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EC number: 439-590-3 | CAS number: 12158-75-7
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Link to relevant study records
- Endpoint:
- two-generation reproductive toxicity
- Remarks:
- based on test type (migrated information)
- Type of information:
- migrated information: read-across from supporting substance (structural analogue or surrogate)
- Adequacy of study:
- weight of evidence
- Study period:
- March 4, 2004 to November 14, 2004
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- Free ionic copper is considered the active ingredient in inorganic copper salts, and is believed to be responsible for adverse effects. The bioavailablity of the copper ion at target sites determines the severity of effects. Read-across from copper sulfate is a conservative approach based on differences in water solubility. Copper sulfate is more water soluble than copper hydroxide nitrate, and therefore the bioavailablity of the copper ion from copper hydroxide nitrate is less that from copper sulfate.
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3800 (Reproduction and Fertility Effects)
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- Animal rooms were maintained at an acceptable temperature of 18-26ºC (targeted at 22º-24ºC) and maintained at an acceptable relative humidity of 30%-70% (targeted at 40%- 60%). Occasional excursions outside the accepted ranges were minor and did not affect the study. Animal rooms were artificially illuminated (fluorescent light) on a 12-hour light/dark cycle (approximately 0600-1800 hours).
- Route of administration:
- oral: feed
- Vehicle:
- unchanged (no vehicle)
- Details on exposure:
- Diet Preparation:
The test substance was pulverized using a mortar and pestle, under a nitrogen blanket. A small amount of rodent diet was then added to the test substance. This test substance/rodent diet premix was added to the remaining rodent diet in the mixer and mixed for 6 minutes. The rodent diet used for the control group was also mixed for 6 minutes in the diet mixer. Neither the amount nor nature of the contaminants in the feed was expected to affect the integrity or validity of the study. Diets were prepared weekly and refrigerated until used. Details of diet preparation are documented in study records.
Administration:
The test substance was administered orally as it is a potential route for human exposure. During the test period, rats in each group was fed a diet of PMI Nutrition International, Inc. Certified Rodent LabDiet® 5002 that contained the test substance at the concentrations specified in the
experimental design. - Details on mating procedure:
- Following at least 70 days of diet administration (premating), the P1 and F1 generation males and females were co-housed within their respective
treatment groups to produce F1 and F2 litters, respectively. Dams were allowed to deliver and rear their offspring until weaning (postpartum day 21). At weaning, 30 F1 rats/sex/group were randomly selected to comprise the F1 generation and were given the same dietary concentration level as their respective P1 generation sires and dams. F1 and F2 litters were culled to 4 pups/sex/litter (litter size permitting) on postnatal day 4; all remaining pups were discarded without further evaluation. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- The concentration verification data indicate that the test substance was present at the targeted levels during the study. Based on this information, it can be concluded that the animals received the targeted dietary concentrations of test material during the study. The mean concentration of
copper in the control diet was 13.7 ppm. The range of targeted concentrations added to the diet was 25 - 382 ppm (equivalent to 100 – 1500 ppm copper sulfate). - Duration of treatment / exposure:
- Approximate age at start of dosing:
P1 generation: 56 days
F1 generation: 21
Approximate number of study days before mating:
P1 generation: 70 days (at least)
F1 generation: 70 days (at least)
Duration of dosing:
until sacrifice - Frequency of treatment:
- daily
- Details on study schedule:
- Sacrifice schedule:
Adult males: P1 = test days 109-113 and F1 = test day 119
Pregnant females: P1, F1 = on day of weaning litters (day 21 postpartum)
Non-pregnant females: P1, F1 = approximately day 28 after the end of cohabitation
Culled pups: F1, F2 = day 4 postpartum
Weanlings: F1, F2 = on day of weaning (except F1 rats selected as parental rats) - Remarks:
- Doses / Concentrations:
10, 10, 500, 1000, 1500 ppm
Basis:
other: in feed - No. of animals per sex per dose:
- 10 rats per sex per dose
- Control animals:
- yes, concurrent no treatment
- Parental animals: Observations and examinations:
- Clinical observations, body weight, and food consumption were determined weekly thoughout the study.
- Oestrous cyclicity (parental animals):
- Estrous cycle parameters (percent days in diestrus, proestrus and estrus) and estrous cycle length were evaluated for 3 weeks prior to cohabitation in P1 and F1 rats.
- Sperm parameters (parental animals):
- Sperm motility, morphology and concentration in the cauda epididymis and spermatid concentration in the testis were determined.
- Litter observations:
- Litter examinations including number of live and dead, individual pup weights, clinical observations) were determined at birth, on day 4 and weekly during the lactation period.
- Postmortem examinations (parental animals):
- All P1 and F1 generation rats that were not found dead, were sacrificed by carbon dioxide euthanasia and exsanguination. All P1 and F1 rats received a gross pathological examination.
The uteri of all cohabited females were examined for the presence and number of implantation sites.
Blood (approximately 2 mL) was collected from the caudal vena cava from the first 10 rats (the first 10 consecutive animal numbers in each group) surviving to scheduled sacrifice in each of Copper Sulfate Pentahydrate: Multigeneration Reproduction Study in Rats DuPont-14226- 28 - the P1 and F1 male and female groups. Scheduled sacrifice for these rats was in the morning (to optimize copper content in the blood samples). Blood samples were placed into EDTA tubes, processed to plasma, and frozen at approximately -80°C.
Tissues were collected from all P1 and F1 adult animals and preserved in appropriate fixative for possible future histopathological examination. - Postmortem examinations (offspring):
- Pups were euthanized by decapitation (for pups up to lactation day 4) or by carbon dioxide euthanasia and exsanguination. Pups that died (found dead, sacrificed in extremis, or accidentally killed) during the lactation period underwent a gross pathological evaluation and the carcass was preserved in an appropriate fixative.
