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EC number: - | CAS number: -
- Life Cycle description
- Uses advised against
- Endpoint summary
- Appearance / physical state / colour
- Melting point / freezing point
- Boiling point
- Density
- Particle size distribution (Granulometry)
- Vapour pressure
- Partition coefficient
- Water solubility
- Solubility in organic solvents / fat solubility
- Surface tension
- Flash point
- Auto flammability
- Flammability
- Explosiveness
- Oxidising properties
- Oxidation reduction potential
- Stability in organic solvents and identity of relevant degradation products
- Storage stability and reactivity towards container material
- Stability: thermal, sunlight, metals
- pH
- Dissociation constant
- Viscosity
- Additional physico-chemical information
- Additional physico-chemical properties of nanomaterials
- Nanomaterial agglomeration / aggregation
- Nanomaterial crystalline phase
- Nanomaterial crystallite and grain size
- Nanomaterial aspect ratio / shape
- Nanomaterial specific surface area
- Nanomaterial Zeta potential
- Nanomaterial surface chemistry
- Nanomaterial dustiness
- Nanomaterial porosity
- Nanomaterial pour density
- Nanomaterial photocatalytic activity
- Nanomaterial radical formation potential
- Nanomaterial catalytic activity
- Endpoint summary
- Stability
- Biodegradation
- Bioaccumulation
- Transport and distribution
- Environmental data
- Additional information on environmental fate and behaviour
- Ecotoxicological Summary
- Aquatic toxicity
- Endpoint summary
- Short-term toxicity to fish
- Long-term toxicity to fish
- Short-term toxicity to aquatic invertebrates
- Long-term toxicity to aquatic invertebrates
- Toxicity to aquatic algae and cyanobacteria
- Toxicity to aquatic plants other than algae
- Toxicity to microorganisms
- Endocrine disrupter testing in aquatic vertebrates – in vivo
- Toxicity to other aquatic organisms
- Sediment toxicity
- Terrestrial toxicity
- Biological effects monitoring
- Biotransformation and kinetics
- Additional ecotoxological information
- Toxicological Summary
- Toxicokinetics, metabolism and distribution
- Acute Toxicity
- Irritation / corrosion
- Sensitisation
- Repeated dose toxicity
- Genetic toxicity
- Carcinogenicity
- Toxicity to reproduction
- Specific investigations
- Exposure related observations in humans
- Toxic effects on livestock and pets
- Additional toxicological data
Skin sensitisation
Administrative data
- Endpoint:
- skin sensitisation: in vivo (non-LLNA)
- Remarks:
- in vivo study was conducted prior to REACH implementation
- Type of information:
- experimental study
- Adequacy of study:
- weight of evidence
- Study period:
- 1995-01-10 - 1995-02-17 (experimental phase)
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 995
- Report date:
- 1995
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 406 (Skin Sensitisation)
- Version / remarks:
- OECD-Guideline for Testing of Chemicals Section 4, 406 "Skin Sensitisation", adopted July 17, 1992
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of study:
- guinea pig maximisation test
- Justification for non-LLNA method:
- Study was performed prior to REACH implementation and adoption of LLNA OECD TG.
Test material
- Reference substance name:
- Amines, C11-13 (branched) alkyl, salts with O,O-bis(2-ethylhexyl) hydrogen dithiophosphate
- Molecular formula:
- C27H60NPS2O2 C28H62NPS2O2 C29H64NPS2O2 (main component)
- IUPAC Name:
- Amines, C11-13 (branched) alkyl, salts with O,O-bis(2-ethylhexyl) hydrogen dithiophosphate
- Test material form:
- liquid
- Details on test material:
- Before Substance ID change known as CAS 71888-91-0 EC 276-159-7
Constituent 1
In vivo test system
Test animals
- Species:
- guinea pig
- Strain:
- other: Pirbright White
- Remarks:
- Albino
- Sex:
- male/female
- Details on test animals and environmental conditions:
- TEST ANIMALS
- Source: Interfauna, Süddeutsche Versuchstierfarm, Oberer Bann 37, D-78532 Tuttlingen
- Females (if applicable) nulliparous and non-pregnant: yes
- Age at study initiation: younger than one year
- Housing: The animals housed individually in Macrolon cages (area 780 cm²).
