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Please be aware that this old REACH registration data factsheet is no longer maintained; it remains frozen as of 19th May 2023.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: 213-322-3 | CAS number: 937-14-4
- 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
The potential toxic effects of the substance when given orally by gavage for a minimum of 28 days to Wistar Han rats was determined employing the combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test. The potential to affect male and female reproductive performance such as gonadal function, mating behavior, conception, parturition and early postnatal development was also evaluated in this study.The dose levels in this study were 0, 15, 50 and 150 mg/kg/day, based on the results of the dose range finder.No parental toxicity was observed up to the highest dose level tested (150 mg/kg). A few non-adverse changes were noted at 50 and/or 150 mg/kg and consisted of slight salivation after dosing at 50 and 150 mg/kg (in a dose-related manner), regarded as a physiological response related to the irritant properties of the substance rather than a sign of systemic toxicity, and a gelatinous thyroid gland at 150 mg/kg in 2/10 females. This macroscopic finding was not associated with histopathological alterations in the thyroid gland. No reproduction toxicity was observed up to the highest dose level tested (150 mg/kg). Based on the results of this combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test, the No Observed Adverse Effect Levels (NOAELs) of the substance is 150 mg/kg bw/day for parental and reproductive effects.
Link to relevant study records
- Endpoint:
- screening for reproductive / developmental toxicity
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 09 October 2017 - 02 March 2018
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- guideline study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Version / remarks:
- 2016
- Deviations:
- yes
- Remarks:
- None of the deviations were considered to have impacted the overall integrity of the study or the interpretation of the study results and conclusions.
- GLP compliance:
- yes
- Limit test:
- no
- Specific details on test material used for the study:
- Batch: A0378021
Purity/Composition: 98.8% of 3- Chloroperoxybenzoic acid (72%) balanced with 3- chlorobenzoic acid (8.8%) and water (18%) (Appendix 3)
Test item storage: In refrigerator (2-8°C)
Stable under storage conditions until: 31 October 2019 (retest date) - Species:
- rat
- Strain:
- Wistar
- Remarks:
- Crl: WI(Han)
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- The animals were allowed to acclimate to the Test Facility toxicology accommodation for 7 days prior to start of the pre-test period (females) or 7 days before the commencement of dosing (males). Animals were group housed (up to 5 animals of the same sex and same dosing group together) in polycarbonate cages (Macrolon, MIV type, height 18 cm). Target temperatures of 18 to 24°C with a relative target humidity of 40 to 70% were maintained. The actual daily mean temperature during the study period was 20 to 22°C with an actual daily mean relative humidity of 43 to 49%. A 12 hour light/12 hour dark cycle was maintained, except when interrupted for designated procedures. Ten or greater air changes per hour with 100% fresh air (no air recirculation) were maintained in the animal rooms. Pelleted rodent diet and municipal tap water was provided ad libitum throughout the study, except during designated procedures.
- Route of administration:
- oral: gavage
- Vehicle:
- propylene glycol
- Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Duplicate sets of samples (approximately 500 mg) were sent to the analytical laboratory. Concentration results were considered acceptable if mean sample concentration results were within or equal to ± 10% for solutions of target concentration. Duplicate sets of samples (approximately 500 mg) were sent to the analytical laboratory. Homogeneity results were considered acceptable if the coefficient of variation (CV) of concentrations was =< 10%. Stability analyses performed previously in conjunction with the method development and validation study demonstrated that the substance is stable in the vehicle when prepared and stored under the same conditions at concentrations bracketing those used in the present study.
- Duration of treatment / exposure:
- Males were treated for 29 days, i.e. two weeks prior to mating, during mating and up to and including the day before scheduled necropsy. Females that delivered were treated for 50-56 days (most females) or 63 days (one control female and one female of Group 3), i.e. 14 days prior to mating (with the objective to cover at least two complete estrous cycles), the variable time to conception, the duration of pregnancy and 13 or 15 days after delivery, up to and including the day before scheduled necropsy. Females which failed to deliver were treated for 41 days.
- Frequency of treatment:
- Administration of the substance to the appropriate animals by once daily oral gavage 7 days a week for a minimum of 29 days.
- Dose / conc.:
- 15 mg/kg bw/day (nominal)
- Dose / conc.:
- 50 mg/kg bw/day (nominal)
- Dose / conc.:
- 150 mg/kg bw/day (nominal)
- No. of animals per sex per dose:
- 10/sex/dose
- Control animals:
- yes, concurrent vehicle
- Parental animals: Observations and examinations:
- Throughout the study, animals were observed for general health/mortality and moribundity twice daily.
Clinical observations were performed at least twice daily.
