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EC number: 911-418-6 | CAS number: 55965-84-9
- 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
Repeated dose toxicity: dermal
Administrative data
- Endpoint:
- sub-chronic toxicity: dermal
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 1993-09-02 till 1994-01-05
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Guideline-conform study under GLP without deviations.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 994
- Report date:
- 1994
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 82-3 (Subchronic Dermal Toxicity 90 Days)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Wiga GmbH, Sulzfeld, Germany
- Age at study initiation: 5-6 weeks
- Weight at study initiation: 131-203 g (males) and 137-183 g (females)
- Housing: individually on autoclaved sawdust
- Diet (e.g. ad libitum): Ssniff R10 pelleted diet ad lib.
- Water (e.g. ad libitum): tap water ad lib.
- Acclimation period: 8 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-25°C
- Humidity (%): 30-75 %
- Air changes (per hr): appr. 10
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Type of coverage:
- semiocclusive
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- TEST SITE
- Area of exposure: 5x7 cm on back and flanks
- Type of wrap if used: semiocclusive (Idealhaft, Paul Hartmann AG, 7920 Heidenheim, Germany)
- Time intervals for shavings or clipplings: weekly
REMOVAL OF TEST SUBSTANCE
- Washing (if done): warm water (no detergent)
- Time after start of exposure: 6 h
TEST MATERIAL
- Amount(s) applied (volume or weight with unit):
1738, 8688 , 43438 ppm a.i.
- Concentration (if solution): 13.9%
- Constant volume or concentration used: yes
VEHICLE aqua bidest
- Justification for use and choice of vehicle (if other than water): Since the scheduled dose volumes were too small to be administered, the following dilutions of Acticide 14 (13.9%) were prepared once weekly throughout the study: 1:80; 1:16; 1:3.2
- Amount(s) applied (volume or weight with unit):60 µl/kg bw.
USE OF RESTRAINERS FOR PREVENTING INGESTION: no - Duration of treatment / exposure:
- 90 days
- Frequency of treatment:
- once a day, 6h/d, semi-occlusive dressing
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
0.75 mg Acticide 14/kg bw/day (=0.105 mg a.i./kg bw/day)
Basis:
nominal per unit body weight
- Remarks:
- Doses / Concentrations:
3.75mg Acticide 14/kg bw/day (=0.525 mg a.i./kg bw/day)
Basis:
- Remarks:
- Doses / Concentrations:
18.75mg Acticide 14/kg bw/day (=2.625 mg a.i./kg bw/day)
Basis:
- No. of animals per sex per dose:
- 10
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Post-exposure period: none
- Dose selection rationale: The dose levels were selected on the basis of a 14-day dose range-finding study in the rat (HD Project No. 1154-001)
Examinations
- Observations and examinations performed and frequency:
- MORTALITY: Yes
- Time schedule: All animals were examined twice daily at the beginning and end of the working day for morbidity and mortality
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: All animals were examined at least once daily for signs of ill health or overt signs of toxicity and each finding was recorded
DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations:For all animals, evaluation of cutaneous reactions was performed once a week in the morning before dosing according to the scale in appendix I of the study protocol
BODY WEIGHT: Yes
- Time schedule for examinations:The body weight of the male and female animals was recorded once a week during the treatment period and on the day of necropsy
FOOD CONSUMPTION:
- The food consumption of the males and females was recorded twice weekly during the treatment period and evaluated on a weekly basis
FOOD EFFICIENCY: No
WATER CONSUMPTION: No
OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations:The eyes of all animals of each dose group were examined during the final week of treatment
Before the examination, a mydriatic agent (mydriaticum "Roche"®,Hoffmann-La Roche Aktiengesellschaft, 79639 Grenzach-Wyhlen, Germany) was instilled into the eyes. The following parameters were examined: ocular fundus with macula lutea, papilla and ocular vessels.
HAEMATOLOGY: Yes
- Time schedule for collection of blood:at the end of the treatment before necropsy
- Anaesthetic used for blood collection: Yes (diethyl ether)
- Animals fasted: Yes overnight fast (about 16 hours)
- Parameters checked in table 1 were examined.
CLINICAL CHEMISTRY: Yes / No / No data
- Time schedule for collection of blood:at the end of the treatment before necropsy
- Animals fasted: Yes overnight fast (about 16 hours)
- Parameters checked in table 1 were examined.
URINALYSIS: Yes
- Time schedule for collection of urine:at the end of the treatment before necropsy
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes overnight fast (about 16 hours)
- Parameters checked in table 1 were examined.
NEUROBEHAVIOURAL EXAMINATION: No - Sacrifice and pathology:
- Necropsies: Animals were killed by an intraperitoneal injection of pentobarbitone sodium (Eutha 77®,Coopers Tierarzneimittel GmbH, 30938 Burgwedel, Germany) followed by immediate exsanguination. The necropsies were conducted an 1 day. Animals were sacrificed in randomized order according to the cage plan. All animals were examined externally including all orifices. A full macroscopic examination of all tissues and organs in situ was then performed.
