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EC number: 947-519-7 | CAS number: -
- 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:
- weight of evidence
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study conducted to OECD guidelines to to GLP, and therefore meets the requirements for Klimisch code 1. However as this study is used in the context of a read across, Klimisch 2 is assigned.
Cross-referenceopen allclose all
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- repeated dose toxicity: oral, other
- Remarks:
- one generation reproduction toxicity study
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2003-2004
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: Study conducted to OECD guidelines to to GLP, and therefore meets the requirements for Klimisch code 1. However as this study is used in the context of a read across, Klimisch 2 is assigned.
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD 415
- GLP compliance:
- yes
- Limit test:
- no
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS: Sprague-Dawley Crl: CD®(SD) IGS BR rats,
- Source: Charles River Laboratories
- Age at study initiation: (P) males 5 wks, females 7 weeks
Males approximately 7 weeks of age at initiation of treatment. Females approximately 8 weeks of age at initiation of treatment.
- Weight at study initiation: (P) Males: 154-197 g; Females: 139-184 g
- Housing: Suspended wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS: Corn oil was added to the test substance to achieve the desired volume and then stirred for 30 minutes.
VEHICLE: Justification for use and choice of vehicle (if other than water): Corn oil
The test article was administered orally via gastric intubation - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analytical confirmation of concentration: Homogeneity, stability and weekly dose concentration confirmation.
- Duration of treatment / exposure:
- F0 males - 70 days premating; mating period through completion of parturition
F0 females - 14 days premating; mating; 25 days of gestation and 20 days of lactation. - Frequency of treatment:
- once daily
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 167 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 28 F0 rats/sex/group in control, low, mid and high dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Based on results of a 28 day oral gavage study (according to OECD 407).
- Control and treatment groups: 28 F0 rats/sex/group in the control, low, mid and high dose groups.
- Mating: 1 male mated to 1 female from the same group until evidence of mating (presence of copulatory plug or sperm) was observed. If evidence of mating was not observed mating was discontinued after three weeks. - Observations and examinations performed and frequency:
- Parental animals:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly and daily for females during gestation
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly and on the day on euthanasia for males. After evidence of mating, females were weighed on gestational days 0, 7, 14 and 21 and on lactation days 1, 4, 7, 14 and 21.
Sperm parameters (Parental animals)
Parameters examined in P male parental generations:
testis weight, epididymis weight, sperm count in epididymides, enumeration of cauda epididymal sperm reserve, sperm motility, sperm morphology. - Sacrifice and pathology:
- gross necropsy on death, organ weights and microscopic examination on termination
SACRIFICE
- Male animals: All surviving animals after completion of female parturition.
- Maternal animals: All surviving animals that delivered on lactation day 21; females that failed to deliver were sacrificed on gestation day 25.
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera. - Statistics:
- ANOVA for body weights, changes, food consumption semen parameters, organ weights.
Body weights, body weight changes, food consumption, semen parameters, organ weights, number of days to mating, gestation length, pup viability data, total pups delivered, pup body weights and mean live litter size were analysed by ANOVA followed, as needed, by Dunnett’s test. Count data were analysed by Chi-Square test followed by Fisher’s Exact Test for copulation and fertility indices, pup sex ratios, number of live and dead pups/group and pup survival. All analysis were two-tailed with a minimum significance level of 5%. - Clinical signs:
- no effects observed
- Mortality:
- no mortality observed
- 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
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- There were no remarkable findings in F0 males, with the exception of post dosing salivation.
In F0 females there were no remarkable findings with the exception of negative ammonium sulphide staining in two high dose and one mid dose animal. - Dose descriptor:
- NOAEL
- Effect level:
- > 500 mg/kg bw/day (actual dose received)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No significant adverse effects occurred at 500 mg/kg bw (highest dose tested).
- Critical effects observed:
- not specified
- Conclusions:
- Adverse effects did not occur in parental animals at doses up to 500 mg/kg bw/day, therefore a NOAEL of >500 mg/kg bw was identified with the help of this study.
