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Administrative data

Description of key information

The acute toxicity of the substance has been determined in adequate studies in the rat following oral administration and in the rat and rabbit with dermal administrations. The oral toxicity is determined with a study based on the registered substance. The dermal toxicity is determined by read-across to an analogue substance. No studies are available for inhalation.

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:
2003
Reliability:
2 (reliable with restrictions)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
no
Test type:
acute toxic class method
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: autorised supplier
- Age at study initiation: young and healthy rats
- Weight at study initiation: 208 to 231 g
- Fasting period before study:
- Housing: Makrolon (48 x 27 x 20 cm) Tecniplast brand.
- Diet (e.g. ad libitum):ad libitum
- Water (e.g. ad libitum): ad libitum
- Acclimation period: 7 days

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21° C ( ± 2 °C)
- Humidity (%): 55% (±25%)
- Air changes (per hr): 15
- Photoperiod (hrs dark / hrs light): 12/2

Route of administration:
oral: gavage
Vehicle:
water
Details on oral exposure:
The sample is diluted 1/10 with water
MAXIMUM DOSE VOLUME APPLIED: 1.69 ml per 100 g of body weight, equivalent to 2000mg/kg bw
Doses:
2000 mg/kg
This is a limit test, and the information available suggests that the substance is practically non toxic. If after 14 days of the test there isn't mortality observed the test can be finished.
No. of animals per sex per dose:
3 males and 3 females.
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: every day
- Necropsy of survivors performed: yes
- Other examinations performed: skin, hair, eyes, mucous membranes, respiratory, circulatory, autonomic and central nervous systems, somatomotor activity and behavioral patterns.
-Special attention to: tremors, convulsions, salivation, diarrhea, lethargy, sleep and coma
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 500 mg/kg bw
Based on:
test mat.
Mortality:
Not observed
Clinical signs:
All behaviours registered are considered normal. Not toxicity signs are atributed to the administration of the test material
All animals administered, alive with normality until 14 observation days.
Body weight:
The body weight variation registered is considered normal.
Gross pathology:
Observation at necropsy didn't show significant macroscopic changes in any of the animals.

Mortality in the limit test (male rats, 2000 mg/kg)

 Rat n°  Volum administered  Initial  Death  Remarks
 ML1  3.6  03/01/03  17/01/03  Sacrified to 14 days
 ML2  3.9  03/01/03  17/01/03  Sacrified to 14 days 
 ML3  3.5  03/01/03  17/01/03  Sacrified to 14 days 

Mortality in the limit test (female rats, 2000 mg/kg)

 Rat n°  Volum administered  Initial  Death  Remarks
 ML1 2.8  31/12/02  14/01/03  Sacrified to 14 days
 ML2 2.9   31/12/02   14/01/03  Sacrified to 14 days 
 ML3 2.9   31/12/02   14/01/03  Sacrified to 14 days 

Weight in the limit test (male rats, 2000 mg/kg)

 
 Weight in grams
 
Rat  Initial  7° day Final  Remarks 
ML1 215 280 309 ---
ML2 231 297 320  --- 
 ML3   208  284 313   ---

Weight in the limit test (female rats, 2000 mg/kg)

 
 Weight in grams
 
Rat  Initial  7° day Final  Remarks 
ML1 164 198 207 ---
ML2 170 195 214  --- 
 ML3  171 198  215  ---

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The tested substance presents an acute toxicity by oral route in rats of LD50 >2500 mg/kg.
Executive summary:

After 7 days of acclimatization, a limit dose of 2000 mg/kg bw was administered in several phases in order to analise the presence of letality to 6 rats (3 males and 3 females).

An individual weight control and general examinations during the observation period of 14 days were performed.

It can be concluded that the tested substance presents an acute toxicity LD 50 >2500 mg/kg according to the results presented in the study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Three studies available, one of them done with the substance CAS 1195028-55-7, not GLP, considered as Key study and two supporting studies, one of them GLP compliance. The supporting studies belong to the same organic substance as CAS 1195028-55-7, but with Na cations instead of a mixture of Na and Lithium CAS 1325-54-8, and confirm the result found and used for assessment.

