Sage Journals: Discover world-class research

Abstract

The EYTEX® method is an in vitro test used to predict ocular irritation, based on alterations in a protein matrix. We have evaluated this method with the aim of using it to screen chemicals. One hundred and forty-two products (commodities and specialities), having a wide range of chemical properties and ocular irritation potential in the rabbit, were tested with either the standard, MPA, AMA, KMA or UMA protocols. The results were compared with in vivo data obtained previously for each chemical and with the EEC labelling of eye irritation for dangerous substances. Intralaboratory repeatability and interlaboratory reproducibility were evaluated with seven other laboratories.

Ninety-three per cent of the chemicals tested were qualified with the EYTEX method. The coefficients of the linear correlation between the EYTEX score and the maximal Draize score on the one hand and the maximal corneal score on the other hand, were 0.69 and 0.65, respectively. Compared to the EEC classification, the labelling of dangerous substances and for the prediction of severe irritants, sensitivity, specificity and equivalence were 94%, 89% and 78%, respectively. We observed nine false positives (22%) and two false negatives (2%) for the identification of R41-, R34- and R35-labelled products. The predictive values, for identifying R41, R34 and R35 products and non-irritants or R36 products were 78% and 97%, respectively. Repeatability (6.3) and reproducibility (8.9) were quite satisfactory.

The EYTEX system exhibits the characteristics of a good screening method: compatibility with a large range of chemicals; a simple and rapid procedure; good intralaboratory and interlaboratory reproducibility; cost effectiveness; high sensitivity, specificity and predictive value; and a low incidence of false negative and false positive results. Based on these results, we consider the EYTEX method to be a valuable tool for the screening of eye irritancy.

Keywords

EYTEX®Draize test eye/ocular irritation chemical compounds EEC labelling

Get full access to this article

View all access options for this article.

References

Anon. (1992). Acute eye irritation/corrosion. OECD Guidelines for the Testing of Chemicals 405, 17 July 1992. Paris: OECD.

Anon. (1992). Annex of Council Directive 92/69/EEC of 31 July 1992 amending for the 17th time Directive 67/548/EEC on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances. Official Journal of the European Communities L383, 127–130.

Anon. (1982). Primary eye irritation; health effects test guidelines, PB82-232984. Washington, DC: US Environmental Protection Agency.

Draize

J.H.

, Woodward

, & Calvery

H.O.

(1944). Methods for the study of irritation and toxicity of substances applied topically to the skin and mucous membranes. Journal of Pharmacology and Experimental Therapeutics 82, 377–390.

Talsma

D.M.

, Leach

C.L.

, Hatoum

N.S.

, Gibbons

R.D.

, Roger

J.C.

, & Garvin

J.P.

(1988). Reducing the number of rabbits in the Draize eye irritancy test: a statistical analysis of 155 studies conducted over six years. Fundamental and Applied Toxicology 10, 146–153.

Anon., (1991). Annex of Council Directive 91/325/EEC of 1 March 1991 amending for the 12th time Directive 67/548/EEC on the approximation of laws, regulations and administrative provisions relating to the classification, packaging and labelling of dangerous substances. Official Journal of the European Communities L180, 55–57.

Sharpe

(1985). The Draize test: motivations for change. Food and Chemical Toxicology 23, 139–143.

Griffith

J.F.

, Nixon

G.A.

, Bruce

R.D.

, Reer

P.J.

, & Bannan

E.A.

(1980). Dose-response studies with chemical irritants in the albino rabbit eye as a basis for selecting optimum testing conditions for predicting hazard to the human eye. Toxicology and Applied Pharmacology 55, 501–513.

Weil

C.S.

, & Scalla

R.A.

(1971). Study of intra-laboratory and interlaboratory variability in the results of rabbit eye and skin irritation tests. Toxicology and Applied Pharmacology 19, 276–360.

10.

ECETOC Monograph No. 11. (1988). Eye Irritation Testing, 64 pp. Brussels: ECETOC.

11.

Blein

(1992). L'oeil: de l'animal à l'alternatif? September 1993, pp. 221. Paris: Oeuvre pour 1'Assistance aux Animaux de Laboratoire.

12.

Frazier

J.M.

, Gad

S.C.

, Goldberg

A.M.

, & McCulley

J.P.

, eds. (1987). Alternative Methods in Toxicology, Vol. IV, A Critical Evaluation of Alternatives to Acute Ocular Irritation Testing, 136 pp. New York: Mary Ann Liebert.

13.

Wilcox

D.K.

, & Bruner

L.H.

(1990). In vitro alternatives for ocular safety testing: an outline of assays and possible future developments. ATLA 18, 117–128.

14.

Greaves

(1990). Histopathology of Preclinical Toxicity Studies: Interpretation and Relevance in Drug Safety Evaluation, 784 pp. Amsterdam: Elsevier.

15.

Dierickx

P.J.

, & Gordon

V.C.

