Registration Dossier

Administrative data

Description of key information

No studies on the EC substance [940-223-9] itself are available. A read-across approach using the very close structural analogue [938-147-6] Fatty acid chlorides, C8-14 (even numbered), reaction products with glycine (Public name: Sodium cocoyl glycinate (SCG)) as source substance was chosen. 
With regard to the acute toxicity of Sodium cocoyl glycinate (SCG), test data for the oral and dermal exposure route are available. Based on an OECD 423 acute oral toxicity study, the limit dose of 2000 mg/kg body weight revealed no mortality and no clinical signs of intoxication. Macroscopic findings during gross pathology were not observed. Based on the findings the LD 50 was established to be greater than 2000 mg/kg body weight. The acute dermal toxicity of thesource substance was evaluated in an OECD 402 study according to GLP. After topical treatment with the limit dose of 2000 mg/kg body weight neither mortality nor significant clinical symptoms of intoxication were observed. The LD50 after dermal treatment was established to be greater 2000 mg/kg body weight.
Based on the justified read-across these endpoint data for the source substance are also taken for the target substance.

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
Study period:
2008
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Guideline Study according to GLP. Read-across justification is given in the read-across document attached in IUCLID Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Harlan Laboratories
- Age at study initiation: 11 weeks
- Weight at study initiation: 178 - 200 g
- Fasting period before study: none, except overnight fasting period before dosing
- Housing: in groups of three in Makrolon type-4 cages
- Diet (e.g. ad libitum): ad libitum
- Water (e.g. ad libitum): ad libitum


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22 +/- 3 °C
- Humidity (%): 30 - 70 %
- Air changes (per hr): 10 - 15 per hour
- Photoperiod (hrs dark / hrs light): light / dark cycle of 12 hours
Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 0.2 g/mL
- Amount of vehicle (if gavage): 10 mL/kg
- Justification for choice of vehicle: water

MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg body weight


CLASS METHOD (if applicable)
- Rationale for the selection of the starting dose: Limit dose
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
6 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: Clinical signs and mortality daily, body weighs on test days 1, 8 and 15
- Necropsy of survivors performed: yes
Statistics:
No
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occured during the study
Clinical signs:
No clinical signs observed during the study
Body weight:
not influenced
Gross pathology:
No macroscopic findings were recorded at necropsy
Other findings:
none
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The LD50 of Hostapon SG after single oral administration to female rats is greater than 2000 mg/kg body weight
Executive summary:

The acute oral toxicity of Hostapon SG was investigated in 6 female rats using purified water as vehicle. The study was performed according to OECD test guideline 423 using the acute toxic class method and followed the principles of GLP. 3 female animals per group were administered the test compound by single-dose gavage at a dose-level of 2000 mg/kg body weight. The observation period was 14 days. No deaths occurred during the study. Clinical signs of intoxication were also not observed during the course of the study. Body weight development was normal and within the range commonly recorded for this strain and age. At necropsy no macroscopic findings were recorded. Based on the findings of this limit-test the median lethal dosage (LD50) of Hostapon SG in female rats is greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Data waiving:
exposure considerations
Justification for data waiving:
other:
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
Study period:
2010-08-24 to 2010-11-04
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Study conducted in compliance with agreed protocols, with no or minor deviations from standard test guidelines and/or minor methodological deficiencies, which do not affect the quality of the relevant results. The study report was conclusive, done to a valid guideline and the study was conducted under GLP conditions. Read-across justification is given in the read-across document attached in IUCLID Section 13.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Test Animals:
Animals: Rat, RccHan: WIST(SPF)
Rationale: Recognized by international guidelines as a recommended test system.
Breeder: Harlan Laboratories B.V., Kreuzelweg 53, 5961 NM / The Netherlands
Number of Animals per Group: 5 males and 5 females
Total Number of Animals: 5 males and 5 females
Age (when treated): Males: 9 weeks, Females: 11 weeks
Body Weight Range (when treated): 228 g – 253 g (males), 189 g – 207 g (females)
Identification: Unique cage number and corresponding color-coded spots on the tail. The animals were marked during acclimatization.
Randomization: Selected by hand at time of delivery. No computer generated randomization program.
Acclimatization: Eight days under laboratory conditions, after health examination. Only animals without any visible signs of illness were used for the study.