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: see 'Remark'
Remarks:
Read-across from experimental results for the same organic structure OECD Guideline followed. This substance has an identical structure of CAS 1195028-55-7 in respect of the anionic components, but containing Na cations instead of a mixture of Na+ and Li+.
Qualifier:
according to
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Qualifier:
according to
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
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:
Five male and five female Wistar (RccHanÔ:WIST) strain rats were supplied by Harlan Laboratories UK Ltd., Oxon, UK. On receipt the animals were randomly allocated to cages.
The females were nulliparous and non-pregnant. After an acclimatization period of at least five days the animals were selected at random and given a number unique within the study by indelible ink-marking on the tail and a number written on a cage card. At the start of the study the animals weighed at least 200 g, and were eight to twelve weeks of age. The weight variation did not exceed ±20% of the mean weight for each sex.
The animals were housed in suspended solid floor polypropylene cages furnished with woodflakes. The animals were housed individually during the 24-Hour exposure period and in groups of five, by sex, for the remainder of the study. Free access to mains drinking water and food (2014C Teklad Global Rodent diet supplied by Harlan Laboratories UK Ltd., Oxon, UK) was allowed throughout the study. The diet, drinking water and bedding were routinely analyzed and were considered not to contain any contaminants that could reasonably be expected to affect the purpose or integrity of the study.
The temperature and relative humidity were set to achieve limits of 19 to 25 °C and 30 to 70% respectively. Any occasional deviations from these targets were considered not to have affected the purpose or integrity of the study. The rate of air exchange was at least fifteen changes per hour and the lighting was controlled by a time switch to give twelve hours continuous light (06:00-18:00) and twelve hours darkness.
The animals were provided with environmental enrichment items which were considered not to contain any contaminant of a level that might have affected the purpose or integrity of the study.
Type of coverage:
semiocclusive
Vehicle:
water
Duration of exposure:
24-hour contact period
Doses:
2000 mg/kg
No. of animals per sex per dose:
five (5) male and five (5) female
Details on study design:
On the day before treatment the back and flanks of each animal were clipped free of hair.
Using available information on the toxicity of the test item, a group of five male and five female rats was treated with the test item at a dose level of 2000 mg/kg.
The appropriate amount of test item, moistened with distilled water, was applied as evenly as possible to an area of shorn skin (approximately 10% of the total body surface area). A piece of surgical gauze was placed over the treatment area and semi occluded with a piece of self adhesive bandage. The animals were caged individually for the 24-Hour exposure period.
Shortly after dosing the dressings were examined to ensure that they were securely in place.
After the 24-Hour contact period the bandage was carefully removed and the treated skin and surrounding hair wiped with cotton wool moistened with distilled water to remove any residual test item. The animals were returned to group housing for the remainder of the study period.
The animals were observed for deaths or overt signs of toxicity ½, 1, 2 and 4 hours after dosing and subsequently once daily for fourteen days.
After removal of the dressings and subsequently once daily for fourteen days, the test sites were examined for evidence of primary irritation and scored according to the scale from Draize J H (1977) "Dermal and Eye Toxicity Tests" In: Principles and Procedures for Evaluating the Toxicity of Household Substances, National Academy of Sciences, Washington DC p.31.

Any other skin reactions, if present were also recorded.

Individual body weights were recorded prior to application of the test item on Day 0 and on Days 7 and 14.
At the end of the study the animals were killed by cervical dislocation. All animals were subjected to gross necropsy. This consisted of an external examination and opening of the abdominal and thoracic cavities. The appearance of any macroscopic abnormalities was recorded. No tissues were retained.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths
Clinical signs:
No signs of systemic toxicity were noted during the observation period.
Body weight:
One female showed expected gain in bodyweight during the first week but body weight loss during the second week. Two females showed bodyweight loss or no gain in body weight during the first week with expected gain in bodyweight during the second week. Remaining animals showed expected gains in body weight during the study.
Gross pathology:
No abnormalities were noted at necropsy
Other findings:
Orange coloured staining, not preventing evaluation of skin responses, was noted at the test sites of all animals during the study.
Physical damage caused on bandage removal was noted at the test site of one male 1 to 10 days after dosing. Small superficial scattered scabs and glossy skin were also noted at this test site 11 and 12 days after dosing with glossy skin persisting 13 and 14 days after dosing.
There were no signs of dermal irritation noted at the test sites of the remaining nine animals.

The read-across study supplied supports the feasibility of the approach: see report in the summary endpoint.

Individual Dermal Reactions - Males

 Dose level mg/kg     Animal number and sex     Observation                             Effects noted after initation of exposure (days)               
 1  4  5  6  7  8  9  10  11  12  13  14
2000                                                              1 -0 male  Erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 Other  STAPd  STAPd  STAPd  STAPd  STAPd  Pd  Pd  Pd  Pd  Pd  SsG SsG   G
       1 -1 male  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  0  0  0  0  0  0  0  0  0
       1 -2 male  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA   STA  STA  STA  STA  STA  STA  0  0  0  0  0  0
       1 -3 male  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  0  0  0  0  0  0  0  0  0
       1 -4 male  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0 0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  STA  STA  STA  STA  0  0  0  0  0

Individual Dermal reactions - females                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                                  

0: no reactions; STA: Orange coloured staining; Pd: Physical damage caused on bandage removal; Ss: Small superficial scattered scabs; G: Glossy skin.

Individual Dermal reactions - females

    Dose level mg/kg    animal number and sex     observation                      Effects noted after initiation of exposure (days)                   
 1  2  3  4  5  6  7  8  9  10  11  12  13  14
                                                   2 -0 female  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  0  0  0  0  0  0  0  0  0
       2 -1 female  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  STA  0  0  0  0  0  0  0  0
       2 -2 female  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  STA  STA  0  0  0  0  0  0  0
       2 -3 female  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  0  0  0  0  0  0  0  0  0
       2 -4 female  erythema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 edema  0  0  0  0  0  0  0  0  0  0  0  0  0  0
 other  STA  STA  STA  STA  STA  STA  STA  STA  0  0  0  0  0  0
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute dermal median lethal dose (LD50) of the test item in the Wistar strain rat was found to be greater than 2000 mg/kg body weight
Executive summary:

A group of ten animals (five males and five females) was given a single, 24 hour, semi-occluded dermal application of the test item to intact skin at a dose level of 2000 mg/kg bodyweight. Clinical signs and body weight development were monitored during the study. All animals were subjected to gross necropsy (No abnormalities were noted at necropsy).

