Dimethyl(propyl)amine

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

experimental study

Adequacy of study:

key study

Study period:

28 June 1999- 05 July 1999

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

2000

Report date:

2000

Materials and methods

Test guideline

Test guideline 1

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

Version / remarks:

1987

Deviations:

no

Test guideline 2

Qualifier:

according to guideline

Guideline:

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

Version / remarks:

1992

Deviations:

no

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Dimethyl(propyl)amine

EC Number:

213-139-9

EC Name:

Dimethyl(propyl)amine

Cas Number:

926-63-6

Molecular formula:

C5H13N

IUPAC Name:

dimethyl(propyl)amine

Specific details on test material used for the study:

- Lot/batch No.: K322/1

Test animals / tissue source

Species:

rabbit

Strain:

Himalayan

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Strain as cited in the study report: Himalayan/Chbb:HM (outbred strain)
- Source: Boehringer Ingelheim Pharma KG
- Age at study initiation: young adult animals
- Weight at study initiation: 2.4 kg
- Housing: single housing in stainless steel wire mesh cages with grating, floor area 3000 cm2
- Diet: Kliba-Labordiet (Klingenthalmuehle AG, Kaiseraugst, Switzerland), ad libitum
- Water: tap water, ad libitum
- Acclimation period: at least 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24
- Humidity (%): 30-70
- Photoperiod (hrs dark/hrs light): 12/12

Test system

Vehicle:

unchanged (no vehicle)

Controls:

other: the untreated eye served for control

Amount / concentration applied:

Amount applied: 0.1 mL

Duration of treatment / exposure:

24 h

Observation period (in vivo):

7 days
reading time points: 1, 24, 48 and 72 h, and day 7

Number of animals or in vitro replicates:

1 animal (female)

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing: with tap water
- Time after start of exposure: 24 hours

SCORING SYSTEM: scoring of the findings was done as recommended by the OECD guideline, according to the Draize scoring system.

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: corneal opacity grade 3 still was seen at the end of the observation period, i.e. at day 7.

Results 2

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24/48/72 h

Score:

1

Max. score:

2

Reversibility:

not fully reversible within: 72 hrs

Remarks on result:

other: alteration of the iris grade 1 was seen at 24, 48 and 72 h; due to severe lesions of the eye on day 7, the iris could not be assessed at that time point.

Results 3

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24/48/72 h

Score:

3

Max. score:

3

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: conjunctival redness grade 3 still was seen at the end of observation period of 7 days.

Results 4

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24/48/72 h

Score:

2.3

Max. score:

4

Reversibility:

not fully reversible within: 7 days

Remarks on result:

other: chemosis grade 3 still was seen at the end of observation period of 7 days.

Irritant / corrosive response data:

The animal displayed corneal opacity, conjunctival redness and chemosis as well as discharge during to whole period of observation. Regarding the iris, a reaction grade 1 was seen at 24, 48 and 72 h; because of additional alterations, the iris could not be evaluated at day 7.
A discharge grade of 3 was seen, i.e. with moistening of the lids and hairs affecting a considerable area around the eye, still was seen at the end of observation period of 7 days.

Other effects:

The additional alterations almost consisted of suppuration, bloody discharge, loss of corneal tissue, and discolouration of parts of the conjunctiva and nictitating membrane (yellow-brown to white). These alterations were seen all over the reading time points, from 1 h to day 7.

Any other information on results incl. tables

Table 1: Details on findings and scores:

Readings	animal	cornea score	iris score	conjunctiva redness	chemosis	discharge	additional alterations
1 hr	1	2	0	2	2	2	bloody discharge, loss of corneal tissue, parts of conjunctiva and nictitating membrane yellow-brown discoloured (indicating necrosis in the view of the study director)
24 hrs	1	2	1	3	2	3	bloody discharge, loss of corneal tissue, parts of conjunctiva and nictitating membrane yellow-brown discoloured (indicating necrosis in the view of the study director)
48 hrs	1	2	1	3	2	3	bloody discharge, parts of conjunctiva and nictitating membrane yellow-brown/white discoloured (indicating necrosis in the view of the study director)
72 hrs	1	3	1	3	3	3	suppuration, bloody discharge, parts of conjunctiva and nictitating membrane yellow-brown/white discoloured (indicating necrosis in the view of the study director)
7 d	1	3		3	3	3	suppuration, bloody discharge, loss of corneal tissue, parts of conjunctiva and nictitating membrane white discoloured (indicating necrosis in the view of the study director). Due to the severity of the findings, the study was stopped.
mean		2.3	1	3	2.3

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

Taking into account the mean scores for corneal opacity, iris, conjunctiva redness and chemosis over the reading time points 24, 48 and 72 h, and regarding the severity of the additional lesions and the absence of reversibility, the test item is to be considered as causing serious damages to the eye according to current evaluation criteria.

Executive summary:

DMPA was tested for eye irritation in one female rabbit according to the OECD TG 405 (1987). The test item was applied undiluted into the conjunctival sac of one eye. After 24 h exposure, the eye was washed and examined for signs of irritation at the following reading time points: 1, 24, 48 and 72 h, and day 7. Due to the severity of the findings, the test was stopped at day 7. The eye findings were assessed by scoring according to the Draize scoring system.

Severe occular lesions affecting the cornea, iris, conjunctiva and the lids were detected at all observation time points; thus, the effects were not reversible within the 7 day period of observation. Additional lesions also were reported, including severe discharge, suppuration, discharge with blood, and yellow-brown to white discolouration of the conjunctiva and nictitating membrane, which, according to the study director, indicated necrosis. No further animals needed to be tested.

Taking into account the mean scores for corneal opacity, iris, conjunctiva redness and chemosis over the reading time points 24, 48 and 72 h, and regarding the severity of the additional lesions and the absence of reversibility, the test item is to be considered as causing serious damages to the eye according to current evaluation criteria.