- Diet (e.g. ad libitum): Raiffeisen Ringfutter, Trockenfutter 52 P, Raiffeisen Kraftfutterwerk Kehl
- Water (e.g. ad libitum): tap water of Karlsruhe, additive:20 mg ascorbic acid and 100 mg citric acid per 100 ml water, free access for the animals by daily changing of the watering-bottles
- Acclimation period: five days
- Indication of any skin lesions: none stated; animals were without morbid signs
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-23°C
- Humidity (%):30-70%
- Photoperiod (hrs dark / hrs light): 12:12
- IN-LIFE DATES:
From: 1995-01-20 (start of acclimatization)
To: 1995-02-17 (reading of challenge reactions)
Study design: in vivo (non-LLNA)
Induction
- Route:
- intradermal and epicutaneous
- Vehicle:
- other: Freund's complete adjuvant & water or sesame oil
- Concentration / amount:
- - Induction, day 0, intradermal: Three intradermal injections were made in a row:
1) Freund's Complete Adjuvant (FCA) (No. F-5881, Sigma Chemical Company, P.O. Box 14508, St. Louis, USA) diluted with aqua ad iniectabilia in the ratio 1+1 and shaken up. The volume of each injection was 0.1 ml.
2) Test item, diluted with sesame oil in the ratio 1 + 3. The volume of each injection was 0.1 ml. The solutions administered were not older than 1 hour.
3) First, the test item is emulsified in FCA in the ratio 2 + 3. This emulsion is further diluted with H2O in the ratio 5 + 3. The resulting mixture containing 25 % of the test item is then injected. The volume of each injection was 0.1 ml
- Induction, dermal (day 8): A filter paper (2x4 cm²) was fully-loaded with approx. 1 ml undiluted test item. It was then applied with the loaded side down to the test area - Day(s)/duration:
- intradermal: single application / epicutaneous: 48 h
- Adequacy of induction:
- highest technically applicable concentration used
Challenge
- No.:
- #1
- Route:
- epicutaneous, occlusive
- Vehicle:
- other: sesame oil
- Concentration / amount:
- a linen patch loaded with the test substance was applied
- Day(s)/duration:
- for 24 h, on day 21, 2 weeks after topical induction; evaluation 24&48h after removal of the bandage
- Adequacy of challenge:
- other: undiluted; highest concentration possible
- No. of animals per dose:
- 10 (test item)
5 (control)
group I: (test substance) (animals No. 220-229)
group II: (control) (animals No. 230-234)
male animals: No. 225-229; 232-234
female animals: No. 220-224; 230-231 - Details on study design:
- RANGE FINDING TESTS:
The concentration of the test substance for each induction exposure should be the highest to cause mild irritation.
In order to check the animal tolerability of the test concentration applied, a small-scale pilot study with two albino guinea pigs was performed. After clipping away their hair the following intradermal injections were made in each dorsal side:
above: 100 µl test item diluted with sesame oil in the ratio 1:3
below: 100 µl test item diluted with sesame oil in the ratio 1:7
During the next 3 days the skin area around each prick spot was checked for skin irritation effects. No erythema or oedema could be observed. Further testing with more concentrated test item solution was omitted in consequence of the high viscosity of the test substance.
MAIN STUDY
After randomization and assignment to both groups the animals were acclimatized to the test conditions for 5 days prior to the administration.
The study is chronologically subdivided into the acclimatization period (day -5 to -1), the induction phase (day 0 to 8) with an intradermal administration of the test substance on day 0 and a dermal one on day 8, followed by a phase free from treatment (day 9 to day 19) during which a hypersensitive state is developed in both phases. The challenge phase (dermal administration on day 20) follows with subsequent valuation of potential sensitisation reactions on the days 22 and 23.
A. INDUCTION EXPOSURE
- No. of exposures: 2
- Exposure period: day 0, day 8
- Test groups:
- Induction, day 0, intradermal: An area of 4 x 6 cm² on the dorsum was clipped with an electric clipper. Three intradermal injections were made in a row:
1) Freund's Complete Adjuvant (FCA) (No. F-5881, Sigma Chemical Company, P.O. Box 14508, St. Louis, USA) diluted with aqua ad iniectabilia in the ratio 1+1 and shaken up. The volume of each injection was 0.1 ml.
2) Test item, diluted with sesame oil in the ratio 1 + 3. The volume of each injection was 0.1 ml. The solutions administered were not older than 1 hour.
