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Administrative data

Description of key information

Both the acute oral tests available on C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) indicates GHS classification as acute oral toxicity category 4 (LD50 between 300 and 2000 mg/kg). No data is available on acute toxicity via inhalation or dermal route.

The newest oral LD50 study on C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) has reliability rating 2 and is performed according to the US guideline on  Consumer Product Safety Commission 16 CFR 1500, with some modifications. The reason for the reliability rating 2 is that the study was performed pre-GLP in 1981 and the test is reported in a limited report. No specific certificate of analysis or information on batch is included in the report. The result from this study is considered to be reliable, since the product tested has not changed significantly in its composition since the testing was carried out. Therefore the results are considered valid for the current manufactured C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) and the result will be used for classification of the 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:
experimental study
Adequacy of study:
key study
Study period:
1981
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Inadequate study details and results (2 page service report);
Qualifier:
according to
Guideline:
other: Consumer Product Safety Commission 16 CFR 1500
Deviations:
yes
Remarks:
Only 5 animals per group
GLP compliance:
no
Test type:
standard acute method
Species:
rat
Strain:
Sprague-Dawley
Sex:
male
Details on test animals and environmental conditions:
Five male SpragueDawley derived albino rats from Hilltop Lab Animals, Inc., weight ranging from 200 to 265 grams.

Food was witheld from the rats for approximately 18 hours prior to dosing. Following dosing, food consisting of PURINA LABORATORY CHOW and
water were available ad libitum. The rats were housed in groups in stainless steel wire mesh cages suspended above the droppings. The animals were housed under a 12-hour light/12-hour dark cycle. The rats were acclimated to the laboratory at least seven days prior to dosing and were
individually identified by numbered ear tags and tail marks with permanent ink.
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
The test sample was administered by esophageal intubation to five groups, each composed of five male Sprague-Dawley derived albino rats from
Hilltop Lab Animals, Inc., weight ranging from 200 to 265 grams. Four groups were treated on April 1, 1981, and the fifth group was treated on April 8, 1981. The sample was administered undiluted at dosage levels of 0.464, 1.00, 2.15, 4.64, and 10.0 grams per kilogram of body weight using an
average density value of 1.036 g/ml for administration on a sample volume basis.
Doses:
0.464, 1.00, 2.15, 4.64, and 10.0 grams per kilogram of body weight
No. of animals per sex per dose:
5
Details on study design:
All animals were observed closely for gross signs of systemic toxicity and mortality at one and one-half to two hours, three and three-quarter to four and one-quarter hours, and give and one-half to six hours post administration during the day of dosing, and at least once daily thereafter for a
total of 14 days. Gross necropsies were performed on the animals that died. At the end of the 14-day observation period the surviving rats were
weighed, sacrificed by C02 inhalation and gross necropsies were performed. Statittical analysis of the mortality data was by the moving average
method.
Statistics:
moving average method
Sex:
male
Dose descriptor:
LD50
Effect level:
1.71 other: g/kg bw
95% CL:
1.26 - 2.33
Clinical signs:
The results of the observations for gross signs of systemic toxicity noted throughout the study at the various dosage levels showed central nervous
system depression, piloerection, and diarrhea were found in all animals and persisted up to four days in surviving animals. Sporadic occurrences of
emaciation, anal exudate, and oily matted fur were observed in one rat each from the 0.464 and 2.15 g/kg dosage levels. A second rat from the 0.464
g/kg level exhibited a swollen right eye on day 4. Squinting of the eyelids was noted in the group which received 10.0 g/kg both before and after
treatment. The most prevalent findings included nasal discharge and diarrhea staining externally and excessive gas with a green-yellow colored
liquid in the gastrointestinal tract internally.
Body weight:
All animals which survived the observation period gained weight.
Gross pathology:
Gross necropsies performed at the termination of the study revealed no gross pathological alterations or lesions in any of the surviving animals.
Interpretation of results:
toxic
Remarks:
Migrated information Oral acute toxicity Cat 4 Criteria used for interpretation of results: EU
Conclusions:
Based on these results, the product tested (75 % C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) and 25% water) is classfied as harmful by oral ingestion as that term is defined in the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008.

