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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 200-753-7 | CAS number: 71-43-2
- 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
![](https://echa.europa.eu./o/diss-blank-theme/images/factsheets/A-REACH/factsheet/print_toxicological-information.png)
Developmental toxicity / teratogenicity
Administrative data
- Endpoint:
- developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: GLP-compliant (assumed), near guideline, animal experimental study, published in peer-reviewed literature, some limitations in design but otherwise adequate for assessment
Data source
Reference
- Reference Type:
- publication
- Title:
- Unnamed
- Year:
- 1 981
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- OECD Guideline 414 (Prenatal Developmental Toxicity Study)
- Deviations:
- yes
- Remarks:
- exposure GD6-15. Compliant with guideline of the time but not current (2001) version
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Benzene
- EC Number:
- 200-753-7
- EC Name:
- Benzene
- Cas Number:
- 71-43-2
- Molecular formula:
- C6H6
- IUPAC Name:
- benzene
- Details on test material:
- no information reported
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Wilmington, Mass., USA
- Housing: 5/cage in stainless steel mesh cages
- Diet: Purina Laboratory Chow ad libitum except during exposure
- Water: ad libitum except during exposure
ENVIRONMENTAL CONDITIONS: No details reported
Administration / exposure
- Route of administration:
- inhalation: vapour
- Type of inhalation exposure (if applicable):
- whole body
- Vehicle:
- other: air
- Details on exposure:
- Benzene was generated as vapour by bubbling metered house air through a fritted glass tube submerged in benzene in a 500 mL Erlenmeyer flask
with a glass-wool filter plug in the effluent line. The vapour was mixed with filtered conditioned air drawn into the chamber turret at 1000 L/min
via a tangential duct which assured rapid dispersion within the pyramidal top of the chamber. Analytical concentrations of benzene vapour were determined once daily by gas chromatography. - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analytical concentrations of benzene vapour were determined once daily by gas chromatography. The mean chamber concentrations (±SD) were 9.75±1.16, 52.9±5.33 and 513.9±25.3 ppm for the target concentrations of 10, 50 and 500 ppm respectively.
- Details on mating procedure:
- Two females were housed with one male until signs of insemination were observed by microscopic examination of the returns from a vaginal douche.
If sperm or a vaginal plug were observed, the female was assumed to have mated and was removed from the breeding regimen. The day on which evidence of mating was observed was designated as Day 0 of gestation. - Duration of treatment / exposure:
- gestation days 6-15
- Frequency of treatment:
- daily, 7 h/day
- Duration of test:
- up to gestation day 20
- No. of animals per sex per dose:
- 17, 18, 20, 19 rats for the 0, 10, 50 and 500 ppm groups respectively
- Control animals:
- yes, sham-exposed
Examinations
- Maternal examinations:
- CLINICAL OBSERVATIONS AND MORTALITY: Yes (mortality, signs of toxicity and pregnancy rate)
- Time schedule: Not reported
BODY WEIGHT: Yes
- Time schedule for examinations: Days 0, 5, 15 and 20
POST-MORTEM EXAMINATIONS: Yes
- Sacrifice on gestation day 20
HAEMATOLOGY: At gestation Day 5 and just prior to caesarean delivery on Day 20, venous blood samples were obtained from each female and erythrocyte, total leukocyte, and differential leukocyte counts were determined. - Ovaries and uterine content:
- On day 20 females were sacrificed, caesarean sections were performed and numbers of ovarian corpora lutea, resorption sites and live and dead foetuses examined.
- Fetal examinations:
- Each foetus was examined externally and weighed. Whole-body transverse sections were made and examined microscopically for visceral changes (approximately one third of foetuses). The skeletons of the remaining foetuses were examined microscopically for anomalies and ossification.
- Statistics:
- The variances of the mean changes in maternal body weights and in means of the mean litter foetal body weights and lengths of each treated group were tested for statistical significance (F test). If there were no significant difference among the variances, the differences in means were tested by Student's t test. However, if there were a significant difference among the variances, the differences in means were tested by Cochran's approximation of t . Mean maternal body weights and body weight gains were also evaluated using analysis of covariance and the method of Gomes and Howell. The reproduction indices and the number of foetal variants of the control and treated groups were analyzed by the χ2 method or regression analysis.
All differences that would occur less than 5% of the time by chance were accepted as statistically significant.
