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EC number: 239-491-3 | CAS number: 15471-17-7
- 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: oral
Administrative data
- Endpoint:
- short-term repeated dose toxicity: oral
- Remarks:
- combined repeated dose and reproduction / developmental screening
- Type of information:
- experimental study
- Adequacy of study:
- key study
- Study period:
- 2013-03-05 to 2013-10-18
- Reliability:
- 1 (reliable without restriction)
- Rationale for reliability incl. deficiencies:
- other: GLP guideline study
Data source
Reference
- Reference Type:
- study report
- Title:
- Unnamed
- Year:
- 2 013
- Report date:
- 2013
Materials and methods
Test guideline
- Qualifier:
- according to guideline
- Guideline:
- OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)
- Deviations:
- no
- GLP compliance:
- yes (incl. QA statement)
- Remarks:
- The Department of Health of the Government of the United Kingdom
- Limit test:
- no
Test material
- Reference substance name:
- 1-(3-sulphonatopropyl)pyridinium
- EC Number:
- 239-491-3
- EC Name:
- 1-(3-sulphonatopropyl)pyridinium
- Cas Number:
- 15471-17-7
- Molecular formula:
- C8H11NO3S
- IUPAC Name:
- 1-(2-hydroxy-3-sulphonatopropyl)pyridinium
- Test material form:
- solid: particulate/powder
- Remarks:
- migrated information: powder
- Details on test material:
- - Name of test material (as cited in study report): 1-(3-sulphonatopropyl)pyridinium
- Substance type: organic
- Physical state: white powder
- Analytical purity: > 99 %
- Purity test date: 2013-02-06
- Storage condition of test material: Room temperature in the dark
- Other: The integrity of supplied data relating to the identity, purity and stability of the test item is the responsibility of the Sponsor.
Constituent 1
Test animals
- Species:
- rat
- Strain:
- Wistar
- Sex:
- male/female
- Details on test animals or test system and environmental conditions:
- TEST ANIMALS
- Strain: Han™:RccHan™:WIST.
- Source: Harlan Laboratories U.K. Ltd., Blackthorn, Bicester, Oxon, UK.
- Age at study initiation: 12 weeks.
- Weight at study initiation: 295 to 356 g (males), 188 to 217 g (females).
- Fasting period before study: no.
- Housing: Initially, all animals were housed in groups of four in solid floor polypropylene cages with stainless steel mesh lids and softwood flake bedding (Datesand Ltd., Cheshire, UK). During the pairing phase, animals were transferred to polypropylene grid floor cages suspended over trays lined with absorbent paper on a one male: one female basis within each dose group. Following evidence of successful mating, the males were returned to their original cages. Mated females were housed individually during gestation and lactation in solid floor polypropylene cages with stainless steel mesh lids and softwood flakes.
The animals were housed in a single air-conditioned room within the testing facility.
- Diet (e.g. ad libitum): ad libitum (Rodent 2018C Teklad Global Certified Diet, Harlan Laboratories U.K. Ltd., Oxon, UK).
- Water (e.g. ad libitum): ad libitum.
- Acclimation period: 5 days.
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 ± 2
- Humidity (%): 55 ± 15
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/12
IN-LIFE DATES: From: 2013-04-10 To: 2013-06-05
Administration / exposure
- Route of administration:
- oral: gavage
- Vehicle:
- water
- Remarks:
- distilled
- Details on oral exposure:
- PREPARATION OF DOSING SOLUTIONS:
For the purpose of this study the test item was prepared at the appropriate concentrations as a suspension in Distilled water. The stability and homogeneity of the test item formulations were determined by Harlan Laboratories Ltd., Shardlow, UK, Analytical Services. Results show the formulations to be stable for at least twenty two days. Formulations were therefore prepared fortnightly and stored at approximately 4 °C in the dark.
VEHICLE
- Concentration in vehicle: 0, 20, 60 and 200 mg/mL for dose levels of 0, 100, 300 and 1000 mg/kg bw, respectively.
