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Description of key information

In a reliable acute toxicity study the substance was administered to Wistar rats (5 female animals) by oral gavage at a dose level of 2000 mg/kg bw (single administration) following a sighting test with one animal at a dose of 300 mg/kg bw. There was one death 2 days after dosing and hunched posture and noisy respiration were noted during the day of dosing in the initial treated animal. Surviving animals showed expected gains in body weight, except for two animals which showed either no gain in body weight or body weight loss during the first week, but expected gain in body weight during the second week. Abnormalities noted at necropsy of the animal that died during the study were dark and patchy pallor of the liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study. The acute oral median lethal dose (LD50) of the substance in the female Wistar strain rat was estimated to be greater than 2000 mg/kg bw.

In a reliable acute oral toxicity study test performed according to the OECD Guideline 423, 2001, 6 female HanRcc:WIST (SPF) rats were given a single oral dose of a structurally similar substance (100 % a.i.) in corn oil at doses of 2000 mg/kg bw and observed for 14 days. All animals survived until the end of the study period. No clinical signs were observed during the course of the study. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. Oral LD50 in Females: > 2000 mg/kg bw.

In an acute oral toxicity study in accordance with US Federal Hazardous Substances Act (FHSA), groups of fasted adult male rats of the Sprague-Dawley strain were given a single oral dose of oleic-acid based IQAC, DMS quaternised (76 % solids) at doses of 5000, 10000 or 20000  mg/kg bw and observed for 14 days.

 The Oral LD50Males > 20000  mg/kg bw (76% solids)

In a reliable acute dermal toxicity study 5 male and 5 female young adult HanRcc: WIST(SPF) rats were dermally exposed to a structurally similar substance suspended in corn oil for 24 hours under a semi-occlusive dressing to approx. 10 % of body surface area at doses of 2000 or 200 mg/kg bw. The high dose animals were euthanized due to severe local effects after ten days. No symptoms of systemic toxicity were observed. The local skin reactions affected the study and prevented the full assessment of the LD50. However, even though the 14 day observation period could not be completed the onset of systemic toxicity should have been apparent on day 10. No mortality occurred.

No clinical signs or gross pathological findings were observed. No weight gain or slight (< 1 %) weight loss was observed in three females of the high dose group (2000 mg/kg bw) and a slight (0.7 % during the first week) but reversible weight loss in one female of the low dose group (200 mg/kg bw).

Dermal LD50  in Males > 2000 mg/kg bw,  Females > 2000 mg/kg bw and Combined > 2000 mg/kg bw.

 

         

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records

Referenceopen allclose all

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
24 April 2017 - 16 May 2017
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to guideline
Guideline:
OECD Guideline 420 (Acute Oral Toxicity - Fixed Dose Method)
Version / remarks:
2001
Deviations:
yes
Remarks:
The 1-hour observation for the animals treated at a dose level of 300 mg/kg bw was performed 8 minutes late due to a fire drill. This deviation was considered to have not affected the integrity or validity of the study.
GLP compliance:
yes
Test type:
fixed dose procedure
Limit test:
no
Species:
rat
Strain:
Wistar
Remarks:
RccHan:WIST
Sex:
female
Details on test animals or test system and environmental conditions:
Batch: RL55/17
Purity: 100%
Physical state/Appearance: yellow to brown paste
Expiry Date: 15 March 2018
Storage Conditions: room temperature in the dark
Route of administration:
oral: gavage
Vehicle:
DMSO
Doses:
Sighting test: 300 mg/kg bw and 2000 mg/kg bw
Actual test: 2000 mg/kg bw
No. of animals per sex per dose:
Five animals at 2000 mg/kg bw
One animal at 300 mg/kg bw
Control animals:
no
Preliminary study:
At 300 mg/kg bw there was no mortality and hunched posture was noted 4 hours after dosing. No other signs of systemic toxicity were noted during the observation period. The animal showed expected gains in body weight over the observation period and no abnormalities were noted during necropsy.
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
One animal (of 5) was found dead 2 days after dosing.
Clinical signs:
Hunched posture and noisy respiration were noted during the day of dosing, in the initial treated animal. No signs of systemic toxicity were noted during the observation period in the surviving animals.
Body weight:
Surviving animals showed expected gains in body weight , except for two animals which showed either no gain in body weight or body weight loss during the first week, but expected gain in body weight during the second week.
Gross pathology:
Abnormalities noted at necropsy of the animal that died during the study were dark and patchy pallor of the liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study.
Interpretation of results:
GHS criteria not met
Conclusions:
The acute oral median lethal dose (LD50) of the substance in the female Wistar strain rat was estimnated to be greater than 2000 mg/kg bw.
Executive summary:

In an acute toxicity study the substance was administered to Wistar rats (5 female animals) by oral gavage at a dose level of 2000 mg/kg bw (single administration) following a sighting test with one animal at a dose of 300 mg/kg bw. There was one death 2 days after dosing and hunched posture and noisy respiration were noted during the day of dosing in the initial treated animal. Surviving animals showed expected gains in body weight , except for two animals which showed either no gain in body weight or body weight loss during the first week, but expected gain in body weight during the second week. Abnormalities noted at necropsy of the animal that died during the study were dark and patchy pallor of the liver and dark kidneys. No abnormalities were noted at necropsy of animals that were killed at the end of the study. The acute oral median lethal dose (LD50) of the substance in the female Wistar strain rat was estimnated to be greater than 2000 mg/kg bw.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Read-across to K1 study therefore K2 is the maximum Klimisch value.
Justification for type of information:
Read-across approach - see read-across justification in section 13.
Reason / purpose for cross-reference:
read-across source
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
other: HanRcc: WIST(SPF)
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: 11 weeks
- Weight at study initiation: 165.1 - 186.2 9 at day of application
- Fasting period before study: for approximately 17 to 18 hours (access to water was permitted). Food was provided again approximately 3 hours after dosing
- Housing: In groups of three in Makrolon type-4 cages with wire mesh tops and standard softwood bedding ('Lignocel' Schill AG, CH-4132 Muttenz/Switzerland).
- Diet: ad libitum; pelleted standard Provimi Kliba 3433 rat/mouse maintenance diet, batch no. 23/07 (Provimi Kliba AG, CH-4303 Kaiseraugst/Switzerland)
- Water: ad libitum; community tap water from Füllinsdorf
- Acclimation period: 6 days


ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C ± 3°C
- Humidity (%): 30 -70 %
- Air changes (per hr): 10-15 air changes per hour
- Photoperiod (hrs dark / hrs light): the Iightening was in a 12-hour Iight/dark-cycle.
Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED:
2000 mg/kg body weight


Doses:
Dose levels: 2000 mg/kg body weight
Concentrations: 0.2 g/mL
Dosing: one single application by gavage
Dosing volume: 10 mL/kg bw
The test item was weighed into a tared glass beaker on a suitable precision balance and the vehicle added (weight:volume).
Afterwards, the test item preparation was warmed up to 50°C. The formulations were prepared using a suitable homogenizer. The test item preparation was kept at room temperature for cooling and was administered when a temperature between 20°C and 30°C is reached. The temperature was measured before treatment with a thermometer and reached 24°C and 25.8°C.
No. of animals per sex per dose:
3
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Necropsy of survivors performed: yes
All animals were killed at the end of the observation period by carbon dioxide asphyxiation and discarded after macroscopic examinations were
performed. No organs or tissues were retained.

- Frequency of observations and weighing:

Mortality / Viability and Clinical Signs:
Daily during the acclimatization period, during the first 30 minutes and at approximately 1, 2, 3 and 5 hours after administration on test day 1 and
twice daily during days 2-15. All abnormalities were recorded.

Body Weights:
On test days 1 (prior to administration), 8 and 15.

Statistics:
No statistical analysis was used.
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: no animal died
Mortality:
No deaths occurred during the study.
Clinical signs:
No clinical signs were observed during the course of the study.
Body weight:
The body weight of the animals was within the range commonly recorded for this strain and age.
Gross pathology:
No macroscopic findings were recorded at necropsy.
Interpretation of results:
GHS criteria not met
Conclusions:
The substance (100 % a.i.) is practically nontoxic based on the oral LD50 of greater than 2000 mg/kg body weight in female rats.  
Executive summary:

In an acute oral toxicity study test performed according to the OECD Guideline 423, 2001, 6 female 11 weeks old HanRcc:WIST (SPF) rats were given a single oral dose of the substance (100 % a.i.) in corn oil at doses of 2000 mg/kg bw and observed for 14 days. All animals survived until the end of the study period. No clinical signs were observed during the course of the study. The body weight of the animals was within the range commonly recorded for this strain and age. No macroscopic findings were recorded at necropsy. Oral LD50 in Females: > 2000 mg/kg bw.

