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EC number: 620-056-5 | CAS number: 874195-61-6
- 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:
- 04 Aug 2011 - 19 April 2012
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Referenceopen allclose all
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 012
- Report date:
- 2012
- Reference Type:
- other: Amendment No. 1
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
- Reference Type:
- other: Amendment No. 2
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EU Method B.31 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- EPA OPPTS 870.3700 (Prenatal Developmental Toxicity Study)
- Deviations:
- no
- Qualifier:
- according to guideline
- Guideline:
- other: Japenese Ministry of Agriculture, Forestry and Fisheries, notification 12 Nousan N°8147 (November, 2000)
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- N-[2-(4,6-dimethoxy-1,3,5-triazine-2-carbonyl)-6-fluorophenyl]-1,1-difluoro-N-methylmethanesulfonamide
- EC Number:
- 620-056-5
- Cas Number:
- 874195-61-6
- Molecular formula:
- C14H13F3N4O5S
- IUPAC Name:
- N-[2-(4,6-dimethoxy-1,3,5-triazine-2-carbonyl)-6-fluorophenyl]-1,1-difluoro-N-methylmethanesulfonamide
Constituent 1
Test animals
- Species:
- rabbit
- Strain:
- other: New Zealand White Crl:KBL (NZW) rabbit
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Châtillon-sur-Chalaronne, France
- Age at study initiation: 18±1 weeks old
- Weight at study initiation: between 2.96 and 3.89 kg
- Housing: Individual housing of pregnant females in suspended stainless steel wire mesh cages.
- Diet: 110 C-10 pelleted animal diet from S.A.F.E. (Scientific Animal Food and Engineering, Augy, France) ad libitum.
- Water: Filtered and softened tap water from the municipal water supply, ad libitum.
- Acclimation period: 4 or 5 days prior to commencement of dosing
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 17-21
- Humidity (%): 40-70
- Air changes (per hr): 10-15
- Photoperiod: 16 h light/8 hrs dark ( 5am-9pm)
IN-LIFE DATES: From: 2011-08-04 To: 2012-04-19
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- other: 0.5% methylcellulose 400
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: The appropriate amount of test item was suspended (w/w) in an aqueous solution of 0.5% methylcellulose 400 and stored at approximately 5 °C (±3 °C). Test formulations were prepared 6 times (F1 to F6) during the study. The suspensions were mixed continuously before and during treatment with an electromagnetic stirrer.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Stability of the test item in 0.5% aqueous methylcellulose was demonstrated in study SA 08145 at concentrations of 0.5 and 250 g/L for up to 29 days under similar conditions to those of the current study. Homogeneity of the suspensions was checked on the first formulation (F1) for the lowest and the highest concentrations (3.75 and 18.75 g/L). The mean values obtained from the homogeneity check were used as measured concentrations. In addition, the intermediate concentration (7.5 g/L) of the first formulation (F1) and all concentrations of the remaining formulations (F2 to F6) were checked. Data were recorded and analyzed using Empower 2 (Build 2154).
Results: Homogeneity and concentration analysis: 95 to 100% of nominal concentrations, which is within the in-house target range of 90 to 110% of nominal concentration. Therefore dose preparations were considered acceptable for use on this study. - Details on mating procedure:
- - Impregnation procedure: purchased timed pregnant
- Time-mated female rabbits were received from the supplier on GD 1 or GD 2. Nulliparous females were mated with stock males of the same strain and same supplier. The day of mating was designated as gestation Day 0 (GD 0). - Duration of treatment / exposure:
- GD 6-28
- Frequency of treatment:
- daily
- Duration of test:
- On GD 29, all surviving females were sacrificed (34 days).
