Registration Dossier

Administrative data

Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Study based on OECD guideline 410. Read across from SCI to SLMI

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1991
Report Date:
1991

Materials and methods

Test guideline
Qualifier:
equivalent or similar to
Guideline:
other: OECD Guideline 410 (Repeated Dose Dermal Toxicity: 21/28-Day Study)
Deviations:
yes
Remarks:
No ophthalmological observations were performed.
Principles of method if other than guideline:
This repeat dose study up to a limit dose of 2 g/kg bw is considered suitable to estimate the acute dermal LD50.
GLP compliance:
yes (incl. certificate)
Test type:
other:

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
- Name of test material: Sodium cocoyl isethionate
- Analytical purity: 72.45%
- Lot/batch No.: 1247
- Stability under test conditions: Stable for the duration of the study

Test animals

Species:
rat
Strain:
other: Charles River COBS CDR
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles River Breeding Laboratories, Portage, MI, U.S.
- Age at study initiation: 5-7 weeks
- Weight at study initiation: 176-200g

Administration / exposure

Type of coverage:
semiocclusive
Vehicle:
water
Details on dermal exposure:
TEST SITE
- Area of exposure: Clipped dorsal area, 32 cm2 for body weights below 350 g, 36 cm2 for body weights of 350 to 400 g and 40 cm2 for body weights of 400 g
- Type of wrap if used: Gauze
- Time intervals for shavings or clipplings:


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


TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 0.08 g a.i./kg (1.0% w/w), 0.91 g a.i./kg (14.0% w/w) and 2.07 g a.i./kg (36.0% w/w)


VEHICLE
- Millipore filtered water
Duration of exposure:
6 h per day for 28 days
Doses:
0.08 g a.i./kg (1.0% w/w), 0.91 g a.i./kg (14.0% w/w) and 2.07 g a.i./kg (36.0% w/w) nominal per unit body weight
No. of animals per sex per dose:
10/sex/dose
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Remarks on result:
other: LOAEL 2.07 g/kg
Mortality:
No treatment related effects. One male rat in the vehicle control group and one male rat in the 14.0% (w/w) group died during the study but these deaths were attributed to mechanical trauma due to struggling during the gauze wrapping procedure.
Clinical signs:
Very slight erythema (+1) was observed in two males during weeks 3 and 4. Dermal irritation in females was observed in each treatment group during week 1 of the study. Very slight erythema was observed in four females in the 1.0% (w/w) and 14.0% (w/w) treatment groups during the first week but no irritation was observed during the remainder of the study. Females in the 36.0% (w/w) group showed very slight and well-defined erythema (+2) which showed a significant difference from the control on days 4, 5, 6 and 7 of the study only Very slight oedema (+1) was also observed in females in this group but the difference was not significant.
Body weight:
No significant difference between any group means during the test. Individual body weight data showed transient low weight gains and losses for males and females in all test groups, including the control.
Gross pathology:
Necropsy revealed red patchy areas on the lungs of rats occurring randomly throughout the control and test groups, with one rat showing pale lungs in the 1.0% (w/w) test group. None of these findings were considered to be treatment related.
Histopathology results showed no treatment related effects as all findings were considered to be incidental, except microscopic findings in the liver of one male in the 36.0% (w/w) treatment which showed fibrous trabeculae, increased Kupffer cell macrophages and lipofuscin pigment and one female in the vehicle control which showed coagulative necrosis of one liver lobe. These findings were determined to be due to mechanical trauma.
Excised skin sections showed slight microscopic differences in morphology between treated and untreated sites in each of the control and test groups. Skin from the treated sites showed a slight thickening of the epithelium and slightly increased cornification. The basal cell layer showed a slight increase in the mitotic rate in the treated skin sites compared to the untreated sites. These differences were attributed to the vehicle and semi-occlusive gauze dressing since there were no difference between the vehicle control and SCI treated groups. In addition, no inflammatory changes were observed.

Any other information on results incl. tables

Necropsy revealed red patchy areas on the lungs of rats occurring randomly throughout the control and test groups, with one rat showing pale lungs in the 1.0% (w/w) test group. None of these findings were considered to be treatment related. Histopathology results showed no treatment related effects as all findings were considered to be incidental, except microscopic findings in the liver of one male in the 36.0% (w/w) treatment which showed fibrous trabeculae, increased Kupffer cell macrophages and lipofuscin pigment and one female in the vehicle control which showed coagulative necrosis of one liver lobe. These findings were determined to be due to mechanical trauma. Excised skin sections showed slight microscopic differences in morphology between treated and untreated sites in each of the control and test groups. Skin from the treated sites showed a slight thickening of the epithelium and slightly increased cornification. The basal cell layer showed a slight increase in the mitotic rate in the treated skin sites compared to the untreated sites. These differences were attributed to the vehicle and semi-occlusive gauze dressing since there were no difference between the vehicle control and SCI treated groups. In addition, no inflammatory changes were observed.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In a study performed to OECD 410, there was no evidence of systemic toxicity in the treated animals during the study up to the highest dose of 2.07 g/kg/day. Observations revealed very slight erythema in a few males at the highest dose and slight erythema and oedema in females at the highest dose. Both findings decreased in incidence and severity towards the end of the study. There was no evidence of skin irritation on day 1 of the study and thus the NOAEL for acute local effects is 2.07 g/kg bw.