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Description of key information

In an acute oral toxicity study with rats (WIL Research 507498, key study) performed according to OECD/EC test guidelines, the oral LD50 of disodium isodecyl sulfosuccinate in Wistar rats was established to be within the range 300-2000 mg/kg body weight. The acute dermal toxicity showed an LD50 > 5000 mg/kg in rabbits.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
30 Oct 2014 - 20 Nov 2014
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study has been performed according to OECD and/or EC guidelines and according to GLP principles.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
2001
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)
Version / remarks:
Official Journal of the European Union No. L142, May 2008
Deviations:
no
Qualifier:
according to
Guideline:
EPA OPPTS 870.1100 (Acute Oral Toxicity)
Version / remarks:
Office of Prevention, Pesticides and Toxic Substances (7101), EPA 712-C-02-190, 2002
Deviations:
no
Qualifier:
according to
Guideline:
other: Japanese Ministry of Agriculture, Forestry and Fisheries (JMAFF), 12 Nousan, Notification No 8147, November 2000, including the most recent partial revisions.
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: Crl:WI (Han)
Sex:
female
Details on test animals and environmental conditions:
- Source: Charles River Deutschland, Sulzfeld, Germany
- Age at study initiation: Young adult animals (approx. 9-10 weeks old)
- Weight at study initiation: 178-205 g
- Fasting period before study: yes (prior to dosing and until 3-4 hours after administration of the test substance)
- Housing: Group housing of 3 animals per cage in labeled Makrolon cages
- Diet: Free access to pelleted rodent diet (SM R/M-Z from SSNIFF® Spezialdiäten GmbH, Soest, Germany)
- Water: Free access to tap water
- Acclimation period: At least 5 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 18 – 24
- Humidity (%): 40 - 70
- Air changes (per hr): at least 10
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From 30 October 2014 to 20 November 2014
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
GAVAGE METHOD: plastic feeding tubes

Frequency: single dosage, on day 1

VEHICLE
Justification for choice of vehicle: The vehicle was selected based on trial formulations performed at WIL Research Europe and on test substance data supplied by the sponsor.

MAXIMUM DOSE VOLUME APPLIED:
10 mL/kg bw

DOSAGE PREPARATION:
The formulations (w/w) were kept at room temperature and dosed within 4 hours after adding the vehicle to the test substance. Homogeneity was obtained to visually acceptable levels and the formulations were stirred during dosing, which ensures homogeneity sufficient for these kinds of studies. No correction was made for purity of the test substance. The concentration of the test substance in vehicle was varied to allow constant dosage volume in terms of mL/kg body weight.
Doses:
2000 mg/kg body weight, 300 mg/kg body weight

No. of animals per sex per dose:
2000 mg/kg bw: 3
300 mg/kg bw: 6 (2 groups of three females in a stepwise manner)
Control animals:
no
Details on study design:
The toxicity of the test substance was assessed by stepwise treatment of groups of 3 females. The first group was treated at a dose level of 2000 mg/kg bw. The absence or presence of mortality of animals dosed at one step determined the next step, based on the test procedure defined in the guidelines. The onset, duration and severity of the signs of toxicity were taken into account for determination of the time interval between the dose groups.

- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Mortality/Viability: Twice daily
Body weights: Days 1 (pre-administration), 8 and 15 and at death (if found dead after day 1)
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15
- Necropsy of survivors performed: The animals surviving to the end of the observation period were sacrificed by oxygen/carbon dioxide procedure. All animals assigned to the study were subjected to necropsy and descriptions of all internal macroscopic abnormalities recorded.
- Other examinations performed: none
Statistics:
No statistical analysis was performed (the method used is not intended to allow the calculation of a precise LD50 value).
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
At 2000 mg/kg bw, two animals were found dead on day 2. At 300 mg/kg bw, no mortality occurred.
Clinical signs:
At 2000 mg/kg bw, hunched posture and piloerection were noted for the all animals on days 1 and/or 2. At 300 mg/kg bw, hunched posture was noted for all animals between days 1 and 3.
Body weight:
The mean body weight gain shown by the surviving animals over the study period was considered to be similar to that expected for normal untreated animals of the same age and strain.
Gross pathology:
At 2000 mg/kg bw, gelatinous contents of the small intestines were found in both animals that died during the study. Macroscopic post mortem examination of the surviving animal at termination did not reveal any abnormalities. At 300 mg/kg bw, macroscopic examination did not reveal any abnormalities.
Advanced autolysis was noted for both animals found dead. This finding was considered not toxicologically significant
Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In an acute oral toxicity study with female rats, performed according to OECD/EC test guidelines, the LD50 of disodium isodecyl sulfosuccinate in Wistar rats was established to be within the range 300-2000 mg/kg body weight.
Executive summary:

An acute oral toxicity study with disodium isodecyl sulfosuccinate was performed in female rats according to OECD/EC test guidelines and GLP principles. After exposure to 2000 mg/ kg bw, two rats died within 48 hours. No mortality occurred at 300 mg/ kg bw. Clinical signs were noted for all three rats, and consisted of hunched posture and piloerection on days 1 and/or 2. Gelatinous contents of the small intestines were found in both animals that died during the study (further examination was not possible due to autolysis), no abnormalities were found in the surviving rat at necropsy. Two groups of three rats were successively exposed to 300 mg/ kg bw. Hunched posture was noted for all animals on days 1 to 3. No changes in body weight gain were observed for these animals and no macroscopic abnormalities were found.

Based on these data, the LD50 of disodium isodecyl sulfosuccinate in Wistar rats was established to be between 300-2000 mg/kg body weight, therefore the substance is classified category 4 for oral toxicity according to Regulation (EC) 1272/2008.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
300 mg/kg bw
Quality of whole database:
Four studies are available. One study has reliability Klimisch 1 (WIL Research 507498). The other available studies were performed with formulations of the test substance. The reliability of these studies was found to be not assignable (Klimisch 4).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Quality of whole database:
Two supporting studies are available, conducted with formulations of the test substance. As the tested formulations contain additional compounds, which could influence the acute effects of disodium isodecyl sulfosuccinate, the reliability of the studies was found to be not assignable (Klimisch 4).

Additional information

Acute oral toxicity

An acute oral toxicity study with Registered substance was performed in female rats according to OECD/EC test guidelines and GLP principles (WIL Research Europe, 2014). After exposure to 2000 mg/ kg bw, two rats died within 48 hours. No mortality occurred at 300 mg/ kg bw. Clinical signs were noted for all three rats, and consisted of hunched posture and piloerection on days 1 and/or 2. Gelatinous contents of the small intestines were found in both animals that died during the study (further examination was not possible due to autolysis), no abnormalities were found in the surviving rat at necropsy. Two groups of three rats were successively exposed to 300 mg/ kg bw. Hunched posture was noted for all animals on days 1 to 3. No changes in body weight gain were observed for these animals and no macroscopic abnormalities were found. Based on these data, the LD50 of disodium isodecyl sulfosuccinate in Wistar rats was established to be between 300-2000 mg/kg body weight. As dermal absorption is not expected to exceed oral adsorption, it is scientifically justified to assume that the dermal LD50 is >300 mg/kg bw.

Furthermore, several supporting studies are available, performed with formulations of the same test substance. The results of the supporting studies are in line with the results found in the key study.

 

Acute dermal toxicity Two acute dermal toxicity studies were available with Registered substance. In a key acute dermal toxicity test with 5 male rabbits, an LD50 > 10 mL/kg bw was found for formulation containing50% aqueous formulation; this corresponds to an LD50 for Registered substance of >5000 mg/kg bw (Carpenter, 1971). In a supporting acute dermal toxicity test with 5 male rabbits, no mortality was observed at 2000 mg/kg bw for an aqueous formulation with ≥20% disodium isodecyl sulfosuccinate (Gilotti, 2005).

 

Acute inhalation toxicity Testing for inhalation toxicity with the Registered substance is waived, based on the low vapour pressure ( <= 0.0022 Pa at 20°C).

Justification for classification or non-classification

Based on the available data, the oral LD50 of Registered substance in Wistar rats was established to be between 300-2000 mg/ kg body weight, therefore the substance is classified category 4 for oral toxicity according to CLP Regulation (EC) No. 1272/2008. Based on a dermal LD50 >2000 mg/ kg bw/ day no classification is needed for dermal toxicity.