(1990). The EYTEX™ system and the neutral red uptake inhibition assay in cultured Hep G2 cells as alternative methods for in vivo eye irritation following the EEC protocol. ATLA 17, 325–333.

16.

Gordon

V.C.

, & Bergman

H.C.

(1988). External evaluation of the EYTEX™ system in twelve laboratories to determine the correlation of results with in vivo results. In Alternative Methods in Toxicology, Vol. VI, Progress in In vitro Toxicology (ed. Goldberg

A.M.

), pp. 325–331. New York: Mary Ann Liebert.

17.

Gordon

V.C.

, & Bergman

H.C.

(1988). The EYTEX™-MPA system, an in vitro method for evaluation of ocular safety. In Alternative Methods in Toxicology, Vol. VI, Progress in In vitro Toxicology (ed. Goldberg

A.M.

), pp. 309–316. New York: Mary Ann Liebert.

18.

Gordon

V.C.

, & Kelly

C.P.

(1989). An in vitro method for determining ocular irritation. Cosmetics and Toiletries 104, 69–73.

19.

Gordon

V.C.

, & Kelly

C.P.

(1989). Validation of an in vitro method for determining ocular irritation of cosmetic ingredients and products. Cosmetics and Toiletries 104, 67–69.

20.

Gordon

V.C.

, Kelly

C.P.

, & Bergman

H.C.

(1990). Applications of the EYTEX™ method. Toxicology in Vitro 4, 314–317.

21.

Kelly

C.P.

(1989). EYTEX™: an in vitro method of predicting ocular safety. Pharmacopeial Forum, January/February 1989, 4815–4824.

22.

Kruszewski

F.H.

, Hearn

L.H.

, Smith

K.T.

, Teal

J.J.

, Gordon

V.C.

, & Dickens

M.S.

(1992). Application of the EYTEX™ system to the evaluation of cosmetic products and their ingredients. ATLA 20, 146–163.

23.

Gordon

V.C.

(1992). The scientific basis of the EYTEX™ system. ATLA 20, 537–548.

24.

Courtellemont

, Hebert

, & Redziniak

(1992). Evaluation of the EYTEX™ system as a screening method for ocular tolerance: application to raw materials and finished products. ATLA 20, 466–470.

25.

Anon., (1981). Norme Internationale 5725. Fidélité des méthodes d'essai: détermination de la répét-abilité et de la reproductibilité par essais inter-laboratoires, 1er edn. Ref. no. ISO 5725–1981. Paris: ISO.

26.

Cooper

J.A.

, Saracci

, & Cole

(1979). Describing the validity of carcinogen screening tests. British Journal of Cancer 39, 87–89.

27.

O'Brien

K.A.F.

, Dixit

M.B.

, McCall

J.C.

, Botham

P.A.

, & Lewis

R.W.

(1992). An interlaboratory assessment of the EYTEX™ system. Toxicology in Vitro 6, 549–556.

28.

Fleiss

J.L.

(1973). The measurement and control of misclassification error. In Statistical Methods for Rates and Proportions, pp. 140–154. London: John Wiley & Son.

29.

Purchase

I.F.

(1990). Strategic considerations in industry's use of in vitro toxicology. Toxicology in Vitro 4, 667–674.

30.

Prinsen

M.K.

, & Koëter

H.B.W.M.

(1993). Justification of the enucleated eye test with eyes of slaughterhouse animals as an alternative to the Draize eye irritation test with rabbits. Food and Chemical Toxicology 31, 69–76.

31.

Anon., (1992). Technical Report No. 48: eye irritation reference chemicals data bank. 155 pp. Brussels: ECETOC.

32.

Jacobs

, & Martens

(1987). Evaluation of the enucleated eye test against the in vivo irritation test in the rabbit. 45 pp. Brussels: Institute of Hygiene and Epidemiology.

33.

Duprat

, Delsaut

, & Gradiski

(1976). Irritant power of the principal aliphatic chlorinated solvents on rabbit skin and ocular mucosa. European Journal of Toxicology and Environmental Hygiene 9, 171–177.

34.

Jacobs

, & Martens

(1989). An objective method for the evaluation of eye irritation in vivo. Food and Chemical Toxicology 27, 255–258.

35.

Kay

J.H.

, & Calandra

J.C.

(1962). Interpretation of eye irritation tests. Journal of the Society of Cosmetic Chemists 13, 281–289.

36.

Grant

W.M.

(1986). Toxicology of the Eye, 3rd edn. 1083 pp. Springfield, IL, USA: Charles C. Thomas.

37.

Regnier

J-F.

, & Imbert

(1992). Contributions of physicochemical properties to the evaluation of ocular irritation. ATLA 20, 457–465.

38.

Bruner

L.H.

, Kain

D.J.

, Roberts

D.A.

, & Parker

R.D.

(1991). Evaluation of seven in vitro alternatives for ocular safety testing. Fundamental and Applied Toxicology 17, 136–149.

Evaluation of the EYTEX® System as a Screening Method for the Ocular Irritancy of Chemical Products

Abstract

Keywords

Get full access to this article

References