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EC number: 944-461-4 | CAS number: -
- 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
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- comparable to guideline study with acceptable restrictions
- Remarks:
- The age of the animals was not reported; no data on individual animals was given; the body weight of females was not recorded during the mating period; the time of onset, duration, number affected and severity of the clinical signs was not reported; the number of implantation sites was not recorded.
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 014
- Report date:
- 2014
Materials and methods
Test guidelineopen allclose all
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 421 (Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- adopted Jul 1995
- Deviations:
- yes
- Remarks:
- animal age not reported; no data on individual animals given; time of onset, duration, number affected and severity of the clinical signs not reported; number implantation sites not given
- Qualifier:
- according to guideline
- Guideline:
- other: The Guidelines for the Testing of Chemicals (State Environmental Protection Administration of China) 2004.5
- Deviations:
- not specified
- GLP compliance:
- not specified
- Limit test:
- no
Test material
- Reference substance name:
- 1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene]
- EC Number:
- 306-832-3
- EC Name:
- 1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene]
- Cas Number:
- 97416-84-7
- Molecular formula:
- C23H24Br8O2
- IUPAC Name:
- 1,1'-(isopropylidene)bis[3,5-dibromo-4-(2,3-dibromo-2-methylpropoxy)benzene]
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Vital River Laboratory Animal Technology Co., Ltd., Beijing, China
- Weight at study initiation: (P) Males: 225 - 305 g; Females: 205 -267 g
- Fasting period before study: no
- Housing: the animals were housed individually, except during the mating period
- Diet: reproductive diet (Certificate No. SCXK(JING) 2009-0008, HFK BIOSCIENCE Co., Ltd., Tianjin, China), ad libitum
- Water: tap water, ad libitum
- Acclimation period: 5 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20 - 25
- Humidity (%): 40 - 70
- Air changes (per hr): 12
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Dosing solutions were prepared at least once every 7 days. Each aliquot was stirred prior to dosing.
VEHICLE
- Concentration in vehicle: 50, 100 and 200 mg/mL
- Amount of vehicle (if gavage): 5 mL/ kg bw - Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation: up to 2 weeks
- Proof of pregnancy: vaginal plug or sperm in vaginal smear referred to as day 0 of pregnancy
- After 10 days of unsuccessful pairing replacement of first male by another male with proven fertility for a maximum of 5 days
- After successful mating each pregnant female was caged: individually - Analytical verification of doses or concentrations:
- no
- Duration of treatment / exposure:
- (P) males: 42 days (from 14 days prior to mating, during mating until Day 43)
(P) females: up to 54 days (from 14 days prior to mating, up to 14 days during mating, up to 22 days during gestation, 4 days during lactation; for non-pregnant females, until 25 days after vaginal plug was observed) - Frequency of treatment:
- daily, 7 days/week
Doses / concentrationsopen allclose all
- Dose / conc.:
- 250 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 1 000 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 15
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: the dose levels were based on the results of the acute oral toxicity study (study report not available), in which the LD50 was > 5000 mg/kg bw.
Examinations
- Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
DETAILED CLINICAL OBSERVATIONS: No
BODY WEIGHT: Yes
- Time schedule for examinations: females: week 1 and 2 (prior to mating), gestation day 0, 7 and 14, and lactation day 0 and 4; males: week 1, 2 (prior to mating), 3, 4 and 5
FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes, food consumption was measured in females during week 1 and 2 (prior to mating), and gestation week 1 and 2; and in males during the whole treatment period (week 1 - 6).
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: No
WATER CONSUMPTION: No - Sperm parameters (parental animals):
- Parameters examined in all male parental generations:
testis weight, epididymis weight - Litter observations:
- STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: no
PARAMETERS EXAMINED
The following parameters were examined in F1 offspring:
number and sex of pups, stillbirths, live births, presence of gross anomalies, weight gain, physical or behavioural abnormalities
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was not determined for pups born or found dead - Postmortem examinations (parental animals):
- SACRIFICE
- Male animals: All surviving animals on Day 43
- Maternal animals: All surviving animals on lactation day 4; non-pregnant females were sacrificed on the same day
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations for abnormalities
HISTOPATHOLOGY / ORGAN WEIGHTS
The following organs/tissues were prepared for microscopic examination and weighed, respectively: testes, epididymes, ovaries and uterus. Any organs with lesions were prepared and subjected to a histopathological examination. - Postmortem examinations (offspring):
- SACRIFICE
- The F1 offspring were sacrificed at 4 days of age
- These animals were subjected to postmortem examinations (macroscopic examination) as follows: all pups were examined for external and visceral abnormalities
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations for abnormalities
HISTOPATHOLOGY / ORGAN WEIGTHS
No histopathological examinations were performed. - Statistics:
- Continuous data, including body weight, body weight gain, feed consumption, organ weight, pup body weight, gestation length and mean live litter size were analysed using a one-way analysis of variance (ANOVA). If significance (p < 0.05) was noted, group by group comparisons were performed using Dunnet's test. Count data were analysed using chi-square test for copulation and fertility indices, pup sex ratio, number of live and dead pups per group on lactation day 0, and pup survival after lactation day 0. All anaylses used two-tailed tests for a minimum significance level of 5% comparing the control to the treated groups. A p value of less than 0.5% was judged a significant difference.