Doses / concentrations
- Remarks:
- Doses / Concentrations:
15, 30, 75 mg/kg bw/day
Basis:
actual ingested
- No. of animals per sex per dose:
- animals assigned: 23
animals pregnant at start of treatment: 22, 22, 20, 21 (in the control group, in the 15, 30 and 75 mg/kg bw/d group, respectively) - Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: The range of doses was selected based on the severity of maternal toxic effects obtained in a range-finding study (SA 08261), where groups of 8 presumed-pregnant rabbits were administered the test item by gavage at 0, 25, 75 or 200 mg/kg bw/day, from GD 6-28 inclusive. A dose level of 200 mg/kg bw/day resulted in marked maternal toxicity as evidenced by clinical signs, body weight losses, reduced food consumption and increased liver weight (+21%; p < 0.01). At 75 mg/kg bw/day, there was a slight maternal toxicity as evidenced by a slight reduction of 22% in body weight gain between GD 6-29 (not statistically significant). Mean maternal corrected body weight change (maternal body weight change independent of the uterine weight) was slightly more pronounced than in the controls (-0.27 kg compared to -0.21 kg, not statistically significant) and was slightly outside the range of in-house HCD (-0.08 to -0.25 kg). At necropsy, mean liver weight was unaffected by the treatment. At the macroscopic examination, no treatment-related findings were noted. At 25 mg/kg bw/day, no treatment-related maternal findings were noted.
Examinations
- Maternal examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All cages were checked for dead or moribund animals twice daily, once in the morning and again in the afternoon (except at weekends and public holidays when checking was carried out once daily).
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: All clinical signs were recorded for individual animals. All animals were examined daily from GD 2-29.
BODY WEIGHT: Yes
- Time schedule for examinations: Body weights were recorded on GD: 3, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 29
FOOD CONSUMPTION: Yes
- Full feeder weights were measured on GD: 3, 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26 and 28
- Empty feeder weights were measured on GD: 4, 5, 6, 8, 10, 12, 14, 16, 18, 20, 22, 24, 26, 28 and 29
From these records the mean daily consumption was calculated. Food spillage was also noted.
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on GD 29
- Organs examined: visceral organs - 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
- Number of live and dead fetuses: Yes
- Individual weights of live fetuses: Yes - Fetal examinations:
- - External examinations: Yes: all per litter
- Visceral examinations: Yes: half per litter
- Skeletal examinations: Yes: half per litter - Statistics:
- Mean and standard deviation for all maternal, litter and fetal parameters were calculated for each group.
Statistical analyses were performed separately for all pregnant females and for all pregnant females with live fetuses.
Statistical analyses were performed on the following parameters using SAS programs (Version 9.2).
- Maternal endpoints: body weight changes calculated according to interval periods; calculated corrected body weight change (body weight data measured on different days throughout gestation were not statistically analyzed; only descriptive statistics are presented); average food consumption calculated according to interval periods, liver weight
- Litter based endpoints: number of corpora lutea; number of implantation sites; number of resorptions (early, late); pre- and post-implantation loss percentages; fetal body weight (combinded sexes and per sex)
If one or more group variance(s) equaled 0, means were compared using non-parametric procedures.
- Fetal endpoints: fetal sex; fetal death status
If one or more group variance(s) equaled 0, means were compared using non-parametric procedures.
For fetal sex (male vs. female fetuses) and fetal death status (live vs. dead fetuses) endpoints, control group and each exposed group were compared using the Chi-square test for fetal sex parameter, using the Fisher Exact test (2-sided) for fetal death status parameter. Death status was analyzed both using the fetus as the statistical unit and using the litter as the statistical unit. Group means were compared at the 5% and 1% levels of significance.
In addition, statistical analysis was conducted on selected visceral and skeletal fetal observations. - Indices:
- Pre-implantation loss
Post-implantation loss
Number of live fetuses per litter
Number of dead fetuses per litter - Historical control data:
- Historical control data from studies conducted in-house were referred to in order to allow comparison with concurrent controls.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
Mortality
There was no treatment-related mortality throughout the study.
One female in the control group was found dead on GD 7. At the macroscopic examination, the left lobes of the lungs were found collapsed. Thus, the death was attributed to a gavage error.
One animal treated at 75 mg/kg bw/day AE 1887196 aborted on GD 28 after having lost 250 g between GD 20-26 and 330 g between GD 26-28 (early necropsy). Food consumption was reduced between GD 20-26. There were no macroscopic findings at necropsy. In isolation and as there was no severe maternal toxicity noted in the other animals of this dose group, this abortion was not attributed to the treatment.
Clinical observation
At 75 mg/kg bw/day, 12/21 animals had few feces (compared to 6/23 in the controls) on several days.
The other clinical signs were those commonly encountered in pregnant rabbits or were observed with no dose-relationship.
