Registration Dossier

Administrative data

Endpoint:
short-term repeated dose toxicity: dermal
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1975
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:
1975
Report Date:
1975

Materials and methods

Test guideline
Qualifier:
no guideline followed
Principles of method if other than guideline:
Subacute (4 and 5 week exposure periods) dermal toxicity study
GLP compliance:
no
Remarks:
not required at time of performance
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
- Structural formula attached as image file (if other than submission substance): see Fig.
- Physical state: slurry
- Analytical purity: 60%
- Composition of test material, percentage of components: 60% Hostapur SAS 93, water
- Isomers composition: n.a.
- Purity test date: 1974-09-03
- Lot/batch No.: no data
- Expiration date of the lot/batch: 1976-09-01
- 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:
mouse
Strain:
CD-1
Sex:
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: 16 - 18 g
- Fasting period before study: no
- Housing: polypropylene cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21 +/- 2 °C
- Humidity (%): no data
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12 hours

Administration / exposure

Type of coverage:
open
Vehicle:
water
Details on exposure:
TEST SITE
- Area of exposure: 4 cm2
- % coverage: 100
- Type of wrap if used: n.a.
- Time intervals for shavings or clipplings: 2 - 3 days


REMOVAL OF TEST SUBSTANCE
- Washing (if done): n.a.
- Time after start of exposure: n.a.


TEST MATERIAL
- Concentration (if solution): 0, 0.1, 0.5 (increasing to 8.0 up to 16.0) and 1.0 (increasing to 2.0 up to 32) % (w/v)
- Constant volume or concentration used: yes (0.1 mL per animal)
- For solids, paste formed: n.a.


VEHICLE
- Justification for use and choice of vehicle (if other than water): water
- Amount(s) applied (volume or weight with unit): n.a.
- Concentration (if solution): n.a.
- Lot/batch no. (if required): n.a.
- Purity: n.a.


USE OF RESTRAINERS FOR PREVENTING INGESTION: no data
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
4 and 5 weeks according to experimental group
Frequency of treatment:
5 days/week
Doses / concentrations
Remarks:
Doses / Concentrations:
0.1 mL of 0.1 up to 32 % (w/v) test solutions
Basis:
nominal per unit area
No. of animals per sex per dose:
25 female animals per group
Control animals:
yes
Details on study design:
- Dose selection rationale: expert judgement
- Rationale for animal assignment (if not random): random
- Rationale for selecting satellite groups: n.a.
- Post-exposure recovery period in satellite groups: n.a.
- Section schedule rationale (if not random): random

Examinations

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


DETAILED CLINICAL OBSERVATIONS: Yes
- Time schedule: daily


DERMAL IRRITATION (if dermal study): Yes
- Time schedule for examinations: daily


BODY WEIGHT: Yes
- Time schedule for examinations: weekly


FOOD CONSUMPTION:
- Food consumption for each animal determined and mean daily diet consumption calculated as g food/kg body weight/day: 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: Yes
- Time schedule for examinations: daily


OPHTHALMOSCOPIC EXAMINATION: No data


HAEMATOLOGY: No data


CLINICAL CHEMISTRY: No data


URINALYSIS: No data


NEUROBEHAVIOURAL EXAMINATION: No data


OTHER:
Sacrifice and pathology:
GROSS PATHOLOGY: Yes
HISTOPATHOLOGY: No data
Other examinations:
Organ weight analysis
Statistics:
As appropriate

Results and discussion

Results of examinations

Clinical signs:
no effects observed
Dermal irritation:
effects observed, treatment-related
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):
no effects observed
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:
effects observed, treatment-related
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
not specified
Histopathological findings: neoplastic:
not specified
Details on results:
OTHER FINDINGS: Repeated dermal treatment with test concentrations of 16% and higher led to irritative skin changes. Secondary responses due to
the inflammatory and infective condition affecting the skin at higher test concentrations included sligtly increased spleen weights.

Effect levels

Dose descriptor:
NOEL
Effect level:
ca. 500 other: mg/kg bw / day (calculated)
Sex:
male/female
Basis for effect level:
other: NOEL is based on local irritation / inflammation at treated skin sites

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
Concentrations up to 8% were tolerated without any signs of intoxication.
Executive summary:

A subacute dermal toxicity study with sec-alkane sulfonate-sodium salts SAS (60%) was performed in CD-1 mice using aqueous solutions of the test material at different concentrations. 4 groups of 25 female mice were topically administered 0.1 mL of 0% (control), o.1% (group 2), 0.5% (group 3) or 1% (group 4) sec-alkane sulfonate-sodium salts SAS (60%) (w/v). After 3 weeks of exposure the concentration applied to group 3 was increased to 8% and after 4 weeks to 16% (w/v). The concentration of the test solution applied to group 4 was increased after one week to 2% and after 3 weeks to 32% (w/v). Treatment was continued 5 days per week for 4 consecutive weeks in the case of groups 2 and 4, and for 5 weeks in groups 1 and 3. Encrustation, skin thickening, erythema and skin sloughing were observed at the treated skin sites in all mice within two days of commencement of treatment with solutions containing 32% (w/v). Mice given 16% showed skin thickening after one week of treatment. Mice treated with solutions containing 8% sec-alkane sulfonate-sodium salts SAS (60%) and below showed no detectable reactions at the exposed skin sites. Weight losses, without concomitant reduction of food intake, were seen in all mice receiving 32% in the first week of treatment. However, a return to normal growth was observed during the second week of exposure at this level. Mice dermally treated at 8% or below showed no weight retardation. Organ weight analysis showed increased absolute and relative spleen weights in mice given 32%. This was considered a secondary response to the inflammatory and infective condition affecting the skin. Absolute and relative weights of liver and kidneys in mice given 32%, and all three organs at lower levels of administration were unaltered by the treatment. In summary, the NO(A)EL in mice for local effects calculated on body weight is approximately 500 mg/kg body weight per day whereas for systemic effects a NO(A)EL of 1000 mg/kg body weight per day can be assumed.