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EC number: 248-890-1 | CAS number: 28188-41-2
- 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
Endpoint summary
Administrative data
Key value for chemical safety assessment
Effects on fertility
Description of key information
Toxicity to reproduction
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for 3-(bromomethyl)benzonitrile (28188-41-2).NOAEL was estimated to be 58.69mg/kg bw. When male and female Sprague-Dawley rats were exposed with 3-(bromomethyl)benzonitrile (28188-41-2) orally.
Thus, based on the studies and predictions on 3-(bromomethyl)benzonitrile (28188-41-2). It was considered that no adverse effects on reproductive parameter were observed. Thus, comparing this value with the criteria of CLP regulation 3-(bromomethyl)benzonitrile (28188-41-2) cannot be classified as reproductive toxicant.
Link to relevant study records
- Endpoint:
- toxicity to reproduction
- Type of information:
- (Q)SAR
- Adequacy of study:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- results derived from a valid (Q)SAR model and falling into its applicability domain, with limited documentation / justification
- Justification for type of information:
- Data is from OECD QSAR toolbox v3.3 and the QMRF report has been attached.
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: As mentioned below
- Principles of method if other than guideline:
- Prediction was done using OECD QSAR toolbox v3.3, 2017
- GLP compliance:
- not specified
- Limit test:
- no
- Justification for study design:
- No data available
- Specific details on test material used for the study:
- - Name of the test material: α-bromo-m-toluonitrile
- IUPAC name: 3-(bromomethyl)benzonitrile
- Molecular formula: C8H6BrN
- Molecular weight: 196.046 g/mol
- Smiles: N#Cc1cc(CBr)ccc1
- Inchi: 1S/C8H6BrN/c9-5-7-2-1-3-8(4-7)6-10/h1-4H,5H2
- Substance type: Organic
- Physical state : Solid crystalline powder (Off white) - Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- No data available
- Route of administration:
- oral: gavage
- Vehicle:
- not specified
- Details on exposure:
- No data available
- Details on mating procedure:
- No data available
- Analytical verification of doses or concentrations:
- not specified
- Duration of treatment / exposure:
- Exposure period: male: 14 days before mating and thereafter 31 days, female: 14 days before mating to day 3 of lactationPremating exposure period (males): 14 daysPremating exposure period (females): 14 daysDuration of test: male: to day 45 female: to day 3 of lactation
- Frequency of treatment:
- daily
- Dose / conc.:
- 58.69 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 12
- Control animals:
- yes
- Details on study design:
- No data available
- Positive control:
- No data available
- Parental animals: Observations and examinations:
- No data available
- Oestrous cyclicity (parental animals):
- No data available
- Sperm parameters (parental animals):
- No data available
- Litter observations:
- No data available
- Postmortem examinations (parental animals):
- No data available
- Postmortem examinations (offspring):
- No data available
- Statistics:
- No data available
- Reproductive indices:
- No data available
- Offspring viability indices:
- No data available
- Clinical signs:
- no effects observed
- Dermal irritation (if dermal study):
- not specified
- Mortality:
- not specified
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Behaviour (functional findings):
- not specified
- Immunological findings:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- not specified
- Other effects:
- no effects observed
- Reproductive function: oestrous cycle:
- not specified
- Reproductive function: sperm measures:
- not specified
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- 58.69 mg/kg bw/day
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- body weight and weight gain
- food consumption and compound intake
- gross pathology
- histopathology: non-neoplastic
- reproductive performance
- Remarks on result:
- other: No effects on reperoductive parameters
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Clinical signs:
- not specified
- Dermal irritation (if dermal study):
- not specified
- Mortality / viability:
- not specified
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- not specified
- Food efficiency:
- not specified
- Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not specified
- Haematological findings:
- not specified
- Clinical biochemistry findings:
- not specified
- Urinalysis findings:
- not specified
- Sexual maturation:
- not specified
- Organ weight findings including organ / body weight ratios:
- not specified
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Other effects:
- not specified
- Behaviour (functional findings):
- not specified
- Developmental immunotoxicity:
- not specified
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 58.69 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- not specified
- Basis for effect level:
- body weight and weight gain
- gross pathology
- histopathology: non-neoplastic
- Remarks on result:
- other: No overall developmental effects was observed
- Critical effects observed:
- not specified
- System:
- other: not specified
- Organ:
- not specified
- Treatment related:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Reproductive effects observed:
- not specified
- Treatment related:
- not specified
- Relation to other toxic effects:
- not specified
- Dose response relationship:
- not specified
- Relevant for humans:
- not specified
- Conclusions:
- In reproductive toxicity study, NOAEL was estimated to be 58.69mg/kg bw. When male and female Sprague-Dawley rats were exposed with 3-(bromomethyl)benzonitrile (28188-41-2) orally.
- Executive summary:
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for 3-(bromomethyl)benzonitrile (28188-41-2).Male and female reproductive parameters were unaffected by test material administration. Hence, NOAEL was estimated to be 58.69mg/kg bw. When male and femaleSprague-Dawley ratswere exposed with 3-(bromomethyl)benzonitrile (28188-41-2) orally.
