)

Basis:

mean

Time point:

other: 48 hours

Score:

0.7

Max. score:

2

Reversibility:

not fully reversible within: 72 hours

Irritant / corrosive response data:

Positive ocular scores were observed at 1 hour after treatment. All ocular scores returned to normal at 72 hours post treatment. Please refer to tables 2 to 5 for tablulated results under section Remarks on results including tables and figures.

Other effects:

All animals exhibited an increase in body weight during the study (please refer to table 1 under section Remarks on results including tables and figures)

Any other information on results incl. tables

Table 1: Bodyweights pre- and post-dosing

 

Animal No.	Sex	Initial bodyweight (kg)	Final bodyweight (kg)
3264	M	2.622	2.650
3265	M	2.849	2.876
3266	M	2.618	2.713

 

Table 2: Eye irritation scoring for animal 3264

 

		Time after treatment (hr)
		Pre dose	1 hr	24 hr	48 hr	72 hr
Conjunctivae	Redness score (a)	0	3	0	0	0
	Chemosis score (b)	0	2	1	1	0
	Discharge score (c)	0	2	0	0	0
	(a + b + c) x 2 =	0	14	2	2	0
Iris	Score (d)	0	0	0	0	0
	(d) x 5 =	0	0	0	0	0
Cornea	Degree score (e)	0	0	0	0	0
	Area score (f)	0	0	0	0	0
	(e x f) x 5 =	0	0	0	0	0
Total score =		0	14	2	2	0

 

Table 3: Eye irritation scoring for animal 3265

 

		Time after treatment (hr)
		Pre dose	1 hr	24 hr	48 hr	72 hr
Conjunctivae	Redness score (a)	0	3	0	0	0
	Chemosis score (b)	0	2	0	0	0
	Discharge score (c)	0	1	0	0	0
	(a + b + c) x 2 =	0	12	0	0	0
Iris	Score (d)	0	0	0	0	0
	(d) x 5 =	0	0	0	0	0
Cornea	Degree score (e)	0	0	0	0	0
	Area score (f)	0	0	0	0	0
	(e x f) x 5 =	0	0	0	0	0
Total score =		0	12	0	0	0

 

Table 4: Eye irritation scoring for animal 3266

 

		Time after treatment (hr)
		Pre dose	1 hr	24 hr	48 hr	72 hr
Conjunctivae	Redness score (a)	0	2	0	0	0
	Chemosis score (b)	0	2	0	0	0
	Discharge score (c)	0	2	0	0	0
	(a + b + c) x 2 =	0	12	0	0	0
Iris	Score (d)	0	0	0	0	0
	(d) x 5 =	0	0	0	0	0
Cornea	Degree score (e)	0	0	0	0	0
	Area score (f)	0	0	0	0	0
	(e x f) x 5 =	0	0	0	0	0
Total score =		0	12	0	0	0

 

Table 5: Group scores

 

	Time after treatment (hr)
	Pre dose	1 hr	24 hr	48 hr	72 hr
Total group score	0	38	2	2	0
Group mean score	0	12.7	0.7	0.7	0

Applicant's summary and conclusion

Interpretation of results:

Category 2B (mildly irritating to eyes) based on GHS criteria

Remarks:

Migrated information: All effects were reversible within 72 hours.

Conclusions:

The test material was determined to be a mild irritant (class 4 in the Modified Kay and Calandra system). The maximum Group mean score was 12.7.