GROSS PATHOLOGY: Yes (see table2)
HISTOPATHOLOGY: Yes (see table2) - Statistics:
- body weight, body weight change and food consumption: Levene's testl for homogeneity of variances , followed by a rank transformation and the Levene's test in the case of heterogeneity only (p 5_ 0.05, equivalent to 95% confidence level) and the one-way Analysis of Variancel,(ANOVA). If significant results for the ANOVA (p 5_ 0.05 and p 0.01), Dunnett's two-tailed t-test was used to compare each group against the control group.
organ weights: Bartlett's test for homogeneity of variances was performed, followed by a rank transformation and the Bartlett's testl in the case of heterogeneity only (p 5_0.05, equivalent to 95 per cent probability). For homogeneous data, the one-way Analysis of Variancel, (ANOVA) was performed. In the event of significant results for the ANOVAI, (p 0.05, equivalent to 95 per cent probability), by the Dunnett's1,3 two-tailed t-test was used to compare each treated group against the control group. In the case of heterogeneity of the rank-transformed data, the Kruskal-Wallis testl,2,4 was performed together with the Wilcoxon rank-sum test to compare each treated group against the control group.
hematology data, clinical chemistry and organ/body weight ratio: rank transformation followed by the Bartlett's test for homogeneity of variances. For homogeneous data, the one-way Analysis of Variancel, (ANOVA) was performed, followed in the case of significant results (p 5_0.05, equivalent to 95 per cent probability), by the Dunnett's two-tailed t-test was used to compare each treated group against the control group. In the case of heterogeneity of the rank-transformed data, the Kruskal-Wallis test was performed together with the Wilcoxon rank-sum test to compare each treated group against the control group.
Results of the ANOVA and all significances found (at least p <_ 0.05 or p<0.01) are presented in the respective tables.
The statistical evaluation was performed with the standard package SAS(Statistical Analysis System) release 6.042
Results and discussion
Results of examinations
- Clinical signs:
- no effects observed
- Dermal irritation:
- effects observed, treatment-related
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- no effects observed
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- no effects observed
- Behaviour (functional findings):
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
Two control animals (4M, 44F)) and one high-dose animal (33M) were found dead an days 12,3 and 3 respectively. These mortalities are considered to be incidental and not related to the application of the test material. The high-dose animal and the control female were found dead when the bandages were removed and it is thought that the cause of death was that the bandage was bound too tightly. The cause of death in the control male was probably a focal pneumonitis
No treatment-related clinical changes throughout the treatment period that could be ascribed to the test article.
On a few occasions, kinked tail, incrusted eyes, pinched off teeth, injuries at skull or ears, fur staining, lesions of skin and red fluid in the bedding material were recorded. These findings are considered to be unrelated to treatment.
BODY WEIGHT AND WEIGHT GAIN
There were no adverse effects on body weight gain in animals of either sex.
FOOD CONSUMPTION
There were no adverse effects on overall food consumption throughout the experimental period in male and female animals
OPHTHALMOSCOPIC EXAMINATION
There were no treatment-related findings
HAEMATOLOGY
Although statistical evaluation revealed a few significantly different minimal changes, there were no treatment-related findings observed at the end of the experimental period
CLINICAL CHEMISTRY
Although statistical evaluation revealed a few significantly different minimal changes, there were no treatment-related findings observed at the end of the experimental period
URINALYSIS
There were no treatment-related urine analysis findings at the end of the experimental period
ORGAN WEIGHTS
Although there were a few significant values for single organs in different groups, there were no apparent organ weight changes in animals of either sex when compared with the control group.
GROSS PATHOLOGY
Skin observations: see table 3
Male animals
There were no skin lesions in group 2, minimal individual reactions of single animals in group 3 and numerous individual reactions in the majority of all high-dose males throughout the experimental period.
Cutaneous reactions observed at the high dose level included, above all, slight to moderate erythema and desquamation, slight edema and atonia as well as eschar formation. Fissures and exfoliation were not observed in any animal.Group mean total score for local reactions revealed only slight cutaneous reactions (grade: 0.3) for high-dose males.
Female animals
There were minimal individual skin reactions in single group 2 animals, few reactions in some group 3 animals and numerous individual reactions in the majority of all high-dose females throughout the experimental period.
Cutaneous reactions observed included, above all, dose-related slight to moderate erythema and desquamation, slight edema and atonia as well as eschar formation. Fissures and exfoliation were not observed in any animal.
Group mean total score for local reactions revealed only minimal changes for group 3 (grade: 0.1) and slight changes for high-dose females (grade: 0.4).
