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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 406-080-7 | CAS number: 83016-70-0 JEFFCAT ZF-10; TEXACAT ZF-10
- 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:
- 1985
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Non GLP, and animals were only treated from gestation days 6-18. However, study was well documented, sufficient number of animals and doses were employed, and a vehicle and untreated control group were included.
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 985
- Report date:
- 1985
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 986
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- treatment period limited to gestation day 6-18
- GLP compliance:
- no
- Limit test:
- no
Test material
- Test material form:
- liquid
Constituent 1
- Specific details on test material used for the study:
- - Name of test material (as cited in study report): NIAX Catalyst A-99, (bis(2-dimethylaminoethyl)ether)
- Physical state: transparent, yellowish, non-viscous liquid
- Analytical purity: 98.7 %
- Lot/batch No.: 897066
- Impurities (identity and concentrations): 0.723 % 2(2-dimethylaminoethoxy) ethanol, and the rest water
Test animals
- Species:
- rabbit
- Strain:
- New Zealand White
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Hazleton Dutchland Laboratories, Inc., Denver, PA
- Age at study initiation: 5-5.5 months
- Weight at study initiation: 3-3.5 kg
- Housing: Animals were individually housed in stainless steel wire-mesh cages (46 cm x 61 cm x 36 cm high)
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: at least 2 weeks
ENVIRONMENTAL CONDITIONS
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: September 22, 1984 To: October 19, 1984
Administration / exposure
- Route of administration:
- dermal
- Vehicle:
- other: distilled water
- Details on exposure:
- TEST SITE
- Area of exposure: a 3x3 inch area on the mid dorsum
- Type of wrap if used: After application a 3x3 inch, 12-ply, sterile gauze was applied over the dosing site. The gauze was held in place by two strips (approximately 8 inches long) of 3-inch wide, elastic adhesive tape.
- Time intervals for shavings or clipplings: A 3x3 inch area on the mid dorsum of all dosed female rabbits was clipped and shaved one to two days prior to treatment initiation (gestation day 4 or 5) and any time throughout treatment as deemed necessary due to rapid hair growth.
REMOVAL OF TEST SUBSTANCE
- Washing (if done): The application site was wiped gently with a gauze strip dampened with warm water and blotted dry with a disposable wiper.
- Time after start of exposure: 6 hours
TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 1 ml of test substance in vehicle
- Concentration (if solution): 1, 5 or 10 %
- Constant volume or concentration used: yes
VEHICLE
- Amount(s) applied (volume or weight with unit): 1 ml
USE OF RESTRAINERS FOR PREVENTING INGESTION: yes - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analyses of the dosing formulations for stability and test substance content (pre-and post-doing) were provided by Dr. R.A. Budnik, Union Carbide Corporation, Research and Development, Silicones and Urethane Intermediates Division, Tarrytown, NY. The weight % test substance values were determined by potentiometric titration. The volume % values were calculated from the weight % using a density of 0.8492 g/cc for the test substance.
The analysis of dosing formulations prepared on September 10, 1984 indicated that all formulations were within 99.8-104.0 % of target prior to dosing period. According to the Sponsor, aqueous formulations were stable for at least several months in stoppered containers at ambient temperate. The post dosing analysis indicated the formulations were within 93-96.2 % of target. - Details on mating procedure:
- - Impregnation procedure: cohoused
- If cohoused:
- M/F ratio per cage: Rabbits were mated consecutively to two males (if possible). After the second copulation, females were individually housed.
- Verification of same strain and source of both sexes: yes
- Proof of pregnancy: The date of copulation(s) was designated gestation day 0. - Duration of treatment / exposure:
- 6 hours/day
- Frequency of treatment:
- Animals were exposed daily on gestation days 6-18.
- Duration of test:
- Females were sacrificed on gestation day 29.
Doses / concentrationsopen allclose all
- Dose / conc.:
- 1 other: %
- Remarks:
- 2.4 mg/kg (average for dose group)
- Dose / conc.:
- 5 other: %
- Remarks:
- 12 mg/kg (average for dose group)
- Dose / conc.:
- 10 other: %
- Remarks:
- 24 mg/kg (average for dose group)
- No. of animals per sex per dose:
- 22
- Control animals:
- yes, concurrent no treatment
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The doses were based on results from a dose range-finding study also performed on timed-pregnant New Zealand White rabbits.
