Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, acetates

Eye irritation

Administrative data

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

from 1990-12-13 to 1990-12-14

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

guideline study with acceptable restrictions

Remarks:

Although this study is guideline and GLP compliant and would normally be assigned a reliability of 1 (reliable without restrictions), this study is used for read-across and therefore has been assigned a reliability of 2 (reliable with restrictions).

Justification for type of information:

The primary component of all substances provide complete coverage of 68334-33-8. 68334-33-8 shares high structural similarity with 61789-80-8, 68783-78-8, 107-64-2, and 112-02-7. As 68334-33-8 is a UVCB its components encapsulate the other substances except for the counter ion (Cl-). In solution, the counter ions will dissociate from the parent structures. Therefore, we are comparing substances of equivalent nature. CAS 107-64-2 represents the C18 boundary of the 61789-80-8. Ignoring the salt component CAS 61789-80-8 is equivalent to CAS 68334-33-8. 68783-78-8 is a worst case of both 68334-33-8 and 61789-80-8 since it is unsaturated and the SP2 carbon-carbon bonds are of higher reactivity and a more likely site of metabolic activation. The primary component of CAS 112-02-7 is a substructure of all the other substances. Additional documentation, provided within the IUCLID Assessment Reports section, supports the read-across approach.

Cross-reference

Reason / purpose for cross-reference:

read-across: supporting information

Reference

Endpoint:

eye irritation: in vivo

Type of information:

read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Justification for type of information:

The primary component of all substances provide complete coverage of 68334-33-8. 68334-33-8 shares high structural similarity with 61789-80-8, 68783-78-8, 107-64-2, and 112-02-7. As 68334-33-8 is a UVCB its components encapsulate the other substances except for the counter ion (Cl-). In solution, the counter ions will dissociate from the parent structures. Therefore, we are comparing substances of equivalent nature. CAS 107-64-2 represents the C18 boundary of the 61789-80-8. Ignoring the salt component CAS 61789-80-8 is equivalent to CAS 68334-33-8. 68783-78-8 is a worst case of both 68334-33-8 and 61789-80-8 since it is unsaturated and the SP2 carbon-carbon bonds are of higher reactivity and a more likely site of metabolic activation. The primary component of CAS 112-02-7 is a substructure of all the other substances. Additional documentation, provided within the IUCLID Assessment Reports section, supports the read-across approach.

Reason / purpose for cross-reference:

read-across source

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: 1-hour and 24-hour readings

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: the ocular lesions noted after 24 hours in the rabbit were so severe that the animal was sacrificed for ethical grounds

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Remarks on result:

probability of severe irritation

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Remarks on result:

probability of severe irritation

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Remarks on result:

not determinable

Remarks:

the animal was sacrificed for ethical grounds before the nature of the reactions concerning the iris and the cornea could have been checked

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Remarks on result:

not determinable

Remarks:

the animal was sacrificed for ethical grounds before the nature of the reactions concerning the iris and the cornea could have been checked

Data source

Reference

Reference Type:

study report

Title:

Unnamed

Year:

1991

Report date:

1991

Materials and methods

Test guideline

Qualifier:

according to guideline

Guideline:

OECD Guideline 405 (Acute Eye Irritation / Corrosion)

GLP compliance:

yes

Test material

Test material information

Constituent 1

Reference substance name:

Quaternary ammonium compounds, di-C16-18-alkyldimethyl, chlorides

EC Number:

295-835-2

EC Name:

Quaternary ammonium compounds, di-C16-18-alkyldimethyl, chlorides

Cas Number:

92129-33-4

Molecular formula:

R2N+(CH3)2, Cl- with R is fatty alkyl with chainlengths C16-C18 (even numbered)

IUPAC Name:

N-C16-C18(even numbered)-alkyl-N,N-dimethyl-C16-C18(even numbered)-alkyl-1-aminium chloride

Test animals / tissue source

Species:

rabbit

Strain:

New Zealand White

Details on test animals or tissues and environmental conditions:

TEST ANIMALS
- Source: Elevage cunicole de Val de Selle, Prouzel, France.
- Weight at study initiation: 2,5 kg.
- Housing: individually in polystyren cage.
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least five days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 ± 3 °C
- Humidity (%): 50 ± 20 %
- Photoperiod: 12 hrs dark /12 hrs light

Test system

Controls:

other: each animal served as its own control

Amount / concentration applied:

TEST MATERIAL
- Amount(s) applied : 0.1ml previously melted at 20 - 25°C.

Duration of treatment / exposure:

Single exposure

Observation period (in vivo):

1 hour and 24 hours after instillation

Number of animals or in vitro replicates:

1 male

Details on study design:

REMOVAL OF TEST SUBSTANCE
- Washing : eye not rinsed

SCORING SYSTEM: according to OECD guideline 405 (draize scoring system)

Results and discussion

In vivo

Results

Results 1

Irritation parameter:

overall irritation score

Basis:

animal #1

Time point:

other: 1-hour and 24-hour readings

Score:

4

Max. score:

4

Reversibility:

not reversible

Remarks on result:

other: the ocular lesions noted after 24 hours in the rabbit were so severe that the animal was sacrificed for ethical grounds

Results 2

Irritation parameter:

conjunctivae score

Basis:

animal #1

Time point:

24 h

Remarks on result:

probability of severe irritation

Results 3

Irritation parameter:

chemosis score

Basis:

animal #1

Time point:

24 h

Remarks on result:

probability of severe irritation

Results 4

Irritation parameter:

iris score

Basis:

animal #1

Time point:

24 h

Remarks on result:

not determinable

Remarks:

the animal was sacrificed for ethical grounds before the nature of the reactions concerning the iris and the cornea could have been checked

Results 5

Irritation parameter:

cornea opacity score

Basis:

animal #1

Time point:

24 h

Remarks on result:

not determinable

Remarks:

the animal was sacrificed for ethical grounds before the nature of the reactions concerning the iris and the cornea could have been checked

Irritant / corrosive response data:

1 hour then 24 hours after instillation of the test substance, the ocular reactions were severe and the conjunctival chemosis (score of 4) obscured the evaluation of the reactions at the iris and cornea. The flowing of a whitish purulent substance was also noted.
Some severe ocular lesions were expected at the next reading times but taking into consideration the severity of the lesions noted after 24 hours, the animal was sacrificed for ethical grounds before the nature of the reactions concerning the iris and the cornea could have been checked.

Applicant's summary and conclusion

Interpretation of results:

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

Conclusions:

Under the experimental conditions, the test material was considered as severely irritating when administered by ocular route to rabbits.

Executive summary:

The potential of the technical grade dehydrogenated tallow dimethylammonium, chlorides (78% active in isopropanol/water) to induce eye irritation was assessed in 1 rabbit according to the OECD guideline 405 in compliance with the principles of Good Laboratory Practice regulations. Taking into account the highly irritating effects observed in the acute dermal irritation/ corrosion test previously performed in rabbits, it was decided for ethical considerations, to perform the assay with one animal. A single dose of 0.1 mL of the test material was instilled into one eye, the other eye was not treated and served as control. The eyes were not rinsed after administration of the test item. Ocular reactions were observed 1 hour and 24 hours later.

 

1 hour then 24 hours after instillation of the test substance, the ocular reactions were severe and the conjunctival chemosis (score of 4) obscured the evaluation of the reactions at the iris and cornea. The flowing of a whitish purulent substance was also noted. Some severe ocular lesions were expected at the next reading times but taking into consideration the severity of the lesions noted after 24 hours, the animal was sacrificed for ethical grounds before the nature of the reactions concerning the iris and the cornea could have been checked. Under these experimental conditions, the test material was considered as severely irritating when administered by ocular route to rabbits.