Registration Dossier
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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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
Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 616-995-5 | CAS number: 8018-01-7
- 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
Genetic toxicity: in vivo
Administrative data
- Endpoint:
- in vivo mammalian somatic cell study: cytogenicity / erythrocyte micronucleus
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 26 November 1996 - 02 May 1997
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 997
- Report date:
- 1997
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- other: Japanese MHW Guidelines on Toxicity Studies
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 474 (Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- 1997
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.12 (Mutagenicity - In Vivo Mammalian Erythrocyte Micronucleus Test)
- Version / remarks:
- EC Guideline B.12
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 84-2
- Version / remarks:
- US EPA Pesticide Assessment Guidelines Subdivision F Series 84-2
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Type of assay:
- mammalian erythrocyte micronucleus test
Test material
- Reference substance name:
- Complexation products of manganese and zinc with ethylenebis(dithiocarbamate)
- EC Number:
- 616-995-5
- Cas Number:
- 8018-01-7
- Molecular formula:
- (x+y)[C4H6N2S4]2- + xMn2+ + yZn2+, x:y ranges between 1:0.062 to 1:0.12 (mean 1:0.091)
- IUPAC Name:
- Complexation products of manganese and zinc with ethylenebis(dithiocarbamate)
- Test material form:
- solid: particulate/powder
Constituent 1
Test animals
- Species:
- mouse
- Strain:
- CD-1
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Harlan Olac Limited, Shaw's Farm, Blackthorn, Bicester, Oxfordshire.
- Age at study initiation: 6 - 7 weeks
- Weight at study initiation: males: 27 - 35 g; females: 20 - 27 g
- Assigned to test groups randomly: yes
- Fasting period before study: 2-3 h period prior to dosing
- Housing: All mice were housed individually in polypropylene cages with stainless steel tops.
- Diet: ad libitum, except for a brief 2-3 h period prior to dosing and 1-2 h after dosing.
- Water: ad libitum, except for a brief 2-3 h period prior to dosing and 1-2 h after dosing.
- Acclimation period: 7 to 8 days between arrival and exposure
ENVIRONMENTAL CONDITIONS
- Temperature (°C): Toxicity study: 16 - 19°C; Micronucleus test: 18 - 20°C
- Humidity (%): Toxicity study: 26 - 51°C; Micronucleus test: 27 - 49°C
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 07 January 1997 To: 20 February 1997
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- - Vehicle / solvent used: maize oil
- Concentration of test material in vehicle: 50 to 2000 mg/kg (5 to 200 mg/mL)
- Amount of vehicle (gavage): 10 mL/kg body weight
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Immediately prior to dosing, the test material was dissolved in maize oil to give the required dosing concentrations. The dose volume used for both the control and test material treated animals was a constant 10 mL/kg body weight. - Duration of treatment / exposure:
- 48 h
- Frequency of treatment:
- twice (at 0 and 24 h)
- Post exposure period:
- Sampling (scheduled kill) was done at 48 h. Animal health status checks were done at frequent intervals after dosing and prior to the scheduled kill.
Doses / concentrations
- Dose / conc.:
- 2 000 mg/kg bw/day
- No. of animals per sex per dose:
- 10 males / 10 females
- Control animals:
- yes, concurrent vehicle
- Positive control(s):
- cyclophosphamide
- Route of administration: oral, gavage
- Doses / concentrations: The positive control Cyclophosphamide was prepared freshly as a 5 mg/mL solution in distilled water. It was administered to the positive control animals in dose volumes of 10 mL/kg to give the required target dose of 50 mg/kg bw.
Examinations
- Tissues and cell types examined:
- bone marrow cells of femur
- Details of tissue and slide preparation:
- CRITERIA FOR DOSE SELECTION:
Based on toxicity investigations, the test substance was judged to be non-toxic at the maximum recommended dose of 2000 mg/kg bw/day. Therefore, in the micronucleus test a single group of male and female CD-1 mice were accordingly dosed orally at 0 h and 24 h with the test substance at the pre-determined concentration of 2000 mg/kg bw/day.