3) First, the test item is emulsified in FCA in the ratio 2 + 3. This emulsion is further diluted with H2O in the ratio 5 + 3. The resulting mixture containing 25 % of the test item is then injected. The volume of each injection was 0.1 ml
- Causing of a local irritation (day 7): As expected no dermal irritations were noticed in both groups. Therefore, the fur of all guinea pigs was clipped in the dorsal test area with an electric clipper once again. Twenty-four hours before topical induction application the test area was painted with 0.5 ml of a mixture of 10 % sodium lauryl sulfate (No. 20763, anal. grade, Serva Feinbiochemica GmbH & Co. KG, Heidelberg, Germany) in vaseline (DAB 10, Carl Roth GmbH + Co., Karlsruhe, Germany) in order to create a local dermal irritation.
- Induction, dermal (day 8): Eight days after intradermal induction the topical dermal induction was performed. A filter paper (2x4 cm2) was fully-loaded with approx. 1 ml undiluted Additin M 10306. It was then applied with the loaded side down to the test area marked with a rectangular outline and held in contact by an occlusive dressing for a period of 48 hours. In detail, the filter paper was covered with the impermeable non-stripped, non-irritating plastic material of the reverse of a patch (width 6 cm) (Werovil, No. 15 00 20, WERO-MEDICAL, D-65232 Taunusstein, Germany). It was held in place by an occlusive bandage made from a dressing (width 8 cm, with selvages, coated completely with cellophane) (No. 09 00 22, WERO-MEDICAL). The bandage was fixed with 1.25 cm broad strips of Adhesive Tape ST (WERO-MEDICAL).
- Control group:
- Induction, day 0, intradermal: An area of 4 x 6 cm² on the dorsum was clipped with an electric clipper. Three intradermal injections were made in a row: Volume of each injection: 0.1 ml.
1) Freund's Complete Adjuvant (FCA) (No. F-5881, Sigma Chemical Company, P.O. Box 14508, St. Louis, USA) diluted with aqua ad iniectabilia in the ratio 1+1 and shaken up. The volume of each injection was 0.1 ml.
2) Sesame oil; the volume of each injection was 0.1ml.
3) Sesame oil emulsified in FCA m the ratio 2+1. This emulsion is further diluted with H2O in the ratio 3 + 1. The resulting mixture containing 50 % sesame oil is the injected. The volume of each injection was 0.1 ml.
- Causing of a local irritation (day 7): As expected no dermal irritations were noticed in both groups. Therefore, the fur of all guinea pigs was clipped in the dorsal test area with an electric clipper once again. Twenty-four hours before topical induction application the test area was painted with 0.5 ml of a mixture of 10 % sodium lauryl sulfate (No. 20763, anal. grade, Serva Feinbiochemica GmbH & Co. KG, Heidelberg, Germany) in vaseline (DAB 10, Carl Roth GmbH + Co., Karlsruhe, Germany) in order to create a local dermal irritation.
- Induction, dermal (day 8): The animals of the control group were treated in the same way as the test item group. However, instead of the test substance the pure vehicle sesame oil was applied dermally under the filter paper. The exposure area was protected with an occlusive bandage, too.
- Site: dorsum
- Frequency of applications: single application per day
- Duration: single application (day 0), 48h (day 8)
B. CHALLENGE EXPOSURE
- No. of exposures: 1
- Day(s) of challenge: The challenge phase (dermal administration on day 20, 2 weeks after last induction) follows with subsequent valuation of potential sensitisation reactions on the days 22 and 23.
- Exposure period: 24h
- Test groups / Control group:
Challenge (day 21): The animals were challenged two weeks after the topical dermal induction.
The hair was removed from two 3x5 cm2 areas on both flanks by clipping with an electric clipper. To both groups a linen patch loaded with the test substance was applied to the left flank and a linen patch loaded with the vehicle (sesame oil) was applied to the right flank.
An occlusive dressing made from the materials specified above protected the exposure areas during a period of 24 hours.
- Site: flanks
- Concentrations: undiluted
- Evaluation (hr after challenge): Reading of challenge reactions (days 23 + 24): The challenge sites were evaluated 24 and 48 hours after removal of the bandage. - Challenge controls:
- none
- Positive control substance(s):
- yes
- Remarks:
- The sensitivity of the guinea pig strain used and the reliability of the experimental technique were assessed by use of p-phenylenediamine which is known to have mild-to-moderate skin sensitization properties in a separate study.
Results and discussion
- Positive control results:
- Mortality / toxicological symptoms
Group III (reference substance): Guinea pig No. 187 was found dead on day 21 of the reference substance study. None of the surviving animals of group III showed signs of toxicological symptoms.
Group IV (control): Guinea pig No. 192 was found dead on day 20 of the reference substance study. Guinea pig No. 194 was found dead on day 21 of the reference substance study. None of the surviving animals of group IV showed signs of toxicological symptoms.
