Registration Dossier

Toxicological information

Eye irritation

Currently viewing:

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:
other: No OECD guideline or GLP defined; limited observation period, well documented.

Data source

Referenceopen allclose all

Reference Type:
publication
Title:
The acute toxicity and primary irritancy of N-Benzyl-N,N-Dimethylamine
Author:
Ballantyne B, Dodd DE, Nachreiner, Myers RC
Year:
1985
Bibliographic source:
Drug and Chemical Toxicology, 8; 43-56 (1985)
Reference Type:
publication
Title:
Comparative acute toxicity and primary irritancy of various classes of amines
Author:
Myers R.C. et al.
Year:
1997
Bibliographic source:
Toxic Substance Mechanisms, 16: 151-193 (1997)
Reference Type:
other: Microfiche
Title:
Unnamed
Year:
1980
Report Date:
1980

Materials and methods

Principles of method if other than guideline:
Rabbits whose corneas did not stain with 5% fluorescein, applied for 20 sec, were used.
different tests were performed:
Groups of 5 rabbits received into the conjunctival sac of one eye of each rabbit (second eye served as control),
(1) 0.005 ml of undiluted test material,
(2) 0.5 ml of a 5% test material solution in propylene glycol, and
(3) 0.5 ml of a 1% test material solution in propylene glycol.
Observations were made 24 hours later
In order to determine the rate of resolution of any inflammation,
(4) 0.005 ml undiluted test substance was applied into the eyes of rabbits
(5) 0.5 ml of a 5% solution of test substance in propylene glycol was applied into the eyes of rabbits.
Eyes were inspected for the degree of inflammation at 1, 2, 3, 4 and 7 days after dosing.
GLP compliance:
not specified

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
Purity: 99.2 %
Density: 890 mg/ml at 25 C
Molecular Weight: 135.23
Boiling Point: 179.6°C
Vapor Pressure: 1.31 Torr at 20°C
1.82 Torr at 25°C
10.00 Torr at 55°C
50.00 Torr at 91°C
Flash Point: 57°C (Cleveland Open Cup)
Solubility: Readily soluble in aqueous acids, methanol, acetone and benzene. Water solubility, 0.12 g/dl.
Specific Gravity: 0.89 (25°C)
Saturated Vapor Concentration: 14430 mg/m³ (25°C)
Conversion Factors: 1 ppm= 5.53 mg/m³ (25°C, 760 Torr)
1 mg/m³= 0.181 ppm (25°C, 760 Torr)

Test animals / tissue source

Species:
rabbit
Strain:
other: albino
Details on test animals or tissues and environmental conditions:
TEST ANIMALS
- Age at study initiation: 3-5 months
- Weight at study initiation: 2.5-3.1 kg

ENVIRONMENTAL CONDITIONS
- Temperature (°F): 68-80
- Humidity (%): 39-65
- Photoperiod (hrs dark / hrs light): 12/12

Test system

Vehicle:
other: propylene glycol
Controls:
other: the opposite eye of each rabbit in test
Amount / concentration applied:
Groups of 5 rabbits received
(1) 0.005 ml of undiluted test material,
(2) 0.5 ml of a 5% test material solution in propylene glycol, and
(3) 0.5 ml of a 1% test material solution in propylene glycol.
(4) the eyes of 4 rabbits had 0.005 ml undiluted test substance applied to the cornea, and
(5) 4 rabbits received 0.5 ml of a 5% solution of test substance in propylene glycol into the inferior conjunctival sac.
Duration of treatment / exposure:
24 hrs
Observation period (in vivo):
Eyes were inspected for the degree of inflammation at 1, 2, 3, 4 and 7 days after dosing.
Number of animals or in vitro replicates:
Groups of 5 rabbits
(1) 0.005 ml of undiluted test material,
(2) 0.5 ml of a 5% test material solution in propylene glycol, and
(3) 0.5 ml of a 1% test material solution in propylene glycol.

(4) 4 rabbits eyes had 0.005 ml undiluted test substance applied to the cornea, and
(5) 4 rabbits received 0.5 ml of a 5% solution of test substance in propylene glycol into the inferior conjunctival sac.
.
Details on study design:
Rabbits whose corneas did not stain with 5% fluorescein, applied for 20 sec, were used.
different tests were performed:
Groups of 5 rabbits received into the conjunctival sac of one eye of each rabbit (second eye served as control),
(1) 0.005 ml of undiluted test material,
(2) 0.5 ml of a 5% test material solution in propylene glycol, and
(3) 0.5 ml of a 1% test material solution in propylene glycol. The smaller volume of test material was applied directly to the central corneal area, and the larger volumes of test substance dilutions were instilled into the inferior conjunctival sac.
Observations were made 24 hours later for signs of inflammation or injury to the cornea, conjunctiva, nictitating membrane, iris, and eyelid margins.
In order to determine the rate of resolution of any inflammation,
(4) the eyes of 4 rabbits had 0.005 ml undiluted test substance applied to the cornea, and
(5) 4 rabbits received 0.5 ml of a 5% solution of test substance in propylene glycol into the inferior conjunctival sac.
Eyes were inspected for the degree of inflammation at 1, 2, 3, 4 and 7 days after dosing.

Results and discussion

In vivo

Irritant / corrosive response data:
----- After application of 0.005 ml neat N,N-dimethylbenzylamine to the cornea of rabbits severe damage to the entire cornea occurred accompanied by marked conjunctivitis and iritis. The observed effect cleared within 7 days.
-----When 0.5 ml of a 5 % solution of N,N-dimethylbenzylamine in propylene glycol was applied to the cornea of rabbitsmoderate to severe corneal damage developed with irits and chemosis. Complete healing occurred in 4 of 5 rabbits after 7 to 10 days. Corneal and conjunctival damage were still evidentin the remaining animal fáfter 10 days.
-----the istillation of 0.5 ml of a 1% solutionof N,N-dimethylbenzylamine in propylene glycol was tolerated without irritation

Any other information on results incl. tables

RS-Freetext:
Undiluted BDMA:
Severe injury over a major portion of the cornea with conjunctivitis and iritis that resolved within 7 days.

5% BDMA:
moderate to severe corneal injury with iritis and marked chemosis complete resolution after 7 days. One rabbit did not recover completely within 10 days

1% BDMA:
No signs of irritation

Applicant's summary and conclusion

Interpretation of results:
highly irritating
Remarks:
Migrated information
Executive summary:

Groups of 5 rabbits received N,N-dimethylbenzylamine into the conjunctival sac of one eye of each rabbit (second eye served as control) and were observed up to 7 days post dosing: (1) 0.005 ml of undiluted test material resulting in severe corneal opacity and iritis and marked chemosis but eyes recovered by 7 days, (2) 0.5 ml of a 5% test material solution in propylene glycol resulting in moderate to severe corneal injury and iritis and chemosis; the eyes of 4/5 rabbits recovered within 10 days. One rabbit exhibited corneal injury, with vascularization, and conjunctival irritation after 10 days. (3) 0.5 ml of a 1% test material solution in propylene glycol which caused no reactions in the eyes during the observation period. Overall, N,N-Dimethylbenzylamine was evaluated as a severe irritant (Ballantyne 1985).