- Executive summary:
In a key 1-generation reproduction study, the calcium sulfonate read across substance (CAS 115733-09-0) was administered in corn oil via oral gavage to 28 Sprague-Dawley rats/sex at dose levels of 0, 50, 167 and 500 mg/kg bw/day (Bjorn, 2004, according to OECD 415). All F0 males were dosed for 70 days prior to mating, mating (maximum 3 weeks) and through the completion of parturition. All F0 females were dosed for up to 70 days (14 days prior to mating, during mating and gestation, and through day 20 of lactation). The animals were observed twice daily for appearance and behaviour, and a detailed clinical observation was performed weekly and daily for females during gestation. Cage site observations were performed daily approximately 30 to 120 minutes post dosing. In addition, the bodyweights were determined weekly and on the day of euthanasia for males. Females were weighed after evidence of mating on gestational days 0, 7, 14 and 21 and on lactation days 1, 4, 7, 14 and 21. Food consumption was recorded on the same days as body weights except during the mating period and during lactation. Animals were paired 1:1 for mating, after successful mating each pregnant female was caged individually. Positive evidence of mating was confirmed by the presence of sperm or a vaginal copulatory plug (day 0 of gestation). If evidence of mating was not present after three weeks, mating was discontinued. All of the surviving F0 females were allowed to deliver and rear their pups to lactation day 21.
Gross necropsies (consisting of external and internal examinations including the cervical, thoracic and abdominal viscera) were performed on death, organ weights and microscopic examinations were performed on termination. The surviving F0 dams were necropsied on lactation day 21, following a minimum of 60 days of dosing. The surviving F0 males were necropsied at the conclusion of parturition following a minimum of 96 days of dosing. F0 females that failed to deliver were necropsied on post-mating day 25 (with evidence of mating) or 25 days following the termination of the mating period (with no evidence of mating). Organ weights were determined and microscopic examinations were conducted for all surviving control and high dose F0 animals. Tissues examined microscopically included the liver, kidney, brain, right epididymides, cervix, coagulation gland, ovaries, pituitary, prostrate, seminal vesicles, testes, uterus, vagina and gross lesions. F0 animals from all groups found dead or sacrificed early were subjected to a gross necropsy and the microscopic evaluation of all tissues. Sperm was collected from all surviving F0 males and evaluated for sperm count, concentration, motility and morphology assessment. The parameters examined in P males included: testis weight, epididymis weight, sperm count in epididymides, enumeration of cauda epididymal sperm reserve, sperm motility and sperm morphology.
No substance related effects occurred in treated animals, except for the observation of post dosing salivation and dark material around the nose in the mid and high dose groups in F0 males and the negative ammonium sulfide staining in two high dose and one mid dose F0-female. As no effects occurred at the highest dose, a NOAEL of > 500 mg/kg bw was identified.
Results of the homogeneity analysis indicate that the test article was homogeneous in the vehicle and stable for ten days when stored under ambient conditions. Concentration analysis confirmed that the test article was at the appropriate concentration in the dosing solutions.
Results
F0 males exhibited a dose related increase in post dosing salivation and dark material around the nose in the mid and high dose groups The remaining F0 male parameters were unremarkable including: mean body weight and food consumption, mating and fertility indicies, absolute and relative organ weights, sperm evaluation parameters and macro and microscopic pathology.
The clinical signs of the Fo females were generally unremarkable. There were no toxicologically meaningful differences between the control low, mid and high dose groups with respect to F0 female mean body weights, body weight change, food consumption, mating and fertility indicies, precoital intervals or gestation length. A macroscopic finding observed in two high dose and one mid female sacrificed on post mating day 25 was a finding of negative ammonium sulfide staining in animals that failed to deliver and were euthanized on gestation day 25.
No other remarkable findings were noted in the F0 females at necropsy and no meaningful microscopic lesions were observed in any of the treated F0 females.
- Reason / purpose for cross-reference:
- reference to same study
Reference
- Endpoint:
- one-generation reproductive toxicity
- Remarks:
- based on test guideline (migrated information)
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2003-2004
- Reliability:
- 2 (reliable with restrictions)
- Rationale for reliability incl. deficiencies:
- other: study meets the criteria for Klimisch code 1. However, as the study is used in a read-across approach, Klimisch 2 is assigned.