- Rationale for animal assignment: Mated females were assigned by stratified randomization by body weight to each experimental group.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations included. All females were examined for clinical signs of toxicity.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: The treated does were observed daily for skin irritation, erythema, eschar formation and edema.
BODY WEIGHT: Yes
- Time schedule for examinations: All females were weighed on gestation day 0, 6 (prior to onset of dosing), 12, 18 (during the dosing period), and 29.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day # 29
- Organs examined: the gravid uterus, ovaries (including corpora lutea), cervix, vagina, and peritoneal and thoracic cavities were examined grossly. Maternal liver, kidneys and uterine weights were determined. Kidneys were bisected, fixed in buffered neutral 10 %formalin and processed for histopathological examination. One square inch of skin from treated animals was removed from the application site and fixed in buffered neutral 10 % formalin. The uteri were immediately ligated at their cervical end to prevent the expulsion of conceptuses by myometrial peristalsis. Uteri were externally examined for signs of hemorrhage. The ligated uteri and attached ovaries and oviducts were removed from the peritoneal cavity and weighed.
- Ovaries and uterine content:
- The ovaries and uterine content were 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: number of live and dead fetuses - Fetal examinations:
- - External examinations: Yes, all live fetuses per litter
- Soft tissue examinations: Yes, approx. half per litter
- Skeletal examinations: Yes, remaining fetuses not used for soft tissue examinations - Statistics:
- The unit of comparison was the pregnant female or the litter. Results of the quantitative continuous variables (e.g., maternal body weights, liver weights, fetal weights, etc.) were intercompared for the test substance groups, the untreated control group and vehicle control group by use of Levene's test for equal variances, analysis of variance (ANOVA), and t-tests with Bonferroni probabilities. The t-tests were used when the F value from the ANOVA was significant. When Levene's test indicated homogenous variances and the ANOVA was significant, the pooled t-test was used. When Levene's test indicated heterogeneous variances, all groups were compared by an ANOVA for unequal variances followed, when necessary, by the separate variance t-test.
Non parametric data obtained following laparohysterectomy were statistically treated using the Kruskal-Wallis test followed by the Mann-Whitney U test when appropriate. Incidence data were compared using Fisher's Exact Test. For all statistical tests, the fiducial limit of 0.05 (two-tailed) was used as the criterion for significance.
Results and discussion
Results: maternal animals
General toxicity (maternal animals)
- Clinical signs:
- no effects observed
- Description (incidence and severity):
- No clinical signs, not related to dermal irritation, appeared to be treatment-related.
- Dermal irritation (if dermal study):
- effects observed, treatment-related
- Description (incidence and severity):
- The clinical observations at the application site of treated does exhibited a dose-response pattern of eschar formation, erythema, and edema. The high dose does were the first to show signs of skin irritation and after the treatment stopped, they were the last to show signs of healing. The low and middle dose groups also showed signs of irritation. The edema present during dosing on the does from the 1 % group ceased immediately when the treatment was stopped and the erythema healed completely by gestation day 20. The does at the middle and high dose levels never completely healed from the edema and erythema caused by treatment. The more severe observations at the application site (rippled skin, open sore, black scabs, pus-filled sacs, discoloration and fissuring) appeared on the does from the middle and high does only.
- Mortality:
- no mortality observed
- Description (incidence):
- No mortalities occurred throughout the study.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Although not statistically significant, there was an apparent dose-related trend toward decreased body weight on gestation days 12, 18 and 29. There was also a significant decrease in body weight gain for the does from the high dose group on gestation days 12-18, 6-18 (exposure period) and 6-29. The does from the middle and low dose groups had lower body weight gains than the treated control group, but the values were not statistically significant. The body weight gain during the post exposure period (gestation days 18-29) indicated that the high dose animals gained more weight than the treated controls, but this value was not statistically significant. The untreated control group does had a significantly greater gain in body weight than the treated controls on gestation days 6-12 while the gestation days 12-29 body weight gain was significantly lower than the treated controls. This may indicate that the treatment procedures per se induced stress in pregnant rabbits resulting in a decrease in body weight gain. When treatment ceased, the animals gained more weight than the untreated control which compensated for the initial decrease in weight gain. By sacrifice on gestation day 29, there were no statistically significant differences among groups for body weight. Body weight and corrected body weight at terminal sacrifice were unaffected by treatment.
