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EC number: 619-447-3 | CAS number: 99607-70-2
- 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

Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 15 September 1987 – 31 January 1988
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: see 'Remark'
- Remarks:
- GLP study compliant with test guidelines of the time. However, current guidelines for prenatal developmental toxicity require an extended dosing period - from implantation to termination. Available as unpublished report, fully adequate for assessment.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 989
- Report date:
- 1989
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- 1981 (current guideline adopted 2001)
- Deviations:
- yes
- Remarks:
- does not meet current guideline specification
- Qualifier:
- according to guideline
- Guideline:
- EPA OPP 83-3 (Prenatal Developmental Toxicity Study)
- Version / remarks:
- 1982 (current guideline adopted 1998)
- Deviations:
- yes
- Remarks:
- does not meet current guideline specification
- Principles of method if other than guideline:
- Not applicable
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- heptan-2-yl [(5-chloroquinolin-8-yl)oxy]acetate
- EC Number:
- 619-447-3
- Cas Number:
- 99607-70-2
- Molecular formula:
- C18H22ClNO3
- IUPAC Name:
- heptan-2-yl [(5-chloroquinolin-8-yl)oxy]acetate
- Details on test material:
- - Name of test material (as cited in study report): CGA185072 technical
- Analytical purity: 91.6%
Constituent 1
Test animals
- Species:
- rat
- Strain:
- other: strain Tif:RAIf (SPF), hybrids of RII/1 x RII/2
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Age at study initiation: about 2 months
- Weight at study initiation: 200-203 g
- Housing: Individually in standard macrolon cages with wire mesh tops and granulated soft wood bedding material
- Diet: pelleted, certified standard diet (Nafag No. 890 Tox) ad libitum
- Water: tap water in plastic bottles ad libitum
- Acclimatisation: between mating and start of dosing
ENVIRONMENTAL CONDITIONS
- Temperature: 21±2°C
- Humidity: 55±10%
- Air changes (per hr): 16
- Photoperiod: 12 hrs dark / 12 hrs light
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- peanut oil
- Remarks:
- arachidis oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Made on 2 occasions (for dosing September 21-October 6 and for October 7 & 8). The test substance was mixed with the vehicle in a grinder using glass beads and a low speed rotor, portioned for each dosing day and refrigerated until use. Homogeneity was maintained using a magnetic stirrer. Doses were adjusted daily for body weight. Dose volume was 5 mL/kg body weight. The dosing solutions contained 0, 2, 20 or 80 mg/mL CGA185072 tech.
VEHICLE
- arachidis oil, PHHVI (Siegfried AG, Zofingen, Switzerland) - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Achieved concentration was determined for both batches. Homogeneity and chemical stability were confirmed.
The achieved concentrations varied: 67.9-80% low dose; 90.7-95.9% mid dose and 83.1-99.6% high dose. Values were considered to be within acceptable limits. - Details on mating procedure:
- Nulliparous females were mated overnight with males of the same strain and of proven fertility; 3 females were housed with 1 male. Successful mating was confirmed by a vaginal plug or by spermatozoa in a vaginal smear and was defined as day 0 of pregnancy.
- Duration of treatment / exposure:
- Pregnancy days 6 - 15 inclusive
- Frequency of treatment:
- Once daily
- Duration of test:
- Pregnancy days 0 - 21; termination on day 21
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 10, 100, 400 mg/kg bw/day
Basis:
nominal conc.
- No. of animals per sex per dose:
- 24 mated females
- Control animals:
- yes, concurrent vehicle
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily
BODY WEIGHT: Yes
- Time schedule for examinations: daily
FOOD CONSUMPTION: Yes
- Time schedule: days 6, 11, 16 and 21
WATER CONSUMPTION: Not measured, visually assessed
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 21
- Macroscopic examination: main organs of the thoracic and abdominal cavities - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: Yes
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of early resorptions: Yes
- Number of late resorptions: Yes
- Other: abortion sites and dead foetuses. Uteri without visible signs of implantation were stained with ammonium sulphide to confirm pregnancy status. - Fetal examinations:
- - Body weight and sex: Yes: all per litter
- External examinations: Yes: all per litter
- Soft tissue examinations: Yes: one third of each litter. Examination of fixed foetus by slicing technique of Wilson - head and body.