- Reason / purpose for cross-reference:
- reference to same study
- Reason / purpose for cross-reference:
- reference to same study
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 415 [One-Generation Reproduction Toxicity Study (before 9 October 2017)]
- Deviations:
- no
- GLP compliance:
- yes
- Limit test:
- yes
- Species:
- rat
- Strain:
- Sprague-Dawley
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS: Sprague-Dawley Crl: CD®(SD) IGS BR rats,
- Source: Charles River Laboratories
- Age at study initiation: (P) males 5 wks, females 7 weeks; (F1) x wks
Males approximately 7 weeks of age at initiation of treatment. Females approximately 8 weeks of age at initiation of treatment.
- Weight at study initiation: (P) Males: 154-197 g; Females: 139-184 g; (F1) Males: x-x g; Females: x-x g
- Housing: Suspended wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle - Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Corn oil was added to the test substance to achieve the desired volume and then stirred for 30 minutes.
VEHICLE: Justification for use and choice of vehicle (if other than water): Corn oil
The test article was administered orally via gastric intubation - Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation:
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged (how): individually - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analytical confirmation of concentration: Homogeneity, stability and weekly dose concentration confirmation.
- Duration of treatment / exposure:
- F0 males - 70 days premating; mating period through completion of parturition
F0 females - 14 days premating; mating; 25 days of gestation and 20 days of lactation.
F1 pups - gestation through day 20 of lactation - Frequency of treatment:
- once daily
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Remarks:
- gavage
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 167 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 28 F0 rats/sex/group in control, low, mid and high dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Based on results of a 28 day oral gavage study (according to OECD 407).
- Control and treatment groups: 28 F0 rats/sex/group in the control, low, mid and high dose groups.
- Mating: 1 male mated to 1 female from the same group until evidence of mating (presence of copulatory plug or sperm) was observed. If evidence of mating was not observed mating was discontinued after three weeks. - Parental animals: Observations and examinations:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly and daily for females during gestation
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly and on the day on euthanasia for males. After evidence of mating, females were weighed on gestational days 0, 7, 14 and 21 and on lactation days 1, 4, 7, 14 and 21. - Sperm parameters (parental animals):
- Parameters examined in P male parental generations:
testis weight, epididymis weight, sperm count in epididymides, enumeration of cauda epididymal sperm reserve, sperm motility, sperm morphology. - 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.
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was determined for pups born or found dead. - Postmortem examinations (parental animals):
- gross necropsy on death, organ weights and microscopic examination on termination
SACRIFICE
- Male animals: All surviving animals after completion of female parturition.
- Maternal animals: All surviving animals that delivered on lactation day 21; females that failed to deliver were sacrificed on gestation day 25.
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera. - Postmortem examinations (offspring):
- SACRIFICE - These animals were subjected to maroscopic postmortem examinations
GROSS NECROPSY - Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera. - Statistics:
- ANOVA for body weights, changes, food consumption semen parameters, organ weights.
Body weights, body weight changes, food consumption, semen parameters, organ weights, number of days to mating, gestation length, pup viability data, total pups delivered, pup body weights and mean live litter size were analysed by ANOVA followed, as needed, by Dunnett’s test. Count data were analysed by Chi-Square test followed by Fisher’s Exact Test for copulation and fertility indices, pup sex ratios, number of live and dead pups/group and pup survival. All analysis were two-tailed with a minimum significance level of 5%. - Reproductive indices:
- yes
- Offspring viability indices:
- yes
- Clinical signs:
- no effects observed
- Body weight and weight changes:
- no effects observed
- Food consumption and compound intake (if feeding study):
- no effects observed
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Histopathological findings: non-neoplastic:
- effects observed, treatment-related
- Other effects:
- not specified
- Reproductive function: oestrous cycle:
- not examined
- Reproductive function: sperm measures:
- no effects observed
- Reproductive performance:
- no effects observed
- Dose descriptor:
- NOAEL
- Effect level:
- > 500 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: No significant adverse effects occurred at 500 mg/kg/bw (highest dose tested).
