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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 212-572-0 | CAS number: 827-52-1
- 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
- Remarks:
- based on test type (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: Recent and well documented study in according to OECD and GLP guidelines.
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Limit test:
- no
Test material
- Reference substance name:
- Cyclohexylbenzene
- EC Number:
- 212-572-0
- EC Name:
- Cyclohexylbenzene
- Cas Number:
- 827-52-1
- Molecular formula:
- C12H16
- IUPAC Name:
- cyclohexylbenzene
- Test material form:
- other: liquid
- Details on test material:
- - Physical state: liquid, colorless, clear
- Analytical purity: 99.4%
- Lot/batch No.: B9107
- Expiration date of the lot/batch: Jan 2015
- Stability under test conditions: garanted by the sponsor
- Storage condition of test material: room temperature
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Laboratories, Research Models and services, Germany GmbH
- Age at study initiation: 10-11 weeks old
- Housing: Makrolon type M III cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 20-24°C
- Humidity (%): 30-70%
- Air changes (per hr): 15/hour
- Photoperiod (hrs dark / hrs light): 12/12
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- + 1% carbocymethylcellulose with about 5mg/100ml Cremophor.EL
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS:
Phenylcyclohexan was applied as a emulsion. To prepare this suspension, the appropriate amount of test substance was weighed out depending on the desired concentration. Then, drinking water containing 1% Carboxymethylcellulose with about 5 mg/100 mL Cremophor EL was filled up to the desired volume, subsequently released with a high speed homogenizer. During administration of the test substance preparations were kept homogeneous by stirring with a magnetic stirrer. The test substance preparations were produced at least once a week.
VEHICLE
- Concentration in vehicle: 0.4, 2.0 and 10.0 mg/100 mL
- Amount of vehicle: 10 mg/kg bw/d - Details on mating procedure:
- On the day of arrival the animals were subjected to an acclimatization period during which they received ground diet and drinking water ad libitum. Prior to the first detailed clinical observation, the animals were distributed according to weight among the individual test groups, separated by sex. The weight variation of the animals used did not exceed 20 percent of the mean weight of each sex. The list of randomization instructions was compiled with a computer.
At the start of the administration period (study day 0) the rats were 11-12 weeks old.
After the acclimatization period, the test substance was administered orally via gavage to the F0 generation parental animals, daily at the same time in the morning (exception: no administration to animals being in labor). The treatment lasted up to one day prior to sacrifice. The animals of the control group were treated in the same way with the vehicle only (drinking water containing 1% Carboxymethylcellulose with about 5 mg/100 mL Cremophor EL). The calculation of the administered volume was generally based on the most recent individual body weights.
Two weeks after the beginning of treatment, males and females from the same test group were mated overnight in a ratio of 1:1. In general, each of the male and female animals was mated overnight in a 1:1 ratio for a maximum of 2 weeks. Throughout the mating period, each female animal was paired with a predetermined male animal from the same test group.
The animals were paired by placing the female in the cage of the male mating partner from about 16.00 h until 07.00 - 09.00 h of the following morning. Deviations from the specified times were possible on weekends and public holidays and were reported in the raw data. A vaginal smear was prepared after each mating and examined for the presence of sperm. If sperm was detected, pairing of the animals was discontinued. The day on which sperm was detected was denoted gestation day (GD) 0 and the following day "GD 1". - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Detail of analytical dose concentration carried out at the analytical chemistry laboratory of experimental toxicology and ecotoxicology of BASF SE.
The purity was performed by capillary GC with area % evaluation corrected with the content of water.
The concentration analyse of all concentration revealed that the value were in the expected range of the target concentration (about 90-110% of nominal concentration) - Duration of treatment / exposure:
- for male: treatment started after acclimatisation (6 days) during 2 weeks before the mating, during the mating and 2 weeks after the end of the mating
for female: treatment started after acclimatisation (6 days) during 2 weeks before the mating, during the mating, during the gestation and 4 days after delivery. - Frequency of treatment:
- Administrate every day at the same time in the morning
Doses / concentrationsopen allclose all
- Remarks:
- Doses / Concentrations:
40 mg/kg bw/d
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
200 mg/kg bw/d
Basis:
actual ingested
- Remarks:
- Doses / Concentrations:
1000 mg/kg bw/d
Basis:
actual ingested
- No. of animals per sex per dose:
- 10 per dose per sex
- Control animals:
- yes, concurrent vehicle
Examinations
- Parental animals: Observations and examinations:
- This information is covered in the robust study summary under the endpoint "repeated dose toxicity".