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- not examined
- Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Description (incidence and severity):
- At scheduled sacrifice on gestation day 29, the only statistically significant effect of treatment on the does was an increase in the maternal kidney weight relative to body weight. Although not significant, a dose- response of increased relative liver weight was apparent across the dosed groups.
At terminal sacrifice, there was no treatment-related effect on gravid uterine weight, absolute liver and kidney weights. - Gross pathological findings:
- not specified
- Neuropathological findings:
- not examined
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- Histopathological examination showed effects only in the maternal kidneys where the only treatment related effect was a significant increase of does (20/22) at the high dose and at 5 % (4/22) with vacuolar swelling of the collecting ducts compared with the incidence in the vehicle controls (0/22). The lesion was characterized by a markedly swollen clear cytoplasm within the epithelial cells lining at a particular level of the collecting ducts, with no evidence of concomitant cell degeneration. The lesion was observed almost exclusively in that portion of the ducts present in the outer zone of the inner medulla, i.e. that region where the smaller ducts join to form the larger ducts which pass through the renal papilla.
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- not specified
Maternal developmental toxicity
- Number of abortions:
- not specified
- Pre- and post-implantation loss:
- not specified
- Total litter losses by resorption:
- not specified
- Early or late resorptions:
- not specified
- Dead fetuses:
- not specified
- Changes in pregnancy duration:
- not specified
- Changes in number of pregnant:
- not specified
- Other effects:
- not specified
Effect levels (maternal animals)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- maternal toxicity
- Effect level:
- >= 2.4 - < 12 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Basis for effect level:
- body weight and weight gain
- histopathology: non-neoplastic
- other: Significant decrease in body weight gain at 24 mg/kg bw/d. Histopathologic changes in the kidneys at 12 and 24 mg/kg bw/d with an increase in incidence of does with vacuolar swelling of the collecting ducts.
Maternal abnormalities
- Abnormalities:
- no effects observed
Results (fetuses)
- Fetal body weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean litter weight and female fetal body weights per litter, taken at sacrifice on gestation day 29, were significantly decreased in the 24 mg/kg bw/day dose group when compared to the treated controls. Female fetal body weight was also decreased at 2.4 mg/kg bw/day but not at 12 mg/kg bw/day. The male fetal body weights per litter did not differ significantly across groups although the male fetal weight at 24 mg/kg bw/day was apparently lower than those in the treated control group.
- Reduction in number of live offspring:
- not specified
- Changes in sex ratio:
- not specified
- Changes in litter size and weights:
- effects observed, treatment-related
- Description (incidence and severity):
- Mean litter weight, taken at sacrifice on gestation day 29, were significantly decreased in the high dose group when compared to the treated controls.
- Changes in postnatal survival:
- not specified
- External malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no treatment related changes in the incidence of any external variation. The incidence of litters with one or more fetuses with external variations was significantly elevated at the 2.4 mg/kg bw/day dose group but not at higher doses for ecchymoses on the trunk (but not on the head or extremities).
There was no significant increase in the number of litters with one or more affected fetuses in any exposure group or untreated control group relative to the treated control group for individual and total external, visceral (including cranio-facial) and skeletal malformations, or total malformations (all categories combined) (see Table 2 below). - Skeletal malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no treatment related changes in the incidence of any skeletal variations. The incidence of six skeletal findings in the test substance groups differed significantly from that of the treated controls for the following observations the incidence of poorly ossified cervical centrum 1 was elevated at 2.4 mg/kg bw/day (but also in the untreated controls), the incidence of bilobed thoracic centrum 6 was decreased at 2.4 mg/kg bw/day, the incidence of poorly ossified sternebrae 2 and 3 was elevated at 2.4 mg/kg bw/day, the incidence of poorly ossified supraoccipital bone of skull was elevated at 2.4 mg/kg bw/day and the incidence of poorly ossified interparietal bone was elevated at 2.4 mg/kg bw/day. The untreated control group exhibited significant increases in the incidence of two skeletal findings relative to the untreated control group: poorly ossified cervical centrum 1 (mentioned above) and poorly ossified parietal bone of the skull.