Reference
The
prediction was based on dataset comprised from the following
descriptors: NOAEL
Estimation method: Takes average value from the 6 nearest neighbours
Domain logical expression:Result: In Domain
((("a"
or "b" or "c" or "d" or "e" )
and "f" )
and ("g"
and "h" )
)
Domain
logical expression index: "a"
Referential
boundary: The
target chemical should be classified as Benzyl Halides by Aquatic
toxicity classification by ECOSAR
Domain
logical expression index: "b"
Referential
boundary: The
target chemical should be classified as SN2 OR SN2 >> SN2 reaction at
sp3 carbon atom OR SN2 >> SN2 reaction at sp3 carbon atom >> Alkyl
halides OR SN2 >> SN2 reaction at sp3 carbon atom >> alpha-Halobenzyls
(and related cyano, sulfate and sulphonate subs. chem.) by Protein
binding by OECD ONLY
Domain
logical expression index: "c"
Referential
boundary: The
target chemical should be classified as SN2 OR SN2 >> Nucleophilic
substitution at sp3 carbon atom OR SN2 >> Nucleophilic substitution at
sp3 carbon atom >> Alkyl halides OR SN2 >> Nucleophilic substitution on
benzilyc carbon atom OR SN2 >> Nucleophilic substitution on benzilyc
carbon atom >> alpha-Activated benzyls by Protein binding by OASIS v1.3
ONLY
Domain
logical expression index: "d"
Referential
boundary: The
target chemical should be classified as SN2 OR SN2 >> SN2 at an sp3
Carbon atom OR SN2 >> SN2 at an sp3 Carbon atom >> Aliphatic halides by
DNA binding by OECD ONLY
Domain
logical expression index: "e"
Referential
boundary: The
target chemical should be classified as AN2 OR AN2 >> Shiff base
formation for aldehydes OR AN2 >> Shiff base formation for aldehydes >>
Haloalkane Derivatives with Labile Halogen OR SN2 OR SN2 >> Acylation
involving a leaving group OR SN2 >> Acylation involving a leaving group
>> Haloalkane Derivatives with Labile Halogen OR SN2 >> Alkylation,
nucleophilic substitution at sp3-carbon atom OR SN2 >> Alkylation,
nucleophilic substitution at sp3-carbon atom >> Haloalkane Derivatives
with Labile Halogen by DNA binding by OASIS v.1.3 ONLY
Domain
logical expression index: "f"
Referential
boundary: The
target chemical should be classified as Not calculated by Hydrolysis
half-life (Ka, pH 7)(Hydrowin) ONLY
Domain
logical expression index: "g"
Parametric
boundary:The
target chemical should have a value of log Kow which is >= -0.538
Domain
logical expression index: "h"
Parametric
boundary:The
target chemical should have a value of log Kow which is <= 7.75
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 58.69 mg/kg bw/day
- Study duration:
- subchronic
- Species:
- rat
- Quality of whole database:
- Data is Klimicsh 2 and from QSAR Toolbox 3.3. (2017)
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Additional information
Reproductive toxicity
In different studies, 3-(bromomethyl)benzonitrile (28188-41-2) has been investigated for reproductive toxicity to a greater or lesser extent. Often are the studies based on in vivo experiments and estimated data in rodents, i.e. most commonly in rats for 3-(bromomethyl)benzonitrile (28188-41-2).The predicted data using the OECD QSAR toolbox has also been compared with the experimental studies performed on structurally similar read across substance.
In a prediction done by SSS (2017) using the OECD QSAR toolbox with log kow as the primary descriptor, the reproductive toxicity was estimated for 3-(bromomethyl)benzonitrile (28188-41-2).NOAEL was estimated to be 58.69mg/kg bw. When male and female Sprague-Dawley rats were exposed with 3-(bromomethyl)benzonitrile (28188-41-2) orally.
It is supported by experimental study conducted by HPVIS (HPVIS, United States Environmental protection, 2006)on structurally similar read across substance 1,3-Benzenedicarbonitrile (626-17-5). The reproductive toxicity study of 1,3-Benzenedicarbonitrile (626-17-5) was performed in male and female rats. The teat material mixed with fed Purina B Certified Rodent Chow No. 5002 in dose concentration 0, 5, 10, 25 and 50 mg/kg/day. The concentration of test material administered to the rats was adjusted weekly in order to achieve as closely as possible the desired dietary intake of treatment. The achieved dosages of test material were calculated at the end of each week based on the dietary concentrations and body weights and food consumption for that week. After initiation of mating on Study Day 81, diets were prepared weekly at constant concentration based on Week 11 body weight and food consumption data for the remainder of the study. Control animals were fed PurinaB Certified Rodent Chow No. 5002 without test substance ad libitum and fresh tap water was available ad libitum. 25 rats of each sex were assigned to each group. Ten animals per sex from each group were killed after at least 31 days on the test diets, and the remaining 15 of each sex per group were exposed to test material for a total of at least 122 days. For the one-generation reproduction phase, mating commenced of Week 11. Rats were mated for a total of 14 days during which no body weight or food consumption measurements were recorded.