- Litter observations:
- PUP NUMBER AND STATUS AT DELIVERY
All pups delivered from the F0 parents (F1 litter) were examined as soon as possible on the day of birth to determine the total number of pups, the sex and the number of liveborn and stillborn pups in each litter. At the same time, the pups were also being examined for macroscopically evident changes. Pups, which died before this initial examination, were defined as stillborn pups.
PUP VIABILITY / MORTALITY
In general, a check was made for any dead or moribund pups twice daily on workdays (once in the morning and once in the afternoon) or as a rule, only in the morning on Saturdays, Sundays or public holidays.
The number and percentage of dead pups on the day of birth (PND 0) and of pups dying between PND 1 - 4 (lactation period) were determined. Pups which died accidentally or were sacrificed due to maternal death were not included in these calculations. The number of live pups/litter was calculated on the day after birth, and on lactation day 4. The viability index was calculated according to the following formula:
Viability index (%) = number of live pups on day 4 after birth * 100 / number of live pups on the day of birth
SEX RATIO
On the day of birth (PND 0) the sex of the pups was determined by observing the distance between the anus and the base of the genital tubercle; normally, the anogenital distance is considerably greater in male than in female pups. The sex of the pups was finally confirmed at necropsy.
The sex ratio was calculated at day 0 and day 4 after birth according to the following formula:
Sex ratio = number of live male or female pups on da 0-4 * 100 / number of live male and female pups on day 0-4
PUP CLINICAL OBSERVATIONS
The live pups were examined daily for clinical symptoms (including gross-morphological findings) during the clinical inspection of the dams.
PUP BODY WEIGHT DATA
The pups were weighed on the day after birth (PND 1) and on PND 4. Pups' body weight change was calculated from these results.
The individual weights were always determined at about the same time of the day (in the morning).
In the summary tables pup body weights and pup body weight change are listed for males, females and males + females.
“Runts” were defined on the basis of the body weights on PND 1. "Runts" are pups that weigh less than 75% of the mean weight of the respective control pups. - Postmortem examinations (parental animals):
- This information is covered in the robust study summary under the endpoint "repeated dose toxicity".
- Postmortem examinations (offspring):
- All pups with scheduled sacrifice on PND 4 were sacrificed under isoflurane anesthesia with CO2. All pups were examined externally and eviscerated; their organs were assessed macroscopically.
All stillborn pups and all pups that died before PND 4 were examined externally, eviscerated and their organs were assessed macroscopically.
All pups without notable findings or abnormalities were discarded after their macroscopic evaluation. Animals with notable findings or abnormalities were evaluated on a case-by- case basis, depending on the type of finding noted. - Statistics:
- See "other information" section.
- Reproductive indices:
- Parameters examined in the F0 parental generation:
the pairing partners, the number of mating days until vaginal sperm was detected in and the gestation status were recorded for F0 females.
Calculation of inidces:
Female mating index (%) = number of females mated * 100 / number of females placed with males
with “females mated” defined as the number of females with vaginal sperm or with implants in utero
Female fertility index (%) = number of females pregnant * 100 / number of females mated
with “females pregnant” defined as the number of females with implants in utero, and “females mated” defined as above
Gestation index (%) = number of females with live pups on the day of birth * 100 / number of females pregnant
The total number of pups delivered and the number of liveborn and stillborn pups were noted, and the live birth index was calculated for F1 litters according to the following formula:
Live birth index (%) = number of liveborn pups at birth * 100 / total number of pups born
The implantations were counted and the post-implantation loss (in %) was calculated according to the following formula:
Post implantation loss (%) = [number of implantations – number of pups delivered] * 100 / number of implantations
Parameters examined in the F0 parental generation: the pairing partners, the number of mating days until vaginal sperm was detected in the female animals, and the gestation status of the females was recorded for F0 breeding pairs.