- Amount of vehicle (if gavage): 5 mL/kg bw. The volume of test and control item administered to each animal was based on the most recent scheduled body weight and was adjusted at weekly intervals.
- Lot/batch no. (if required):
- Purity: distilled water - Analytical verification of doses or concentrations:
- yes
- Details on analytical verification of doses or concentrations:
- Samples of the test item formulation were taken and analysed for concentration of 1-(3- sulphonatopropyl)pyridinium at Harlan Laboratories Ltd., Shardlow, UK, Analytical Services. The methods used for analysis of formulations was HPLC/UV. The results indicate that the prepared formulations were within ± 6% of the nominal concentration.
- Duration of treatment / exposure:
- up to 8 weeks ((including a two week pre-pairing phase, pairing, gestation and early lactation for females).
- Frequency of treatment:
- once daily
Doses / concentrations
- Remarks:
- Doses / Concentrations:
0, 100, 300 and 1000 mg/kg bw
Basis:
actual ingested
- No. of animals per sex per dose:
- 12
- Control animals:
- yes, concurrent vehicle
- Details on study design:
- - Dose selection rationale:
The dose levels were chosen based on the results of previous toxicity work (Harlan Laboratories Ltd., Project Number 41300261).
- Rationale for animal assignment: The animals were randomly allocated to treatment groups using a stratified body weight randomisation procedure and the group mean body weights were then determined to ensure similarity between the treatment groups. The cage distribution within the holding rack was also randomised.
Chronological Sequence of Study
i. Groups of twelve male and twelve female animals were treated daily at the appropriate
dose level throughout the study (except for females during parturition where applicable).
The first day of dosing was designated as Day 1 of the study.
ii. Prior to the start of treatment and once weekly thereafter, all animals were observed for
signs of functional/behavioural toxicity.
iii. On Day 15, animals were paired on a 1 male: 1 female basis within each dose group for a
maximum of fourteen days.
iv. Following evidence of mating (designated as Day 0 post coitum) the males were returned
to their original cages and females were transferred to individual cages.
v. On completion of the pairing phase (during Week 6), five selected males per dose group
were evaluated for functional/sensory responses to various stimuli.
vi. Pregnant females were allowed to give birth and maintain their offspring until Day 5 post
partum. Litter size, offspring weight and sex, surface righting and clinical signs were
also recorded during this period.
vii. At Day 4 post partum, five selected females per dose group were evaluated for
functional/sensory responses to various stimuli.
viii. Blood samples were taken from five males from each dose group for haematological and
blood chemical assessments on Day 42. The male dose groups were killed and examined
macroscopically on Day 43.
ix. Blood samples were taken from five randomly selected females from each dose group for
haematological and blood chemical assessment on Day 4 post partum. At Day 5 post
partum, all females and surviving offspring were killed and examined macroscopically.
Any female which did not show positive evidence of mating or produce a pregnancy was
also killed and examined macroscopically. - Positive control:
- None.
Examinations
- Observations and examinations performed and frequency:
- CAGE SIDE OBSERVATIONS: Yes
- Time schedule: All animals were examined for overt signs of toxicity, ill-health and behavioural change immediately before dosing, soon after dosing, and one hour and five hours after dosing during the working week. Animals were observed immediately before dosing, soon after dosing and
one hour after dosing at weekends and public holidays (except for females during parturition where applicable). All observations were recorded.
DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: Prior to the start of treatment and at weekly intervals thereafter, all animals were observed for signs of functional/behavioural toxicity. Detailed individual clinical observations were performed for each animal using a purpose built arena. The following parameters were observed: Gait, Hyper/Hypothermia, Tremors, Skin colour, Twitches, Respiration, Convulsions, Palpebral closure, Bizarre/Abnormal/Stereotypic behaviour, Urination, Salivation Defecation, Pilo-erection, Transfer arousal, Exophthalmia, Tail elevation, Lachrymation.
