Registration Dossier

Administrative data

Description of key information

OECD 404, rabbit, 95% active powder, semiocclusive 4h: Irritating to skin, Xi, R38; CLP Skin Irrit. 2, H315: Causes skin iritation

OECD 404, rabbit, 5% active aqueous solution, occlusive 24h: Irritating to skin, Xi, R38; CLP Skin Irrit. 2, H315: Causes skin irritation

OECD 405, rabbit, 90% active powder: Severe eye damage, Xi, R41; CLP Eye Dam. 1, H318: Causes serious eye damage

OECD 405, rabbit, 38% active aqueous solution: Irritating to eyes, Xi, R36; CLP Eye Irrit. 2, H319: Causes serious eye irritation

OECD 405, rabbit, 34.1% active aqueous solution: Not classified DSD; CLP Eye Irrit. 2, H319: Causes serious eye irritation

OECD 405, rabbit, 5% active aqueous solution: Not classified DSD; not classified CLP

Key value for chemical safety assessment

Skin irritation / corrosion

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Eye irritation

Endpoint conclusion
Endpoint conclusion:
adverse effect observed (irritating)

Respiratory irritation

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

There is a variety of studies available addressing skin irritation, conducted with test materials containing substance concentrations ranging from 95% in powder down to 5% in aqueous solution. Two of these studies are important for the establishment of specific concentration limits, therefore they were chosen as key studies. The study performed with the highest concentration was conducted with a powder containing 95% test substance (Kreiling, 1994). If applied as moistened powder for 4 hours under semiocclusive conditions, the test substance caused well defined erythema and very slight to slight edema in the skin of rabbits (Xi, R38). At the end of the observation period of 7 days dry and rough skin surface and fine scaling were still observed in 2/3 animals. Additionally, desquamation of fine scales was observed in 1/3 animals. Although the observed scores were only sufficient for a classification according to the criteria of the DSD, the occurrence of scaling at the end of the observation period fulfilled the criteria for a classification according to the criteria of the CLP regulation, as well (CLP Skin Irrit. 2). According to bridging principles the same classifications can be assumed for the neat test substance.

In the second key study focusing on skin irritation (Sterner and Grahwit, 1975), performed under occlusive exposure for 24 hours with an aqueous solution containing 37% and 5% active, respectively, the test substance still induced irritation to the skin of rabbits even at the lowest tested concentration of 5% (Xi, R38; CLP Skin irrit. 2). This study is especially important for the derivation of specific concentration limits, as it demonstrates irritant effects below the generic concentration limits of the DSD and the CLP regulation. This result is further supported by the other available older studies performed under occlusive exposure with test substance concentrations ranging from 38% down to 5% in aqueous solution or at unspecified concentrations.

Additionally, there is a study available in which a 40% solution was tested for 4 hours under semiocclusive conditions that suggests a classification according to the criteria of the DSD only, but not the CLP regulation (Hoechst AG, 1988). However, other studies conducted at lower concentrations, but with longer exposure durations and occlusive conditions according to older guidelines, induced effects, especially at 37% and 38%, that would lead to a classification according to the CLP criteria, as well. Missing information on reversibility in most of these studies further supports a classification as irritant to the skin. The described irritant characteristics of the test substance were also supported in vitro by the observed effects on isolated human stratum corneum (Rhein et al., 1985).

Several studies are available addressing eye irritation, conducted with concentrations ranging from 5% to 90 %. Three studies, performed with test materials containing 90%, 38%, 34.1% and 5%, respectively, were chosen as key studies, as the results obtained at the respective concentrations were important for the derivation of specific concentration limits. The first one (Rupprich and Weigand, 1984) was conducted with a test material in powder form containing 90% test substance. Between 1 and 72 hours after application clearly injected vessels up to diffuse, beefy red erythemae and slight to severe swellings of the conjunctivae were observed. Furthermore, circumcorneal injection and corneal opacity were noticed. Most of these symptoms were not fully reversible within the observation period of 21 days, and corneal opacity even deteriorated; at the end of the observation period corneal scores of grade 4 (opaque cornea, iris not discernible through the opacity according to the OECD grading table of ocular lesions) were observed (DSD: Xi, R41; CLP: Eye Dam.1). Concentrations higher than 90% were assumed to induce effects comparable to those observed, according to bridging principles. Therefore, the same classification has to be assumed for the neat substance.