TREATMENT AND SAMPLING TIMES:
In the micronucleus test, groups of CD-1 mice (male and females) were dosed (orally) at 0 h and 24 h with test substance, vehicle or positive control. The animals were sacrificed and the bone marrow samples were taken 24 h after the last treatment (48 h after the first treatment). Animal health status checks were done at frequent intervals after dosing and prior to the scheduled kill. Mice were killed by cervical dislocation. The femora were quickly dissected out and freed of adherent tissue. A small hole was made in the neck of one femur and the bone marrow flushed, using a syringe fitted with a gauge needle.
DETAILS OF SLIDE PREPARATION:
The bone marrow cells were centrifuged for 5 min. at 1000 r.p.m. to pellet the cells. All but a few drops of supernatant fluid were discarded. The cells were then resuspended on a vortex mixer in this residual amount of supernatant liquid. A drop of the suspension was placed at one end of the slide and a smear made by drawing the top of a Pasteur pipette horizontally along the slide. Two slides were prepared from each tube/animal. The smear was left to air dry, fixed in methanol for ca. 5 min. and then immersed for 15 min in 15% Giemsa stain, prepared in tap water, to give optimum erythrocyte discrimination.
The stained smears were finally rinsed in distilled water for ca. 1 min. and left to air dry overnight. Permanent slide preparations were made by sealing coverslips onto the glass slides using DPX mounting medium.
METHOD OF ANALYSIS:
2 prepared slides were selected for examination and the coded slides assessed blind by the same operator. Slides were scored in an ordered sequential fashion using the random number of each slide as guidance. Two thousand (2000) polychromatic erythrocytes (PCE) per animal were scored for micronuclei and the frequency of micro nucleated cells (MN-PCE) determined.
As a control against inclusion of artefacts, or action of a mutagen on the G2 and/or mitotic phase of the cell cycle, the numbers of micro nucleated normochromatic erythrocytes (MN-NCE) in mature red blood corpuscles were also recorded. In addition, scored micronuclei were assigned on the basis of size into small or large categories, historically defined as micronuclei occupying less or more than 25% of the visible cellular area. This classification provided a non-specific measure of compound induced spindle disfunction, as large micronuclei appear to derive from lagging chromosomes caused by damage to the mitotic apparatus during bone marrow erythropoiesis.
The PCE/NCE ratio, a measure of any induced systemic toxicity, was determined by counting a minimum total of 1000 erythrocytes (PCE +NCE) per marrow preparation. Binocular microscopes were used for the assessment. The scoring was done under a nominal magnification of x 1250 using x 12.5 magnification eye pieces and a x 100 oil immersion objective. - Evaluation criteria:
- Please refer to the 'Attached background material'.
- Statistics:
- Please refer to the Evaluation critieria.
Results and discussion
Test results
- Key result
- Sex:
- male/female
- Genotoxicity:
- negative
- Toxicity:
- no effects
- Vehicle controls validity:
- valid
- Negative controls validity:
- not applicable
- Positive controls validity:
- valid
- Additional information on results:
- RESULTS OF RANGE-FINDING STUDY
Dose Range Finding Test
In the dose range finding test, 5 groups of one male and one female animal received oral doses of Mancozeb 85% Technical ranging from 50 to 2000 mg/kg bw/day at 0 and 24 h. The highest dose was defined as the maximum routine in vivo exposure level normally administered. One animal death occurred following exposure to 800 mg Mancozeb 85% Technical./kg bw. Clinical signs of subdued behaviour, laboured breathing, hunched appearance, piloerection and hypothermia were observed following treatment.
Main Toxicity Test
In the main toxicity test, 3 groups of 3 male and 3 female animals were given 2 daily doses of Mancozeb 85% Technical ranging from 1200 to 2000 mg/kg bw/day. No deaths or adverse reactions occurred following dosing.
Since no clinical signs or deaths occurred in the main toxicity test, it was considered that the one animal death at 800 mg/kg bw/day in the dose range finding test was of an incidental nature and unrelated to treatment with the test material. Based on these toxicity investigations, Mancozeb 85% Technical was judged to be non-toxic at the maximum recommended dose of 2000 mg/kg bw/d.
MICRONUCLEUS TEST
No animal deaths or clinical signs were observed following treatment.