Calculation of mating and fertility inidces:
Male mating index (%) = number of males with confirmed mating * 100 / number of males placed with females
with "confirmed mating" defined by a female with vaginal sperm or implants in utero
Male fertility index (%) = number of males providing their fertility * 100 / number of males placed with females
with "providing their fertility" defined by a female with implants in utero
Results and discussion
Results: P0 (first parental generation)
General toxicity (P0)
- Clinical signs:
- effects observed, treatment-related
- Description (incidence and severity):
- see repeated dose section
- Body weight and weight changes:
- effects observed, treatment-related
- Description (incidence and severity):
- see repeated dose section
- Food consumption and compound intake (if feeding study):
- effects observed, treatment-related
- Description (incidence and severity):
- see repeated dose section
- Organ weight findings including organ / body weight ratios:
- effects observed, treatment-related
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Description (incidence and severity):
- see repeated dose section
Reproductive function / performance (P0)
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
Details on results (P0)
MALE MATING INDEX
The male mating index was 100% in test groups 0, 1 and 3 and 90% in test group 2. This finding reflected the normal range of biological variation inherent in the strain of rats used for this study as all respective values were within the range of the historical control data.
MALE FERTILITY INDEX
Fertility was proven for most of the F0 parental males within the scheduled mating interval to produce F1 litter.
One male of test group 2 (No. 24 mated with female No. 124) did not generate F1 pups.
The male fertility index was 90% in test group 2 and 100% in test groups 0, 1 and 3.
This finding reflected the normal range of biological variation inherent in the strain of rats used for this study as all respective values were within the range of the historical control data
FEMALE MATING INDEX
The female mating index calculated after the mating period for F1 litter was 100% in test groups 0, 1 and 3 and 90% in test group 2. The mean duration until sperm was detected (GD 0) was 3.0, 3.0, 1.8 and 2.7 days in test groups 0-3. This finding reflected the normal range of biological variation inherent in the strain of rats used for this study as all respective values were within the range of the historical control data.
FEMALE FERTILITY INDEX
All sperm positive rats delivered pups. Female animal No. 124 (test group 2) which was mated with male No. 24 did not get sperm in vaginal smear. The female fertility index was 100% in in all test groups. Female animal No. 124, which delivered no pups, showed no implantation sites.
The mean duration of gestation was similar in all test groups (i.e. between 22.0 and 22.2 days). This finding reflected the normal range of biological variation inherent in the strain of rats used for this study as all respective values were within the range of the historical control data.
GESTATION INDEX
The gestation index was 100% in test group 0, 1 and 2 and 80% in test group 3. The value of test group 3 was not in the historical control data and therefore assessed as being substance-related and as an adverse effect.
LIVE BIRTH INDEX
The rate live birth indices were 99% in test group 0, 98.4% in test group 1, 99.1% in test group 2 and 87.6% in test group 3. The value of test group 3 was not in the historical control data and therefore assessed as being substance-related and as an adverse effect.
POST-IMPLANTATION LOSS
The postimplantation loss was 3.21 % in test group 0, 3.1 % in test group 1, 4.3 % in test group 2 and 15.93 % in test group 3. These findings were assessed as being substance-related and as an adverse effect. The postimplantation loss of 15.93% in test group 3 was increased mainly because of the high postimplantation loss found in one animal (No. 131).
Effect levels (P0)
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- parental toxicity - systemic effects
- Effect level:
- 200 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: Clinical findings, clinical pathology, pathology.
- Dose descriptor:
- NOAEL
- Remarks:
- fertility and reproductive performance
- Effect level:
- 1 000 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no effects observed at highest tested dose
Results: F1 generation
General toxicity (F1)
- Clinical signs:
- no effects observed
- Mortality / viability:
- mortality observed, treatment-related
- Body weight and weight changes:
- effects observed, treatment-related
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- not examined
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- not examined
Details on results (F1)
The mean number of delivered F1 pups per dam was evenly distributed about the groups.
PUP VIABILITY / MORTALITY
The viability index indicating pup mortality during lactation (PND 0 - 4) was 98.3% (test group 0), 100.0% (test group 1), 99.2% (test group 2), 84.6% (test group 3). Due to a dose dependency, this finding was assessed as being substance-related and as an adverse effect.
One male pup of control group and one female pup of test group 2, two male pups of test group 1, six male pups and 5 female pups of test group 3 were found stillborn.
One male pup of test group 2, seven male pups and five female pups of test group 3 were cannibalized.
These findings were assessed as being substance-related however no final conclusion can be drawn concerning whether this is an adverse finding or not.
SEX RATIO
The sex distribution and sex ratios of live F1 pups on the day of birth and PND 4 did not show substantial differences between the control and the test substance-treated groups; slight differences were regarded to be spontaneous in nature.
PUP CLINCAL OBSERVATIONS
The surviving F1 pups of any test group did not show adverse clinical signs up to scheduled sacrifice on PND 4.