General Pathology:
There were no macroscopic lesions in any of the organs or tissues examined that could be ascribed to the test article Acticide 14.
The only treatment-related findings were compound-related lesions such as inflammation, parakeratosis and acanthosis in the treated skin sites of males and females.
There were no histopathological lesions in the other organs and tissues suggestive of systemic target organ toxicity due to the test article.
No treatment-related changes were found in decedents and a relationship between the causes of death and test article toxicity could not be established. The cause of death of the male group 1 (4M) was probably a focal pneumonitis. In the other two animals (44F, group 1 and 33M, group 4) the cause of death was probably due to stress or other unspecified causes.
HISTOPATHOLOGY: NON-NEOPLASTIC
HISTOPATHOLOGY: NEOPLASTIC (if applicable)
HISTORICAL CONTROL DATA (if applicable)
OTHER FINDINGS
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- (systemic)
- Effect level:
- 2.625 mg/kg bw/day
- Sex:
- male/female
- Basis for effect level:
- other: systemic toxicity
- Dose descriptor:
- NOAEL
- Remarks:
- (local)
- Effect level:
- 0.105 mg/kg bw/day
- Sex:
- male
- Basis for effect level:
- other: local skin reactions
- Dose descriptor:
- LOAEL
- Remarks:
- (local)
- Effect level:
- 0.525 mg/kg bw/day
- Sex:
- male
- Basis for effect level:
- other: skin reactions
- Dose descriptor:
- NOAEL
- Remarks:
- (local)
- Effect level:
- other: none observed
- Sex:
- female
- Basis for effect level:
- other: skin reactions
- Remarks on result:
- not determinable
- Remarks:
- no NOAEL identified
Target system / organ toxicity
- Critical effects observed:
- not specified
Any other information on results incl. tables
table 3: skin abnormalities
Males | Females | |||||||
mg/kg bw/d | 0 | 0.75 | 3.75 | 18.75 | 0 | 0.75 | 3.75 | 18.75 |
Erythema | 0.0 | 0.0 | 0.0 | 0.6 | 0.0 | 0.1 | 0.4 | 1.0 |
Edema | 0.0 | 0.0 | 0.0 | 0.2 | 0.0 | 0.0 | 0.0 | 0.3 |
Atonia | 0.0 | 0.0 | 0.0 | 0.1 | 0.0 | 0.0 | 0.0 | 0.1 |
Desquamation | 0.0 | 0.0 | 0.0 | 0.7 | 0.0 | 0.0 | 0.1 | 0.8 |
Fissures | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 | 0.0 |
% Eschar | 0 | 0 | 0 | 60 | 0 | 2 | 7 | 75 |
% Exfoliation | 0 | 0 | 0 | 0 | 0 | 0 | 0 | 0 |
Group mean total score | 0.0 | 0.0 | 0.0 | 0.3 | 0.0 | 0.0 | 0.1 | 0.4 |
Applicant's summary and conclusion
- Conclusions:
- In the absence of any organ or systemic toxicity, the dermal treatment-related effects of Acticide 14 were limited to local skin reactions.
NOAEL (systemic toxicity): 18.75 mg/kg bw/day (=2.625 mg a.i./kg bw/day)
NOAEL (local irritation): 0.75 mg/kg bw/day (males; =0.105 mg a.i./kg bw/day)/none observed (females) - Executive summary:
The toxic potential of a13.9 % aqueous solution of a 3:1 mixture of 5 -chloro-2 -methyl-2H-isothiazol-3 -one and 2 -methyl-2H-isothiazol-3 -one in water (named Acticide 14 in this study report) was evaluated in a 90 day repeated dose dermal toxicity study in rats according to EPA OPP 82 -3 guideline. Male and female Sprague-Dawley rats were treated with the test item on exposed skin daily for 6 hours over a period of 90 days. The test article was kept in place and prevented from oral ingestion by means of a semi-occlusive dressing for exposure and remainders of the test item were then removed with water. The animals were observed for mortality, clinical signs, body weight gain and food consumption. At the end of the tretament period, blood and urine were collected for haematology and clinical chemistry. The animals were subjected to detailed macroscopic and microscopic pathological evaluation, including scoring of observed skin abnormalities.
Mortalities observed in two control animals and one high-dose male are considered to be incidental and not related to the application of the test material. Treatment with the test article Acticide 14 applied dermally to intact skin produced skin reactions (slight to moderate erythema and desquamation, slight edema and atonia as well as eschar formation) with dose-dependent grades of severity. Females appeared to be more sensitive than males. There were no other effects at the end of the treatment period that could be attributed to ACTICIDE 14.
NOAEL (local, male rat): 0.75 mg Acticide 14/kg bw/day
NOAEL (local, female rat): none observed
NOAEL (systemic): 18.75 mg Acticide 14/kg bw/day
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.
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