There was no significant increase in the number of litters with one or more affected fetuses in any exposure group or untreated control group relative to the treated control group for individual and total external, visceral (including cranio-facial) and skeletal malformations, or total malformations (all categories combined) (see Table 2 below). - Visceral malformations:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no treatment related changes in the incidence of any visceral variations. The incidence of red foci on the thymus was significantly elevated at the 2.4 mg/kg bw/day level. No other statistically significant visceral variations were noted in any dose groups.
There was no significant increase in the number of litters with one or more affected fetuses in any exposure group or untreated control group relative to the treated control group for individual and total external, visceral (including cranio-facial) and skeletal malformations, or total malformations (all categories combined) (see Table 2 below). The middle dose group, however, did exhibit an increase in the number of fetuses and litters with ventricular septal defect (four fetuses in four litters) relative to vehicle controls (one fetus from one liter). This increase was not statistically significant and did not exhibit a dose-response (there was only one fetus at 24 mg/kg bw/day with this malformation). This observation was not considered treatment related. - Other effects:
- not specified
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- fetotoxicity
- Effect level:
- >= 12 - < 24 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Basis for effect level:
- fetal/pup body weight changes
- changes in litter size and weights
- other: At the 24 mg/kg bw/d dose, there was a significant decrease in mean litter weight and female fetal body weight per litter. At the 24 mg/kg bw/d dose there was a lower (although not significant) male fetal body weight.
- Dose descriptor:
- NOAEL
- Remarks:
- teratogenecity
- Effect level:
- >= 24 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Basis for effect level:
- other: No significant increase in the incidence of individual malformations or of external, visceral, skeletal, or total (external, visceral, plus skeletal) malformations by fetus or by litter in any exposed group.
- Dose descriptor:
- NOAEL
- Remarks:
- embryotoxicity
- Effect level:
- >= 24 mg/kg bw/day (nominal)
- Based on:
- act. ingr.
- Basis for effect level:
- other: No embryotoxic effects were reported at any dose level studied.
Fetal abnormalities
- Abnormalities:
- effects observed, non-treatment-related
Overall developmental toxicity
- Developmental effects observed:
- no
Any other information on results incl. tables
Evaluation of reproductive parameters indicated no treatment related effects on number of ovarian corpora lutea of pregnancy, total implantations, viable or non-viable implantations per litter, percent pre-implantation loss, percent live fetuses per litter, or on sex ratio (% males) (see Table 1).
Table 1. Reproductive Parameters and Fetal Weights in NZW Rabbit Does Exposed to NIAX Catalyst A-99
Parameter | A-99 (volume %, dermally) Gestational Days 6 Through 18 |
||||
0.0 | Untreated Controls | 1.0 | 5.0 | 10.0 | |
(Number of does) | (22) | (21) | (21) | (21) | (22) |
Corpora lutea per doe | 10.0 +/- 1.6a | 9.7 +/- 2.8 | 9.4 +/- 2.9 | 8.5 +/- 3.7 | 9.1 +/- 2.6 |
Total implants per litter | 8.0 +/- 3.0 | 8.9 +/- 2.4 | 9.4 +/- 2.0 | 8.1 +/- 2.5 | 8.0 +/- 2.6 |
Percent preimiplantation loss | 20.9 +/- 27.0 | 9.9 +/- 15.6 | 5.6 +/- 5.3 | 11.4 +/- 11.7 | 15.2 +/- 20.9 |
Viable implantations per litter | 7.2 +/- 3.3 | 7.8 +/- 3.5 | 8.1 +/- 3.2 | 7.3 +/- 3.5 | 7.3 +/- 3.0 |
Non-viable implants per litter | 0.8 +/- 1.5 | 1.1 +/- 1.4 | 1.3 +/- 2.3 | 0.8 +/- 1.7 | 0.7 +/- 1.5 |
Early resorptions | 0.4 +/- 1.1 | 0.6 +/- 1.4 | 0.9 +/- 2.1 | 0.7 +/- 1.7 | 0.5 +/- 1.5 |
Late resorptions | 0.0 +/- 0.0 | 0.0 +/- 0.2 | 0.0 +/- 0.0 | 0.0 +/- 0.0 | 0.0 +/- 0.0 |
Dead fetuses | 0.4 +/- 1.0 | 0.4 +/- 0.9 | 0.4 +/- 1.0 | 0.1 +/- 0.5 | 0.2 +/- 0.4 |
Percent live fetuses per litter | 88.1 +/- 25.4 | 80.7 +/- 32.0 | 84.7 +/- 30.5 | 83.8 +/- 35.4 | 90.9 +/- 21.4 |
Sex Ration (% males) | 52.3 +/- 26.4 | 50.2 +/- 23.1 | 61.0 +/- 15.9 | 54.9 +/- 16.2 | 52.9 +/- 18.2 |
(Number litters with live fetuses) | (21) | (19) | (19)b | (18) | (21) |
Fetal body weight per litter, g | 45.36 +/- 5.82 | 42.42 +/- 5.08 | 41.93 +/- 4.00 | 42.36 +/- 3.19 | 39.86 +/- 5.13** |
Male fetal body weight per litter, g | 44.24 +/- 5.23c | 42.50 +/- 3.83d | 42.82 +/- 4.61 | 43.24 +/- 4.56 | 40.37 +/- 5.99 |
Female fetal body weight per litter, g | 45.29 +/- 5.90e | 41.95 +/- 5.73 | 40.92 +/- 4.47* | 41.50 +/- 2.83 | 39.32 +/- 5.32e** |
a Data presented as mean +/- standard deviation.