         

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Study period:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
comparable to guideline study
Remarks:
Read-across to K2 study therefore K2 is the maximum Klimisch value.
Justification for type of information:
Read-across approach - see read-across justification in section 13.
Reason / purpose for cross-reference:
read-across source
GLP compliance:
no
Remarks:
study performed before implementation of GLP
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: no data
- Age at study initiation: adult
- Weight at study initiation: 150 - 250 g
- Fasting period before study: 24 hours
- Housing: screen bottom cages
- Diet (e.g. ad libitum): laboratory chow ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: no data


ENVIRONMENTAL CONDITIONS
- Temperature (°C): no data
- Humidity (%): no data
- Air changes (per hr): no data
- Photoperiod (hrs dark / hrs light): no data

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
Administration:
Method: stomach tube
Concentration of test material: as submitted
Sample preparation: none
Doses:
5, 10 and 20 gm/kg
No. of animals per sex per dose:
6
Details on study design:
Method: Adult male rats of the Sprague-Dawley strain, weighing 150-250 grams were fasted for 24 hours, then given a single calculated dose and placed in screen bottom cages with free access to water and laboratory chow for a two week observation period.

- Frequency of observations and weighing: no data
- Necropsy of survivors performed: no
- Other examinations performed: no data
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 20 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 76 % a.i.
Key result
Sex:
male
Dose descriptor:
LD50
Effect level:
> 15 200 mg/kg bw
Based on:
act. ingr.
Mortality:
5 gm/kg bw: 0/6
10 gm/kg bw: 0/6
20 gm/kg bw: 1/6 (day of death: 3)
Clinical signs:
no data
Body weight:
no data
Gross pathology:
no data
Interpretation of results:
GHS criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
Under the conditions specified the oleic-acid based IQAC, DMS quaternised (76 % solids) has an oral LD50 of > 20000 mg/kg bw (test material) referring to > 15200 mg/kg bw (a.i.) in male rats.
Executive summary:

In an acute oral toxicity study in accordance with US Federal Hazardous Substances Act (FHSA), groups of fasted adult male rats of the Sprague-Dawley strain were given a single oral dose of oleic-acid based IQAC, DMS quaternised (76 % solids) at doses of   5000, 10000 or 20000  mg/kg bw and observed for 14 days.

 

Oral LD50Males > 20000  mg/kg bw

LD50value determined refers to the test substance as specified above (76 % solids).LD50 referring to 100 % solids: > 15200 mg/kg bw

  

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Sufficient to address requirements.

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
guideline study
Remarks:
Read-across to K1 study therefore K2 is the maximum Klimisch value.
Justification for type of information:
Read-across approach - see read-across justification in section 13.
Reason / purpose for cross-reference:
read-across source
GLP compliance:
yes (incl. QA statement)
Limit test:
no
Species:
rat
Strain:
other: HanRcc:WIST (SPF)
Sex:
male/female
Details on test animals or test system and environmental 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% (values above 70% during cleaning process possible), automatically controlled light cycle of 12 hours light and 12 hours dark, music during the daytime light period.
Type of coverage:
semiocclusive
Vehicle:
corn oil
Details on dermal exposure:
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 at a dose of 2000 mg/kg body weight evenly on the intact skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped around the abdomen and fixed with an elastic adhesive bandage.
Further dosing (200 mg/kg) was administered to 10 naive animals as follows: a single animal of each sex was treated first. Since moderate local effects were observed in one animal of each sex after the 24-hour exposure and by considering the previous results at 2000 mg/kg, the treatment of the remaining four male and four female animals was postponed for 1 week.
The application volume/kg body weight was 4 mL.
Twenty-four hours after the application the dressing was removed and the skin was flushed with lukewarm tap water and dried with disposable paper towels. Thereafter, the reaction sites were assessed.
Seven animals of the first group treated at 2000 mg/kg were superficially re-shaved on test day 6 to facilitate the reading of the local reactions. The two animals treated first at 200 mg/kg were re-shaved on test days 8, 11 and 15 while the remaining animals treated at 200 mg/kg were re-shaved on test days 4, 8 and 11.
Duration of exposure:
24 hours
Doses:
200, 2000 mg/kg bw
No. of animals per sex per dose:
5
Control animals:
not required
Details on study design:
Twenty HanRcc:WIST (SPF) rats, which consisted of one group of 5 males and 5 females, a second group of 1 male and 1 female and a third group of 4 males and 4 females, were treated with the test substance by dermal application. The first group was treated at the dose of 2000 mg/kg b.w. while the remaining two groups were treated at 200 mg/kg. b.w The test item was prepared in vehicle (corn oil) at a concentration of 0.5 or 0.05 g/mL, respectively and administered at a volume dosage of 4 mL/kg. The application period was 24 hours.

