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EC number: 203-628-5 | CAS number: 108-90-7
- 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
Repeated dose toxicity: inhalation
Administrative data
- Endpoint:
- sub-chronic toxicity: inhalation
- Remarks:
- other: 2-generation reproduction toxicity study
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: 2-generation reproduction toxicity study as surrogate for a subchronic inhalation toxicity study
Cross-reference
- Reason / purpose for cross-reference:
- reference to same study
Data source
Referenceopen allclose all
- Reference Type:
- publication
- Title:
- A two-generation reproduction study with monochlorobenzene vapor in rats
- Author:
- Nair RS, Barter JA, Schroeder RE, Knezevich A & Stack CR
- Year:
- 1 987
- Bibliographic source:
- Fundamental and Applied Toxicology, 9:678-686
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 1 986
- Report date:
- 1986
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD Guideline 416 (Two-Generation Reproduction Toxicity Study)
- Deviations:
- yes
- Remarks:
- - F1 generation was exposed to test substance 1 week after weaning instead of being exposed at weaning. Sperm parameters oestrus cycle not examined,. only brain, liver and kidney were weighed,reproductive organs (m+f), liver, kidneys microscopically
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Chlorobenzene
- EC Number:
- 203-628-5
- EC Name:
- Chlorobenzene
- Cas Number:
- 108-90-7
- Molecular formula:
- C6H5Cl
- IUPAC Name:
- chlorobenzene
- Details on test material:
- - Name of test material (as cited in study report): monochlorobenzene (MCB)
- Physical state: liquid
- Analytical purity: 99.9 %
-Boiling point: 132.1°C
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
Administration / exposure
- Route of administration:
- inhalation
- Type of inhalation exposure:
- whole body
- Vehicle:
- other: preconditioned air
- Details on inhalation exposure:
- TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, MI
- Age at study initiation: (P) 6 wks; (F1) 6 wks
- Weight at study initiation: Males: 129-233 g; Females: 131-162 g
- Housing: all animals were individually housed in suspended stainless stell cages with wire mesh floors except during lactation.
- Diet (e.g. ad libitum): Rodent Laboratory Chow/5002 (registered trademark of Ralston Purina Company, St. Louis, MO) ad libitum.
- Water (e.g. ad libitum) :ad libitum during non-exposure period.
- Acclimation period: 13 days prior to initiation of exposure during non-exposure period.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 65-77°F
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12hrs dark/12hrs light cycle.
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- MIRAN 1 A organic vapour analyzer was used. At least 4 samples were drawn daily at hourly intervals from each exposure chamber.
- Duration of treatment / exposure:
- Premating exposure period (males): F0 males: 10 weeks; F1 males: 11 weeks
Premating exposure period (females): F0 females: 10 weeks; F1 females: 11 weeks
Exposure period: F0 and F1 generation: during mating period, d0 - 20 of gestation and d4 - 21 of lactation
Duration of test: until weaning (day 21 of lactation) of F2 pups - Frequency of treatment:
- 6 hour per day, 7 days per week
Doses / concentrations
- Remarks:
- Doses / Concentrations:
F0 and F1 generation: 0, 50, 150 or 450 ppm (0, 234, 702 or 2106 mg/m³)
Basis:
- No. of animals per sex per dose:
- 30
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- Groups of 30 males and 30 females CD rats, designed as P generation, were exposed to vapor of monochlorobenzene (MCB) at target concentrations of 0 , 50 , 150, or 450 ppm (0, 234, 702 or 2106 mg/m³) for 10 weeks prior to mating and during mating, gestation, and lactation. The progeny of the P generation was designed as the F1 generation and groups of 30 male and 30 female F1 animals were exposed to the same concentration of MCB as the F0 parents. Exposure of F1 animals was initiated 1 week postweaning and lasted 11 weeks prior to the mating and through mating, gestation, and lactation. All F2 pups were observed through weaning at which time they were killed.
Observations made during the study included body weights, food consumption, mating and fertility indices, pup and litter survival indices, and histopathology of selected tissues. - Positive control:
- not required
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All adult and weanling animals were observed for mortality and clinical signs twice daily.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Detailed physical examinations were performed weekly.