Clinical observations were conducted in a standard arena beginning before the first administration of the test item and then once weekly throughout treatment. These observations were conducted 3 hours post-dose.
Animals were weighed individually on the first day of treatment (prior to dosing), and weekly thereafter.
Food consumption was quantitatively measured weekly, except for males and females which were housed together for mating and for females without evidence of mating.
Functional tests (hearing ability, pupillary reflex, static righting reflex, locomotor activity and fore- and hind-limb grip strength) were performed on the selected 5 males during Week 4 of treatment and the selected 5 females during the last week of lactation (i.e. PND 6-13). These tests were performed 3 hours post-dose, after completion of clinical observations. - Oestrous cyclicity (parental animals):
- Estrous cycles were evaluated by examining the vaginal cytology of samples obtained by vaginal lavage.
Daily vaginal lavage was performed for all females beginning 14 days prior to treatment (pre-test period), the first 14 days of treatment and during mating until evidence of copulation was observed. Vaginal lavage was continued for those females with no evidence of copulation until termination of the mating period.
On the day of necropsy, a vaginal lavage was also taken to determine the stage of estrus. This was done for all females. - Sperm parameters (parental animals):
- Parameters examined in male parental generations: testis weight, epididymis weight.
- Litter observations:
- PARAMETERS EXAMINED
The following parameters were examined in F1 offspring: number and sex of pups, stillbirths, live births, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities, anogenital distance (AGD), presence of nipples/areolae in male pups.
GROSS EXAMINATION OF DEAD PUPS: yes, for external and internal abnormalities.
- Postmortem examinations (parental animals):
- All animals were subjected to a full post mortem examination, with special attention being paid to the reproductive organs.The numbers of former implantation sites were recorded for all paired females. In case no macroscopically visible implantation sites were present, nongravid uteri were stained using the Salewski technique in order to detect any former implantation sites and the number of corpora lutea was recorded in addition.
- Postmortem examinations (offspring):
- Pups, younger than 7 days were euthanized by decapitation.
All remaining pups (PND 14-16), except for the two pups per litter selected for blood collection were euthanized by an intraperitoneal injection of sodium pentobarbital (Euthasol® 20%).
Pups that died before scheduled termination were examined externally and sexed (both externally and internally).
On PND 4, the surplus pups (> 8 pups per litter) were euthanized by decapitation.
Sex was determined both externally and internally. Descriptions of all external abnormalities were recorded. Particular attention was paid to the external reproductive genitals to examine signs of altered development.
In addition, blood was collected from two pups per litter (see also section 4.11), and the thyroid from two pups per litter (one male and one female pup) was preserved in 10% buffered formalin. The pups selected for blood sampling were the same pups as selected for thyroid preservation.
The pups selected for blood collection on PND 14-16 were anesthetized using isoflurane followed by exsanguination. - Statistics:
- All statistical tests were conducted at the 5% significance level. All pairwise comparisons were conducted using two sided tests and were reported at the 5% levels.
- Reproductive indices:
- Mating index
Precoital time
Fertility index
Gestation index
Duration of gestation
Post-implantation survival index
Live birth index - Offspring viability indices:
- Live birth index
Percentage live males at First Litter Check
Percentage live females at First Litter Check
Viability index
Lactation index - Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No substance-related clinical signs of toxicity were noted during daily clinical observations or during weekly arena observations.
Salivation was noted at 150 mg/kg in all animals on most days of the study and, less frequently, at 50 mg/kg. This salivation was considered to be a physiological response rather than a sign of systemic toxicity considering its slight severity and the time of occurrence (i.e. immediately after dosing). The salivation observed on a few occasions at 15 mg/kg was regarded as a background finding as salivation occurred with comparable frequency in concurrent controls.
Any other clinical signs noted incidentally occurred within the range of background findings to be expected for rats of this age and strain which are housed and treated under the conditions in this study and showed no dose-related trend. At the incidence observed, these were considered to be unrelated to treatment. - Mortality:
- mortality observed, non-treatment-related
- Description (incidence):
- No mortality occurred during the study period that was considered to be substance-related.
Female no. 68 (Group 3) died after blood sampling on the scheduled day of necropsy. Her death was considered to be related to the blood sampling procedure under anesthesia and regarded as unrelated to the treatment with the substance. - Body weight and weight changes:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no changes in body weights or body weight gain that were considered to be toxicologically relevant.
In males at 150 mg/kg, mean body weight gain over the 4-week treatment period was lower than that in controls, resulting in a 6% lower mean body weight at the end of the study. This change was considered not to be toxicologically relevant based on its slight magnitude and lack of statistical significance.