b The sex of one fetus was inadvertently not recorded. Its body weight (34.94 g) was included in the mean litter weight calculations but was not included in fetal body weights by sex.
c N = 19, two litters had only female fetuses.
d N = 18, one litter had only female fetuses.
e N = 20, one litter each at 0.0 and 10.0% had only male fetuses.
* = p < 0.05 versus control (0.0%)
** = p < 0.01 versus control (0.0%)
The type and frequency of fetal malformations observed in the study are provided in Table 2.
Table 2. Malformations Observed in NZW Rabbit Fetuses Exposed to NIAX Catalyst A-99 in Uteroa
A-99 (%, dermally) | Fetusesb | Littersc | ||||||||||
0.0 | Untreated Controls |
1.0 | 5.0 | 10.0 | 0.0 | Untreated Controls |
1.0 | 5.0 | 10.0 | |||
NO. EXAMINED EXTERNALLYd | 158 | 163 | 170 | 153 | 161 | 21 | 19 | 19 | 18 | 21 | ||
Umbilical hernia | No. (%) |
1 (0.6) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (0.6) |
1 (4.8) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (4.8) |
|
NO. EXAMINED VISCERALLYe | 84 | 86 | 88 | 83 | 84 | 21 | 19 | 19 | 18 | 21 | ||
Portion of lower left cerebral hemisphere, missing |
No. (%) |
0 (0.0) |
1 (1.2) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (5.3) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
Dysphagia lusoria (right subclavian artery) |
No. (%) |
0 (0.0) |
0 (0.0) |
1 (1.1) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (5.3) |
0 (0.0) |
0 (0.0) |
|
Pulmonary artery forms dorsal aorta |
No. (%) |
1 (1.2) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (4.8) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
Ventricular septal defect | No. (%) |
1 (1.2) |
0 (0.0) |
0 (0.0) |
4 (4.8) |
1 (1.2) |
1 (4.8) |
0 (0.0) |
0 (0.0) |
4 (22.2) |
1 (4.8) |
|
Immediate (median) lung lobe, missing |
No. (%) |
4 (4.8) |
0 (0.0) |
2 (2.3) |
2 (2.4) |
0 (0.0) |
3 (14.3) |
0 (0.0) |
1 (5.3) |
2 (11.1) |
0 (0.0) |
|
Hydronephrosis, unilateral | No. (%) |
0 (0.0) |
1 (1.2) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (5.3) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
Right testis, missing | No. (%) |
1 (1.2) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (4.8) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
Two gallbladders, both smaller than normal |
No. (%) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (1.2) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (5.6) |
0 (0.0) |
|
Gallbladder and cystc duct, missing |
No. (%) |
1 (1.2) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (4.8) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
NO. EXAMINED SKELETALLYf | 74 | 77 | 72 | 70 | 66 | 20g | 18g | 18 | 17 | 21 | ||
Cervical arch #2, only a bone island right side (no anlage) |
No. (%) |
0 (0.0) |
0 (0.0) |
1 (1.2) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (5.3) |
0 (0.0) |
0 (0.0) |
|
Extra thoracic arch between arches #9 and #10, unilateral |
No. (%) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (1.3) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (4.8) |
|
Extra thoracic centrum (partial) between centra #9 and #10 (same fetus as above) |
No. (%) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (1.3) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (4.8) |
|
Extra rib between ribs #9 and #10 (with extra arch), (same fetus as above) |
No. (%) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (1.3) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (4.8) |
|
NO. EXAMINED SKELETALLYf | 74 | 77 | 82 | 70 | 77 | 20g | 18g | 19 | 18 | 21 | ||