BODY WEIGHT: Yes
- Time schedule for examinations: Male body weights were recorded weekly; female body weights were recorded weekly prior to mating, on days 0, 4, 14, and 20 of gestation, on days 0, 4, 7, 14 and 21 of lactation, and weekly again following lactation.
STANDARDISATION OF LITTERS
- Performed on day 4 postpartum: yes
- If yes, maximum of 8 pups/litter (4/sex/litter as nearly as possible).
PARAMETERS EXAMINED
The following parameters were examined in [F0 / F1/ F2] offspring:
number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical abnormalities.
- Sacrifice and pathology:
- GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was not determined for pups born or found dead.
SACRIFICE (parental animals)
- Male animals: All surviving animals were sacrificed after weaning of the F1 generation.
- Maternal animals: All surviving animals were sacrificed after weaning of the F1 generation.
HISTOPATHOLOGY / ORGAN WEIGHTS
The tissues indicated in Table 1 were prepared for microscopic examination and weighed, respectively.
SACRIFICE (offspring)
- The F1 offspring not selected as parental animals and all F2 offspring were sacrificed at 21 days of age (weaning). - Other examinations:
- The mating index for males (ratio of number of males for which mating was confirmed in at least one female to total number of males) and
the mating index for females (ratio of number of females showing evidence of mating to total number of females),
pregnancy rate (ratio of number pregnant to number mated), and
fertlity index for males (ratio of number of males impregnating a female to number mating) were calculated for each of the two matings.
Pup viability index at birth (total number of live pups at day 0 / total number of pups observed (live plus dead pups at day 0 for individual females
Pup survival index at day 4: total number of live pups at day 4 (precull) / total number of live pups at day 0 for individual females
Pup survival index at day 21: total no of live pups at day 21 / total number of live pups at day 4 (postcull) for individual females
Litter survival index: total number of litters with live pups at weaning (day 21) / total number of litters with live pups at birth - Statistics:
- Mean body weights, food consumption, organ weights, organ to body weight ratios, gestation lengths, and numbers of offspring were evaluated statistically using the following methods: Bartlett´s test, parametric methods (one-way analysis of variance which was followed by a Dunnett test) , Kruskal- Wallis test, and Dunn´s summed rank test.
Results and discussion
Results of examinations
- Details on results:
- Parental animals
--Results on reproductive toxicity are reported under 7.81
--Results on general toxicity
ORGAN WEIGHTS (PARENTAL ANIMALS)
Significant increases in mean absolute and/or relative liver weight were observed in the both P+F1 generation in the 150 and 450 ppm groups.
In the low-concentration group, only the relative liver weights of the F1 male rats were elevated.
males
absolute liver weights(g): control, 50, 150, 450 ppm
P: 19.25, 19.03, 21.48(p<=0.01), 21.84(p<=0.01) F1: 18.31, 19.46, 21.71(p<=0.01), 23.35(p<=0.01)
relative liver weights
P: 3.61, 3.60, 4.06(p<=0.01), 4.12(p<=0.01) F1: 3.47, 3.73(p<=0.05), 4.15(p<=0.01), 4.44(p<=0.01)
females
absolute liver weights(g): control, 50, 150, 450 ppm
P 11.45, 12, 12.08, 13.27(p<=0.01) F1: 12.36,12.7, 13.13, 13.95(p<=0.01)
relative liver weights
P: 3.77, 3.89, 3.95(p<=0.05), 4.41(p<=0.01) F1: 4.16, 4.17, 4.36, 4.59 (p<=0.01)
GROSS PATHOLOGY (PARENTAL ANIMALS)
--male, Increase in the incidence of small flaccid testes (50, 150, 450 ppm):
P: 0/30, 1/30, 3/30 F1: 0/30, 1/30, 5/30
--increase in incidence of dilated renal pelvis (control, 50, 150, 450 ppm)
male
P: 1/30, 1/30, 2/30, 4/30 F1: 1/30, 4/30, 6/30, 4/30
female:
P: 5/30, 4/30, 6/30, 5/30 F1: 0/30, 1/30, 2/30, 2/30
HISTOPATHOLOGY (PARENTAL ANIMALS)
Microscopic changes related to treatment were observed in the liver and kidney.
--Hepatocellular hypertrophy- incidence (0, 50, 150, 450 ppm)
male
P: 0/30, 0/30, 5/30, 14/30 F1: 2/30, 0/30, 3/30, 7/30.