BODY WEIGHT: Yes
- Time schedule for examinations: Individual body weights were recorded on Day 1 (prior to dosing) and then weekly for males until termination and weekly for females until mating was evident. Body weights were then recorded for females on Days 0, 7, 14 and 20 post coitum, and on Days 1 and 4 post partum. Body weights were also recorded at terminal kill.
FOOD CONSUMPTION AND COMPOUND INTAKE:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: Yes
During the pre-pairing period, weekly food consumption was recorded for each cage of adults. This was continued for males after the mating phase. For females showing evidence of mating, food consumption was recorded for the periods covering post coitum Days 0-7, 7-14 and 14-20.
For females with live litters, food consumption was recorded on Days 1 and 4 post partum.
FOOD EFFICIENCY:
- Body weight gain in kg/food consumption in kg per unit time X 100 calculated as time-weighted averages from the consumption and body weight gain data: Yes
Food efficiency (the ratio of body weight change/dietary intake) was calculated retrospectively for males throughout the study period (with the exception of the mating phase) and for females during the pre-pairing phase. Due to offspring growth and milk production, food efficiency could not be accurately calculated for females during gestation and lactation.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): Yes
Water intake was observed daily by visual inspection of water bottles for any overt changes.
OPHTHALMOSCOPIC EXAMINATION: No
HAEMATOLOGY: Yes
- Time schedule for collection of blood: prior to termination (Day 42 for males and Day 4 post partum for females).
- Anaesthetic used for blood collection: Yes (identity) / No / No data
- Animals fasted: No
- How many animals: five males and five females selected from each test and control group
- Parameters checked in table [No.1] were examined.
CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: prior to termination (Day 42 for males and Day 4 post partum for females).
- Animals fasted: No
- How many animals: five males and five females selected from each test and control group.
- Parameters checked in table [No.1] were examined.
URINALYSIS: No
NEUROBEHAVIOURAL EXAMINATION: Yes
- Time schedule for examinations: prior to termination
- Dose groups that were examined: Functional performance tests were also performed on five selected males and females from each dose level, prior to termination, together with an assessment of sensory reactivity to various stimuli.
- Battery of functions tested: sensory activity / grip strength / motor activity
Motor Activity:
Purpose-built 44 infra-red beam automated activity monitors were used to assess motor activity. Animals were randomly allocated to the activity monitors. The tests were performed at approximately the same time on each occasion (at least two hours after dosing), under similar laboratory conditions. The evaluation period was thirty minutes for each animal. The percentage of time each animal was active and mobile was recorded for the overall thirty minute period and also during the final 20% of the period (considered to be the asymptotic period, Reiter and Macphail, 1979).
Forelimb/Hindlimb Grip Strength:
An automated meter was used. Each animal was allowed to grip the proximal metal bar of the meter with its forepaws. The animal was pulled by the base of the tail until its grip was broken. The animal was drawn along the trough of the meter by the tail until its hind paws gripped the distal metal bar. The animal was pulled by the base of the tail until its grip was broken. A record of the force required to break the grip for each animal was made. Three consecutive trials were performed for each animal. The assessment was developed from the method employed by Meyer et al (1979).
Sensor reactivity:
Each animal was individually assessed for sensory reactivity to auditory, visual and proprioceptive stimuli. The following parameters were observed: Grasp response, Vocalisation, Toe pinch, Tail pinch, Finger approach, Touch escape, Pupil reflex, Blink reflex, Startle reflex.
OTHER:
Reproductive Performance (see section 7.8.1.) - Sacrifice and pathology:
- GROSS PATHOLOGY: Yes
Adult males were killed by intravenous overdose of sodium pentobarbitone followed by exsanguination on Day 43. Adult females were killed by intravenous overdose of sodium pentobarbitone followed by exsanguination on Day 5 post partum. Surviving offspring were terminated via intracardiac overdose of sodium pentobarbitone. Any females which failed to achieve pregnancy or produce a litter were killed on or after Day 25 post coitum. Any female which failed to mate was terminated on Day 57.