The observation on mortality showed that there were no deaths. Clinical observations showed no signs of systemic toxicity. Observation on dermal irritation showed a physical damage caused on bandage removal, small superficial scattered scabs and glossy skin were confined to the test site of one male. There were no signs of dermal irritation noted at the test sites of the remaining nine animals. Observations in body weight gave as a result that one female showed expected gain in bodyweight during the first week but body weight loss during the second week. Two females showed bodyweight loss or no gain in body weight during the first week with expected gain in bodyweight during the second week. Remaining animals showed expected gains in body weight during the study.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Two studies available on substance CAS 1325-54-8, one of them according to GLP standards (key study) used for read-across. The supporting study confirms the result found and used for assessment. A Read-across is done considering the testing results and taking into consideration the cationic form of the substance.

Additional information

Acute oral toxicity:

One oral acute toxicity study is available for CAS 1195028-55-7 following the EU method B.1, Alvarez i Genoher N (2003), and gave a result of LD50>2500 mg/kg/bw. This study has been chosen as key study.

Additionally, there are two oral toxicity studies available for CAS 1325-54-8 used as supporting studies. One of these two tests is a limit test done according to OECD Guideline 401, Hartmann HR (1993), where rats were administrated orally (gavage) 0 and 2000 mg/kg bw. No remarkable clinical signs were observed (male/female), no death occurred and no remarkable macroscopic changes were observed in both male/female. With this study a LD50> 2000 mg/kg bw was determined. In an older test from Thomann P (1973) the rats were fed with different doses of substance from 1000 to 10.000 mg/kg and a LD50 of 8700 mg/kg was obtained by calculation of probit analysis.

 

Acute inhalation toxicity:

There isn't any test available for acute inhalation toxicity. The exposure of humans via inhalation is unlikely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

 

Acute dermal toxicity:

Two studies of dermal toxicity of CAS 1325 -54 -8/ EC 215 -397 -8 are available. This substance is considered as structural analogue to CAS 1195028 -55 -7: has the same organic part but contains only Na+ cations instead of a mixture of Na+ and Li+. The read-across study supplied supports the feasibility of the approach.

One of the studies Morena M (1980), was done following the guidances of 16 CFR Part 1500 - HAZARDOUS SUBSTANCES AND ARTICLES; ADMINISTRATION AND ENFORCEMENT REGULATIONS. The substance was applied dissolved into the skin of rabbit and observations were done on toxicity and mortality. An LD50 >2000 mg/kg bw was determined.

The other study of Pooles A (2013) followed OECD Guideline 402 and EU Method B.2. In this study the substance was applied to the skin of Wistar rat at a limit dose of 2000 mg/kg bw. Erythema and edema were monitored and scored. No deaths occurred during or/and after the observation period and no signs of systemic toxicity were observed. Also no abnormalities were found at necropsy. As a remark, and as consequence of the nature of the substance, an orange coloured staining was seen in the site of application, but this effect didn't prevent to evaluate the skin responses. With this study an LD50 > 2000 mg/kg bw has been determined. The study of Pooles A (2013) concluded that the substance CAS 1325 -54 -8 has not dermal toxicity, and using the read-accross approach it can been concluded that CAS 1195028 -55 -7 has a low dermal acute toxicity profile.

Justification for selection of acute toxicity – oral endpoint

The study, made in 2003, is not GLP compliant, but has Klimisch score 2 and the test material used for this study is the same of the substance to be registered (CAS 1195028-55-7)

Justification for selection of acute toxicity – dermal endpoint

Read-across from experimental results for the same organic structure.

Justification for classification or non-classification

Acute oral toxicity

Based on the results of acute oral toxicity testing, CAS 1195028-55-7 is not classified as "Harmful if swallowed" according to the EU DSD classification criteria (EU Directive 67/548/EEC). According to the EU CLP classification criteria (EU Regulation 1272/2008), CAS 1195028-55-7 is not classified as hazardous.

The criteria in CLP Regulation establishes the limit for classification as Acute Tox Oral Category 4 in 2000 mg/kg, and the value obtained is >2000 mg/kg bw.

 

Acute inhalation toxicity

There isn't any test available for acute inhalation toxicity. The exposure of humans via inhalation is unlikely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size.

 

Acute dermal toxicity

Based on the results of acute dermal toxicity testing with CAS 1325 -54 -8 and the read-across study, it is concluded that CAS 1195028 -55 -7 is not classified as harmful for skin according to the EU DSD classification criteria (EU Directive 67/548/EEC), and not harmful for skin according to the EU CLP classification criteria (EU Regulation 1272/2008).