Compound-related effects on body weight and body weight gain with corresponding changes in food consumption were observed in males at 25 and 50 mg/kg/day and females at 10, 25 and 50 mg/kg/day during the 28- day feeding phase of the study. Histopathologic examinations revealed compound-related increases in the incidence of centrilobular hepatocytomegaly in males and females at 50 mg/kg/day and males at 25 mg/kg/day. Furthermore, a compound related increase in hyaline droplet formation was noted in the kidneys of males when compared to controls. No females exhibited this finding. Hyaline droplet formation in the proximal tubular epithelium of kidneys in male rats is indicative of abnormal accumulation of alpha-2 m-globulin, a protein reported to be unique to the rat. Clinical chemistry analyses revealed significant increases in ALT in males at 10 and 50 mg/kg/day and in females at 10 mg/kg/day and higher. In addition, serum cholesterol was in 50mg/kg bw dose group males than controls.
Urine volume was higher and specific gravity was lower in males at 25 and 50 mg/kg/day and females at 50 mg/kg/day. Parental reproductive parameters appeared to be unaffected. No compound-related effects were seen on mating, fertility or gestation length .Apparent compound-related reproductive effects on offspring survival in utero were noted. This was evidenced by an increase in the number of stillborn pups with a corresponding decrease in the number of live born pups and litter size at 50 mg/kg/day. Similar effects were not observed at lower dietary concentrations,(10,25 mg/kg /day).Hence in the 28-day feeding phase ,LOEL was considered to be 5mg/kg bw in male rats because of the increased incidence of hyaline droplet formation in the kidneys of males at all dietary levels. The LOEL was considered to be 10mg/kg bw for females. Based on the reductions in body weight, body weight gain, food consumption and increases in ALT at 10 mg/kg/day and higher, While for the reproductive phase No Observed Adverse Effect Level (NOAEL) was considered to be 25mg/kg/day, on the bases of No compound-related effects were seen on mating, fertility or gestation length and LOAEL was considered to be 50mg/g bw , on the bases of an increase in the number of stillborn pups with a corresponding decrease in the number of live born pups and litter size at 50 mg/kg/day. When male and female rats were treated with1,3-Benzenedicarbonitrile (626-17-5)orally.
It is further supported by experimental study conducted by OECD SIDS (SIDS initial assessment report for SIAM 17(benzene, 1-chloro-2-(chloromethyl) 2003) on structurally similar read across substance 2-Chlorobenzyl chloride (611-19 -8) The reproductive toxicity study of 2-Chlorobenzyl chloride (611-19-8) was performed in male and female Sprague-Dawley rats according OECD Guideline 422, "Combined Repeated Dose Toxicity Study with the Reproduction/Developmental Toxicity Screening Test". The test material diluted with 0.1% Tween 80 solution and administered in dose concentration0, 2, 10, and 50 mg/kg/day by oral gavage.12 males and 12 females were used in each dose level. Males were dosed for 14 days before mating; during the mating period and up to the day before scheduled kill (total 45 days). Females were dosed for 14 days before mating, during the mating period, during the gestation and four days after delivery (total 41-48 days). For mating, one male to one female mating was used, and the female was placed with the same male until pregnancy occurs or 7 days have elapsed. Day 0 of pregnancy was defined as the day a vaginal plug or sperm was found. The rats were weighed at Day 3, 7 and 14, and weekly thereafter. During the gestation, females were weighed at Day 0, 7, 14 and 20 of gestation, and Day 0 and 4 of lactation. The body weights of the live pups were also recorded. Gestated females were delivered and lactated through Day 4 of lactation. At the termination of the experiment, all rats were sacrificed and necropsied. All pups were also sacrificed and necropsied.
Test substance had no effects in reproductive parameters such as the mating index, the fertility index, number of corpora lutea or implantations, the implantation index, the delivery index, the gestation index, gestation length, parturition or maternal behaviour., On examination of neonates, there were no significant differences in number of offspring or live offspring, the sex ratio, the live birth index, the viability index or body weight. No abnormal findings related to the test substance were found for external features, clinical signs or necropsy of the offspring. Hence NOAEL was considered to >50mg/kg bw for parental and F1 offspring on the bases no effects were observed on reproductive and developmental parameters. When male and female were treated with 2-Chlorobenzyl chloride (611-19-8) orally.
Thus, based on the above studies and predictions on 3-(bromomethyl)benzonitrile (28188-41-2). It was considered that no adverse effects on reproductive parameter were observed. Thus, comparing this value with the criteria of CLP regulation 3-(bromomethyl)benzonitrile (28188-41-2) cannot be classified as reproductive toxicant.
Effects on developmental toxicity
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via inhalation route
- Endpoint conclusion:
- no study available
Effect on developmental toxicity: via dermal route
- Endpoint conclusion:
- no study available
Justification for classification or non-classification
Thus, comparing this value with the criteria of CLP regulation 3-(bromomethyl)benzonitrile (28188-41-2) cannot be classified as reproductive toxicant.
Additional information
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