The second key study (Nicholas and Gale, 1975) was performed with an aqueous solution containing 38% test substance. In this study the animals were only observed up to 72 hours. Redness and edema of the conjunctivae sufficient for a classification as eye irritant according to the criteria of the DSD (Xi, R36) and the CLP regulation (Eye Irrit. 2) were observed. Although the observed effects were not fully reversible until the end of the observation period, a classification as inducing eye damage deemed not appropriate due to the short duration of the observation period of only 72 hours and the mild characteristics of the symptoms at the final 72-hour reading. Full reversibility of the symptoms within a slightly longer observation period was reasonable to assume.

In the third key study (Sterner, 1973) aqueous solutions containing 34.1% and 5% of test substance were tested. At 34.1% erythema of the conjunctivae and slight chemosis were observed; the conjunctiva scores were sufficient for a classification according to the criteria of the CLP regulation (Eye Irrit. 2), but not according to the criteria of the DSD; therefore, 34.1% were considered as specific concentration limit for a classification according to the criteria of the DSD. At a concentration of 5% only very slight edema of the conjunctivae (mean score 0.33) was observed, therefore not fulfilling the critera for a classification. Therefore, this concentration was considered as specific concentration limit for a classification according to the criteria of the CLP regulation. The irritant characteristics of the test substance were further supported by the majority of the other available in vivo studies and by the EpiOcular Tissue Model in vitro (Stern et al., 1998).

Justification for selection of skin irritation / corrosion endpoint:

Hazard assessment is based on information from two different studies; both were considered as key studies as the information provided by the different studies was used for the derivation of specific concentration limits.

Justification for selection of eye irritation endpoint:

Hazard assessment is based on information from three different studies; all were considered as key studies as the information provided by the different studies was used for the derivation of specific concentration limits.

Effects on skin irritation/corrosion: irritating

Effects on eye irritation: corrosive

Justification for classification or non-classification

The test substance in powder form with 95% and 90% active caused irritation to skin and serious damage to eyes, respectively, and has therefore to be classified as:

Xi, R41: Risk of serious damage to eyes; Xi, R38: Irritation to skin according to EU Directive 67/548/EEC and

Eye Dam. 1, H318: Causes serious eye damage; Skin Irrit. 2, H315: Causes skin irritation according to Regulation (EC) No 1272/2008.

The test substance in its mainly sold form as aqueous solution containing 40% active causes severe damage to the eyes and irritation to the skin and has therefore to be classified as:

Xi, R41: Severe eye damage; R38: Irritating to skin according to EU Directive 67/548/EEC and

Eye Dam. 1, H318: Causes serious eye damage; Skin Irrit. 2, H315: Causes skin irritation according to Regulation (EC) No 1272/2008.

Concentrations ≤ 38% and > 5% active are irritating to eyes and skin and have to be considered as Eye Irrit. 2, H319: Causes serious eye irritation; Skin Irrit. 2, H315: Causes skin irritation according to Regulation (EC) No 1272/2008. A concentration of 5% active has to be classified as Skin Irrit. 2, H315: Causes skin irritation according to Regulation (EC) No 1272/2008.

According to the criteria of EU Directive 67/548/EEC concentrations >34.1% and ≤ 38% active are irritating to eyes and skin and have to be classified as Xi, R36/38 Irritating to eyes and skin.

Concentrations ≤ 34,1% and ≥ 5% active are only irritating to the skin according to the criteria of EU Directive 67/548/EEC and have to be classified as Xi, R38 Irritating to skin.