- Clinical signs:
- no effects observed
- Mortality / viability:
- no mortality observed
- Body weight and weight changes:
- no effects observed
- Sexual maturation:
- not examined
- Organ weight findings including organ / body weight ratios:
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings:
- no effects observed
- Dose descriptor:
- NOAEL
- Generation:
- F1
- Effect level:
- > 500 mg/kg bw/day (actual dose received)
- Sex:
- male/female
- Basis for effect level:
- other: No adverse effects occurred in animals in the top dose group, therefore a NOAEL cannot be identified from this study.
- Reproductive effects observed:
- not specified
- Conclusions:
- Adverse effects did not occur in parental animals or offspring at doses up to 500 mg/kg bw/day, therefore the NOAEL was identified as > 500 mg/kg bw/day (the highest dose tested in this study).
- Executive summary:
In a 1-generation reproduction study, benzenesulfonic acid, C14-C24 branched and linear alkyl derivatives (CAS 115733 -09 -0) was administered in corn oil via oral gavage to 28 Sprague-Dawley rats/sex at dose levels of 0, 50, 167 and 500 mg/kg bw/day (Bjorn, 2004, according to OECD 415). All F0 males were dosed for 70 days prior to mating, mating (maximum 3 weeks) and through the completion of parturition. All F0 females were dosed for 14 days prior to mating, mating (maximum 3 weeks), 25 days of gestation and through day 20 of lactation. The F1 pups were treated in gestation and through day 20 of lactation (via lactation). The animals were observed twice daily for appearance and behaviour, and a detailed clinical observation was performed weekly and daily for females during gestation. Cage site observations were performed daily approximately 30 to 120 minutes post dosing. In addition, the bodyweights were determined weekly and on the day of euthanasia for males. Females were weighed after evidence of mating on gestational days 0, 7, 14 and 21 and on lactation fays 1, 4, 7, 14 and 21. Food consumption was recorded on the same days as body weights except during the mating period and during lactation. Animals were paired 1:1 for mating, after successful mating each pregnant females was caged individually. Positive evidence of mating was confirmed by the presence of sperm or a vaginal copulatory plug (day 0 of gestation). If evidence of mating was not present after three weeks, mating was discontinued. All of the surviving F0 females were allowed to deliver and rear their pups to lactation day 21. The offspring were potentially exposed to the test substance in utero and through nursing during lactation days 1-21 until euthanization on post-natal day 21. On lactation day 4 each litter was randomly culled to a maximum of eight pups, 4/sex/litter, when possible. Detailed pup examinations were performed on lactation days 0, 4, 7, 14 and 21. Pup sex was determined on lactation day 0 and verified on lactation days 4, 7, 14 and 21. Individual pup weights were determined on lactation days 1, 4, 7 14 and 21. Pups that were stillborn, cannibalized or found dead were subjected to a gross necropsy with emphasis on developmental morphology. Pups culled on day 4 were subjected to an abbreviated gross necropsy with emphasis on the reproductive system. All surviving pups were euthanized on lactation day 21 and examined macroscopically. All internal gross lesions were preserved for possible future microscopic examination.
Gross necropsies (consisting of external and internal examinations including the cervical, thoracic and abdominal viscera) were performed on death, organ weights and microscopic examinations were performed on termination. The surviving F0 dams were necropsied on lactation day 21, following a minimum of 60 days of dosing. The surviving F0 males were necropsied at the conclusion of parturition following a minimum of 96 days of dosing. F0 females that failed to deliver were necropsied on post-mating day 25 (with evidence of mating) or 25 days following the termination of the mating period (with no evidence of mating). Organ weights were determined and microscopic examinations were conducted for all surviving control and high dose F0 animals. Tissues examined microscopically included the liver, kidney, brain, right epididymides, cervix, coagulation gland, ovaries, pituitary, prostrate, seminal vesicles, testes, uterus, vagina and gross lesions. F0 animals from all groups found dead or sacrificed early were subjected to a gross necropsy and the microscopic evaluation of all tissues. Sperm was collected from all surviving F0 males and evaluated for sperm count, concentration, motility and morphology assessment. The parameters examined in P males included: testis weight, epididymis weight, sperm count in epididymides, enumeration of cauda epididymal sperm reserve, sperm motility and sperm morphology. The F1 offsprings were examined for number and sex of pups, stillbirths, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities. Moreover a gross examination of dead pups was conducted for external and internal abnormalities. So the possible cause of death fro pups born or found dead was evaluated.
