Classification and Labelling of Surfactants for human health hazards according to the Dangerous Substances Directive
CESIO recommendations for Anionic and Non-ionic surfactants
(including 1990 recommendations on Quaternary Ammonium
Compounds and Fatty Amines and Derivatives)
1On two separate occasions during the 1980’s, CESIO reviewed company reports of toxicology
studies on marketed surfactants to provide guidance for classification and labelling in line with the requirements of Annex VI of the Dangerous Substances Directive [DSD] (1). By reviewing all available experimental results, CESIO believed that “weight of evidence” enabled them to provide the most accurate guidance. The first of these reviews was reported in 1984 (2). At this time many of the studies had not been conducted strictly according to developing OECD/EC guidelines (3, 4-Annex V) and for that reason, a second review was undertaken several years later. This was completed in 1990 (5).
For both reviews, surfactants were grouped into 4 categories (anionics [for convenience this group also contained 3 amphoteric categories], non-ionics, quaternary ammonium compounds and fatty amines and their derivatives) and several sub-categories on the basis of their chemical and physical properties. Acute oral toxicity, skin and eye irritation and skin sensitisation studies were reviewed by an expert task force (TF) and recommendations for classification and labelling were made.
In 1993, the European Union revised their criteria for classification and labelling of substances and preparations based on their potential to cause ocular lesions (6). Two of these new criteria are very specific for the use of risk phrase R41 (Risk of serious damage to eyes). Additionally, in 1995 new experimental data on the irritation potential of several surfactant raw materials became available, which were considered to be of value for a further refinement of the classification and labelling recommendations given in 1990. Consequently, CESIO established a new TF to review their guidance on the classification and labelling of anionic and non-ionic surfactants. This report describes the objectives of this exercise, the composition of the TF, the process followed, it presents results and updates recommendations for classification and labelling. Only studies conducted according to DSD Annex V methodology were taken account thof in this exercise and interpretation was strictly according to the 18 ATP (6).
As a result, several classification and labelling recommendations are increased from those currently in place. The implications of these changes are discussed later in this document. For completeness, the tables on quaternary ammonium compounds and fatty amines and derivatives from the 1990 TF report are appended.
The following terms of references formed the basis of this task:
1. Review all available studies for acute oral toxicity and skin and eye irritation on anionic
and non-ionic surfactants that conform to DSD (4) Annex V.
2. Determine whether existing CESIO classification and labelling recommendations for these
endpoints are appropriate. Where not, revise recommendations. Classification for eye
irritation was a particular issue since the previous TF had recommended a risk phrase of R
36* for surfactants that cause persistent effects on the eye. R 36* is not an official EC
The Task Force
The following toxicologists and classification and labelling specialists participated. D Calcinai Condea Augusta ChB Jassogne Cesio
H Certa Condea Chemie W Kohl Henkel
1 CESIO = Comité Européen des Agents de Surface et leurs Intermédiaires
W M Clous Akzo Nobel R Kreiling Hoechst, now
S Dechert Hüls, now Degussa Hüls P A Martin Albright & Wilson
O-J Grundler BASF B Molinier Elf-Atochem
B Hendrickx Rhone-Poulenc, now Rhodia RAJ Priston Shell Chemicals
G Holland Unilever J-F Regnier Elf-Atochem
L Hughes ICI Performance Chemicals, now C Verge Petresa
The intent of this TF was to re-assess existing animal studies and to review as many new ones as possible whilst maintaining confidentiality of privileged information. To achieve this, questionnaires, developed for each of the end-points, were completed by participating companies and returned to CESIO secretariat. Confidential information (e.g. product name, company name) was then obscured and the questionnaires were coded before being passed to the TF for review. Questionnaires for each of the end points are shown in appendices 1-3 (skin irritation, eye irritation and acute oral toxicity, respectively). For inclusion in the final assessment, questionnaires were judged on the details provided on the test material and on compliance with current OECD/EC methodology. Adherence to Good Laboratory Practice was not a requisite if the test was otherwise well conducted.
The assessment was conducted during 2 meetings of the TF. Questionnaires were evaluated and classifications derived using EC criteria (6). Additionally, for some sub-categories and 2particularly for eye irritation, the TF ensured that its conclusions were in line with the ECETOC
report on eye irritancy (7) and took account of the findings of previous CESIO reviews.
Results and Discussion
Existing and proposed classification and labelling recommendations for anionic and non-ionic surfactants are summarised in tables 4 and 5, respectively. Supplementary information is provided in the following paragraphs:
A total of 421 questionnaires (see table 1) were returned from the following companies: Akzo Nobel Goldschmidt Muenzing Chemie
Albright and Wilson Henkel Rhodia
BASF Hoechst Shell Chemicals
Dr Th.Bohme Huels Unger Fabrikker
Condea ICI Surfactants Union Carbide
Elf-Atochem Kao Corporation Zschimmer & Schwarz
Table 1. Breakdown of questionnaires by study
Surfactant Datasets Totals
category Acute oral Skin irritation Eye irritation
Non-ionics 109 94 102 305
Anionics 45 31 40 116
Totals 154 125 142 421
2 ECETOC = European Centre for Ecotoxicology and Toxicology of Chemicals
From chemical descriptions provided, several new anionic surfactant classes were identified, extending the coverage of sub-categories 4, 5 and 11. Data were not available for sub-categories 10 and 16 (anionics), 2.1 or 4.2 (non-ionics) in this or the previous review so the TF has deleted from the tables and renumbered categories as appropriate.
Acute oral LD50
No changes to current recommendations are proposed. alkylnaphthalene sulphonates (sub-category 16) and certain of the alkyl sulphates (sub-category 2), alkylaryl sulphonate salts (sub-category 6) and fluorine surfactants (sub-category 14) are correctly classified as “harmful
if swallowed” (R 22). New animal study data on alkyl sulphates and alkylaryl sulphonate salts are consistent with this recommendation. New data were not available on alkylnaphthalene sulphonates or fluorine surfactants.
No changes to current recommendations are proposed. fluorine surfactants (sub-category 11) and certain of the ethoxylated fatty alcohols (sub-category 1) and ethoxylated alkylphenols (sub-category 3) are correctly classified as “harmful if swallowed” (R 22). New animal data on ethoxylated fatty alcohols and ethoxylated alkylphenols are consistent with this recommendation. New data were not available for sub-category 11.
In the absence of new data, the TF recommends no change to existing recommendations. This applies to the majority of the anionic surfactants.
New experimental data generally support existing classification and labelling guidance. For sub-category 5 (olefin sulphonates), new skin irritation data were available on materials with an active matter concentration >80 %, at which concentration they were irritant (Xi, R 38). New data were not available on olefin sulphonates at 40-80 %, but, because in the previous review they were also found to be irritant (Xi, R 38) at 40 %, this TF recommends the same classification. Based on new data, the cocoamphodiacetates (amphoterics, sub-category 16) need not be considered irritant.
In general, classification and labelling recommendations derived from the new animal data are consistent with existing ones.
For three sub-categories, however, new animal data (table 2) strongly support a change from “irritating to skin” (R 38) to “not classified”, due mainly to the increasing availability of studies using a 4 hour skin exposure period, as in the OECD/EC test protocol, rather than 24 hours used in the conventional “Draize” test.
Table 2. Non-ionics: Revised recommendations for skin irritation
Sub-category EO chain Conc. Existing Proposed
1. Fatty alcohol +EO 2-5 8-18 100 R 38 NC
>5-15 8-18 100 R 38 NC
3. Alkylphenol+EO >7