Body weight
Up to the highest dose of 75 mg/kg bw/day, there were no treatment-related effects on mean maternal body weights, body weight gains and maternal corrected body weight change. One animal treated at 15 mg/kg bw/day had total litter resorptions (no live fetuses).
Food consumption
At 75 mg/kg bw/day, the mean food consumption of all pregnant females with live fetuses was slightly reduced by 13% between GD 6-8 (p < 0.05) and by approximately 10 % between GD 8-14 compared to the controls (not statistically significant). Thereafter, mean food consumption was unaffected by treatment. This effect was considered to be treatment-related, though it remained within the range of in-house Historical Control Data (HCD). Up to the dose of 30 mg/kg bw/day, mean food consumption was unaffected by treatment.
Gross pathology and organ weights
The few macroscopic findings observed occurred in isolation and/or with no doserelationship and were thus considered to be incidental.
At 75 mg/kg bw/day, the mean liver weight of pregnant females was increased by 8% when compared to the concurrent control group (not statistically significant). Individual values of liver weight from animals treated at 75 mg/kg bw/day ranged between 73-141 g compared to 73-117 g in the control group. There was no other change in mean liver weights at any dose level.
Histopathology
No microscopic changes were considered to be treatment-related
Cesarean section data
Pregnancy rate was unaffected by treatment. The pregnancy rate was 91% in the 30 and 75 mg/kg bw/day dose groups, 96% in the 15 mg/kg bw/day dose group and 100% in control group. Litter parameters including the number of live fetuses, the number of implant sites per dam, the percentages of pre and post implantation losses, the number of early and late resorptions, the fetal death status, the percentage of male fetuses, and the fetal body weight for combined and separate sexes were unaffected by treatment.
One animal treated at 15 mg/kg bw/day had a total litter loss (resorptions). This finding was considered incidental and not treatment-related.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- >= 75 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- >= 75 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
External observations (Table 3)
There were no treatment-related malformations or variations noted at the fetal external examination. The few variations observed were considered to be incidental, as they occurred in isolation and were well within the range of in-house HCD.
Visceral observations (Table 4)
There were no treatment-related malformations or variations noted at the fetal visceral examination. The visceral malformations observed in a total of 10 fetuses were distributed between the different doses groups including the control (1, 2, 5, 2 malformed fetuses at 0, 15, 30 and 75 mg/kg bw/day groups, respectively).
One fetus from the high dose group, 3 fetuses from the mid dose group, 2 fetuses from the low dose group and one fetus from the controls had cardiac malformations. One fetus from the high dose group and one from the medium dose group had retina fold unilateral. One fetus from the mid dose group had an absence of kidney. Since these findings were observed with no dose-effect relationship and as they were well within the in-house HCD, they were considered to have occurred spontaneously.
The incidences of the visceral variation “Thymic remnant present (uni/bi)” and “Ureter retrocaval (uni)” were higher at 75 mg/kg bw/day than in control group, at both litter and fetal levels. However, since the incidences were well within or at the border of the in-house HCD and since the differences from controls were not statistically significant; these findings were considered not to be treatment-related.
Other variations observed did not occur in a dose-related manner, were within the in-house HCD or occurred as isolated findings and were considered incidental.
Skeletal observations (Table 5)
There were no treatment-related malformations or variations noted at the fetal skeletal examination. Skeletal malformations were observed in a total of 8 fetuses from all dose groups including the control.
One fetus from each treated group had thoracic malformations. Two fetuses in two different litters from the high dose group had lumbar malformations. With the exception of hemivertebrae, each finding on these fetuses was however observed within the range of the in-house HCD. There were 2 cases of 1 lumbar hemivertebra (1.1% fetuses, 10% litters) compared to 1 case (0.5% fetuses, 4.2% litters) in the HCD. Therefore, and in the absence of any other treatment-related malformations in the skeletal axis, these malformations were considered to be incidental.
The incidences of the skeletal variations “Extra ossification point(s) (uni/bi) on 7th cervical vertebra” and “Insertion point(s) (uni/bi) of pelvic girdle on 2nd sacral vertebra” were higher in all treated groups than in the control group, at the litter and/or fetal level. However, as the values were not statistically different from controls, did not occur in a dose-related manner and were well within the in-house HCD, these findings were considered not to be treatment-related.