All affected male rats showed only minimal to mild hepatocellular hypertrophy.
female
Only one high-concentration level female rat in the P generation showed hepatocellular hypertrophy (data not shown).
--Renal degeneration and inflammatory lesions were limited to the male rats.
The incidence and severity of renal changes were elevated in the mid-and high-concentration groups.
P. 30 males examined from each group: (0, 50, 150, 450 ppm)
bilateral tubular dilation/eosinophilic material : 0, 1, 4, 15
bilateral chronic interstitial nephritis : 1, 2, 7, 9
bilateral foci if regenerative epithelium : 0, 1, 5, 8
P: 30 females were examined of the control and 450 ppm group:
bilateral chronic interstitiial nephritis 0/30; 2/30
F1. 30 males examined from each group: (0, 50, 150, 450 ppm)
bilateral tubular dilation/eosinophilic material : 4, 3, 8, 16
bilateral chronic interstitial nephritis : 0, 1, 6, 11
bilateral foci if regenerative epithelium : 1, 0, 4, 10
F1: 30 females were examined of the control and the 450 ppm group
Unilateral tubular dilatation /eosinophilic material: 0/30; 3/30
VIABILITY (OFFSPRING)
No mortality was observed in the treated and control groups of the F1 generation.
In F2 litters, a slight decrease in pup survival index (days 0-4) was observed in the higest concentration level only.
The majority of the decrease in pup survival index(day 0-4) at the highest concentration level was attributed to two dams; one dam lost 12 of 15 pups during lactation days 0-4, and the other dam lost all 10 pups during the same time period. The authors stated that excluding pup survival data for these 2 litters the day 0-4 pup survival index for the high-concentration group was94.5 % which is similar to control value. they concluded that if this had been a compound-related response, more affected litters would have been expected.
Therefore, pup survival indices for control and treated animals for both litters were considered comparable.
further details . see section 7.8.1
Effect levels
open allclose all
- Key result
- Dose descriptor:
- LOAEC
- Remarks:
- (systemic toxicity)
- Effect level:
- ca. 50 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: see 'Remark'
- Dose descriptor:
- NOAEC
- Remarks:
- (fertility)
- Effect level:
- ca. 450 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effect observed
- Key result
- Dose descriptor:
- NOAEC
- Remarks:
- (offspring)
- Effect level:
- ca. 450 ppm
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: no adverse effect observed
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Executive summary:
Groups of 30 males and 30 females CD rats, designed as P generation, were exposed to vapor of monochlorobenzene (MCB) at target concentrations of 0 , 50 , 150, or 450 ppm (0, 234, 702 or 2106 mg/m³) for 10 weeks prior to mating and during mating, gestation, and lactation. The progeny of the P generation was designed as the F1 generation and groups of 30 male and 30 female F1 animals were exposed to the same concentration of MCB as the F0 parents. Exposure of F1 animals was initiated 1 week postweaning and lasted 11 weeks prior to the mating and through mating, gestation, and lactation. All F2 pups were observed through weaning at which time they were killed. Observations made during the study included body weights, food consumption, mating and fertility indices, pup and litter survival indices, and histopathology of selected tissues.
No mortality was observed during the course of this study. No adverse effect of treatment was evident on body weight, food consumption, and physical observation. Overall, reproductive performance, fertility and development of pups were not affected by treatment with monochlorobenzene yielding a NOAEC of 450 ppm (corresponding to 2106 mg/m³) for reproduction and development.
However, post mortem examinations revealed significantly elevated absolute and relative liver weights in F0 and F1 male and female rats at 150 and 450 ppm and at 50 ppm in F1 males accompanied by hepatocellular hypertrophy in F0 and F1 males exposed to 150 and 450 ppm. In addition, renal changes (tubular dilation with eosinophilic material, interstitial nephritis, and foci of regenerative epithelium) were observed mainly in F0 and F1 male rats exposed to 150 and 450 ppm. The significance of reported degeneration of the testicular germinal epithelium in male rats at 450 ppm is unclear because no histopathological correlate is reported. Thus, the LOAEC (systemic toxicity) is considered to be 50 ppm (corresponding to 234 mg/m³).
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