Vehicle Control Group
The numbers of micronucleated bone marrow polychromatic erythrocytes (MN-PCE) in mice dosed with the vehicle, 10 mL maize oil/kg bw/d averaged 0.04 %. This MN-PCE frequency conformed to the established in-house control range for vehicle treated mice of the CD-I strain (=0.00-0. 28 % per 10 mice or 0.00-0.24 % per 5 mice).
Positive Control Group
Exposure of mice to the positive control agent, 50 mg cyclophosphamide/kg bw, induced large increases in bone marrow micronuclei. The mean MN-PCE frequency for the mice was 1.78%. An evident increase in the number of MN-NCE was also observed. Bone marrow toxicity accompanied these findings a shown by a supression of the PCE/NCE ratios.
Test Material Group
There was no indication that Mancozeb 85% Technical induced bone marrow micronuclei in the treated mice. The highest MN-PCE frequency recorded for the test material was in the females where an incidence of 0.08%o was observed. There was also nothing to suggest bone marrow toxicity in the exposed mice.
Any other information on results incl. tables
Table 1 Summary of Assessment Data
Treatment | Time of | Sex | No. of | Erythrocytes | ||||
| Dosing |
| Mice | Normochromatic Cells (NCE) | Polychromatic Cells (PCE) | PCE/NCE | ||
| 00 |
| Assessed | No. ofMN-NCE | PCE Analysed | No. of MN-PCE | % MN-PCE | Mean ± S.D. |
10 mL | 0 + 24 | m | 5 | 1 | 10000 | 4 | 0.04 | 0.88 ±0.10 |
Maize oil/ kg bw/day |
| f | 5 | 6 | 10000 | 3 | 0.03 | 1.08 ± 0.17 |
|
| m+f | 10 | 7 | 20000 | 7 | 0.04 | 0.98 ±0.17 |
2000 mg | 0 + 24 | m | 5 | 4 | 10000 | 7 | 0.07 | 1.07 ±0.16 |
Mancozeb 85% Technical/kg bw/ |
| f | 5 | 6 | 10000 | 8 | 0.08 | 0.93 ±0.13 |
day |
| m+f | 10 | 10 | 20000 | 15 | 0.08 | 1.00±0.16 |
50 mg Cyclophosphamide/kg bw/day | 0 + 24 | m | 5 | 38 <t> | 10000 | 178 a | 1.78 | 0.57 ±0.11 |
PCE = Polychromatic erythrocytes
MN-PCE = Micronucleated PCE
NCE =Normochromatic erythrocytes
MN-NCE = Micronucleated NCE
a = Positive response in PCE
<t>=Evident response in NCE
Applicant's summary and conclusion
- Conclusions:
- Mancozeb 85% Technical did not induce micronuclei in bone marrow cells when tested to the maximum recommended dose of 2000 mg/kg bw/ day in male and female CD-1 mice using a twice (0 h + 24 h) oral dosing and 48 h sampling regimen.
- Executive summary:
The in vivo genotoxic potential of Mancozeb 85% Technical was evaluated in a micronucleus test in bone marrow erythrocytes of young, male and female CD-1 mice following a 0 h and 24 h oral dosing and 48 h sampling regimen at a single dose level.
A toxicity study was undertaken to establish a suitable dose level for the micronucleus test. Based on the findings of the toxicity study, Mancozeb 85% Technical was judged to be non-toxic at the maximum recommended dose of 2000 mg/kg bw/day.
In the micronucleus test, one group of CD-1 mice were therefore dosed at 0 h and 24 h orally with the test material at a concentration of 2000 mg/kg bw/day. Bone marrow samples were taken 48 h after the initial 0 h dose. Two control groups of CD-1 mice were also dosed orally with either the vehicle, 10 mL maize oil/kg bw/day, or the positive control agent, 50 mg cyclophosphamide/kg bw/day. The experimental schedule for the control groups followed that of the test material treated mice.
No micronucleus induction was detected in bone marrow erythrocytes of mice dosed with 2000 mg Mancozeb 85% Technical/kg bw/day.
Animals treated with the vehicle alone showed normal background levels of micronuclei, while animals dosed with cyclophosphamide responded with substantial increases in the numbers of bone marrow micronuclei.
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.
Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.