The incidence of the skeletal variation “13th thoracic rib (bi)” was higher at 30 and 75 mg/kg bw/day than in the control group, at both litter and fetal levels, and statistically significant (p < 0.01) only at the fetal level at the high dose group. However, the incidences were well within the in-house HCD, this finding was therefore considered not to be treatment-related.
Other variations observed did not occur in a dose-related manner, were within the in-house HCD or occurred as isolated findings and were considered incidental.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Effect level:
- >= 75 mg/kg bw/day (actual dose received)
- 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: Mean (±SD) Maternal Body Weight Gain (kg) of all pregnant females
Interval |
Dose level of AE 1887196 in mg/kg bw/day |
|||
0 |
15 |
30 |
75 |
|
Number of pregnant females at start of treatment |
22 |
22(21) |
21 |
20 |
Pretreatment, GD 3-6: |
0.04 ± 0.060 |
0.05 ± 0.083 (0.05 ± 0.085) |
0.04 ± 0.050 |
0.04 ± 0.058 |
Treatment, GD 6-8: |
0.03 ± 0.034 |
0.03 ± 0.036 (0.03 ± 0.037) |
0.01 ± 0.072 |
0.02 ± 0.035 |
Treatment, GD 8-10: |
0.04 ± 0.033 |
0.04 ± 0.034 (0.04 ± 0.035) |
0.04 ± 0.026 |
0.03 ± 0.023 |
Treatment, GD 10-14: |
0.07 ± 0.047 |
0.09 ± 0.060 (0.09 ± 0.061) |
0.08 ± 0.051 |
0.09 ± 0.041 |
Treatment, GD 14-18: |
0.07 ± 0.051 |
0.04 ± 0.098 (0.05 ± 0.089) |
0.08 ± 0.052 |
0.05 ±0.065 |
Treatment, GD 18-22: |
0.05 ± 0.044 |
0.05 ± 0.041 (0.04 ± 0.037) |
0.07 ± 0.040 |
0.04 ± 0.046 |
Treatment, GD 22-26: |
0.05 ± 0.074 |
0.05 ± 0.061 (0.04 ± 0.059) |
0.07 ± 0.046 |
0.05 ± 0.084 |
Treatment, GD 26-29: |
0.06 ± 0.038 |
0.08 ± 0.044 (0.08 ± 0.045) |
0.08 ± 0.045 |
0.06 ± 0.051 |
Treatment, GD 6-29: |
0.37 ± 0.129 |
0.36 ± 0.148 (0.36 ± 0.151) |
0.43 ± 0.113 |
0.36 ± 0.151 |
Corrected BW gain |
-0.17 ± 0.121 |
-0.16 ± 0.154 (-0.16 ± 0.154) |
-0.11 ± 0.158 |
-0.15 ± 0.147 |
SD: standard deviation
One animal treated at 15 mg/kg bw/day had total litter loss. For this reason, the figures in parentheses are the means calculated once the data for this female are excluded.
Table 2: Cesarean Section Observations
Observation |
Dose Level of AE 1887196 (mg/kg bw/day) |
|||
|
0 |
15 |
30 |
75 |
Maternal data: |
|
|
|
|
No. Animals assigned |
23 |
23 |
23 |
23 |
No. Animals pregnant |
23 |
22 |
21 |
21 |
Pregnancy rate, % |
100 |
96 |
91 |
91 |
No. Animals non-pregnant |
0 |
1 |
2 |
2 |
Uterine data at scheduled sacrifice: |
|
|
|
|
Total No. corpora lutea (c)
|
256 |
253 |
242 |
226 |
Total No. Implantations (c)
|
229 |
217 |
203 |
194 |
Total No. Litters (c)
|
22 |
22 |
21 |
20 |
Total No. live fetuses (c)
|
207 |
196 |
190 |
178 |
Total No. dead fetuses
|
6 |
9 |
4 |
8 |
Total No. early resorptions (c)
Total No. late resorptions (c)
Litters with total resorptions (c,d) |
13
3
0 |
12 (7)
0
1 |
8
1
0
|
6
2
0 |
Mean fetal weight, combined sexes [g]
|
39.36 ± 4.17
|
38.87 ± 4.17
|
41.37 ± 2.86
|
37.84 ± 3.30
|
Sex ratio, % male |
44.0 ± 21.6 |
47.2 ± 17.2 |
49.4 ± 19.3 |
54.0 ± 20.8 |
Preimplantation loss per litter, % |
10.55 ± 13.07 |
13.46 ± 15.49 (14.10 ±15.58) |
15.65 ± 15.17 |
14.16 ± 10.51 |
Postimplantation loss per litter, % |
9.2 ± 8.8 |
10.8 ± 21.4 (6.6 ± 8.1) |
5.9 ± 8.0 |
9.1 ± 16.0 |
(c) statistical analysis was not conducted on this endpoints
(d) Also includes litters with dead fetuses only or dead fetuses and resorptions
The figures in parentheses are the means calculated once the data for the animal having total litter loss are excluded.
