Registration Dossier

Administrative data

Description of key information

Two repeat dose studies are available for this substance, one is a 14 -day oral gavage exposure study on C6-8 alkane sulfonate itself, and the other is a 90 -day repeat study via the dietary route on a read-across substance sodium dodecyl sulfate. Together they provide a weight of evidence basis for the evaluation of repeat dose toxicological properties of C6-8 alkane sulfonate.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records
Reference
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Comparable to guideline study
Reference:
Composition 0
Qualifier:
equivalent or similar to
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity in Rodents)
GLP compliance:
no
Test material information:
Composition 1
Species:
rat
Strain:
other: Carworth Farm 'E'
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Tunstall Laboratory, "Shell" Reseach Ltd., Sittingbourne, Kent, UK
- Age at study initiation: 5 weeks
- Weight at study initiation: no data
- Fasting period before study: no data
- Housing: Individually caged
- Diet: ad libitum
- Water: as libitum
- Acclimation period: no data

ENVIRONMENTAL CONDITIONS
no data

Route of administration:
oral: feed
Details on oral exposure:
PREPARATION OF DOSING SOLUTIONS:

DIET PREPARATION
- Rate of preparation of diet (frequency): no data
- Mixing appropriate amounts with (Type of food): Diet 86 powder
- Storage temperature of food: no data

VEHICLE
no data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
90 d
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:
0, 40, 200, 1000 or 5000 ppm
Basis:
nominal in diet
Remarks:
Doses / Concentrations:
0, 3, 17, 86 or 430 mg/kg bw/day
Basis:
actual ingested
No. of animals per sex per dose:
12 animals/sex/group in test groups, 18 animals/sex/group in control group
Control animals:
yes, plain diet
Details on study design:
- Dose selection rationale: no data
Positive control:
not applicable
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS: Yes
- Time schedule: daily

DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily

BODY WEIGHT: Yes
- Time schedule for examinations: weekly

FOOD CONSUMPTION AND COMPOUND INTAKE (if feeding study):
- Food consumption for each animal recorded weekly

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

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

OPHTHALMOSCOPIC EXAMINATION: No

HAEMATOLOGY: Yes
- Time schedule for collection of blood: Termination
- Anaesthetic used for blood collection: No data
- Animals fasted: No data
- How many animals: all
- Parameters checked: erythrocyte and leucocyte counts, haematocrit and haemoglobin.

CLINICAL CHEMISTRY: Yes
- Time schedule for collection of blood: Termination
- Animals fasted: No data
- How many animals: all
- Parameters checked: Total plasma protein, urea, serum protein.

URINALYSIS: Yes
- Time schedule for collection of urine: week 12 for 5000 ppm group and controls
- Metabolism cages used for collection of urine: Yes (16 hr collection)
- Animals fasted: No data
- Parameters checked: colour, pH, protein, reducing substances, bile salts and microscopic constituents

NEUROBEHAVIOURAL EXAMINATION: No
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: Yes (controls and 5000 ppm group)
Other examinations:
ORGAN WEIGHTS
Statistics:
Statistical analyses of terminal body weights, food intakes and organ weights were made using the initial body weight as a covariate in covariance analysis.
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 examined
Water consumption and compound intake (if drinking water study):
not examined
Ophthalmological findings:
not examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
Organ weight findings including organ / body weight ratios:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Details on results:
ORGAN WEIGHTS: Increase in liver weight in females at 5000 ppm. The increase is considered to be an adaptive response to treatment.

GROSS PATHOLOGY: Spontaneous lesions, mainly hydronephrosis were present in all groups of animals.