The following organs were dissected free from fat and weighed before fixation from five selected males and five selected females from each dose group: Adrenals, Brain, Epididymides, Heart, Kidneys, Liver, Ovaries, Pituitary (post fixation), Prostate, Seminal vesicles, Spleen, Testes, Thymus, Thyroid (weighed post-fixation with Parathyroid), Uterus (weighed with Cervix). The following tissues were weighed from all remaining animals: Epididymides, Ovaries, Pituitary (post fixation), Prostate, Seminal vesicles, Testes, Uterus (weighed with Cervix).
HISTOPATHOLOGY: Yes (see table 2)
Samples of the tissues mentioned in table 2 were removed from five selected males and five selected females from each dose group and preserved in buffered 10% formalin.
The following tissues were preserved from all remaining animals: Coagulating gland, Epididymides, Gross lesions, Mammary gland, Ovaries, Pituitary, Prostate, Seminal vesicles, Testes, Uterus/Cervix, Vagina. - Other examinations:
- For all females, the uterus was examined for signs of implantation and the number of uterine implantations in each horn was recorded. This procedure was enhanced; as necessary, by staining the uteri with a 0.5% ammonium polysulphide solution (Salewski 1964). The corpora lutea were also counted.
All adult animals and offspring, including those dying during the study, were subjected to a full external and internal examination, and any macroscopic abnormalities were recorded. - Statistics:
- See "Any other information on materials and methods incl.tables".
Results and discussion
Results of examinations
- 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:
- no effects observed
- Water consumption and compound intake (if drinking water study):
- no effects observed
- Ophthalmological findings:
- not examined
- Haematological findings:
- no effects observed
- Clinical biochemistry findings:
- no effects observed
- Urinalysis findings:
- not examined
- Behaviour (functional findings):
- no effects observed
- Gross pathological findings:
- no effects observed
- Histopathological findings: non-neoplastic:
- no effects observed
- Histopathological findings: neoplastic:
- no effects observed
- Details on results:
- CLINICAL SIGNS AND MORTALITY
There were no treatment-related deaths. One female treated with 100 mg/kg bw/day died during the bleeding procedure on Day 4 post partum. This death was considered procedure related and therefore is of no toxicological significance.
There were no toxicologically significant clinical signs detected in treated animals. One male treated with 300 mg/kg bw/day had generalised scab formation between Days 19 and 23. Observations of this nature are commonly observed in group housed animals and is considered not to be of toxicological significance.
BODY WEIGHT AND WEIGHT GAIN
There were no toxicologically significant effects detected in body weight development. Males treated with 1000 and 300 mg/kg bw/day showed a statistically significant increase in body weight gain during Weeks 2 and 4 (p<0.05). Males treated with 100 mg/kg bw/day also showed a statistically significant increase in body weight gain during Week 4 (p<0.05). An increase in body weight gain is considered not to represent an adverse effect of treatment therefore the intergroup differences are of no toxicological importance.
FOOD CONSUMPTION AND FOOD EFFICIENCY
No adverse effect on food consumption or food efficiency was detected in treated animals when compared to control animals.
WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study)
Daily visual inspection of water bottles did not reveal any significant intergroup differences.
HAEMATOLOGY
No toxicologically significant effects were detected in the haematological parameters examined.
Males from all treatment groups showed a statistically significant increase in neutrophil count when compared to controls. The majority of individual values were within normal ranges for rats of the strain and age used, and in the absence of true dose related response the intergroup differences were considered not to be of toxicological importance.
Males treated with 1000 mg/kg bw/day also showed a statistically significant increase in total leucocyte count. All of the individual values were within normal range for rats of the strain and age used, therefore the intergroup difference was considered not to be of toxicological importance.
CLINICAL CHEMISTRY
No toxicologically significant effects were detected in the blood chemical parameters examined. Males from all treatment groups showed a statistically significant increase (p<0.05 - p<0.01) in total protein, calcium concentration and cholesterol. Males treated with 1000 and 300 mg/kg bw/day also showed a statistically significant increase (p<0.05) in albumin. Males treated with 1000 mg/kg bw/day showed a statistically significant reduction (p<0.01) in albumin/globulin ratio. Females from all treatment groups showed a statistically significant increase (p<0.05) in glucose. The majority of individual values were within the normal ranges for rats of the strain and age used. In the case of total protein, albumin and calcium concentration a true dose related response was not evident and also in the absence of any associated histology correlates the intergroup differences were considered not to be of toxicological importance.