In females at 150 mg/kg, mean body weight gain during lactation was slightly higher (not statistically significantly) compared to controls. This finding was judged to be unrelated to treatment as absolute body weights remained comparable to that of controls.
Statistically significantly higher mean body weights were noted in 50 mg/kg females on post-coitum Days 11-20 and lactation Day 4 (6-7% difference from control). There was no dose-related trend and mean body weights of 50 mg/kg females were already slightly higher than those of controls at initiation of treatment. Therefore, these intergroup differences were regarded as unrelated to treatment. - Food consumption and compound intake (if feeding study):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Food consumption (before and after correction for body weigh) was considered not to be affected by treatment.
Compared to controls, mean food consumption values (absolute and relative to body weight) of females at 150 mg/kg were about 10% higher throughout the lactation period. The differences were not statistically significant and food consumption of individual 150 mg/kg females generally remained within the concurrent control range. It was noted that one control female (no. 45) with a small litter consumed markedly less food than the other females, which lowered mean food consumption values for the control group. For these reasons, the higher food consumption values at 150 mg/kg were considered not to represent an effect of the substance.
An isolated, statistically significant difference noted in females at 50 mg/kg (higher food consumption between post-coitum Days 4-7) was regarded as a chance finding unrelated to treatment. - Water consumption and compound intake (if drinking water study):
- not specified
- Ophthalmological findings:
- not examined
- Haematological findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- Treatment up to 150 mg/kg was not associated with changes in red blood cell parameters, white blood cell parameters or number of platelets.
An isolated, statistically significant difference noted in males (lower number of platelets at 50 mg/kg) was considered to be unrelated to treatment due to the lack of a dose-related trend. - Clinical biochemistry findings:
- effects observed, non-treatment-related
- Description (incidence and severity):
- There were no treatment-related changes in clinical chemistry parameters.
An isolated, statistically significant difference noted in females (higher sodium at 15 mg/kg) was not attributed to treatment due to the lack of a dose-related trend.
The higher mean plasma concentration of inorganic phosphate noted in females at 150 mg/kg was regarded as unrelated to treatment as the difference from controls was not statistically significant and values in 150 mg/kg females remained within the historical control range (mean inorganic phosphate at 150 mg/kg was close to the historical control mean). - Urinalysis findings:
- not examined
- Behaviour (functional findings):
- effects observed, non-treatment-related
- Description (incidence and severity):
- Functional observation parameters were considered not to be affected by treatment.
Values for females at 15 mg/kg were lower (not statistically significant) compared to the other groups. In the absence of a dose response, this finding was not considered treatment related. - Immunological findings:
- not examined
- Organ weight findings including organ / body weight ratios:
- effects observed, non-treatment-related
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Reproductive function: oestrous cycle:
- no effects observed
- Reproductive function: sperm measures:
- not examined
- Reproductive performance:
- no effects observed
- Description (incidence and severity):
- Fertility index was considered not to be affected by treatment. Except for one control female (no. 49), one female at 50 mg/kg (no. 64) and two females at 150 mg/kg (nos. 72 and 80), all females were pregnant. The fertility indices were 90, 100, 90 and 80% for the control, 15, 50 and 150 mg/kg groups, respectively.
These cases of non-pregnancy occurred without related histopathology changes in reproductive organs, except for 150 mg/kg female no. 80. The non-pregnancy of female no. 80 was related to reduced fertility of the male (no. 40) she was paired with (this male had histopathological changes in the testes and epididymides which were not substance-related, see section 0). The numbers of non-pregnant females in the treatment groups remained in the range normally seen in untreated rats (0-2 out of 10). Therefore, the non-pregnancy of a few treated females was considered not to be substance-related. - Key result
- Dose descriptor:
- NOAEL
- Effect level:
- 150 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- clinical signs
- mortality
- body weight and weight gain
- food consumption and compound intake
- haematology
- clinical biochemistry
- organ weights and organ / body weight ratios
- gross pathology
- histopathology: non-neoplastic
- histopathology: neoplastic
- reproductive function (oestrous cycle)
- reproductive performance
- Critical effects observed:
- no
- Clinical signs:
- effects observed, non-treatment-related
- Description (incidence and severity):
- No clinical signs occurred among pups that were considered to be related to treatment.
The clinical signs noted incidentally remained within the range considered normal for pups of this age, and were therefore considered to be unrelated to treatment. - Mortality / viability:
- mortality observed, non-treatment-related
- Description (incidence and severity):
- Viability index (number of live offspring on PND 4 before culling as percentage of number of live offspring on PND 1) was considered not to be affected by treatment. The viability indices were 100, 99, 100 and 96% for the control, 15, 50 and 150 mg/kg groups, respectively.