No substance related effects occurred in treated animals, except for the observation of post dosing salivation and dark material around the nose in the mid and high dose groups in F0 males and the negative ammonium sulfide staining in two high dose and one mid dose F0-female. No treatment related findings were noted in the F1 pups during lactation. No treatment related gross necropsy findings were evident in any of the F1 pups examined (stillborn, dead during lactation, culled or examined at scheduled sacrifice on lactation day 21). As no effects occurred at the highest dose, a NOAEL cannot be identified, and is greater than 500 mg/kg bw/day for reproductive and developmental toxicity. Based on the results of this study it is concluded that the 500 mg/kg/day dose level is the no observed adverse effect level (NOAEL) for parental F0 and F1 pup toxicity (no significant adverse effects occurred at this dose level).
In F0 females there were no remarkable findings with the exception of negative ammonium sulphide staining in two high dose and one mid dose animal.
Results of the homogeneity analysis indicate that the test article was homogeneous in the vehicle and stable for ten days when stored under ambient conditions. Concentration analysis confirmed that the test article was at the appropriate concentration in the dosing solutions.
Results
F0 Generation:
F0 males exhibited a dose related increase in post dosing salivation and dark material around the nose in the mid and high dose groups The remaining F0 male parameters were unremarkable including: mean body weight and food consumption, mating and fertility indices, absolute and relative organ weights, sperm evaluation parameters and macro- and microscopic pathology.
The clinical signs of the F0 females were generally unremarkable. There were no toxicologically meaningful differences between the control low, mid and high dose groups with respect to F0 female mean body weights, body weight change, food consumption, mating and fertility indicies, precoital intervals or gestation length. A macroscopic finding observed in two high dose and one mid female sacrificed on post mating day 25 was a finding of negative ammonium sulfide staining in animals that failed to deliver and were euthanized on gestation day 25.
No other remarkable findings were noted in the F0 females at necropsy and no meaningful microscopic lesions were observed in any of the treated F0 females.
F1 Generation:
No treatment related findings were noted in the F1 pups during lactation. No treatment related gross necropsy findings were evident in any of the F1 pups examined (stillborn, dead during lactation, culled or examined at scheduled sacrifice on lactation day 21.)
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 004
- Report date:
- 2004
Materials and methods
Test guideline
- Qualifier:
- equivalent or similar to guideline
- Guideline:
- other: OECD 415
- GLP compliance:
- yes
- Limit test:
- no
Test material
- Reference substance name:
- Benzenesulfonic acid, C14-24-branched and linear alkyl derivs., calcium salts
- IUPAC Name:
- Benzenesulfonic acid, C14-24-branched and linear alkyl derivs., calcium salts
- Details on test material:
- The test article (CAS 115733-09-0) is from the chemical group of alkaryl sulfonates.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Sprague-Dawley
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS: Sprague-Dawley Crl: CD®(SD) IGS BR rats,
- Source: Charles River Laboratories
- Age at study initiation: (P) males 5 wks, females 7 weeks; (F1) x wks
Males approximately 7 weeks of age at initiation of treatment. Females approximately 8 weeks of age at initiation of treatment.
- Weight at study initiation: (P) Males: 154-197 g; Females: 139-184 g; (F1) Males: x-x g; Females: x-x g
- Housing: Suspended wire cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 12 days
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18-26°C
- Humidity (%): 30-70%
- Air changes (per hr): 10-15 changes/hour
- Photoperiod (hrs dark / hrs light): 12 hours light/dark cycle
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- corn oil
- Details on exposure:
- PREPARATION OF DOSING SOLUTIONS: Corn oil was added to the test substance to achieve the desired volume and then stirred for 30 minutes.
VEHICLE: Justification for use and choice of vehicle (if other than water): Corn oil
The test article was administered orally via gastric intubation - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Analytical confirmation of concentration: Homogeneity, stability and weekly dose concentration confirmation.
- Details on mating procedure:
- - M/F ratio per cage: 1:1
- Length of cohabitation:
- Proof of pregnancy: vaginal plug / sperm in vaginal smear referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged (how): individually - Duration of treatment / exposure:
- F0 males - 70 days premating; mating period through completion of parturition
F0 females - 14 days premating; mating; 25 days of gestation and 20 days of lactation.
