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EC number: 231-835-0 | CAS number: 7758-16-9
- 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
Administrative data
- Endpoint:
- screening for reproductive / developmental toxicity
- Data waiving:
- study scientifically not necessary / other information available
- Justification for data waiving:
- the study does not need to be conducted because a pre-natal developmental toxicity study is available
Cross-reference
- Reason / purpose for cross-reference:
- data waiving: supporting information
Reference
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- No data
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- study well documented, meets generally accepted scientific principles, acceptable for assessment
- Remarks:
- Meets generally accepted scientific standards with acceptable restrictions. Deficiencies: Food consumption not reported Uterine weights not determined Test substance identification (Batch etc) missing No details on housing conditions/source of animals Administration only during periods of organogenesis, not until day before pregnancy
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- other: no data
- Deviations:
- not specified
- Principles of method if other than guideline:
- Adult female Dutch-belted rabbits were dosed on Day 0 with a single injection of 0.4 mL human chorionic gonadotropin (400 IU) via the marginal ear vein. After three hours each doe was artificially inseminated with 0.3 mL diluted semen from a donor buck using 20 x 10E06 motile sperm. Dosing by oral intubation with a control (Vehicle at level equivalent to group receiving the highest dose) or test article in a water suspension at 1.28, 5.95, 27.6 and 128.0 mg/kg was carried out daily on Days 6 to 18 of gestation. The positive control 6-aminonicotinamide at 2.5 mg/kg was dosed on Day 9. Observations of body weight, appearence, behaviour, and food consumption were performed. On Day 29 all does underwent Caesarean section. Number of corpora lutea, implantation sites, resorption sites and live/dead foetuses recorded. Body weights of live pups recorded. Urogenital tract of each dam examined for anatomical normality. All foetuses examined grossly for presence of external congenital abnormalities. Live foetuses of each litter were then placed in an incubator for 24 hours for evaluation of neonatal survival. All pups underwent detailed visceral examination. All foetuses were cleared in potassium hydroxide, stained with alizarin red S dye and examined for skeletal defects.
- GLP compliance:
- no
- Remarks:
- Study predates GLP
- Limit test:
- no
- Species:
- rabbit
- Strain:
- Dutch
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Outbred
- Age at study initiation: No data
- Weight at study initiation: 2.17 - 2.51 kg
- Fasting period before study: No data
- Housing: Individually housed in mesh-bottomed cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: No data
ENVIRONMENTAL CONDITIONS
- Temperature (°C): No data
- Humidity (%): No data
IN-LIFE DATES: No data - Route of administration:
- oral: gavage
- Vehicle:
- water
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
VEHICLE: Water
- Amount of vehicle (if gavage): 1 mL/kg bw at doses equal to or below 250 mg/kg bw and 2 mL/kg at doses up to 500 mg/kg bw - Analytical verification of doses or concentrations:
- not specified
- Details on mating procedure:
- - Impregnation procedure: artificial insemination
- Proof of pregnancy: No data - Duration of treatment / exposure:
- 13 days (Day 6 to Day 18 of gestation)
- Frequency of treatment:
- Daily
- Duration of test:
- 29 days
- No. of animals per sex per dose:
- Table 1 Number of animals dosed
Material Dose (mg/kg) Total
Mated Pregnant
Sham 0.0 17 11
6-AN 2.5 15 10
FDA 71-61 1.28 15 12
5.95 16 12
27.6 20 9
128.0 15 11 - Control animals:
- yes, sham-exposed
- other: positive control: 2.5 mg/kg 6-aminonicotinamide (6-AN)
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Appearence, behaviour, food consumption and weight observed daily.
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: Body weights recorded on days 0, 6, 12, 18 and 29.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 29
- Organs examined: uterus and urogenital tract - Ovaries and uterine content:
- The ovaries and uterine content was examined after termination: Yes
Examinations included:
- Gravid uterus weight: No
- Number of corpora lutea: Yes
- Number of implantations: Yes
- Number of resorptions: Yes - Fetal examinations:
- - External examinations: Yes
- Soft tissue examinations: Yes
- Skeletal examinations: Yes
- Head examinations: Yes - Statistics:
- No data
- Indices:
- No data
- Historical control data:
- No
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
- Dose descriptor:
- NOAEL
- Effect level:
- > 128 mg/kg bw/day
- Based on:
- test mat.
- Basis for effect level:
- other: no effects observed
- Abnormalities:
- no effects observed
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
No dose related response observed. - Dose descriptor:
- NOAEL
- Effect level:
- > 128 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed
- Abnormalities:
- no effects observed
- Developmental effects observed:
- no
- Conclusions:
- Under the conditions of the study, the test material administered to pregnant rabbits for 13 days up to a dose level of 128 mg/kg bw showed no maternal or developmental toxicity. The NOAEL for both maternal and fetotoxicity is > 128 mg/kg bw.