At culling on lactation day 4, twelve randomly selected pups (6 male and 6 female) per dose group had samples of liver and brain collected, frozen in liquid nitrogen and stored at approximately -80°C. - Statistics:
- Parameters : body weight, body weight gain, food consumption, food efficiency, gestation length, implantation site numbers, implantation efficiency, mean number of pups per litter, percent born alive, 0-4 day viability, viability index, lactation index, precoital interval, vaginal patency, preputial separation, estrous cycle parameters, sperm parameters, ovarian follicle counts, organ weight
Preliminary test: Levene’s test for homogeneity and Shapiro-Wilk test for normality
If preliminary test is not significant: One-way analysis of variance and Dunnett's test
If preliminary test is significant: Kruskal-Wallis test and Dunn's test
Parameters: incidence of clinical observations, mating index, fertility index, gestation index, litter survival
Preliminary test: none
If preliminary test is not significant or significant: Cochran-Armitage test for trend
Parameters: sex ratio (covariate: litter size), mean pup weights (covariates: litter size)
Preliminary test: Levene’s test for homogeneity and Shapiro-Wilk test for normality
If preliminary test is not significant: Analysis of covariance and Dunnett-Hsu
If preliminary test is significant: Non-parametric analysis of covariance - Reproductive indices:
- Calculated for P1 and F1 parental animals: mating index(%), fertility index (%), gestation index (%), implantation efficiency (%), pups born alive (%), viability index (%), lactatio index (%), litter survival (%).
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- decreased spleen weight in P1 adult females
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- decreased spleen weight in P1 adult females
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- not examined
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOEL
- Remarks:
- reproductive toxicity
- Effect level:
- 1 500 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Highest concentration tested
- Remarks on result:
- other: Generation: P1, F1, F2 (migrated information)
- Dose descriptor:
- NOEL
- Remarks:
- lactation
- Effect level:
- 1 000 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Decreased spleen weight in P1 adult females, and F1 and F2 male and female weanlings.
- Remarks on result:
- other: Generation: P1 adult females, F1 and F2 male and female weanlings (migrated information)
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- decreased spleen wieight in F1 and F2 male and female weanlings
- Sexual maturation:
- no effects observed
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- decreased spleen wieight in F1 and F2 male and female weanlings
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not specified
- Reproductive effects observed:
- not specified
- Conclusions:
- Under the conditions of this study, the no-observed-effect level (NOEL) for reproductive toxicity was 1500 ppm of Copper sulfate pentahydrate, the highest concentration tested. The NOEL for P1 and F1 rats and F1 and F2 offspring during lactation was 1000 ppm of Copper sulfate pentahydrate, based on reduced spleen weight in P1 adult females, and F1 and F2 male and female weanlings at 1500 ppm of Copper sulfate pentahydrate. The dietary concentration of 1000 ppm of Copper sulfate pentahydrate was equivalent to mean daily intakes of Copper of 15.2-23.5 mg/kg body weight/day for male rats during premating and 17.0-26.7 mg/kg body weight/day for female rats during premating and gestation.
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- Study duration:
- chronic
- Species:
- rat
- Quality of whole database:
- Klimish score = 1
Additional information
A two-generation reproduction study was conducted with Copper sulfate pentahydrate. Read-across was applied based on the fact that free ionic copper is considered the active ingredient in inorganic copper salts, and is believed to be responsible for adverse effects. The bioavailablity of the copper ion at target sites determines the severity of effects. Read-across from copper sulfate is a conservative approach based on differences in water solubility. Copper sulfate is more water soluble than copper hydroxide nitrate, and therefore the bioavailablity of the copper ion from copper hydroxide nitrate is less that from copper sulfate.
Under the conditions of this study, the no-observed-effect level (NOEL) for reproductive toxicity was 1500 ppm of Copper sulfate pentahydrate, the highest concentration tested. The NOEL for P1 and F1 rats and F1 and F2 offspring during lactation was 1000 ppm of Copper sulfate pentahydrate, based on reduced spleen weight in P1 adult females, and F1 and F2 male and female weanlings at 1500 ppm of Copper sulfate pentahydrate. The dietary concentration of 1000 ppm of Copper sulfate pentahydrate was equivalent to mean daily intakes of Copper of 15.2-23.5 mg/kg body weight/day for male rats during premating and 17.0-26.7 mg/kg body weight/day for female rats during premating and gestation.
Justification for selection of Effect on fertility via oral route:
NOAEL = 1500 ppm Copper sulfate tetrahydrate
Effects on developmental toxicity
Link to relevant study records
- Endpoint:
- developmental toxicity
- Data waiving:
- other justification
- Justification for data waiving:
- other:
- Abnormalities:
- not specified
- Developmental effects observed:
- not specified
Reference
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
Additional information
Testing was considered unnecessary based on the following information:
(1) There is evidence of low toxicological activity as shown in the submitted study Two Generation Reproduction Study, Copper sulfate pentahydrate, Mylchreest et al., 2005. The no-observed-effect level (NOEL) for reproductive toxicity was 1500 ppm, the highest concentration tested.
(2) This substance is highly insoluble in water, and as such would be poorly absorbed.
(3) There is no significant human exposure as evidenced by submitted exposure scenarios – Workers: Closed systems, automatic dust removal, local exhaust ventilation, safe work practices, and personal protective equipment. Consumers: No contact between consumers and this substance during normal use.
Justification for classification or non-classification
No classification required based on 2-generation reproduction study conducted on Copper sulfate pentahydrate.
Additional information
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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