Dose descriptor:
NOAEL
Effect level:
> 5 000 ppm
Based on:
test mat.
Sex:
female
Basis for effect level:
other: increased liver weight
Dose descriptor:
NOAEL
Effect level:
> 430 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: increased liver weights
Critical effects observed:
not specified
Executive summary:

Sodium dodecyl sulfate was tested in a 90-day feeding study on rats. Twelve male and 12 female rats/group were fed dietary levels of 40, 200, 1000 or 5000 ppm (corresponding to 3, 17, 86 or 430 mg/kg bw/day). The control group (18 males, 18 females) received the diet alone.Daily observations were made on health. Body weight and food intake were recorded weekly. Urine samples were obtained from the 5000 ppm and control groups during week 12. The urine was examined for color, pH, protein, reducing substances, bile salts and microscopic constituents. Terminal blood samples were taken by cardiac puncture and erythrocyte and leucocyte counts and determinations of hematocrit and hemoglobin were made. Total plasma protein and urea were determined. Gross pathological and histological examination of a wide range of organs were made.The only effects observed occurred at 5000 ppm and comprised increases in liver weights in female animals.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
NOAEL
430 mg/kg bw/day
Study duration:
subchronic
Species:
rat
Quality of whole database:
Two studies are available, a 90-day study on a read across substance (Klimisch 2) and a 14-day extended range finding study on the substance itself (Klimisch 1).

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

Mode of Action Analysis / Human Relevance Framework

Additional information

Two repeat dose studies are available for this substance, one is a 14 -day oral gavage exposure study on C6-8 alkane sulfonate itself, and the other is a 90 -day repeat study via the dietary route on a read-across substance sodium dodecyl sulfate. Together they provide a weight of evidence basis for the evaluation of repeat dose toxicological properties of C6-8 alkane sulfonate. The full read-across argument for the validity of the 90 -day study is given in the toxicokinetic section but the toxicological basis may be summarised as follows: The toxicological profile of the alkyl sulfates and the alkane sulfonates reveals many similarities. For all compounds where data are available, the acute oral toxicity as well as repeated oral toxicity is low. After multiple oral dosing, the gastrointestinal tract (dosing via gavage), and the liver were identified as target organs. The similarity between both subgroups is evident also for other endpoints such as skin and eye irritation, sensitization, mutagenicity, carcinogenicity and reproductive and developmental toxicity. Longer-term studies as well as data concerning carcinogenicity or reproduction toxicity are missing. However, based on metabolism studies it can be concluded that the properties of the alkyl sulfates and sulfonates are similar.

Sodium dodecyl sulfate was tested in a 90-day feeding study on rats. Twelve male and 12 female rats/group were fed dietary levels of 40, 200, 1000 or 5000 ppm (corresponding to 3, 17, 86 or 430 mg/kg bw/day). The control group (18 males, 18 females) received the diet alone. Daily observations were made on health. Body weight and food intake were recorded weekly. Urine samples were obtained from the 5000 ppm and control groups during week 12. The urine was examined for color, pH, protein, reducing substances, bile salts and microscopic constituents. Terminal blood samples were taken by cardiac puncture and erythrocyte and leucocyte counts and determinations of haematocrit and haemoglobin were made. Total plasma protein and urea were determined. Gross pathological and histological examination of a wide range of organs were made. The only effects observed occurred at 5000 ppm and comprised increases in liver weights in female animals.

C6 -8 alkane sulfonate was administered daily by oral administration to CD® rats for 14 days. The rats were treated with 100, 300 or 1000 mg/kg b. w. /day. None of the animals died prematurely. All animals treated with 100, 300 or 1000 mg/kg b. w. /day revealed salivation immediately after administration that lasted for 10 to 15 minutes on up to 5 test days starting on test day 2.

No test item-related influence was noted on body weight and body weight gain, food and drinking water consumption, haematological and biochemical parameters.

Treatment with 1000 mg/kg b. w. /day resulted in a slight increase in the relative and absolute weight of the stomach (statistically not significant at p<0.01).

The macroscopic post mortem examination did not reveal any test item-related changes at any dose level.

Histopathological examination revealed a focal squamous cell hyperplasia with hyperkeratosis in the forestomach mucosa near the borderline to the squamosa of the animals treated with 1000 mg/kg b. w. /day. Further, a moderate sub-epithelial oedema with mixed cell infiltrations was noted in the forestomach of one high dosed female. The histopathological findings correlated with the increase in the stomach weight.


Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
90-day study.

Repeated dose toxicity: via oral route - systemic effects (target organ) digestive: liver

Justification for classification or non-classification

The NOAEL from a 90 -day study performed using a member of the ANS category and read across to the substance was > 100 mg/kg bw/day. Classification is not required.