PUP BODY WEIGHT DATA
Mean pup body weights was significantly decreased in males of test group 3 (1000 mg/kg bw/d) on PND 1 and 4 and in females on PND 4. Pup body weight changes were significantly decreased in both gender of test group 3 (1000 mg/kg bw/d).
Mean pup body weights was significantly decreased in males and females of test group 2 (200 mg/kg bw/d) on PND 4. Pup body weight changes were significantly decreased in males of test group 2 (200 mg/kg bw/d) and in females of test group 1 (40 mg/kg bw/d).
Mean pup body weights/ pup body weight changes of all pups in all other test groups were comparable to the control group.
These findings reflected the normal range of biological variation inherent in the strain of rats used for this study as all respective values were within the range of the historical control data.
One male and one female runt were seen in test group 2 (200 mg/kg bw/d). Nine male and five female runts were seen in test group 3 (1000 mg/kg bw/d).
These findings were assessed as being substance-related however no final conclusion can be drawn concerning whether this is an adverse finding or not.
PUP NECROPSY OBSERVATIONS
In test group 3 (1000 mg/kg bw/d) five pups showed post mortem autolysis, one pup was partly cannibalized and one pup showed empty stomach. These findings were assessed as being spontaneous in nature and without biological relevance.
Effect levels (F1)
- Dose descriptor:
- NOAEL
- Remarks:
- developmental toxicity
- Generation:
- F1
- Effect level:
- 200 mg/kg bw (total dose)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: gestation index, live birth index, postimplantation loss
Overall reproductive toxicity
- Reproductive effects observed:
- not specified
Any other information on results incl. tables
Systemic toxicity effects are described under Section 7.5.1, therefore they are not repeated in this section. The NOAEL for general systemic toxicity was 200 mg/kg bw/d for the parental rats because of the major clinical findings, clinical pathology and pathology findings. Here below further details are given on the clinical observations and body weights in parents in terms of relation between maternal and litter toxicity.
In the male parents (Table 1), salivation was observed at 200 and 1000 mg/kg bw during all phases, which was considered to be due to local irritation in the stomach, therefore it was not of systemic nature. Poor conditions was seen pre-mating in one animal at 1000 mg/kg bw. There were no relevant effects on body weight during various phases.
Table 1. Clinical observations & body weights in male parents
Parameter |
Group: |
I |
II |
III |
IV |
|
Dose mg/kg: |
0 |
40 |
200 |
1000 |
No. of parents |
total No. |
10 |
10 |
10 |
10 |
Mortality |
incidence |
0 |
0 |
0 |
0 |
Clinical observations |
|
|
|
|
|
Salivation - premating |
incidence |
0 |
0 |
8 |
10 |
Salivation - mating |
incidence |
0 |
0 |
10 |
10 |
Salivation - postmating |
incidence |
0 |
0 |
8 |
9 |
Poor condition - premating |
incidence |
0 |
0 |
0 |
1 |
Mean bw day 0 - premating |
g |
318,9 |
316,2 |
315,9 |
312,8 |
Mean bw day 7 - premating |
g |
338,1 |
340,1 |
338,5 |
327,1 |
Mean bw day 13 - premating |
g |
357,2 |
358,6 |
354,7 |
338,8 |
Mean bw day 0 - mating |
g |
369,3 |
367,3 |
364,5 |
352,2 |
Mean bw day 0 - postmating |
g |
377,1 |
379,2 |
371,2 |
358,7 |
In the female parents (Table 2), salivation was observed at all dose levels during all phases, which was considered to be due to local irritation in the stomach, therefore it was not of systemic nature. Poor conditions and related findings (e.g. fur piloerection, nose encrusted) were seen during gestation and lactation in two animals at 1000 mg/kg bw. There were no statistically significant effects on body weight premating and during gestation, however there was a statistically significant decrease in mean body weight during lactation (-8.3 and -6% versus control on day 1 and 4, respectively), which was already preceded by a non-significant decrease in mean body weight towards the end of gestation.
