Sodium 3-(allyloxy)-2-hydroxypropanesulphonate

Endpoint summary

Description of key information

A 28-days repeated dose toxicity study regarding oral application is available. A NOAEL of 150 mg/kg bw/day is found and no target organ was identified.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

14 June - 3 October 2007

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

comparable to guideline study

Qualifier:

according to guideline

Guideline:

other: Guideline for Toxicity Testings of New Chemical Substances, Notification No. 1121002 of Pharmaceutical and Food Safety Bureau, Ministry of Health, Labour and Wlfare, Japan

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Details on test animals or test system and environmental conditions:

TEST ANIMALS
- Source: Charles River Japan Inc.
- Age at study initiation: 5 weeks
- Weight at study initiation: 129.3 - 144.9 g (males); 109.0 - 130.3 g (females)
- Fasting period before study:
- Housing: individually; stainless steel wired cages
- Diet: MF, lot No. 070808, Oriental Yeast Co.,Ltd. ad libitum
- Water: ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 to 25 °C
- Humidity (%): 40 to 70 %
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12

Route of administration:

oral: gavage

Vehicle:

water

Details on oral exposure:

PREPARATION OF DOSING SOLUTIONS:

VEHICLE
- Concentration in vehicle: 10 w/v%, 1.5 w/v%, 0.25 w/v%

- Amount of vehicle (if gavage): 10 mL
- Lot/batch no. (if required): 070719A

Analytical verification of doses or concentrations:

yes

Details on analytical verification of doses or concentrations:

The stability of the test item and the concentration in the vehicle was determined by IR absorption spectroscopy and High performance liquid chromatography. No changes in the IR spectrum (400 to 4000 cm-1) and in the chromatogram were observed.

Duration of treatment / exposure:

28 days

Frequency of treatment:

once daily

Dose / conc.:

0 mg/kg bw/day (nominal)

Dose / conc.:

25 mg/kg bw/day (nominal)

Dose / conc.:

150 mg/kg bw/day (nominal)

Dose / conc.:

1 000 mg/kg bw/day (nominal)

No. of animals per sex per dose:

5

Control animals:

yes, concurrent vehicle

Details on study design:

- Dose selection rationale: a 7-day repeated-dose oral toxicity study was conducted, indicating the choosen doses
- Rationale for selecting satellite groups: highest concentration and therefore most likly affected group
- Post-exposure recovery period in satellite groups: 14 days

Observations and examinations performed and frequency:

CAGE SIDE OBSERVATIONS: Yes
- Time schedule: three times daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: weekly

BODY WEIGHT: Yes
- Time schedule for examinations: on day 1, 3, 8, 12, 17, 21, 26, 28 recovery period: day 1, 5, 10, 14

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: on day 28 (not recovery group) or day 14 of recovery period
- Anaesthetic used for blood collection: Yes (Ether)
- Animals fasted: Yes
- How many animals: all

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: on day 28 (not recovery group) or day 14 of recovery period
- Animals fasted: Yes
- How many animals: all

URINALYSIS: Yes
- Time schedule for collection of urine: on day 28 (not recovery group) or day 14 of recovery period
- Metabolism cages used for collection of urine: Yes
- Animals fasted: Yes

NEUROBEHAVIOURAL EXAMINATION: Yes / No / No data
- Time schedule for examinations: in the last week of the study
- Dose groups that were examined: all
- Battery of functions tested: sensory activity / grip strength / motor activity

Sacrifice and pathology:

GROSS PATHOLOGY: Yes (see table)
Macroscopic observation of body surface, openings, subcutaneous tissue, cranial cavity, thoracic cavity, abdominal cavity, pelvic cavity and their contents.
HISTOPATHOLOGY:
Trachea and lungs, stomach, intestines, liver, heart, kidneys, bladder, testes, epididymides, prostate, seminal vesicles, ovaries, uterus, vagina, brain, spinal cord, sciatic nerve, bone marrow, lymph nodes, spleen, thymus, pituitary gland, throid gland, adrenal glands, eyeballs