F1 pups - gestation through day 20 of lactation - Frequency of treatment:
- once daily
- Duration of test:
- 96 d (males)
min. 60 (females)
Doses / concentrationsopen allclose all
- Dose / conc.:
- 0 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 50 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 167 mg/kg bw/day (actual dose received)
- Dose / conc.:
- 500 mg/kg bw/day (actual dose received)
- No. of animals per sex per dose:
- 28 F0 rats/sex/group in control, low, mid and high dose
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale: Based on results of a 28 day oral gavage study (according to OECD 407).
- Control and treatment groups: 28 F0 rats/sex/group in the control, low, mid and high dose groups.
- Mating: 1 male mated to 1 female from the same group until evidence of mating (presence of copulatory plug or sperm) was observed. If evidence of mating was not observed mating was discontinued after three weeks.
Examinations
- Maternal examinations:
- Parental animals: Observations and examinations
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: Twice daily
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Weekly and daily for females during gestation
BODY WEIGHT: Yes
- Time schedule for examinations: Weekly and on the day on euthanasia for males. After evidence of mating, females were weighed on gestational days 0, 7, 14 and 21 and on lactation days 1, 4, 7, 14 and 21.
gross necropsy on death, organ weights and microscopic examination on termination
SACRIFICE
- Male animals: All surviving animals after completion of female parturition.
- Maternal animals: All surviving animals that delivered on lactation day 21; females that failed to deliver were sacrificed on gestation day 25.
GROSS NECROPSY
- Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera. - Ovaries and uterine content:
- Parameters examined in P male parental generations:
testis weight, epididymis weight, sperm count in epididymides, enumeration of cauda epididymal sperm reserve, sperm motility, sperm morphology. - Fetal examinations:
- 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.
GROSS EXAMINATION OF DEAD PUPS:
yes, for external and internal abnormalities; possible cause of death was determined for pups born or found dead.
SACRIFICE - These animals were subjected to maroscopic postmortem examinations
GROSS NECROPSY - Gross necropsy consisted of external and internal examinations including the cervical, thoracic, and abdominal viscera.
- Statistics:
- ANOVA for body weights, changes, food consumption semen parameters, organ weights.
Body weights, body weight changes, food consumption, semen parameters, organ weights, number of days to mating, gestation length, pup viability data, total pups delivered, pup body weights and mean live litter size were analysed by ANOVA followed, as needed, by Dunnett’s test. Count data were analysed by Chi-Square test followed by Fisher’s Exact Test for copulation and fertility indices, pup sex ratios, number of live and dead pups/group and pup survival. All analysis were two-tailed with a minimum significance level of 5%. - Indices:
- Reproduktive indices: YES
Offspring viability indices: YES
Results and discussion
Results: maternal animals
Maternal developmental toxicity
- Details on maternal toxic effects:
- Maternal toxic effects:no effects
Details on maternal toxic effects:
Clinical signs (parental animals): no effects
Body weight and food consumption (parental animals): no effects
Test substance intake (parental animals): no data
Reproductive function: estrous cycle (parental animals): not examined
Reproductive function: sperm measures (parental animals): no effects
Reproductive performance (parental animals): no effects
Organ weights (parental animals): no effects
Gross pathology (parental animals): no effects
Histopathology (parental animals): yes
Details on results (parental animals): There were no remarkable findings in F0 males, with the exception of post dosing salivation.
In F0 females there were no remarkable findings with the exception of negative ammonium sulphide staining in two high dose and one mid dose animal.
Effect levels (maternal animals)
open allclose all
- Dose descriptor:
- NOAEL
- Effect level:
- > 500 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Basis for effect level:
- other: maternal toxicity
- Dose descriptor:
- NOAEL
- Effect level:
- > 500 mg/kg bw/day (actual dose received)
- Based on:
- act. ingr.