The animals were examined daily during the acclimatization period and mortality, viability and clinical signs were recorded. All animals were examined for clinical signs at approximately 30 minutes, 1, 2, 3 and 5 hours after treatment on day 1 and once daily during test days 2-15. Local signs were noted once daily from test day 2 to 15. Mortality/viability was recorded at approximately 30 minutes, 1, 2, 3 and 5 hours after administration on test day 1 (with the clinical signs) and twice daily during days 2-15. Body weights were recorded on day 1 (prior to administration) and on days 8 and 15. All animals were necropsied and examined macroscopically.
Statistics:
No statistical analysis was used
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
act. ingr.
Remarks on result:
other: no animals died
Mortality:
Due to the severity of the irritations, all animals treated at 2000 mg/kg were humanely sacrificed on test day 10.
Clinical signs:
No sign of systemic toxicity was noted
Body weight:
Three females treated at 2000 mg/kg lost or did not gain weight (body weight loss <1%) during the course of the study. One female treated at 200 mg/kg lost weight (body weight loss 0.7%) during the first week but it recovered until the end of the observation period. The body weight of the remaining animals was within the range commonly recorded for this strain and age
Gross pathology:
No macroscopic findings were recorded at necropsy apart from severe to moderate skin irritation.
Other findings:
Severe signs of dermal irritation at 2000 mg/kg bw. Mild to moderate symptoms of dermal irriation were observed at 200 mg/kg bw.
Interpretation of results:
GHS criteria not met
Conclusions:
On the basis of the results obtained after a single dermal administration, the dermal LD50 of the substance was determined to be > 2000 mg/kg bw.
Executive summary:

In an acute dermal toxicity study according to OECD guideline 402, 1987 and EU method B.3, 1992, 5 male and 5 female young adult HanRcc: WIST(SPF) rats were dermally exposed to the substance suspended in corn oil for 24 hours under a semi-occlusive dressing to approx. 10 % of body surface area at doses of 2000 or 200 mg/kg bw. Low dose group animals then were observed for 14 days. The high dose animals were euthanized due to severe local effects after ten days. No symptoms of systemic toxicity were observed. The local skin reactions affected the study and prevented the full assessment of the LD50. However, even though the 14 day observation period could not be completed the onset of systemic toxicity should have been apparent on day 10.

 

Dermal LD50           Males > 2000 mg/kg bw                                  

Females > 2000 mg/kg bw

                          Combined > 2000 mg/kg bw

 

No mortality occurred in this test.

No clinical signs or gross pathological findings were observed. No weight gain or slight (< 1 %) weight loss was observed in three females of the high dose group (2000 mg/kg bw) and a slight (0.7 % during the first week) but reversible weight loss in one female of the low dose group (200 mg/kg bw).

The minor body weight loss or absence of body weight gain in a few number of females is generally well associated to the female animals which are more sensitive or body weight-affected than the males after dermal exposure. Therefore, the affected body weight suggested a relationship to the type of application and sex of animals rather than any local (the local findings were comparable in both sexes) or systemic toxicity of the test item.The test item is a palmoil – based partially unsaturated IQAC and a read across from fully saturated tallow fatty acid based IQACs can be done. The latter are well-known to have very little (quantified) dermal penetration and no systemic toxicity. The lack of systemic toxicity has been demonstrated in a 91-day percutaneous study with a tallow based IQAC. The findings of this study consisted of moderate erythema, edema, desquamation and fissuring in the high-dose (27 mg/kg/day) animals. Any indication of systemic toxicity or haematologic changes from 13 weeks of dermal application were not observed. Also, no systemic toxicity was observed in the skin sensitisation study, skin irritation or acute oral toxicity study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Sufficient to address requirements.

Additional information

Justification for classification or non-classification

Based on the findings of a reliable acute oral toxicity studies conducted on the substance itself and structurally similar substances, classification of the substance is not justified.

Based on the findings of a reliable acute dermal toxicity study conducted on a structurally similar substance, classification of the substance is not justified.