Ribs #5 and #6, fused | No. (%) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (1.3) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (4.8) |
|
Fused ribs (#4 to #5) at distal end, unilateral |
No. (%) |
0 (0.0) |
1 (1.3) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (5.6) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
|
TOTAL MALFORMATIONS | ||||||||||||
External Malformationsd | No. (%) |
1 (0.6) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (0.6) |
1 (4.8) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (4.8) |
|
Visceral Malforamtionse | No. (%) |
7 (8.3) |
2 (2.3) |
3 (3.4) |
7 (8.4) |
1 (1.2) |
5 (23.8) |
2 (10.5) |
2 (10.5) |
6 (33.3) |
1 (4.8) |
|
Skeletal Malformationsf | No. (%) |
0 (0.0) |
1 (1.3) |
1 (1.2) |
0 (0.0) |
2 (2.6) |
0 (0.0) |
1 (5.6) |
1 (5.3) |
0 (0.0) |
2 (9.5) |
|
TOTAL MALFORMATIONS | No. (%) |
7 (4.4) |
3 (1.8) |
4 (2.4) |
7 (4.6) |
4 (2.5) |
5 (23.8) |
3 (15.8) |
3 (15.8) |
6 (33.3) |
4 (19.0) |
a A single fetus may be represented more than once in listing individual defects.
b Only live fetuses were examined for malformations.
c Includes litters with one or more malformed fetuses.
d All fetuses were examined externally.
e Approximately 50% of each litter were examined viscerally, and for soft tissue craniofacial malformations.
f Approximately 50% of each litter were examined for skeletal malformations after staining with Alizarin Red S.
g One dam had only one live fetus. By convention, it was subjected to a visceral and craniofacial examination.
Table 3. Estimation of Theoretical Dose for 3033 -62 -3
Estimated Dose (mg/kg bw) | ||||||
Assuming Body Weight Satistic Equal to: | ||||||
Dose | Minimum for Dose Group | Maximum for Dose Group | Average for Dose Group | Overall Minimum |
Overall Maximum |
|
(% v/v in water) | GD6-18 | GD6-18 | GD6-18 | GD0 | GD0 | |
0 | 0 | 0 | 0 | 0 | 0 | |
1 | 2.4 | 2.4 | 2.4 | 2.9 | 2.5 | |
5 | 12 | 12 | 12 | 14 | 12 | |
10 | 25 | 24 | 24 | 29 | 25 |
Where:
Dose (mg/kg bw) = Dose (% v/v in water) x UC1 x SG x Dw x Vw x UC2 / BW
Unit conversion (UC1): 0.01 [to convert dose in % v/v to mL chem / mL water]
Specific gravity (SG): 0.8696 [=density chem / density water, at 20 deg C as reported in Tyl et al., 1986]
Density water (Dw): 0.998 g/mL = g/cm3, at 20 deg C
Volume water applied to skin (Vw): 1 mL
Unit conversion (UC2): 1000 mg chem/g chem
Body weight (BW): kg [As reported in study report]
Applicant's summary and conclusion
- Conclusions:
- Administration of the test substance by dermal application to timed-pregnant New Zealand white rabbits during organogenesis (gestation days 6-18) resulted in maternal toxicity at 24 and 12 mg/kg bw/day, i.e., transient reduced weight gain during exposure at 24 mg/kg bw/day, renal lesions at 12 and 24 mg/kg bw/day and elevated relative kidney weight at 24 mg/kg bw/day. There was no maternal toxicity at 2.4 mg/kg bw/day except for transient irritation at the application site. Toxicity to the fetus (reduced fetal body weight per litter) was observed unaccompanied by any indication of reduced fetal ossification, only at 24 mg/kg bw/day, a dose which also produced signs of maternal toxicity. There was no evidence for embryotoxicity or teratogenicity at any dose level employed.
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.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
This website uses cookies to ensure you get the best experience on our websites.
Find out more on how we use cookies.