Registration Dossier

Data platform availability banner - registered substances factsheets

Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.

The new ECHA CHEM database has been released by ECHA, and it now contains all REACH registration data. There are more details on the transition of ECHA's published data to ECHA CHEM here.

Diss Factsheets

Administrative data

Description of key information

In the study reported by the Commission of the European Communities DG XI (1993) the oral repeated dose toxicity (28 days, subacute, Koerdel et al. 1981) in the rat was determined similar to the OECD guideline 407. Owing to insufficient documentation and the fact that there were minor effects shown by all exposed animals, a reliable NO(A)EL cannot be deduced.
In the study reported by the International Programme on Chemical Safety (IPCS) the inhalative repeated dose toxicity (28 days, subacute, Hazleton 1984) in the rat was determined. A LOAEL was set at 0.06 mg/l air, based on the fact that squamous metaplasia of the epithelium lining the maxillo-turbinates and naso-turbinates was observed in all animals of the 0.06 mg/l air dose group.

Key value for chemical safety assessment

Additional information

Data on the repeated dose toxicity of the test substance is available only as secondary source (Commission of the European Communities DG XI, 1993 and International Programme on Chemical Safety (IPCS)):

 

Subacute study (oral)

In the cited study (Commission of the European Communities DG XI, 1993) the subacute oral toxicity of the test substance was determined in rodents (rats). The study was conducted similar to the OECD-Guideline 407. 5 Wistar rats per sex and dose were administered the test compound in dose levels of 22, 67, and 200 mg/kg bw. No higher doses were administered since the authors wanted to avoid crystallisation of the test substance in the stomach. Control animals were included into the study. No further details were given.

Food intake decreased in high-dose males and in mid- and high-dose females, and final body weight decreased non-significantly in all dosed animals. The absolute liver and kidney weights were decreased in mid-dose animals, and the relative testes weight increased in low- and mid-dose males and decreased in high-dose males. In all dosed animals, the relative and absolute weights of the adrenal glands increased. The haematological examination, clinical chemistry, and histopathological examination of the major organs and tissues did not give any indication of a substance-related toxic effect in comparison with controls. No further details were given. Owing to insufficient documentation and the fact that there were minor effects (weight of adrenal glands) shown by all exposed animals, a reliable NO(A)EL cannot be deduced.

 

Subacute study (inhalative)

In the cited study (International Programme on Chemical Safety (IPCS)) the subacute inhalative toxicity of the test substance was tested. 15 Sprague-Dawley rats each sex and dose group were placed in a whole body inhalation system and exposed to the vapour of the melted test substance at doses of 5, 30, and 60 mg/m³ for 6h/d, 5d/week and 4 weeks. Control animals were included into the study. Except for squamous metaplasia of the epithelium lining the maxillo-turbinates and naso-turbinates in all high-dose animals, the clinical and histopathological examinations gave no consistent exposure-related effects. The methaemoglobin values determined after the 11th exposure were significantly increased only in low-dose animals (males: 1.0, 2.3, 1.8, and 1.6 %; females: 2.0, 4.1, 2.1, and 1.1 %), but were within control values at the end of the study. No further details were given. Based on these findings, a LOAEL was set at 0.06 mg/l air.

As described in the section of acute toxicity, the substance causes methaemoglobin formation in cats. Comoared to rats, both cats and man have a lower capacity to reduce methaemoglobin. Therefore, the repeated dose studies performed with rats give only limited information on long-term systemic toxicity. As the substance already carries a hazard label for the acute effects, this is considered acceptable.

The local effects desribed in the subacute inhalation study are mostly of adaptive nature and are not considered severe in the context of classification and labelling for repeated-dose toxicity.


Repeated dose toxicity: inhalation - systemic effects (target organ) respiratory: nose

Justification for classification or non-classification

Dangerous Substance Directive (67/548/EEC)

Data on long-term toxicity is available for rats, which is not the adequate species for testing substances that induce methaemoglobin formation. No need of classification is derived from the rat studies, but these studies are considered an inadequate database.

In the absence of adequate data of the test substance, under Directive 67/548/EEC the test substance is not classified for repeated-dose toxicity.

 

Classification, Labeling, and Packaging Regulation (EC) No. 1272/2008

In the absence of adequate data of the test substance, under Directive 67/548/EEC the test substance is not classified for repeated-dose toxicity.