Table 2 Reproduction data
Dose (mg/kg) |
Sham |
6-AN |
1.28 |
5.95 |
27.6 |
128.0 |
Pregnancies |
|
|
|
|
|
|
Total No. |
11 |
10 |
12 |
12 |
9 |
11 |
Died or aborted (before Day 29) |
1 |
0 |
0 |
2 |
0 |
0 |
To term (on Day 29) |
10 |
10 |
12 |
10 |
9 |
11 |
Corpora Lutea |
|
|
|
|
|
|
Total no. |
175 |
132 |
146 |
191 |
140 |
159 |
Average/dam mated |
14.6 |
12.0 |
12.2 |
13.6 |
9.33 |
12.2 |
Live litters |
|
|
|
|
|
|
Total No.* |
10 |
6 |
12 |
9 |
9 |
11 |
Implant Sites |
|
|
|
|
|
|
Total No. |
53 |
42 |
70 |
64 |
44 |
80 |
Average/dam* |
5.30 |
4.20 |
5.83 |
6.40 |
4.89 |
7.27 |
Resorptions |
|
|
|
|
|
|
Total No* |
-- |
18 |
3 |
9 |
1 |
7 |
Dams with 1 or more sites resorbed |
-- |
6 |
2 |
3 |
1 |
5 |
Dams with all sites resorbed |
-- |
4 |
-- |
1 |
-- |
-- |
Per cent partial resorptions |
-- |
60.0 |
16.7 |
30.0 |
11.1 |
45.5 |
Per cent complete resorptions |
-- |
40.0 |
-- |
10.0 |
-- |
-- |
Live foetuses |
|
|
|
|
|
|
Total No |
52 |
19 |
67 |
55 |
43 |
73 |
Average/dam* |
5.20 |
1.90 |
5.58 |
5.50 |
4.78 |
6.64 |
Sex ratio (M/F) |
0.73 |
5.00 |
0.63 |
1.04 |
1.26 |
0.92 |
Dead Foetuses |
|
|
|
|
|
|
Total No.* |
1 |
5 |
-- |
-- |
-- |
73 |
Dams with 1 or more dead |
1 |
2 |
-- |
-- |
-- |
-- |
Dams with all dead |
-- |
-- |
- |
-- |
-- |
-- |
Per cent partial dead |
10.0 |
20.0 |
-- |
-- |
-- |
-- |
Per cent all dead |
-- |
-- |
-- |
-- |
-- |
-- |
Average foetus weight (g) |
42.2 |
29.7 |
37.0 |
36.0 |
40.0 |
35.8 |
* Includes only those dams examined at term
** Positive control: 2.5 mg/kg 6-AN dosed on Day 9
Table 3 Summary of skeletal findings
Findings |
Dose (mg/kg) |
|||||
Sham |
6-AN |
1.28 |
5.95 |
27.6 |
128.0 |
|
Live foetuses examined (at term) |
52/10 |
19/6 |
67/12 |
55/9 |
43/9 |
72/11a |
Sternebrae |
|
|
|
|
|
|
Incomplete oss. |
2/2 |
1/1 |
|
1/1 |
2/2 |
|
Scrambled |
|
|
|
|
|
|
Bipartite |
|
1/1 |
|
1/1 |
|
1/1 |
Fused |
|
3/2 |
|
|
|
|
Extra |
|
1/1 |
2/1 |
|
|
6/4 |
Missing |
|
2/2 |
|
|
|
|
Other |
|
|
|
|
|
|
Ribs |
|
|
|
|
|
|
Incomplete oss. |
|
|
|
|
|
|
Fused/split |
|
5/2 |
|
|
3/1 |
|
Wavy |
|
|
|
|
|
|
Less than 12 |
|
|
|
|
|
|
More than 13 |
|
|
|
|
|
|
Other |
|
|
|
|
|
|
Vertebrae |
|
|
|
|
|
|
Incomplete oss. |
|
|
|
|
|
|
Scrambled |
|
4/2 |
|
|
|
|
Fused |
|
|
|
|
|
|
Extra ctrs. oss. |
|
|
|
|
|
|
Scoliosis |
|
4/3 |
|
|
|
|
Tail defects |
|
13/4 |
|
|
1/1 |
1/1 |
Other |
|
|
|
|
|
|
Skull |
|
|
|
|
|
|
Incomplete closure |
|
1/1 |
|
|
|
|
Missing |
|
|
|
|
|
|
Craniostosis |
|
|
|
|
|
|
Other; facial bones, inc |
|
1/1 |
|
|
|
|
Extremities |
|
|
|
|
|
|
Incomplete oss. |
|
|
|
|
|
|
Missing |
|
|
|
|
|
|
Extra |
|
|
|
|
|
|
Miscellaneous |
|
|
|
|
|
|
* Numerator = Number of foetuses affected; Denominator = Number of litters affected
** Positive control: 2.5 mg/kg 6-AN dosed on Day 9
a One pup lost in processing
Table 4 Summary of soft tissue abnormalities
Material |
Dose level (mg/kg) |
Dam |
Number of pups |
Description |
6-AN |
2.5 |
Z 6479 |
1 |
Medial rotation of hind limbs |
|
|
Z 6488 |
1 |
Medial rotation of hind limbs |
|
|
Z 6489 |
1 |
Siamese pups (combined stomach and head) |
|
|
Z 6490 |
3 |
Anopia, Medial rotation of hind limbs |
|
|
|
2 |
Anopia |
FDA 71-61 |
27.6 |
M 6051 |
2 |
Anopia |
Data source
Materials and methods
Results and discussion
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Applicant's summary and conclusion
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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