- Reproductive indices:
- Mating index (%): (numbers of pairs with successful mating/ number of pairs) x 100
Fertility index (%): (Number of pregnant females/ number of pairs with successful mating) x 100 - Offspring viability indices:
- Live birth index (%): (Number of live pups born/ number of pups born) x 100
Viability index (%): (Number of live pups on lacation day 4/ number of live pups born) x 100
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- Decreased activity, disorientation and unkempt fur was observed in most males of the high-dose group. These transient effects are not considered to be toxicologically relevant.
- Dermal irritation (if dermal study):
- not examined
- Mortality:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- The body weight and body weight gain was comparable between the treatment and control groups in males and females. The body weight increase in females of the high-dose group observed on Day 14 of gestation only, is considered to be an incidental effect.
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- The food consumption was significantly reduced in males of the low- and mid-dose group in week 6, and in males of the high-dose group in week 4, 5 and 6 (see Table 1 and 2 under ' Any other information on results incl. tables'). The reduced food intake did not affect the body weight, therefore, the reduced food consumption is not considered to be toxicologically relevant. The test substance intake was adjusted weekly based on the body weight and was considered by the study report authors to be close to the reported dose levels.
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- 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:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not examined
- Other effects:
- no effects observed
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- no effects observed
- Description (incidence and severity):
- The testis and epididymes weights were comparable between the treatment and control groups in males.
- Reproductive performance:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no significant differences in fertility index and dams with live young born between the control and treatment groups. The mating index was slightly, but not significantly reduced in the 500 and 1000 mg/kg bw/day groups (see Table 3 under ' Any other information on results incl. tables'). Two of nine dams in the high-dose group cannibalised their entire litter post-partum, with the study authors indicating the reason was 'abnormal maternal behaviour'. This information was not included in the English translation of the study report (only in the Chinese version) and no additional information was available. Due to the limited information given in the study report and the lack of individual animal data the possibility that this effect is treatment-related cannot be excluded. However, no toxicological relevance was evident in the general health and reproductive health of the dams and cannibalisation is known to occur in rats.
Effect levels (P0)
open allclose all
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- systemic
- Effect level:
- >= 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male
- Basis for effect level:
- other: No toxicologically relevant effects were observed up to and including the highest dose level
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- fertility
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- reproductive function (sperm measures)
- reproductive performance
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not examined
- Mortality / viability:
- mortality observed, treatment-related
- Description (incidence and severity):
- The survival rate (as viability index) of pups in the high-dose group was significantly reduced, compared with the control group (see Table 3 under 'Any other information on results incl. tables'). Two of nine dams cannibalised their entire litter post-partum, which is likely to have caused the reduction in viability.
- Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- The body weight of pups in the high-dose group was significantly reduced on lactation day 0, compared with the control group. The difference was approximately 5%; indicating that the variation in body weight is incidental and not treatment-related. Furthermore, the mean weight for the control and treatment groups fell within the historical data range given for rat pups on lactation day 0 (Lang, P.L. Historical control data for development and reproductive toxicity studies using the Crl:CD BR rat. Charles River Laboratories, September 1993. www.criver.com) No significant difference was noted between the control and treatment groups on lactation day 4.
- Food consumption and compound intake (if feeding study):
- not examined
- Food efficiency:
- not examined
- Water consumption and compound intake (if drinking water study):
- not examined
- Ophthalmological findings:
- not examined
- Haematological findings:
- not examined
- Clinical biochemistry findings:
- not examined
- Urinalysis findings:
- not examined
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
- Other effects:
- no effects observed
- Description (incidence and severity):
- The tail length of the pups in the high-dose group was significantly shorter than that of the control group. However, this is not a standard parameter and is unlikely to affect the survival and development of the pups. Therefore it is not considered to be a toxicologically relevant effect. A significant increase in pup length in the mid-dose group is considered to be incidental.