Table 3: External examinations
Dose level [mg/kg bw/day] |
0 |
15 |
30 |
75 |
Historical control range |
0 |
15 |
30 |
75 |
Historical control range |
Observations |
Number of litters examined |
Number of fetuses examined |
||||||||
22 |
21 |
21 |
20 |
207 |
196 |
190 |
178 |
|||
Number of litters affected (Percentage of litters affected) |
|
Number of fetuses affected (Percentage of fetuses affected) |
|
|||||||
Malformations Omphalocele |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (5.0) |
(0.0-4.5) |
0 (0.0) |
0 (0.0) |
0 (0.0) |
1 (0.6) |
(0.0-0.5) |
Table 4: Visceral examinations
Dose level [mg/kg bw/day] |
0 |
15 |
30 |
75 |
HCR |
0 |
15 |
30 |
75 |
HCR |
||
Observations |
Number of litters examined |
Number of fetuses examined |
||||||||||
22 |
21 |
21 |
20 |
207 |
196 |
190 |
178 |
|||||
Number of heads examined |
||||||||||||
97 |
92 |
90 |
85 |
|||||||||
Number of litters affected (Percentage of litters affected) |
|
Number of fetuses affected (Percentage of fetuses affected) |
|
|||||||||
Variations |
|
|
|
|
|
|
|
|
|
|
||
#Thymic remnant present (uni/bi) |
11 (50.0) |
7 (33.3) |
6 (28.6) |
12 (60.0) |
(20.8 - 84.2) |
25 (12.1) |
10 (5.1) |
8 (4.2) |
25 (14.0) |
(3.8 - 23.9) |
||
#Ureter (uni): retrocaval |
2 (9.1) |
0 (0.0) |
1 (4.8) |
2 (10.0) |
(0.0 - 18.2) |
3 (1.4) |
0 (0.0) |
1 (0.5) |
5 (2.8) |
(0.0 - 2.3) |
# : Statistical analysis was conducted on this observation
HCR: historical control range
Table 5: Summary of skeletal malformations
Dose level [mg/kg bw/day] |
0 |
15 |
30 |
75 |
0 |
15 |
30 |
75 |
||||||||
|
Number of litters examined |
Number of fetuses examined |
||||||||||||||
22 |
21 |
21 |
20 |
207 |
196 |
190 |
178 |
|||||||||
Number of litters examined |
Number of heads examined |
|||||||||||||||
22 |
21 |
21 |
20 |
97 |
92 |
90 |
85 |
|||||||||
Malformations |
Number of litters affected |
Number of fetuses affected |
||||||||||||||
One thoracic vertebra : hemivertebra. One rib (uni) : absent |
1 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
||||||||
Two ribs (uni) : fused. Two thoracic centrum : hemicentrum and fused |
0 |
1 |
1 |
0 |
0 |
1 |
1 |
0 |
||||||||
One lumbar vertebra : hemivertebra. One lumbar hemicentrum and one lumbar centrum : fused |
0 |
0 |
0 |
2 |
0 |
0 |
0 |
2 |
||||||||
Caudal and all sacral vertebrae : fused. Caudal vertebrae : absent |
1 |
0 |
0 |
0 |
1 |
0 |
0 |
0 |
||||||||
All caudal vertebrae (except 1st): fused |
0 |
0 |
1 |
0 |
0 |
0 |
1 |
0 |
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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