NEUROBEHAVIOUR
Weekly open field arena observations did not reveal any treatment-related effects for treated animals when compared to controls. All inter and intra group differences in behavioural scores were considered to be a result of normal variation for rats of the strain and age used, and the differences were of no toxicological importance.
Functional Performance Tests
There were no treatment related changes in functional performance.
Statistical analysis of the data did not reveal any significant intergroup differences.
Sensory Reactivity Assessments
There were no treatment-related changes in sensory reactivity.
ORGAN WEIGHTS
No toxicologically significant effects were detected in the organ weights measured. Males treated with 1000 and 300 mg/kg bw/day showed a statistically significant reduction in thyroid weight both absolute and relative to terminal body weight. The majority of individual values were within normal range for rats of the strain and age used and in the absence of any histology correlates the intergroup differences were considered not to be of toxicological importance.
GROSS PATHOLOGY
No toxicologically significant macroscopic abnormalities were detected. One male treated with 100 mg/kg bw/day had small testes and one male treated with 300 mg/kg bw/day also had small and flaccid testes and small epididymides. Microscopic examinations revealed tubular atrophy in the testes and intratubular cellular debris and reduced sperm in the epididymides. In the absence of a similar effect at 1000 mg/kg bw/day the intergroup differences were considered not to be of toxicological importance. One female treated with 1000 mg/kg bw/day had dark kidneys at necropsy. In the absence of any histology correlates the intergroup difference was considered not to be of toxicological importance. One control male had a small and flaccid left testis and a small left epididymis. A further control male had reddened lungs. In the absence of treatment these were considered to be incidental findings.
HISTOPATHOLOGY: NON-NEOPLASTIC
There were no treatment related microscopic abnormalities detected.
The findings recorded were within the range of normal background lesions which may be recorded in rats of the strain and age used.
OTHER FINDINGS
Reproductive performance (see section 7.8.1. for further details):
There were no treatment-related effects on mating performance and fertility. There were no differences in gestation lengths. The distribution for treated females was comparable to controls.
Litter responses (see section 7.8.2. for further details):
In total eleven females from the control, 100, and 300 mg/kg bw/day dose groups and all females from the 1000 mg/kg bw/day dose group gave birth to a live litter and successfully reared young to Day 5 of age. The following assessment of litter response is based on all litters reared to termination on Day 5 of lactation/age.
No significant differences were detected for corpora lutea, implantation counts, implantation losses, litter size or litter viability for treated animals when compared to controls. Statistical analysis of the data did not reveal any significant intergroup differences. There were no intergroup differences in sex ratio (percentage male offspring) for litters from treated groups compared to controls. Statistical analysis of the data did not reveal any significant intergroup differences.There were no toxicologically significant effects detected in offspring's growth and development.
Effect levels
open allclose all
- Dose descriptor:
- NOAEL
- Remarks:
- systemic toxicity
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No toxicologically significant findings were observed in the treated animals.
- Dose descriptor:
- NOAEL
- Remarks:
- reproductive toxicity
- Effect level:
- 1 000 mg/kg bw/day (nominal)
- Based on:
- test mat.
- Sex:
- male/female
- Basis for effect level:
- other: No effects on reproductive performance were observed.
Target system / organ toxicity
- Critical effects observed:
- not specified
Applicant's summary and conclusion
- Conclusions:
- The oral administration of 1-(3-sulphonatopropyl)pyridinium to rats by gavage, at dose levels of 100, 300 and 1000 mg/kg bw/day, did not result in any toxicologically significant effects. The "No Observed Adverse Effect Level" (NOAEL) for systemic toxicity was therefore considered to be 1000 mg/kg bw/day.
