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Description of key information

In an klimsch score 2 study on SCI an LD50 (oral) of >5000 mg/kg/bw was achieved


In an klimsch score 2 study on SLI an LD50 (dermal) of >2000 mg/kg/bw was achieved

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: This is a one page report with limited details provided. However, the results serve to indicate the low toxicity of the test substance.
Guideline:
other: In house method G.2.2.1.
Principles of method if other than guideline:
5 groups of male Sprague Dawley rats were given a single dose of DEFI (20% concentration) on day 1 doses of 3.3, 4.1, 5.1, 6.4 and 8.0 g/kg. Animals were observed for mortality and clinical signs on days 1, 2, 3, 4, 7 and 14, with bodyweight measured on days 0, 7 and 14.
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
TEST ANIMALS
- Weight at study initiation: 170-201g
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 20%
- Amount of vehicle: not reported
Doses:
Single doses of 3.3, 4.1, 5.1, 6.4 and 8.0 g/kg
No. of animals per sex per dose:
5
Control animals:
not specified
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Animals were observed for mortality and other overt signs on days 1, 2, 3, 4, 7, and 14. Body weights were measured on days 0, 7 and 14.
- Necropsy of survivors performed: yes
Statistics:
Probit (E1-2)
Sex:
male
Dose descriptor:
LD50
Effect level:
8 400 mg/kg bw
Mortality:
Mortalities were observed in the two highest dose groups only. In the 8 g/kg group, 2 animals died on day 1 and 1 on day 2. In the 6.4 g/kg group one animal died on day 4.
Clinical signs:
Slight diarrhea was observed in two animals in the 4.1 g/kg dose within 1-2 hours after dosing. Moderate diarrhea was observed in two, four and five animals about 1 hour after dosing in the 5.1, 6.4, and 8.0 g/kg bw doses, respectively. Lethargy was observed in all 8.0 g/kg dose animals 1 hour after dosing. Some lethargy was also observed at about 22 hours in a single animal each at the 6.4 and 8.0 doses
Body weight:
No significant effects to body weight were observed.
Gross pathology:
Gross pathology at necropsy revealed no significant findings.
Moderate inflammation of the gastric mucosa was observed in the animals that died on day 1 and 2 in the 8.0 g/kg bw dose.

Mortalities were observed in the two highest dose groups only.   In the 8 g/kg group, 2 animals died on day 1 and 1 on day 2.  In the 6.4 mg/kg group one animal died on day 4.

Clinical signs were observed in all dose groups except the lowest (3.1 g/kg).  

Lethargy was observed in all 8 mg/kg dose group animals approximately 1 hour after dosing.  Some lethargy was also observed at about 22 hours in a single animal each at the 6.4 and 8.0 g/kg doses.

Diarrhoea was observed in the 4.1, 5.1, 6.4 and 8 g/kg dose groups.  Moderate diarrhoea was observed in two, four and five animals about 1 hour after dosing in the 5.1, 6.4, and 8.0 g/kg bw doses, respectively. Slight diarrhoea was observed in two animals in the 4.1 g/kg dose within 1-2 hours after dosing.
Interpretation of results:
relatively harmless
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
In an acute oral toxicity study performed similar to current guidelines the SCI is considered to be of low toxicity, with a LD50 of 8.4 g/kg.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
Good, two klimisch score 2 studies and a peer reviewed, review article provide the data

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Link to relevant study records
Reference
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
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:
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
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
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.

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.

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.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Good quality study

Additional information

3 acute oral toxicity studies are available. One key study and two supporting studies

(Unilever, 1982) found in an study performed similar to current guidelines the read across material Sodium Cocoyl Isethionate is considered to be of low toxicity, with a LD50 of 8.4 g/kg.

Two supporting studies support the lack of acute oral toxicity for the read across SCI.

Unilever, (1991) obtained a dermal LD50 in excess of 2000 mg/kg.


Justification for selection of acute toxicity – oral endpoint
Reliable study on read across substance sodium cocoyl isethionate

Justification for selection of acute toxicity – dermal endpoint
data is from OECD 410 study but the findings are relevant.

Justification for classification or non-classification

Acute oral and dermal LD50 values for the read across substances SCI and SLI were in excess of 2000mg/kg bw.

Therefore SLMI has not been classified as acutely toxic for any exposure.