Body weight
At the end of the experiment all surviving animals had an increase in weight compared to the beginning of the study.
Classification of the findings caused by the reference substance p-phenylenediamine
As stated in "Criteria of judgement" the relevance of the observations is based upon the irritation score and the number of animals reacting as compared with the negative control group. Four of the surviving 9 animals showed symptoms of allergic reactions. Therefore, the potency of p-phenylenediamine to cause allergic symptoms is shown as well as the sensitivity of the guinea pig strain used.
allergic reactions animal challenge reaction
No. day 23 day 24
180 1 1
181 0 0
182 0 0
183 1 0
erythemata noted
184 1 0
185 1 1
186 0 0
187 + a)
188 0 0
189 0 0
In vivo (non-LLNA)
Resultsopen allclose all
- Key result
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 4
- Total no. in group:
- 10
- Clinical observations:
- None of the guinea pigs of group I died during the experiment or showed signs of toxicological symptoms.
- Remarks on result:
- positive indication of skin sensitisation
- Remarks:
- Four of the animals of the test group showed symptoms of allergic reactions. Therefore, the test substance shows skin sensitisation potential under the experimental conditions.
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- test chemical
- Dose level:
- 100%
- No. with + reactions:
- 2
- Total no. in group:
- 10
- Clinical observations:
- None of the guinea pigs of group I died during the experiment or showed signs of toxicological symptoms.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- negative control
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- None of the guinea pig of group II died during the experiment or showed signs of toxicological symptoms.
- Remarks on result:
- no indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- negative control
- Dose level:
- 100%
- No. with + reactions:
- 0
- Total no. in group:
- 5
- Clinical observations:
- None of the guinea pig of group II died during the experiment or showed signs of toxicological symptoms.
- Reading:
- 1st reading
- Hours after challenge:
- 24
- Group:
- positive control
- Dose level:
- 0.5% (intradermal, epicutaneus induction & challenge)
- No. with + reactions:
- 4
- Total no. in group:
- 9
- Clinical observations:
- death of the 10th animal
- Remarks on result:
- positive indication of skin sensitisation
- Reading:
- 2nd reading
- Hours after challenge:
- 48
- Group:
- positive control
- Dose level:
- 0.5% (intradermal, epicutaneus induction & challenge)
- No. with + reactions:
- 2
- Total no. in group:
- 9
- Clinical observations:
- death of the 10th animal
Applicant's summary and conclusion
- Interpretation of results:
- Category 1 (skin sensitising) based on GHS criteria
- Remarks:
- EU implementation
- Conclusions:
- This study was performed in compliance with OECD-Guideline 406 under GLP, is well-documented and with sufficient information for classification, the results can hence be considered as reliable. Positive and negative controls gave the appropriate results. Under the conditions of this experiment the test substance produced skin reactions in 4 out of 10 animals of the treatment group.
According to Regulation 1272/2008, when an adjuvant type guinea pig test method for skin sensitisation is used, a response of at least 30 % of the animals is considered as positive.
According to the guideline, a minimum of 10 animals is used in the treatment group and at least 5 animals in the control group. When fewer than 20 test and 10 control guinea pigs have been used, and it is not possible to conclude that the test substance is a sensitiser, testing in additional animals to give a total of at least 20 test and 10 control animals is strongly recommended.
The present test is an adjuvant test, and 40% of the animals showed reactions in the form of discrete or patchy erythema. Hence, the substance gave a positive reaction acc. Regulation 1272/2008, and so also the number of animals is sufficient. According to Commission Regulation (EU) No 286/2011 of 10 March 2011, Table 3.4.4, Animal test results for sub-category 1B, a substance must be classified as skin sensitizer Cat. 1B, if in a GPMT ≥ 30 % of the animals are responding at > 1 % intradermal induction dose. Intradermal induction dose was 25%, and 40% responded, so a subcategorisation into Skin Sens. Cat. 1B ist indicated. - Executive summary:
The skin sensitisation study was performed according to the method of Magnusson & Kligman in compliance with OECD-Guideline 406. Two groups (test substance and control) with 10 guinea pigs (test substance) and 5 guinea pigs (control) were employed, both male and female animals contained.
Under the conditions of this experiment, i.e. after the intradermal and dermal applications of the test item with subsequent challenge four animals showed allergic reactions. As expected, the animals of the control group showed no allergic reactions.
During the experiment the body weight of all animals had a normal physiological growth. Resulting from this study the test substance has skin sensitisation potential. A histopathological examination was not performed.
The substance must be regarded as a potential skin sensitizer.
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