Registration Dossier

Administrative data

Endpoint:
chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1976-1977
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
No guideline study and non-GLP but performed according to scientific standards at time of performance. Acceptable based on nowadays existing guidlines and standards. Well performed and documented. Reliability declaration regarding procedures and performance available.

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1977
Report Date:
1977

Materials and methods

Test guideline
Qualifier:
no guideline available
Principles of method if other than guideline:
One year feeding study to rats with an interim group examined after 26 weeks of exposure
GLP compliance:
no
Remarks:
but reliability declaration included
Limit test:
no

Test material

Reference
Name:
Unnamed
Type:
Constituent
Type:
Constituent
Details on test material:
- Name of test material (as cited in study report): Hostapur SAS 60
- Physical state: liquid
- Analytical purity: 60%
- Composition of test material, percentage of components: 60% Hostapur SAS 93, water
- Purity test date: 1976
- Lot/batch No.: no data
- Expiration date of the lot/batch: 1978
- Radiochemical purity (if radiolabelling): n.a.
- Specific activity (if radiolabelling): n.a.
- Locations of the label (if radiolabelling): n.a.
- Expiration date of radiochemical substance (if radiolabelling): n.a.
- Stability under test conditions: stability and homogeneity guaranteed
- Storage condition of test material: in darkness at room temperature
- Other:

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River U.K.
- Age at study initiation: young adult
- Weight at study initiation: 60 - 80 g
- Fasting period before study: no data
- Housing: polypropylene cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2 °C
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): 12 hours


IN-LIFE DATES: From: 1976 To: 1977

Administration / exposure

Route of administration:
oral: feed
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:


DIET PREPARATION
- Rate of preparation of diet (frequency): weekly
- Mixing appropriate amounts with (Type of food): pet food (powder)
- Storage temperature of food: refrigerator


VEHICLE
- Justification for use and choice of vehicle (if other than water): n.a.
- Concentration in vehicle: n.a.
- Amount of vehicle (if gavage): n.a.
- Purity: 60% active matter
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
26 weeks (interim)
52 weeks (main study)
Frequency of treatment:
daily
Doses / concentrations
Remarks:
Doses / Concentrations:
0, 0.08, 0.4, 2.0 %
Basis:
nominal in diet
No. of animals per sex per dose:
10 per sex per dose for 26 weeks (interim groups)
20 per sex per dose for 52 weeks (main groups)
Control animals:
yes, plain diet
Details on study design:
- Dose selection rationale: expert judgement
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: interim pathological examinations
- Post-exposure recovery period in satellite groups: n.a.
- Section schedule rationale (if not random): n.a.

Examinations

Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily
- Cage side observations: Yes


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: subject to parameter of investigation


BODY WEIGHT: Yes
- Time schedule for examinations:weekly for the first 13 weeks, monthly thereafter


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: No data
- Compound intake calculated as time-weighted averages from the consumption and body weight gain data: Yes


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: No data


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): n.a.
- Time schedule for examinations: n.a.


OPHTHALMOSCOPIC EXAMINATION: Yes
- Time schedule for examinations:
- Dose groups that were examined:


HAEMATOLOGY: Yes / No / No data
- Time schedule for collection of blood: prior first treatment, after 26 and 52 weeks
- Anaesthetic used for blood collection: No
- Animals fasted: No
- How many animals: 10 male and 10 female per group
- Parameters examined: PCV, Hb, RBC, WBC, differential WBC, MCHC, MCV, urea, glucose, total protein, electrophoretic protein fractions, AP, SGPT, sodium, potassium


CLINICAL CHEMISTRY: Yes / No / No data
- Time schedule for collection of blood:
- Animals fasted: Yes / No / No data
- How many animals:
- Parameters checked in table [No.?] were examined.


URINALYSIS: Yes / No / No data
- Time schedule for collection of urine:
- Metabolism cages used for collection of urine: Yes / No / No data
- Animals fasted: Yes / No / No data
- Parameters checked in table [No.?] were examined.


NEUROBEHAVIOURAL EXAMINATION: Yes / No / No data
- Time schedule for examinations:
- Dose groups that were examined:
- Battery of functions tested: sensory activity / grip strength / motor activity / other:


OTHER:
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes
Other examinations:
Urinalysis
Urin concentration test
Statistics:
As appropriate

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
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:
no effects observed
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
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:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Details on results:
CLINICAL SIGNS AND MORTALITY : Lack of grooming activity. No clinical signs. No treatment related mortality


BODY WEIGHT AND WEIGHT GAIN : Decreased rates of body weight gain in males and females of high dose group (2% in diet) throughout treatment period.


FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study) : Food intake reduced by approximately 10% in males at highest dose-level (2% in diet) over the first 19 weeks. Thereafter similar to controls.


FOOD EFFICIENCY : no data


WATER CONSUMPTION AND COMPOUND INTAKE (if drinking water study): no data


OPHTHALMOSCOPIC EXAMINATION : No effects


HAEMATOLOGY : No effects


CLINICAL CHEMISTRY : No treatment related significant effects


URINALYSIS : No effects


NEUROBEHAVIOUR : No data


ORGAN WEIGHTS : No effects


GROSS PATHOLOGY : Type, distribution and nature of macroscopic findings after 26 and 52 weeks of exposure typical for rat strain used and unrelated to treatment


HISTOPATHOLOGY: NON-NEOPLASTIC : No significant histopathological change or variation from normal and/or control


HISTOPATHOLOGY: NEOPLASTIC (if applicable): No significant histopathological change or variation in morphology attributable to treatment


HISTORICAL CONTROL DATA (if applicable). No change or variation compared to historical control data


OTHER FINDINGS : No significant findings

Effect levels

Dose descriptor:
NOAEL
Effect level:
4 000 ppm
Sex:
male/female
Basis for effect level:
other: Even 20000 ppm of the test substance in the diet was tolerated without significant functional and/or morphological changes

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Sec-alkane sulfonate-sodium salts SAS (60%) in the diet up to 0.4 % have been tolerated by the animals in a one-year chronic oral toxicity study without any significant effect (NOEL). As a first approximation this concentration corresponds to about 200 mg/kg body weight per day.

Even at the highest level of 2 % in the diet (approximately 1000 mg/kg body weight per day) only unspecific effects not accompanied by any
functional, morphological or structural changes have been observed.
Executive summary:

Sec-alkane sulfonate-sodium salts SAS (60%) was investigated in a one-year chronic feeding study for potential toxic effects. Although not conducted according to GLP, the study followed the scientific standards at this time and is regarded to be valid with restrictions (Klimisch criteria 2). Groups of 30 male and 30 female Sprague-Dawley rats were fed diets containing 0.08, 0.4 or 2% (w/w) sec-alkane sulfonate-sodium salts SAS (60%) for 52 weeks. A similar sized group received a standard diet and served as controls. 10 male and 10 female rats from each group were killed after 26 weeks of treatment for interim pathological examination. Throughout the study no mortality occurred. A lack of grooming activity was observed throughout the treatment period in both sexes given 2 % (w/w). This was enhanced or caused by the adherence of the diet particles which had a higher moisture content due to admixture with sec-alkane sulfonate-sodium salts SAS (60%). By the end of the fourth week, the leaner body confirmation of rats at the high dose level was discernible on handling. No signs of reaction to treatment were seen at treatment levels of 0.4 % and below. Food intake was reduced in weeks 1 to 19 in males given the highest level. Females at this level and rats of both sexes at lower levels were unaffected in this respect. Bodyweight increments were reduced in rats of both sexes given 2 % sec-alkane sulfonate-sodium salts SAS (60%), but not below. Marginal increases in serum alkaline phosphatase and glutamate-pyruvate transaminase activity, seen at 26 and 52 weeks in animals receiving the highest dietary concentration, did not associate with structural changes in any tissue. Therefore they were not considered to be mainifestations of adverse reactions. Haematological characteristics, urinalysis and urine concentrating ability were unaffected by treatment at 2 % and below. No disturbances of absolute and relative organ weights relating to treatment with sec-alkane sulfonate-sodium salts SAS (60%) were seen in rats killed after 26 or 52 weeks of treatment. Macro- and microscopic examinations of rats killed after 26 or 52 weeks similarly revealed no changes in morphology attributable to treatment. Based on all results, it was concluded that the only detectable evidence of adverse reaction in rats receiving 2 % sec-alkane sulfonate-sodium salts SAS (60%) in their diet for one year was impaired grooming activity and initially retarded weight gain relating only in part to reduced food consumptions. These non-specific changes were not accompanied by any significant functional or structural changes.

Based on the results of this one-year chronic feeding study in rats it is concluded that concentrations of sec-alkane sulfonate-sodium salts SAS (60%) in the diet up to 0.4 % have been tolerated by the animals without any significant effect. As a first approximation this concentration corresponds to about 200 mg/kg body weight per day. Even at the highest level of 2 % in the diet (approximately 1000 mg/kg body weight per day) only unspecific effects not accompanied by any morphological, functional or structural changes have been observed. However, the NO(A)EL of this study was conservatively placed at 0.4 % sec-alkane sulfonate-sodium salts SAS (60%) which approximates 200 mg/kg body weight per day.