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Administrative data

Endpoint:
eye irritation: in vivo
Type of information:
migrated 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:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: GLP guideline study

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

Constituent 1
Reference substance name:
Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, chlorides
EC Number:
263-090-2
EC Name:
Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, chlorides
Cas Number:
61789-80-8
IUPAC Name:
61789-80-8

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
Irritation parameter:
overall irritation score
Remarks:
corrosive
Basis:
animal #1
Time point:
other: 1 hour and 24-hour readings
Score:
4
Max. score:
4
Reversibility:
not reversible
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:
highly irritating
Remarks:
Migrated information Criteria used for interpretation of results: expert judgment
Conclusions:
Further to the highly irritating effects observed in the acute dermal irritation/ corrosion test previously performed in rabbits with the structural analogue 'Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, chlorides', it was decided for ethical considerations, to perform the assay with one animal as severe ocular effects were anticipated.
Indeed, the ocular lesions noted after 24 hours in the rabbit were so severe that the animal was sacrificed for ethical grounds. Based on these results, the test material must be considered as highly irritating for eyes and warrants a classification in category 1 , eye damage according to CLP regulation (Reg 1272/2008/EC) and a classification severely irritating for eyes Xi, R41 according to the directive 67/ 548/ EEC.
Executive summary:

Justification for cross reading of Benzyl-dihydrogenated-methyl ammonium chloride (BDHTMAC) to dihydrogenated-dimethyl-ammonium chloride (DHTDMAC) or its main active component, Dimethyldioctadecyl ammonium choride (DODMAC):

An overview of available data existing on common toxicological endpoints for the two substances demonstrates their similar toxicological behaviour: Both substances have a low acute toxicity but strong skin and eye corrosive properties. They are not sensitising and not mutagenic. The 28-day repeated dose toxicity studies performed by oral route in rats conclude to the same NOAEL of 100 mg/kg bw /day. The same biochemical changes (increase in ALAT enzyme) and the same target organ (adrenals) have been identified by these studies. Based on these results, the two substances display a similar toxic profile and it is scientifically appropriate to use cross-reading.

The potential of the strutural analogue Quaternary ammonium compounds, bis(hydrogenated tallow alkyl)dimethyl, chlorides (DHTDMAC) containing 12% isopropanol and 10% 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 0.1ml 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.

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