Based on the concentration of the product, the same classification is valid for the active ingredient C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2).
Executive summary:

The study was conducted to evaluate the acute oral toxicity of the product (75 % C12 -18 -alkylbis(hydroxyethyl)methyl, chloride and 25% water)

according to US 16CFR 1500. The acute oral LD50 of the product tested was determined to be 1.71 g/kg bw. According to these regulations, the product would be considered harmful if swallowed.

Based on the concentration of the product, the same classification is valid for the active ingredient C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2). The acute oral LD50 of the active ingredient tested was determined to be >300 - 2000 mg/kg bw.

Label requirements under GHS: Symbol "Exclamation mark"; Signal word "Warning"; Hazard statement "Harmful if swallowed"

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 420 mg/kg bw
Quality of whole database:
In accordance with column 2 of REACH Annex VII, an acute oral toxicity study does not need to be conducted as the substance is classified as corrosive. Since two studies were already available, although with validity rating 2 and 3, the most recent performed study with the highest validity rating is used in order to classify the substance. Both the key study and the supporting study indicates GHS cat. 4 (LD50 between 300 and 2000 mg/kg).

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

Oral

Two acute oral studies are available on C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) are available. The newest with the highest validation rating is used as key study, even though it is stated incolumn 2 of REACH legislation Annex VII, that an acute oral toxicity study does not need to be conducted as the substance is classified as corrosive. Since two studies werealready available, although with validity rating 2 and 3, the most recent performed study with the highest validity rating is used in order to classify the substance. Both the key study and the supporting study indicates GHS cat. 4 (LD50 between 300 and 2000 mg/kg). 

 

Inhalation

There is no study on inhalation toxicity available forC12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2). REACH stipulates that testing by the inhalation route is appropriate if exposure of humans via inhalation is likely taking into account the vapour pressure of the substance and/or the possibility of exposure to aerosols, particles or droplets of an inhalable size. REACH guidance R.7.a, chapter. 7.4 Acute toxicity, indicates that in principle no inhalation studies are needed when vp < 0.1 Pa at 20°C or particle size > 100 µm. C12-14-diamine is a liquid with a vapour pressure of 0.00073 Pa at 20°C. Also the use of this substance will not result in aerosols, particles or droplets of an inhalable size, so exposure to humans via the inhalation route will be unlikely to occur, and no acute inhalation test was performed.

 

Dermal
There is an old acute dermal toxicity study from 1958 available on C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2). In the study, all the animals died at the only tested dose level of 2.5 g/kg bw. The dermal LD50 value was therefore identified to be less than 2.5 g/kg bw. Due to the corrosive nature of the substance it is not ethically justified to carry out another animal study to better identify the LD50 value. In accordance with column 2 of REACH Annex VIII, an acute skin toxicity study does not need to be conducted as the substance is classified as corrosive to the skin.

 

Justification for classification or non-classification

Although the key acute oral study has a reliability of 2, it is considered to be correct and C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) is classified for acute oral toxicity Category 4 based upon the classification criteria according to the Regulation (EC) No 1272/2008 of the European Parliament and of the Council of 16 December 2008. Testing for acute dermal toxicity is not required in view of the corrosive properties of the substance and acute inhalational testing is also waived based on the physical/chemical properties of the substance as well as its corrosive properties.

Justification for selection of acute toxicity – oral endpoint

Appropriate study of the highest quality.

Justification for selection of acute toxicity – inhalation endpoint

In accordance with column 2 of REACH Annex VIII, an acute inhalation toxicity study does not need to be conducted as the substance is classified as corrosive. Neither is an inhalation study needed when vapour pressure is < 0.1 Pa at 20°C or particle size > 100 µm. C12-18-alkylbis(hydroxyethyl)methyl, chloride (CAS no 71808-53-2) is a handled as a liquid with a vapour pressure of 0.00073 Pa at 20°C and the identified uses are not expected to cause formation of aerosols, particles or droplets of inhalable size.

Justification for selection of acute toxicity – dermal endpoint

In accordance with column 2 of REACH Annex VIII, an acute skin toxicity study does not need to be conducted as the substance is classified as corrosive to the skin.

Justification for classification or non-classification