Developmental neurotoxicity (F1)
- Behaviour (functional findings):
- not examined
Developmental immunotoxicity (F1)
- Developmental immunotoxicity:
- not examined
Effect levels (F1)
- Key result
- Dose descriptor:
- NOAEL
- Remarks:
- development
- Generation:
- F1
- Effect level:
- >= 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No treatment-related adverse effects were observed up to and including the highest dose level
Target system / organ toxicity (F1)
- Key result
- Critical effects observed:
- no
Overall reproductive toxicity
- Reproductive effects observed:
- no
Any other information on results incl. tables
Table 1: body weight in males
Body weight, g (mean ± SD) |
||||
|
Dose group (mg/kg bw/day) |
|||
|
Control (vehicle) |
250 |
500 |
1000 |
Day 0 |
269.3 ± 17.0 |
268.5 ± 18.3 |
267.3 ± 19.4 |
271.7 ± 13.2 |
Week 1 |
318.1 ± 17.5 |
323.2 ± 14.6 |
320.5 ± 13.7 |
319.7 ± 16.2 |
Week 2 |
357.3 ± 23.5 |
366.0 ± 14.6 |
366.9 ± 17.2 |
357.9 ± 16.4 |
Week 3 |
416.9 ± 31.7 |
423.6 ± 21.6 |
426.3 ± 26.0 |
411.7 ± 21.0 |
Week 4 |
437.0 ± 33.6 |
443.4 ± 25.4 |
445.5 ± 26.5 |
429.3 ± 22.2 |
Week 5 |
460.7 ± 37.1 |
471.9 ± 28.9 |
474.6 ± 28.8 |
454.3 ± 23.5 |
Week 6 |
487.7 ± 43.0 |
492.5 ± 31.5 |
493.6 ± 32.1 |
475.4 ± 24.9 |
Table 2: food consumption in males
Food consumption, g (mean ± SD) |
||||
|
Dose group (mg/kg bw/day) |
|||
|
Control (vehicle) |
250 |
500 |
1000 |
Week 1 |
176.6 ± 11.8 |
180.9 ± 6.5 |
180.9 ± 14.0 |
174.8 ± 9.1 |
Week 2 |
189.3 ± 20.9 |
187.7 ± 11.4 |
188.5 ± 8.2 |
179.7 ± 11.1 |
Week 4 |
195.4 ± 17.9 |
193.7 ± 20.9 |
188.1 ± 14.4 |
177 ± 14.6* |
Week 5 |
183.6 ± 19.3 |
179.3 ± 20.4 |
174.9 ± 11.8 |
166 ± 17.2* |
Week 6 |
200.0 ± 20.3 |
180.7 ± 18.0* |
181.5 ± 11.0* |
173.2 ± 15.2* |
* p < 0.05
Table 3: reproductive performance and development data
|
Dose group (mg/kg bw/day) |
|||
|
Control (vehicle) |
250 |
500 |
1000 |
Females showing evidence of mating (N) |
15 |
14 |
10 |
12 |
Mating index (%) |
100 |
93 |
67 |
80 |
Females achieving pregnancy (N) |
11 |
11 |
10 |
9 |
Fertility index (%) |
73 |
79 |
100 |
75 |
Dams with live young born (N) |
11 |
11 |
10 |
9 |
Pups born (N) |
159 |
154 |
144 |
137 |
Live pups born (N) |
159 |
151 |
142 |
135 |
Live birth index (%) |
100 |
98 |
99 |
99 |
Live pups on day 4 (N) |
156 |
148 |
137 |
117 |
Viability index (%) |
98 |
98 |
96 |
87* |
Sex ratio (male/female) |
84/74 |
74/77 |
69/73 |
71/64 |
Pup weight on day 0 (g) |
6.51 ± 0.63 |
6.54 ± 0.77 |
6.67 ± 0.68 |
6.21 ± 0.85* |
Pup weight on day 4 (g) |
11.14 ± 1.80 |
11.43 ± 2.03 |
11.13 ± 1.43 |
11.04 ± 1.05 |
Pup length on day 0 (cm) |
4.54 ± 0.23 |
4.61 ± 0.32 |
4.63 ± 0.26* |
4.50 ± 0.30 |
Pup tail length on day 0 (cm) |
1.74 ± 0.16 |
1.69 ± 0.21 |
1.77 ± 0.20 |
1.68 ± 0.16* |
* p < 0.05
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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