Registration Dossier

Administrative data

Description of key information

From the study results it is concluded that oleic-acid based IQAC, DMS quaternised is of low toxicity when given to rats by oral or dermal route. 

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:
1975
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Basic data given: comparable to guideline/standards
Guideline:
other: US Federal Hazardous Substances Act (FHSA)
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 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
Sex:
male
Dose descriptor:
LD50
Effect level:
> 20 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: 76 % a.i.
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:
not classified
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
15 200 mg/kg bw

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Read-across from a guideline study
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)
Limit test:
no
Species:
rat
Strain:
other: HanRcc:WIST (SPF)
Sex:
male/female
Details on test animals 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
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:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: other: CLP, EU GHS (Regulation (EC) No 1272/2008)
Conclusions:
On the basis of the results obtained after a single dermal administration, the dermal LD50 of the test article "partially unsaturated IQAC, DMS quaternised" was determined to be > 2000 mg/kg bw. No animal died. 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. No signs of systemic toxicity were observed during the 10 days observation time of the high dose group animals, when the animals in dose group 2000mg/kg were euthanized due to severe local effects.
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 partially unsaturated IQAC, DMS quaternised 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 PC-2007-140 (W 575 NO SOLVENT) is a palmoil – based IQAC and a read across from tallow 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 sensitization study, skin irritation or acute oral toxicity study.

 

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

Additional information

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 LD50 for males was determined to be > 20000 mg/kg bw.

The LD50 value determined refers to the test substance containing 76 % active ingredient (a.i.). The LD50 referring to 100 % a.i. is > 15200 mg/kg bw.

At the highest dose one mortality occurred at day 3 among the six animals tested in this group.

From the study result it is concluded that oleic-acid based IQAC, DMS quaternised (76% a.i.) is practically not toxic when given to male rats by oral gavage.

The NOAEL for acute oral toxicity is 7600 mg/kg bw in the male rat (rel. to active ingredient).

Read-Across from Test material CAS-No. 67846-14-4,oleic-acid based IQAC, DES quaternisedand CAS-No. 98219-51-3, partially unsaturated IQAC,DMS quaternised, chemically closely related substances, revealed an LD50, oral gavage in female Wistar rats of > 2000 mg/kg bw. These study results indicate a comparable sensitivity of both genders and the strains of rats used for testing of this substance class and a practically absent toxicity upon oral exposure.

 

An acute dermal toxicity study carried out with a partially unsaturated IQAC,DMS quaternised(CAS Nr 98219-51-3) showed no systemic toxicity, either at 200 or at 2000 mg/kg bw based on the absence of macroscopic findings at necropsy. 

 

Due to the severe local effects seen on the skin of the highest dose group of 2000 mg/kg bw, all animals of this group were euthanized on day 10. Even though the 14 day observation period could not be completed for the high dose group, necroscopy would have revealed the onset of systemic toxicity already after 10 days of observation. Therefore, the LD50, dermal is considered to be greater than 2000 mg/kg bw. This is supported by other study outcomes, where neither an acute oral, nor a skin sensitization or an acute dermal irritation study gave any indication of systemic toxicity.In addition, toxicokinetic studies with afully saturated IQAC,DMS quaternisedshowed very poor absorption via the dermal route. The lack of systemic toxicity has also been demonstrated in 91-day percutaneous studies in rabbits with a tallow fatty acids based IQAC, where NOELs are identical to the highest doses tested i.e. between 27 mg/kg bw and 300 to 400 mg/kg bwwere determined. No effects other than skin irritation were reported.

The NOAEL for acute dermal toxicity was determined to be 2000 mg/kg bw due to the absence of systemic toxicity up to the highest dose tested.

Justification for read-across:

The structural similarities between the source and the target substances are the basis for the read-across hypothesis. Adequate, reliable and available scientific information indicates that the source and target substances have similar physicochemical properties and toxicity profiles and thus support the read-across hypothesis.

Acute oral toxicity for source substance (partially unsaturated IQAC, DMS quaternised) and target substance (oleic-acid based IQAC, DMS quaternised) is comparably low. Also the skin irritation and sensitizing potential is similar. There is no potential for point mutations and chromosome aberrations indicated by data from both substances.

Therefore, based on the considerations above, it can be concluded that the results for endpoints, mediated by systemically available, are likely to predict the properties of the target substance. Read-across is considered as adequate to fulfil the information requirements of Annex VIII, 8.5.3 (acute dermal toxicity) and results of the acute dermal toxicity study conducted in the rat with the source substance are considered a reliable source to cover the respective endpoint.

A more detailed justification for read-across is outlined in a separate document:

“Justification for read-across - toxicological information”, is attached to the endpoint summary acute toxicity and provided in chapter 13 of Technical dossier.

 

 

 



Justification for selection of acute toxicity – oral endpoint
Data from a GLP compliant guideline study with reliability 1.

Justification for selection of acute toxicity – inhalation endpoint
Inhalation is no relevant route of exposure

Justification for selection of acute toxicity – dermal endpoint
Read-across from a GLP compliant guideline study with reliability 1.

Justification for classification or non-classification

The oral LD50 of oleic-acid based IQAC, DMS or DES quaternised and ofpartially unsaturated IQAC,DMS quaternisedwas determined to be > 2000 mg/kg bw. The dermal LD50 value from an acute dermal toxicity study run with apartially unsaturated IQAC,DMS quaternisedwas also determined to be greater than 2000 mg/kg bw. According to Directive 67/548 EEC as well as the GHS Regulation EC No. 1272/2008, a classification for oleic-acid based IQAC, DMS quaternised is not required and labelling is not necessary.