- Basis for effect level:
- other: developmental toxicity
Results (fetuses)
- Details on embryotoxic / teratogenic effects:
- Embryotoxic / teratogenic effects:no effects
Details on embryotoxic / teratogenic effects:
Viability (offspring): no effects
Clinical signs (offspring): no effects
Body weight (offspring): no effects
Sexual maturation (offspring): not examined
Organ weights (offspring): no effects
Gross pathology (offspring): no effects
Histopathology (offspring): no effects
Details on results (offspring): There were no remarkable observations in F1 animals.
Effect levels (fetuses)
- Dose descriptor:
- NOAEL
- Remarks on result:
- other: not determinable due to study type
Fetal abnormalities
- Abnormalities:
- not specified
Overall developmental toxicity
- Developmental effects observed:
- not specified
Any other information on results incl. tables
Results of the homogeneity analysis indicate that the test article was homogeneous in the vehicle and stable for ten days when stored under ambient conditions. Concentration analysis confirmed that the test article was at the appropriate concentration in the dosing solutions.
Results
F0 Generation:
F0 males exhibited a dose related increase in post dosing salivation and dark material around the nose in the mid and high dose groups The remaining F0 male parameters were unremarkable including: mean body weight and food consumption, mating and fertility indicies, absolute and relative organ weights, sperm evaluation parameters and macro and microscopic pathology.
The clinical signs of the F0 females were generally unremarkable. There were no toxicologically meaningful differences between the control low, mid and high dose groups with respect to F0 female mean body weights, body weight change, food consumption, mating and fertility indicies, precoital intervals or gestation length. A macroscopic finding observed in two high dose and one mid female sacrificed on post mating day 25 was a finding of negative ammonium sulfide staining in animals that failed to deliver and were euthanized on gestation day 25.
No other remarkable findings were noted in the F0 females at necropsy and no meaningful microscopic lesions were observed in any of the treated F0 females.
F1 Generation:
No treatment related findings were noted in the F1 pups during lactation. No treatment related gross necropsy findings were evident in any of the F1 pups examined (stillborn, dead during lactation, culled or examined at scheduled sacrifice on lactation day 21.)
Applicant's summary and conclusion
- Conclusions:
- Adverse effects did not occur in parental animals or offsprings at doses up to 500 mg/kg bw/day, therefore a NOAEL of > 500 mg/kg bw was identified in this study.
- Executive summary:
In a 1-generation reproduction study, benzenesulfonic acid, C14-C24 branched and linear alkyl derivatives (CAS 115733 -09 -0) was administered in corn oil via oral gavage to 28 Sprague-Dawley rats/sex at dose levels of 0, 50, 167 and 500 mg/kg bw/day (Bjorn, 2004, according to OECD 415). All F0 males were dosed for 70 days prior to mating, mating (maximum 3 weeks) and through the completion of parturition. All F0 females were dosed for 14 days prior to mating, mating (maximum 3 weeks), 25 days of gestation and through day 20 of lactation. The offspring (F1) were potentially exposed to the test substance in utero (during gestation) and through nursing during lactation days 1-21 until euthanization on post-natal day 21. On lactation day 4 each litter was randomly culled to a maximum of eight pups, 4/sex/litter, when possible. Detailed pup examinations were performed on lactation days 0, 4, 7, 14 and 21. Pup sex was determined on lactation day 0 and verified on lactation days 4, 7, 14 and 21. Individual pup weights were determined on lactation days 1, 4, 7 14 and 21. Pups that were stillborn, cannibalized or found dead were subjected to a gross necropsy with emphasis on developmental morphology. Pups culled on day 4 were subjected to an abbreviated gross necropsy with emphasis on the reproductive system. All surviving pups were euthanized on lactation day 21 and examined macroscopically. All internal gross lesions were preserved for possible future microscopic examination.
The F1 offsprings were examined for number and sex of pups, stillbirths, postnatal mortality, presence of gross anomalies, weight gain, physical or behavioural abnormalities. Moreover a gross examination of dead pups was conducted for external and internal abnormalities. So the possible cause of death fro pups born or found dead was evaluated.
No treatment related findings were noted in the F1 pups during lactation. No treatment related gross necropsy findings were evident in any of the F1 pups examined (stillborn, dead during lactation, culled or examined at scheduled sacrifice on lactation day 21). As no effects occurred at the highest dose, the NOAEL for developmental toxicity is greater than 500 mg/kg bw/day.
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