- Skeletal examinations: Yes: two thirds of each litter. Examination following staining of the skeleton with Alizarin red S
- Classification of foetal observations: Yes - Statistics:
- Standard methods were applied for statistical analysis. Continuous data were analysed using student’s t-test, foetal observations were analysed using the Chi square test.
- Indices:
- Pre- and post-implantation losses
- Historical control data:
- Yes
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Details on maternal toxic effects:
400 mg/kg bw/day: increased water consumption, increased wet bedding, odorous urine; reduced body weight gain (3-7% from day 9-21); reduced food consumption days 6-11 and 11-16. No effects seen at lower dose levels.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- 100 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Details on embryotoxic / teratogenic effects:
400 mg/kg bw/day: reduced foetal body weight. No effect at lower dose levels. No increase in incidence of external, visceral or skeletal malformations or anomalies due to test substance. There was some indication of a delay in ossification although the incidence of foetuses affected overall was not statistically significant. There was no evidence of teratogenicity at any dose level.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- 400 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: teratogenicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Table 1 Group Mean Maternal Body Weight Change (g) During Gestation
Days |
Dose level (mg/kg bw/day) |
|||
0 |
10 |
100 |
400 |
|
0-6 |
33 |
32 |
32 |
31 |
6-11 |
30 |
30 |
28 |
22** |
11-16 |
42 |
45 |
43 |
31** |
16-21 |
70 |
70 |
73 |
67 |
0-21 |
176 |
176 |
176 |
150** |
6-21 |
142 |
144 |
144 |
119** |
6-16 |
72 |
74 |
71 |
52** |
P<0.01 ** statistically significant difference from control
Table 2 Group Mean Litter data
|
Dose level (mg/kg bw/day) |
|||
0 |
10 |
100 |
400 |
|
No. pregnant females |
24 |
24 |
22 |
24 |
No. corpora lutea |
17.0 |
18.2 |
18.0 |
18.7 |
No. implantations |
15.1 |
15.2 |
15.4 |
15.4 |
% pre-implantation loss |
11.7 |
17.0 |
14.5 |
16.9 |
% post-implantation loss |
3.8 |
3.3 |
3.9 |
7.1 |
No. live foetuses |
14.5 |
14.7 |
14.8 |
14.4 |
% males |
48.0 |
48.3 |
49.8 |
47.0 |
Foetal weight (g) |
5.6 |
5.6 |
5.6 |
5.1** |
P<0.01 ** statistically significant difference from control
Table 3 Group Mean Foetal Observations
|
Dose level (mg/kg bw/day) |
|||
0 |
10 |
100 |
400 |
|
No. litters examined |
24 |
24 |
22 |
24 |
No. foetuses examined – external malformations |
348 |
352 |
325 |
345 |
No. foetuses with external malformations |
7 |
0 |
0 |
1* |
No. foetuses examined – visceral malformations |
110 |
119 |
110 |
115 |
No. foetuses with visceral malformations |
0 |
0 |
0 |
1 |
No. foetuses with visceral anomalies |
0 |
0 |
0 |
1 |
No. foetuses examined – skeletal malformations |
238 |
233 |
215 |
230 |
No. foetuses with skeletal anomalies |
12 |
10 |
4 |
6 |
P<0.05 * statistically significant difference from control
Applicant's summary and conclusion
- Conclusions:
- A dose level of 400 mg CGA185072/kg bw was toxic to the pregnant female and resulted in lower mean foetal weight. There was no increase in incidence of external, visceral or skeletal malformations or anomalies due to the test substance and no evidence of teratogenicity. The NOAEL for maternal and developmental toxicity was 100 mg/kg bw/day.
- Executive summary:
A dose level of 400 mg CGA185072/kg bw was toxic to the pregnant female resulting in increased water consumption, increased wet bedding and odorous urine, reduced body weight and reduced food consumption. Lower mean foetal weight was seen in the presence of this maternal toxicity but there was no increase in incidence of external, visceral or skeletal malformations or anomalies. There was no evidence of teratogenicity at any dose level of CGA185072.
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