One pup at 15 mg/kg (litter no. 51) and four pups at 150 mg/kg (one in litter nos. 74 and 79, two in litter no. 76) were found dead or went missing (presumed cannibalized) on PND 2-3. This early postnatal loss was judged not to be related to treatment as the incidence showed no dose-related trend and remained within the historical control range. - Body weight and weight changes:
- no effects observed
- Description (incidence and severity):
- Body weights of pups were considered not to be affected by treatment.
It was noted that mean pup weights at 50 and 150 mg/kg were lower (7-10%) compared to the control weights at PND 1 and 4. This was likely due to the difference in litter size (lower in the control group). After culling, mean pup weights at 50 and 150 mg/kg approached the control values. - Clinical biochemistry findings:
- no effects observed
- Description (incidence and severity):
- Serum T4 levels in male and female PND 14-16 pups were not affected by treatment.
- Gross pathological findings:
- no effects observed
- Other effects:
- no effects observed
- Description (incidence and severity):
- Sex ratio was considered not to be affected by treatment.
Anogenital distance (absolute and normalized for body weight) in male and female pups was not affected by treatment.
Treatment up to 150 mg/kg had no effect on areola/nipple retention. For none of the examined male pups nipples were observed at PND 13. - Key result
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- 150 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- viability
- clinical signs
- mortality
- clinical biochemistry
- gross pathology
- Critical effects observed:
- no
- Reproductive effects observed:
- no
- Conclusions:
- Based on the results of this combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test, the No Observed Adverse Effect Levels (NOAELs) of the substance for parental, reproductive and developmental effects is 150 mg/kg bw/day.
- Executive summary:
The potential toxic effects of the substance when given orally by gavage for a minimum of 28 days to Wistar Han rats was determined employing the combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test. The potential to affect male and female reproductive performance such as gonadal function, mating behavior, conception, parturition and early postnatal development was also evaluated in this study.The dose levels in this study were 0, 15, 50 and 150 mg/kg/day, based on the results of the dose range finder.No parental toxicity was observed up to the highest dose level tested (150 mg/kg). A few non-adverse changes were noted at 50 and/or 150 mg/kg and consisted of slight salivation after dosing at 50 and 150 mg/kg (in a dose-related manner), regarded as a physiological response related to the irritant properties of the substance rather than a sign of systemic toxicity, and a gelatinous thyroid gland at 150 mg/kg in 2/10 females. This macroscopic finding was not associated with histopathological alterations in the thyroid gland. No reproduction toxicity was observed up to the highest dose level tested (150 mg/kg). No developmental toxicity was observed up to the highest dose level tested (150 mg/kg). Based on the results of this combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test, the No Observed Adverse Effect Levels (NOAELs) of the substance is 150 mg/kg bw/day for parental, reproductive and developmental effects.
Reference
Effect on fertility: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 150 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Sufficient to meet requirements.
Effect on fertility: via inhalation route
- Endpoint conclusion:
- no study available
Effect on fertility: via dermal route
- Endpoint conclusion:
- no study available
Effects on developmental toxicity
Description of key information
The potential toxic effects of the substance when given orally by gavage for a minimum of 28 days to Wistar Han rats was determined employing the combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test. The potential to affect male and female reproductive performance such as gonadal function, mating behavior, conception, parturition and early postnatal development was also evaluated in this study.The dose levels in this study were 0, 15, 50 and 150 mg/kg/day, based on the results of the dose range finder. No parental toxicity was observed up to the highest dose level tested (150 mg/kg). A few non-adverse changes were noted at 50 and/or 150 mg/kg and consisted of slight salivation after dosing at 50 and 150 mg/kg (in a dose-related manner), regarded as a physiological response related to the irritant properties of the substance rather than a sign of systemic toxicity, and a gelatinous thyroid gland at 150 mg/kg in 2/10 females. This macroscopic finding was not associated with histopathological alterations in the thyroid gland. No developmental toxicity was observed up to the highest dose level tested (150 mg/kg). Based on the results of this combined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test, the No Observed Adverse Effect Levels (NOAELs) of the substance is 150 mg/kg bw/day for parental and developmental effects.
Effect on developmental toxicity: via oral route
- Endpoint conclusion:
- no adverse effect observed
- Dose descriptor:
- NOAEL
- 150 mg/kg bw/day
- Study duration:
- subacute
- Species:
- rat
- Quality of whole database:
- Sufficient to meet requirements.
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
Based on the findings of a reliablecombined 28-day repeated dose toxicity study with the reproduction/developmental toxicity screening test
conducted on the substance, classification of the substance is not justified.
Additional information
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.