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:yes
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- 10 ppm (nominal)
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEC
- Effect level:
- 32 mg/m³ air (nominal)
- Basis for effect level:
- other: maternal toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:yes
Effect levels (fetuses)
open allclose all
- Dose descriptor:
- NOAEC
- Effect level:
- 10 ppm (nominal)
- Basis for effect level:
- other: Developmental Toxicity
- Dose descriptor:
- NOAEC
- Effect level:
- 32 mg/m³ air (nominal)
- Basis for effect level:
- other: Developmental Toxicity
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Maternal toxicity
No deaths or signs of toxicity were noted in the dams and the pregnancy rate was within the expected range.
|
0 ppm |
10 ppm |
50 ppm |
500 ppm |
Number of dams mated |
17 |
18 |
20 |
19 |
Number of dams pregnant |
11 |
15 |
15 |
14 |
Pregnancy rate (%) |
64.7 |
83.3 |
75.0 |
73.7 |
Maternal weight at 50 and 500 ppm was significantly lower than control on day 15 and maternal weight gain from days 5 -15 was also reduced at these dose levels:
Maternal bodyweight |
0 ppm |
10 ppm |
50 ppm |
500 ppm |
Day 5: Mean weight (g) |
239 |
252 |
251 |
241 |
Day 15: Mean weight (g) Mean gain days 5-15 (g) |
298 59 |
306 54.2 |
290* 39* |
278* 37* |
Day 20: Mean weight (g) Mean gain days 15-20 (g) |
339 42 |
362 56 |
338 48 |
337 59 |
* significantly different from control
No treatment-related effects were seen in any of the haematology parameters, at necropsy or on the number of implantation sites, resorbed and dead foetuses, incidence of live foetuses or sex distribution of the foetuses.
Foetal effects
Statistically significant decreases in the mean crown-rump distance of the high-dosed foetuses and mean body weights of the mid- and high-dosed live foetuses were noted when compared with the controls.
Live foetuses |
0 ppm |
10 ppm |
50 ppm |
500 ppm |
Mean body weight (g) |
4.4 |
4.4 |
3.8* |
3.6* |
Mean crown-rump length (cm) |
4.1 |
4.1 |
3.9 |
3.8* |
* significantly different from control
Statistically significant increases in the incidence of skeletal findings indicative of incomplete ossification of the skeleton at 50 and 500 ppm. There was no evidence of treatment-related foetal dysmorphogenesis.
Skeletal findings: |
0 ppm |
10 ppm |
50 ppm |
500 ppm |
Number of litters examined |
11 |
15 |
15 |
13 |
Number of foetuses examined |
75 |
134 |
91 |
98 |
Foetuses with delayed ossification: In skull In vertebral column In rib cage In pelvic girdle In extremities |
0 0 0 0 0 |
0 0 0 0 0 |
0 0 17 0 17 |
8 9 23 8 17 |
Foetuses with variants: In ribs In forefeet |
0 0 |
0 0 |
0 0 |
1 2 |
Foetuses with anomalies In skull |
0 |
0 |
0 |
1 |
Mean values: No. of caudals No. of metacarpals and phalages No of metatarsals and phalages |
5.4 10.5 8.9 |
5.3 11.0 9.2 |
4.6 9.4 7.6 |
4.0* 8.9 7.7 |
Table based on Kuna and Kapp, 1981 Table 3
Visceral examination revealed slight dilation of the ventricles in the brain in five mid- and four high-dosed animals but there was no clear evidence for an association with treatment with benzene.
Applicant's summary and conclusion
- Conclusions:
- Benzene inhalation at 50 ppm (160 mg/m3) during pregnancy induces maternal and developmental toxicity. There was no evidence of teratogenicity at the highest dose tested 500 ppm (1600 mg/m3). The NOAEC for teratogenicity was 500 ppm (1600 mg/m3); the NOAEC for maternal and developmental toxicity was 10 ppm (32 mg/m3).
- Executive summary:
Developmental toxicity was investigated in groups of pregnant female rats exposed 7h/day from day 6 to day 15 of gestation to benzene concentrations of 0, 10, 50 or 500 ppm (0, 32, 160, 1600 mg/m3). On gestation day 5 and prior to termination venous blood samples were taken from each female and erythrocyte, total leukocyte and differential leukocyte counts determined. Dams were killed on day 20 and the following observations made: number of corpora lutea, number of resorptions, number of live and dead foetuses. Foetuses were examined for external, skeletal and visceral abnormalities, sex was determined and body weight and crown-rump length measured.
No deaths or signs of toxicity were noted in the dams. Maternal body weight and body weight gain was decreased at 50 and 500 ppm. No treatment-related effects were seen in any of the haematology parameters, necropsy findings or on the number of implantation sites, resorbed and dead foetuses, incidence of live foetuses or sex distribution of the foetuses. Statistically significant decreases in the mean crown-rump length of the 500 ppm group foetuses and mean body weights of the 50 ppm and 500 ppm live foetuses were noted when compared with the controls. As a consequence these foetuses showed signs of incomplete ossification in comparison with the larger and heavier control foetuses. Visceral examination revealed slight dilation of the ventricles in the brain in five 50 ppm and four 500 ppm animals.
The NOAEC for teratogenicity was 500 ppm (1600 mg/m3); the NOAEC for maternal and developmental toxicity was 10 ppm (32 mg/m3).
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.
![ECHA](/o/diss-blank-theme/images/factsheets/A-REACH/factsheet/echa_logo.png)