The "No Observed Effect Level" (NOEL) for reproductive toxicity was considered to be 1000 mg/kg bw/day. - Executive summary:
Introduction
The study was designed to investigate the systemic toxicity and potential adverse effects of the test item on reproduction (including offspring development) and is designed to be compatible with the requirements of the OECD Guidelines for Testing of Chemicals No. 422 “Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test” (adopted 22 March 1996).
This study was also designed to be compatible with Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
Methods
The test item was administered by gavage to three groups, each of twelve male and twelve female Wistar Han™:RccHan™:WIST strain rats, for up to eight weeks (including a two week pre-pairing phase, pairing, gestation and early lactation for females), at dose levels of 100, 300 and 1000 mg/kg bw/day. A control group of twelve males and twelve females was dosed with vehicle alone (Distilled water).
Clinical signs, behavioural assessments, body weight change and food and water consumption were monitored during the study.
Pairing of animals within each dose group was undertaken on a one male: one female basis within each treatment group on Day 15 of the study, with females subsequently being allowed to litter and rear their offspring to Day 5 of lactation.
During the lactation phase, daily clinical observations were performed on all surviving offspring, together with litter size and offspring weights and assessment of surface righting reflex.
Extensive functional observations were performed on five selected males from each dose group after the completion of the pairing phase, and for five selected parental females from each dose group on Day 4 post partum. Haematology and blood chemistry were evaluated prior to termination on five selected males and females from each dose group.
Adult males were terminated on Day 43, followed by the termination of all females and offspring on Day 5 post partum. Any female which did not produce a pregnancy was terminated on or after Day 25 post coitum. Any female which did not show positive evidence of mating and did not produce a pregnancy was terminated on Day 57. All animals were subjected to a gross necropsy examination and histopathological evaluation of selected tissues was performed.
Results
Adult Responses:
Mortality
There were no treatment-related deaths.
Clinical Observations
No toxicologically significant clinical observations were detected.
Behavioural Assessment
There were no treatment-related changes in the behavioural parameters measured.
Functional Performance Tests
There were no treatment-related changes in functional performance.
Sensory Reactivity Assessments
There were no treatment-related changes in sensory reactivity.
Body Weight
There were no toxicologically significant effects in body weight development.
Food Consumption
No adverse effect on food consumption or food efficiency was detected in treated animals.
Water Consumption
No adverse effect on water consumption was detected.
Reproductive Performance
Mating:
There were no treatment-related effects on mating for treated animals.
Fertility:
There were no treatment-related effects in conception rates for treated animals.
Gestation Lengths:
There were no differences in gestation lengths. The distribution for treated females was comparable to controls.
Litter Responses:
Offspring Litter Size, Sex Ratio and Viability:
Of the litters born, litter size at birth and subsequently on Day 1 and 4 post partum was comparable to controls. Sex ratio and surface righting were also comparable to controls.
Offspring Growth and Development
Offspring bodyweight gain and litter weights at birth and subsequently on Day 1 and 4 post partum were comparable to controls. No clinically observable signs of toxicity were detected for offspring from all treatment groups.
Laboratory Investigations
Haematology:
There were no toxicologically significant effects detected in the haematological parameters examined.
Blood Chemistry:
There were no toxicologically significant effects detected in the blood chemical parameters examined.
Pathology
Necropsy
No toxicologically significant macroscopic abnormalities were detected.
Organ Weights
There were no toxicologically significant effects detected in the organ weights measured.
Histopathology
There were no treatment related microscopic abnormalities detected.
Conclusion
The oral administration of 1-(3-sulphonatopropyl)pyridinium to rats by gavage, at dose levels of 100, 300 and 1000 mg/kg bw/day, did not result in any toxicologically significant effects. The “No Observed Adverse Effect Level” (NOAEL) for systemic toxicity was therefore considered to be 1000 mg/kg bw/day. The “No Observed Effect Level” (NOEL) for reproductive toxicity was considered to be 1000 mg/kg bw/day.
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