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EC number: 604-721-7 | CAS number: 150114-71-9
- 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
Toxicity to reproduction: other studies
Administrative data
- Endpoint:
- toxicity to reproduction: other studies
- Type of information:
- experimental study
- Adequacy of study:
- supporting study
- Study period:
- not reported
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 000
- Report date:
- 2000
Materials and methods
Test guideline
- Qualifier:
- no guideline followed
- Principles of method if other than guideline:
- Non-pregnant female rats ("serum donors") received 1000 mg/kg/day of test material via gavage for three consecutive days. Four hours after the last dose the rats were exsanguinated and their blood was centrifuged to obtain serum. Control rats were similarly gavaged with vehicle and bled. Rat conceptuses from a separate group of untreated, timed-pregnant rats were explanted on the afternoon of gestation day 9 and were cultured in the sera (100 %) from the control or test material serum donors. After approximately 42 hours in culture, embryos were evaluated for viability, growth and morphology.
- GLP compliance:
- no
- Type of method:
- other: ex vivo
Test material
- Reference substance name:
- 4-amino-3,6-dichloropyridine-2-carboxylic acid
- EC Number:
- 604-721-7
- Cas Number:
- 150114-71-9
- Molecular formula:
- C6H4Cl2N2O2
- IUPAC Name:
- 4-amino-3,6-dichloropyridine-2-carboxylic acid
- Test material form:
- solid: particulate/powder
- Details on test material:
- - Appearance: tan powder
Constituent 1
- Specific details on test material used for the study:
- Purity: 95.4%
Test animals
- Species:
- rat
- Strain:
- other: Crl:CD
- Sex:
- female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Strain: CD (Crl:CD (SD) IGS BR)
- Age at study initiation: 9 - 10 weeks (serum donors and embryo donors)
- Weight at study initiation: 200 - 250 g (non-pregnant serum doors and time-mated embryo donors)
- Housing: Animals were individually housed in stainless steel cages with wire-mesh floors that were suspended above catch pans and contained a feed crock and pressure activated nipple-type watering system.
- Diet: ad libitum
- Water: municipal water, ad libitum
- Acclimation period: at least 7 days
ENVIRONMENTAL CONDITIONS
- Temperature: 22 ± 3 °C
- Humidity: 40 - 70 % (relative)
- Air changes: 12 - 15 air changes per hour
- Photoperiod: 12 hours of darkness / 12 hours of light (06:00 to 18:00)
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 0.5 % METHOCEL® A4M
- Details on exposure:
- DOSE PREPARATION
The test material was administered as a suspension in an aqueous vehicle of 0.5 % METHOCEL® A4M such that a dose volume of 4 mL/kg body weight yielded the targeted dose. Dose volumes were adjusted daily based on individual body weights of the serum donors. - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- Test material was administered via gavage to the non-pregnant serum donor rats for three consecutive days (test days 1 - 3).
- Frequency of treatment:
- Daily
- Duration of test:
- Approximately four hours after the last dose on test day 3, the rats were sacrificed via carbon dioxide inhalation and immediately exsanguinated
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (nominal)
- Dose / conc.:
- 1 000 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 7 females per group
- Control animals:
- yes
- Details on study design:
- - Dose selection rationale: The dose level of test material was selected based on findings from an existing rat oral acute toxicity study. Furthermore, the dose level of 1000 mg/kg/day represents a limit dose as defined in the Health Effects Test Guideline of the United States Environmental Protection Agency (OPPTS 870.3700 Prenatal Developmental Toxicity Study).
- Rationale for animal assignment: Randomisation of the serum donor rats into dose groups was performed one day prior to the start of dosing (test day -1) using a computer generated procedure designed to increase the probability of uniform group mean weights and standard deviations at the start of exposure. The embryo donor rats were not dosed. Therefore, they were not randomised into groups nor were they individually identified. - Statistics:
- Descriptive statistics were reported (i.e., mean ± SD) for all continuous data. Continuous data (embryo head length, crown-rump length, yolk sac diameter, somite counts and body weight gains from test day 1-3) were analysed by ANOVA. Flexion score was analysed by a non-parametric ANOVA. Percentage data (% viable, % with yolk sac circulation, % abnormal embryos, % embryos with generalised delay) were analysed via Fisher’s exact test.
Results and discussion
Effect levels
- Key result
- Dose descriptor:
- NOEL
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Basis for effect level:
- other: no test substance related effects at the highesst dose level
Any other information on results incl. tables
Serum Donors
All serum donors appeared normal throughout the test period. Body weight gains in the test material treated rats were not significantly different from those of the control rats
Embryo Culture
There were no apparent differences between embryos cultured in test material serum vs. control serum for any parameter of embryo viability, growth or morphology. The only morphological abnormalities noted among the 14 control embryos were two embryos with an open neural tube. The other structures in these embryos exhibited generalised delay. Among the 15 embryos in the test material group, a single embryo exhibited generalised delay, but its pattern of development was otherwise normal.
Table 1: Results
Control |
1000 mg/kg/day |
|
Serum donors |
||
No. of serum donors |
7 |
7 |
No. deaths |
0 |
0 |
Body weight change test day 1-3 (g) |
-0.8 ± 6.6 |
-1.8 ± 8.4 |
Embryo viability |
||
No. embryos cultures |
14 |
15 |
% embryos with beating heart |
100 |
100 |
% embryos with yolk sac circulation |
100 |
100 |
Embryo growth |
||
Yolk sac diameter (mm) |
3.4 ± 0.4 |
3.6 ± 0.2 |
Crown-rump length (mm) |
2.9 ± 0.3 |
3.0 ± 0.2 |
Head length (mm) |
1.5 ± 0.1 |
1.5 ± 0.1 |
Somite number |
19.9 ± 5.5 |
21.8 ± 3.4 |
Flexion score (0-3) |
2.0 ± 1.0 |
2.2 ± 0.8 |
Morphology |
||
% embryos with abnormalities |
14.3 (2/14) |
0 (0/15) |
% embryos with generalised delay |
14.3 (2/14) |
6.7 (1/15) |
Applicant's summary and conclusion
- Conclusions:
- Based on the findings, the test material was considered negative for teratogenic potential in this screening test.
- Executive summary:
The test material was evaluated for preliminary teratogenicity screening in the ex vivo whole embryo culture test. Seven non-pregnant female rats ("serum donors") received 1000 mg/kg/day of test material via gavage for three consecutive days. Four hours after the last dose the rats were exsanguinated and their blood was centrifuged to obtain serum. Seven control rats were similarly gavaged with 0.5 % methylcellulose vehicle and bled. Rat conceptuses from a separate group of untreated, timed-pregnant rats were explanted on the afternoon of gestation day 9 and were cultured in the sera (100 %) from the control or test material serum donors. After approximately 42 hours in culture, embryos were evaluated for viability, growth and morphology.
All serum donors appeared normal throughout the test period. Body weight gains in the test material treated rats were not significantly different from those of the control rats. There were no apparent differences between embryos cultured in test material serum vs. control serum for any parameter of embryo viability, growth or morphology.
Based on these findings, the test material was considered negative for teratogenic potential in this screening test.
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