Other examinations:

measurement of food consumption

Statistics:

body weight, food conssumption, hematological findings, blood biochemical findings, urine volume, urine specific gravity, organ weights, grip strength and ultromotivity were examined for equality of variance by the Bartlett method.
If equality of variance was detected at 5 % significance level, one-way layout analysis of variance was performed.
If a significant difference was detected in the analysis of variance, the test by the Dunnett method was perforemd between the vehicle control group and each of the treatment groups.
If there was no equality of variance, the Kruskal-Wallis test was performed.
If a significant difference was detected the nonparametric Dunnett test was perfomed between the vehicle control group and each of the treatment groups.
the frequencies of evacuation and urination were examined by the Krukal-Wallis test.
If a significant difference was detected the nonparametric Dunnett test was perfomed between the vehicle control group and each of the treatment groups.

Clinical signs:

effects observed, treatment-related

Mortality:

mortality observed, treatment-related

Body weight and weight changes:

no effects observed

Description (incidence and severity):

During the treatment period
No significant change was noted in males or females.
During the recovery period
No significant change was noted in males or females.

Food consumption and compound intake (if feeding study):

effects observed, non-treatment-related

Description (incidence and severity):

During the treatment period
No significant change was noted in males or females.
During the recovery period
Males: No significant change was noted.
Females: The food consumption increased significantly on Day 4 of recovery in the 1000 mg/kg group.

Ophthalmological findings:

not examined

Urinalysis findings:

no effects observed

Behaviour (functional findings):

effects observed, treatment-related

Immunological findings:

not examined

Organ weight findings including organ / body weight ratios:

no effects observed

Gross pathological findings:

no effects observed

Neuropathological findings:

not examined

Histopathological findings: non-neoplastic:

no effects observed

Details on results:

CLINICAL SIGNS AND MORTALITY
no mortality occured
loose feces in 3 animals treated with 150 mg/kg bw/day, loose feces and salivation in all animals and diarrhea in 10 animals treated with 1000 mg/kg bw/day

BODY WEIGHT AND WEIGHT GAIN
normal

FOOD EFFICIENCY
in the recovery group treated with 1000 mg/kg bw/day the food uptake increased

HAEMATOLOGY
the percentage of basophils decreased significantly in the 1000 mg/kg bw/day female recovery group

CLINICAL CHEMISTRY
high gamma-glutamyl transpeptidase level in the 25 and 150 mg/kg bw/day female groups; high A/Gratio and low creatinine level in the 1000 mg/kg bw/day male recovery group

URINALYSIS
normal

NEUROBEHAVIOUR
amount of ultromotivity decreased at 30 to 40 minutes in the 1000 mg/kg bw/day group

ORGAN WEIGHTS
normal

GROSS PATHOLOGY
bulging of the edge of the anterio stomach in one animal of the 1000 mg/kg bw/day male and female group
nodules of the spleen in one animal of the control male group
shrinkage of the left thyroid lobe in one animal of the 25 mg/kg bw/day male group
swollen spleen in one animal of the 150 mg/kg bw/day male group
uterine cyst in one animal of the 25 mg/kg bw/day female group

HISTOPATHOLOGY: NON-NEOPLASTIC
germinal center differentiation of the spleen in one animal of the control male group
hypoplasia of the left thyroid lobe in one animal of the 25 mg/kg bw/day male group
capsulitisof the spleen in one animal of the 150 mg/kg bw/day male group
hyperplasia of the squamous epithelium at the edge of the anterior stomach in two animal of the 1000 mg/kg bw/day male group
uterine cyst in the muscle layer in one animal of the 25 mg/kg bw/day female group
hyperplasia of the squamous epithelium at the edge of the anterior stomach in three animal of the 1000 mg/kg bw/day female group

Key result

Dose descriptor:

NOAEL

Effect level:

150 mg/kg bw/day (actual dose received)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

other: overall effects

Critical effects observed:

not specified

Conclusions:

The study is well performed and gives following results for the Endpoint:
NOAEL = 150 mg/kg bw/day

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

150 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

only one study available. a 90 day repeated dose toxicity test has been proposed.

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion

Endpoint conclusion:

no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
only one study available