N,N,N',N'-tetramethylhexamethylenediamine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

weight of evidence

Study period:

Not specified

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1983

Report date:

1983

Materials and methods

Test guideline

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Deviations:

yes

Remarks:

There is no information on the purity of test, the source and age of the animals, on housing and environmental conditions. However, it is considered that the study still provides scientific and valid information.

GLP compliance:

no

Remarks:

not mandatory when the study was carried out

Test material

Test material information

Constituent 1

Reference substance name:

N,N,N',N'-tetramethylhexamethylenediamine

EC Number:

203-842-9

EC Name:

N,N,N',N'-tetramethylhexamethylenediamine

Cas Number:

111-18-2

Molecular formula:

C10H24N2

IUPAC Name:

[6-(dimethylamino)hexyl]dimethylamine

Specific details on test material used for the study:

- Name of test material (as cited in study report): NIAX Catalyst C-210
- Physical state: Transparent, pale, yellow, non-viscous liquid
- Purity test date: As supplied

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

No information available in the test report

Test system

Vehicle:

unchanged (no vehicle)

Controls:

not required

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.005 mL

Duration of treatment / exposure:

The eyelids were held together for one second following instillation to prevent immediate removal of test material. The eyes were not subsequently rinsed or flushed with water, saline or fluorescein.

Observation period (in vivo):

Up to 21 days. Eye effects were recorded at 1 hour, 4, 24, 48 and 72 hours, 7, 14 and 21 days

Number of animals or in vitro replicates:

6 animals (3 males and 3 females)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing (if done): None reported

SCORING SYSTEM: Similar to the scale described in OECD guideline 405.

TOOL USED TO ASSESS SCORE: fluorescein (2 %) staining was used to determine corneal injury before dosing and at readings after one day.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Results 2

Irritation parameter:

cornea opacity score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Results 3

Irritation parameter:

cornea opacity score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

not reversible

Results 4

Irritation parameter:

cornea opacity score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Results 6

Irritation parameter:

cornea opacity score

Basis:

animal #6

Time point:

24/48/72 h

Score:

3.3

Max. score:

4

Reversibility:

not reversible

Results 7

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Results 8

Irritation parameter:

conjunctivae score

Basis:

animal #2

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Results 9

Irritation parameter:

conjunctivae score

Basis:

animal #3

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Results 10

Irritation parameter:

conjunctivae score

Basis:

animal #4

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Results 11

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Results 12

Irritation parameter:

conjunctivae score

Basis:

animal #6

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not reversible

Results 13

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3.7

Max. score:

4

Reversibility:

not reversible

Results 14

Irritation parameter:

chemosis score

Basis:

animal #2

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 15

Irritation parameter:

chemosis score

Basis:

animal #3

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 16

Irritation parameter:

chemosis score

Basis:

animal #4

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Results 17

Irritation parameter:

conjunctivae score

Basis:

animal #5

Time point:

24/48/72 h

Score:

3

Max. score:

4

Reversibility:

not reversible

Results 18

Irritation parameter:

chemosis score

Basis:

animal #6

Time point:

24/48/72 h

Score:

4

Max. score:

4

Reversibility:

not reversible

Irritant / corrosive response data:

Severe corneal opacity and conjunctival redness and chemosis were reported in all animals. All 6/6 animals at 24 and 48 hours and 4/6 animals at 72 hours displayed opalescent areas, iris details not visible and pupil size barely discernible. Two animals showed corneal opacity at the 72 hour timepoint. On day 7, 4/6 animals showed corneal opacity. By the end of the study all animals were affected. Damage to the cornea did not allow for the examination the iris of each eye.
Diffuse beefy red eyes were seen in all animals throughout the study. Most animals had swelling with lids about half closed to completely closed up to 72 hours after exposure. On day 7, chemosis decreased in one animals but 5/6 animals still showed swelling with lids about half closed to completely closed. On day 14, swelling with lids about half closed remained in 3/6 animals and a decrease in conjunctival chemosis was observed in 3 animals. However at the end of the study swelling with lids about half closed was reported in most animals.
The test substance is highly corrosive and the effects reported 1 hour after exposure persisted until the end of the study. Only chemosis was slightly reduced at the end of the study.

Other effects:

Immediate discomfort was reported by excessive blinking and pawing at eyes. Necrosis on conjunctivae and nictitating membrane along with red brown discharge were noted. At 3 days one rabbit developed a corneal bulge, Corneal bulge abd corneal vascularisation was noted in several animals between day 2 and 14. An opaque white surface on the cornea was also apparent in a few animals.

Any other information on results incl. tables

Table 1: Cornea and Iris irritation scores

	Cornea opacity						Iris
Animal	83-22784	83-22783	83-22782	83-22815	83-22816	83-22820	83-22784	83-22783	83-22782	83-22815	83-22816	83-22820
Readings
1 hour	2	3	3	3	3	2	*	*	*	*	*	*
4 hours	2	3	3	3	3	2	*	*	*	*	*	*
24 hours	3	3	3	3	3	3	*	*	*	*	*	*
48 hours	3	3	3	3	3	3	*	*	*	*	*	*
72 hours	3	3	4	3	3	4	*	*	*	*	*	*
7 days	4	4	4	3	3	4	*	*	*	*	*	*
14 days	4	4	4	4	4	4	*	*	*	*	*	*
21 days	4	4	4	4	4	4	*	*	*	*	*	*
Mean per animal (24-72 hours)	3	3	3.3	3	3	3.3	*	*	*	*	*	*
Mean (24-72 hours)	3.1						*

*Scoring not possible due to cornea opacity

Table 2: Conjunctival redness and chemosis scores

	Conjunctival redness						Chemosis
Animal	83-22784	83-22783	83-22782	83-22815	83-22816	83-22820	83-22784	83-22783	83-22782	83-22815	83-22816	83-22820
Readings
1 hour	3	3	3	3	3	3	3	4	4	3	4	4
4 hour	3	3	3	3	3	3	4	4	4	3	4	4
24 hours	3	3	3	3	3	3	3	4	4	4	3	4
48 hours	3	3	3	3	3	3	4	4	4	4	3	4
72 hours	3	3	3	3	3	3	4	4	4	4	3	4
7 days	3	3	3	3	3	3	4	4	2	3	3	3
14 days	3	3	2	2	2	3	3	3	2	2	2	3
21 days	3	3	2	2	2	3	3	3	3	2	3	3
Mean per animal (24-72 hours)	3	3	3	3	3	3	3.7	4	4	4	3	4
Mean (24-72 hours)	3						3.8

 

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

The substance was shown to cause seious eye damage under the conditions of this study.

Executive summary:

 The test substance NIAX® Catalyst C·210 (0.005 mL) was instilled into the conjunctival sac of one eye of each animal (three males and three females New Zealand White rabbits). The eyelids was held together for one second. The eyes were examined and scored at one hour, 4, 24, 48 and 72 hours, 7, 14 and 21 days. Fluorescein was used to determine corneal injury before dosing and at readings after 24 hours.

Corneal opacity and conjunctival injury was reported in all animals and persisted through the study. Due to corneal opacity, the iris could not be examined. Necrosis of conjunctivae and nictitating membrane were observed. Corneal bulge and corneal vascularisation was apparent in several animals between day 2 and 14.

Under the conditions of this study, NIAX® Catalyst C·210 is classified as serious damage eye damage 1 ( substance according to Regulation (EC) No 1272/2008.