Environmental Conditions:
Conditions: Standard Laboratory Conditions. Air-conditioned with 10-15 air changes per hour, and continuously monitored environment with ranges for room temperature 22 ± 3 °C and for relative humidity between 30-70%, automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.
Accommodation: During acclimatization in groups of five per sex in Makrolon type-4 cages with standard softwood bedding. Individually in Makrolon type-3 cages with standard softwood bedding (‘Lignocel’ J. Rettenmaier&Söhne GmbH&CoKG, 73494 Rosenberg / Germany, imported by Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) during treatment and observation. Paper enrichment, Reference no. 207057, batch no. 67, (Enviro-dri from Lillico, Biotechnology, Surrey / UK) was included.
Diet: Pelleted standard Teklad Rat-Mouse Diet 2914C, irradiated, batch no. 30/10 (Provimi Kliba AG, 4303 Kaiseraugst / Switzerland) ad libitum. Results of analyses for contaminants are archived at Harlan Laboratories Ltd.
Water: Community tap water from Füllinsdorf ad libitum. Results of bacteriological, chemical and contaminant analyses are archived at Harlan Laboratories Ltd.
Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Details on dermal exposure:
Preparation of Dose Formulations:
Dose levels are in terms of the test item as supplied by the Sponsor. The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume). The formulation was prepared shortly before the application using a magnetic stirrer, a spatula and an Ultra-Turrax as homogenizers. Homogeneity of the test item in the vehicle was maintained during administration using a magnetic stirrer.

Test Item Administration:
One day before treatment, the backs of the animals were clipped with an electric clipper, exposing an area of approximately 10% of the total body surface. Only those animals without injury or irritation on the skin were used in the test. On test day 1, the test item was applied evenly on the intact skin with a syringe and covered with a surgical gauze pad (ca. 5 x 5 cm) held in contact with the skin by means of an adhesive hypoallergenic aerated semi-occlusive dressing and an elastic adhesive restrainer bandage wrapped around the abdomen.
The application volume was 6 mL/kg.
Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and drapped off with disposable paper towels. Thereafter, the reaction sites were assessed. All animals were re-shaved on test day 8 to facilitate the reading of the local reactions.
Rationale: Dermal administration was used as this is one possible route of human exposure during manufacture, handling and use of the test item.
Duration of exposure:
24 hours
Doses:
2000 mg/kg body weight
No. of animals per sex per dose:
5 males and 5 females
Control animals:
not required
Details on study design:
Purpose:
The purpose of this study was to assess the acute dermal toxicity of Hostapon SG dried when administered to rats by single semi-occlusive dermal application, followed by an observation period of 14 days. This study should provide a rational basis for risk assessment.

Vehicle:
The vehicle was chosen after a non-GLP solubility trial which was performed before the study initiation date. Therefore, solubility testing was excluded from the statement of compliance. According to the Sponsor, the test item is soluble in water up to a concentration of 25%. Therefore, polyethylene glycol 300 (PEG 300) was used as vehicle and the test item could be dispersed at the technically highest concentration of 33 % (w/w). This was achieved with an Ultra Turrax and resulted in a white liquid, which was considered dermally applicable.
The following information was provided by Harlan Laboratories Ltd.:
Identification: Polyethylene glycol 300 (PEG 300)
Description: Colorless viscous liquid
Lot Number: STBB 3451
Source: Sigma-Aldrich Chemie GmbH, Riedstr. 2, D-89555 / Germany
Stability of the Vehicle: Stable under storage conditions
Expiry Date: 30-Apr-2012
Storage Conditions: At room temperature (range of 20 ± 5 °C), light protected.
Safety Precautions: Routine hygienic procedures were used to ensure the health and safety of the personnel.

Observations:
Viability / Mortality: Daily during the acclimatization period. Once before treatment, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15.
Clinical Signs: Daily during the acclimatization period. Once before treatment, within the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1. Once daily during days 2-15. All abnormalities will be recorded.
Local Dermal Signs: Once daily during days 2 (following dressing removal) through day 15 using the numerical scoring system described in Appendix I.
Body Weights: On test days 1 (prior to administration), 8 and 15.

Pathology:
Necropsy: All animals were sacrificed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were performed. An external examination and opening of the abdominal and thoracic cavities for examinations of major organs was performed. The appearance of any macroscopic abnormalities was recorded. No organs or tissues were retained.