Table 2. Clinical observations & body weights in female parents
Parameter |
Group: |
I |
II |
III |
IV |
|
Dose mg/kg: |
0 |
40 |
200 |
1000 |
Maternal findings |
|
|
|
|
|
No. of dams |
total No. |
10 |
10 |
10 |
10 |
Mortality |
incidence |
0 |
0 |
0 |
0 |
Clinical observations |
|
|
|
|
|
Salivation - premating |
incidence |
0 |
0 |
6 |
10 |
Salivation - mating |
incidence |
0 |
0 |
8 |
9 |
Salivation - gestation |
incidence |
0 |
0 |
8 |
9 |
Poor condition - gestation |
incidence |
0 |
0 |
0 |
2 |
Fur piloerection - gestation |
incidence |
0 |
0 |
0 |
2 |
All pups stillborn - gestation |
incidence |
0 |
0 |
0 |
2 |
Apathy - gestation |
incidence |
0 |
0 |
0 |
1 |
Nose encrusted - gestation |
incidence |
0 |
0 |
0 |
1 |
Salivation - lactation |
incidence |
0 |
2 |
8 |
10 |
Poor condition - lactation |
incidence |
0 |
0 |
0 |
2 |
All pups stillborn - lactation |
incidence |
0 |
0 |
0 |
2 |
Complete litter loss - lactation |
incidence |
0 |
0 |
0 |
1 |
Fur piloerection - lactation |
incidence |
0 |
0 |
0 |
1 |
Skin ulceration - lactation |
incidence |
0 |
1 |
0 |
0 |
Reproduction - lactation |
incidence |
0 |
0 |
0 |
3 |
Mean bw day 0 - premating |
g |
216,5 |
215,5 |
213,8 |
215,2 |
Mean bw day 7 - premating |
g |
219,6 |
221,3 |
218 |
218,1 |
Mean bw day 13 - premating |
g |
223,4 |
228,5 |
223,4 |
232,3 |
Mean bw day 0 - gestation |
g |
224,1 |
228,2 |
221,7 |
227,9 |
Mean bw day 7 - gestation |
g |
257,6 |
257,2 |
253,6 |
260,9 |
Mean bw day 14 - gestation |
g |
286,4 |
287,5 |
283,4 |
285,6 |
Mean bw day 20 - gestation |
g |
343,9 |
351,6 |
347 |
325,9 |
|
% vs Control |
100 |
2,2 |
0,9 |
-5,2 |
Mean bw day 0 - lactation |
g |
274,9 |
268,3 |
267,9 |
252,2* |
|
% vs Control |
100 |
-2,4 |
-2,5 |
-8,3 |
Mean bw day 4 - lactation |
g |
280,2 |
277,1 |
273,2 |
263,5* |
|
% vs Control |
100 |
-1,1 |
-2,5 |
-6,0 |
* Dunnet test (two-sided): * p =<0,05
Applicant's summary and conclusion
- Conclusions:
- Under the conditions of the present reproduction/developmental toxicity screening test the NOAEL for fertility and reproductive performance the NOAEL was 1000 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 progeny of the test substance-treated group was found to be 200 mg/kg bw/d.
- Executive summary:
Cyclohexylbenzene was administered daily as an aqueous suspension to groups of 10 male and 10 female Wistar rats (F0 animals) by gavage at doses of 40, 200 and 1000 mg/kg body weight/day. Control animals were dosed daily with the vehicle only (drinking water containing 1% Carboxymethylcellulose with about 5 mg/100 mL Cremophor EL).
The duration of treatment covered a 2 week premating period and mating in both sexes (mating pairs were from the same dose group) as well as entire gestation and 4 days of lactation period in females up to one day prior to the day of schedule sacrifice of the animals. The effects related to repeated-dose toxicity to parental animals are described under the repeated-dose toxicity endpoint Section 7.5, however it was clear that general systemic toxicity was evident at 1000 mg/kg bw as demonstrated by clnical, clinical pathology and pathological changes. The NOAEL for systemic toxicity is 200 mg/kg bw/day.
Evident systemic toxicity was seen in two mother animals dosed at 1000 mg/kg bw/day, expressed by poor general condition towards the end of pregancy, leading to stillborn pups in these animals (partly due to post-implantation loss). Another animal at this dose group delivered 16 pups with smaller size, of which most were canniblised by the mother on PND 1 -2. When these outlier animals were not taken into account, litter sizes at birth were comparable between groups, whereas litter size on day 4 was slightly lower at 1000 mg/kg bw/day compared to control.
The findings seen in the litters at 1000 mg/kg bw were assumed to be secondary to maternal toxicity and stress and/or coincidental outranging high litter size in a few dams. No other relevant findings were retained between groups for reproductive/developmental changes in parents and litters.
Under the conditions of the present reproduction/developmental toxicity screening test the NOAEL for fertility and reproductive performance the NOAEL was 1000 mg/kg bw/d. The NOAEL for developmental toxicity in the F1 progeny of the test substance-treated group was found to be 200 mg/kg bw/d.
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.