3,3'-methylenebis[5-methyloxazolidine]

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Remarks:

Partly limited documentation; readings only after 24 h.

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1979

Report date:

1979

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

other: FDA Handbook, Appraisal of the Safety of Chemicals in Foods, Drugs and Cosmetics, FDA p. 47

Deviations:

no

GLP compliance:

no

Remarks:

at the time the study was performed, GLP was not compulsory

Test material

Test material information

Constituent 1

Reference substance name:

Grotan® OX

IUPAC Name:

Grotan® OX

Details on test material:

- Name of test material (as cited in study report): Grotan® OX
- Substance type: Reaction product from paraformaldehyde and 2 hydroxypropylamine (ratio of 3:2)
- Physical state: Liquid
- Lot/batch No.: Ch B 9190

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- No data

ENVIRONMENTAL CONDITIONS
- No data

IN-LIFE DATES: No data

Test system

Vehicle:

water

Controls:

other: the untreated eye served as control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.1 mL
- Concentration (if solution): a) undiluted b) 0.2% dilution

Duration of treatment / exposure:

a) 24 h (unwashed) in 3 animals or b) 4 seconds (washed with 20 mL lukewarm water) in 3 animals.
(Procedure used for both, 100% and 0.2% treatment).

Observation period (in vivo):

All animals in a) and b) sacrificed 24 h after instillation

Number of animals or in vitro replicates:

6 per concentration

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done):
- Time after start of exposure: Animals treated with the 100% solution remained unwashed, Animals treated with the 0.2% dilution weer washed 4 seconds after instillation

SCORING SYSTEM:
Scoring system corresponds to OECD guideline 405.
Additionally the area of the cornea involved was scored:
1 one quarter or less but not zero
2 greater than on quarter but less than half
3 greater than half but less than ¾
4 greater than 3/4
Discharge of the conjunctivae also scored:
1 Any amount different from normal
2 Discharge with moistening of lids and hairs just adjacent to lids
3 Discharge with moistening of lids and hairs, and considerable area around the eye

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

mean

Time point:

other: 24 hours

Score:

>= 2.3

Max. score:

3

Reversibility:

not specified

Remarks on result:

other: Score refers to undiluted solution, unwashed

Results 2

Irritation parameter:

iris score

Basis:

mean

Time point:

other: 24 hours

Score:

>= 2

Max. score:

2

Reversibility:

not specified

Remarks on result:

other: Score refers to undiluted solution, unwashed

Results 3

Irritation parameter:

conjunctivae score

Basis:

mean

Time point:

other: 24 hours

Score:

>= 3

Max. score:

3

Reversibility:

not specified

Remarks on result:

other: Score rfers to undiluted solution, unwashed

Results 4

Irritation parameter:

chemosis score

Basis:

mean

Time point:

other: 24 hours

Score:

>= 4

Max. score:

4

Reversibility:

not specified

Remarks on result:

other: Score refers to undiluted solution, unwashed

Irritant / corrosive response data:

The undiluted substance produced severe ocular reactions which are presumed to be permanent. Similar effects were noted after a short exposure period (washed eyes, see Table below)). In view of these effects the animals were sacrificed 24 hours after instillation.
In contrast to the undiluted substance the 0.2% solution in water caused only slight transient conjunctival responses and no effects on iris and cornea (see Table).

Other effects:

No data

Any other information on results incl. tables

Results of eye irritation study (average of 3 animals investigated in each group)

	Cornea	Iris	Conjunctivae
			redness	chemosis
score	0 to 4	0 to 2	0 to 3	0 to 4
undiluted test substance, unwashed
24 h (animals sacrificed, no further readings)	2.3	2.0	3.0	4.0
24 h area effected cornea (score see above)	4.0
24 h maximum average score (including area affected & discharge of conjunctivae, total max. 110)	47 (max 80)	10 (max 10)	20 (max. 20)
Reversibility^*	-	-	-	-
24 h: Discharge of conjunctivae average score 3.0
undiluted test substance, washed
24 h (animals sacrificed, no further readings)	1.7	2.0	3.0	4.0
24 h area effected cornea (score see above)	3.7
24 h maximum average score (including area affected & discharge of conjunctivae, total max. 110)	32 (max 80)	10 (max 10)	20 (max. 20)
Reversibility^*	-	-	-	-
24 h: Discharge of conjunctivae average score 3.0

	Cornea	Iris	Conjunctivae
			redness	chemosis
0.2% test substance in water, unwashed
24 h	0.0	0.0	0.7	0.0
48 h (same results with further readings)	0.0	0.0	0.0	0.0
24 h maximum average score (including area affected & discharge of conjunctivae, total max. 110)	0 (max 80)	0 (max 10)	1.3 (max. 20)
Reversibility	-	-	complete	-
Discharge of conjunctivae average score 0.0 (all readings)
0.2% test substance in water, washed
24 h	0.0	0.0	0.3	0.3
48 h (same results with further readings)	0.0	0.0	0.0	0.0
24 h maximum average score (including area affected & discharge of conjunctivae, total max. 110)	0 (max 80)	0 (max 10)	1.3 (max. 20)
Reversibility	-	-	complete	complete
Discharge of conjunctivae average score 0.0 (all readings)

Reversibility*: No data, as animals were sacrificed due to severity of ocular reactions 24 h after instillation.

Applicant's summary and conclusion

Interpretation of results:

Category 1 (irreversible effects on the eye) based on GHS criteria

Conclusions:

The undiluted test substance causes serious damage of the eye (corrosion) even after a short exposure period od 4 s (washed eyes). This result corresponds to the effects of formaldehyde, the hydrolysis product of the test substance. The 0.2% solution is not irritant.

Executive summary:

Study comparable to OECD guideline 405 with some restrictions but study acceptable for assessment of eye irritant effects. 0.1 mL undiluted test substance instilled into the conjunctival sac of 3 rabbits; eyes unwashed or washed 4 s after application. Readings after 24 h. Same experiments with 0.2% test substance in water.

The undiluted test item is corrosive to eyes. Effects are expected to be permanent.

The 0.2% solution is not irritating.