Data Compilation:
Viability/mortality was recorded on data sheets.
Body weights were recorded on-line with the ToxControl Computer System.
Clinical signs, local dermal signs, mortality data and macroscopic findings were compiled into the ToxControl Computer System during recording.
The ToxControl Computer System has been licenced for Harlan Laboratories Ltd. and validated with respect to data collection, storage and retrievability.
Statistics:
No statistical analysis was used.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No intercurrent deaths occurred during the course of the study.
Clinical signs:
No clinical signs were recorded throughout the entire observation period.
Body weight:
One animal (No. 8) lost body weight (-1.0%) during the first week after test item administration. However, the animal regained weight until the end of the observation period. Otherwise, the body weight of the animals was within the range commonly recorded for animals of this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.

Local dermal signs:

Very slight to slight erythema was observed on test day 2 (1 male) or from test day 2 to test day 4 (1 female) or test day 6 (1 male). Very slight to slight oedema and slightly maculated crusts were observed in one female (No. 10) from test day 2 to 3 or from test day 7 to 15, the end of the observation period. Slight desquamation was noted in one male and three females during test day 3 to test day 7 or 11 and in one male from test day 8 to test day 12. Slight to moderate desquamation was noted in one female from test day 3 to test day 14. The test item caused white to yellow discoloration of the treated skin in two males and one female on test day 2.

Interpretation of results:
not classified
Remarks:
Migrated information
Conclusions:
The median lethal dose of Hostapon SG dried after single dermal administration to rats of both sexes, observed over a period of 14 days, is:
LD50 (rat): greater than 2000 mg/kg body weight
Executive summary:

The acute dermal toxicity of `Hostapon SG dried` was investigated in an OECD 402 study in accordance with the principles of GLP. Five male and five female Wistar rats were treated with the test substance at 2000 mg/kg by dermal application. The test item was formulated in polyethylene glycol 300 as vehicle. The application period was 24 hours. Following a 14 day observation period all animals were necropsied and examined macroscopically. No intercurrent deaths occurred and no clinical signs were recorded throughout the entire observation period. The only substance related effects consisted of very slight to slight dermal irritation reactions in form of erythema and/or oedema in one male and two females during the observation period. No macroscopic findings were observed at necropsy. Based on the study results the median lethal dose (LD50) of Hostapon SG dried after single dermal administration to rats of both sexes was greater than 2000 mg/kg body weight.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Guideline study according to GLP with no deviations. Klimisch rating 1 representing reliability without restrictions. Information is valid and meets data requirements.

Additional information

No studies on the EC substance [940-223-9] itself are available. A read-across approach using the very close structural analogue [938-147-6] Fatty acid chlorides, C8-14 (even numbered), reaction products with glycine (Public name: Sodium cocoyl glycinate (SCG)) as source substance was chosen.

The acute oral toxicity of Sodium cocoyl glycinate (SCG) was investigated in 6 female rats using purified water as vehicle. The study was performed according to OECD test guideline 423 using the acute toxic class method and followed the principles of GLP. 3 female animals per group were administered the test compound by single-dose gavage at a dose-level of 2000 mg/kg body weight. The observation period was 14 days. No deaths occurred during the study. Clinical signs of intoxication were also not observed during the course of the study. Body weight development was normal and within the range commonly recorded for this strain and age. At necropsy no macroscopic findings were recorded. Based on the findings of this limit-test the median lethal dosage (LD50) of the source substance in female rats is greater than 2000 mg/kg body weight.

The acute dermal toxicity of Sodium cocoyl glycinate (SCG) was investigated in five male and five female rats at the limit dose of 2000 mg/kg by dermal application. The study was conducted according to OECD 402 and followed the principles of GLP The application period was 24 hours followed by a 14 day observation period. All animals were necropsied and examined macroscopically. No intercurrent deaths occurred during the course of the study. No clinical signs were recorded throughout the entire observation period. The only test item related findings had been very slight to slight dermal irritation reactions in form of erythema and oedema. No macroscopic findings were observed at necropsy. The median lethal dose (LD50) of the source substance dried after single dermal administration to rats of both sexes, observed over a period of 14 days was established to be greater than 2000 mg/kg body weight.

Based on the justified read-across these endpoint data for the source substance are also taken for the target substance.


Justification for selection of acute toxicity – oral endpoint
Guideline study according to GLP with no deviations. Klimisch rating 1 representing reliability without restrictions. Information is valid and meets data requirements.

Justification for classification or non-classification

Based on the results from available guideline studies, the source substance is not subject to labelling and classification requirements with regard to the oral or dermal route of exposure.

This conclusion is also taken for the target substance.