Registration Dossier

Administrative data

Description of key information

Oral (EPA OPPTS 870.1100), rat: LD50 = 2295 mg/kg bw (RA from CAS 1760-24-3)

Inhalation (EPA OPPTS 870.1300), rat: LC50 = 1.49 -2.44 mg/L (RA from CAS 1760-24-3)

Dermal (EPA OPPTS 870.1200), rabbit: LD50 > 2000 mg/kg bw (RA from CAS1760-24-3)

Furthermore, the registration substance contains 40% silane and 60% methanol. Therefore, the harmonised EU classification of methanol has to be taken into account for the evalulation of the hazard of CAS 171869 -89 -9.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
2 295 mg/kg bw
Based on:
test mat.
95% CL:
>= 1 539 - <= 3 423
Remarks on result:
other:
Remarks:
CAS 1760-24-3, Dow Corning Corporation, 2001

Further supporting studies are available for the source substance CAS 1760-24-3:

Wacker, 1992: LD50 male/female: 2413 mg/kg bw

Mellon Institute, 1975: LD50 male: 7460 mg/kg bw

Mellon Institute, 1966: LD50 male: 7460 mg/kg bw

Tejin: LD50 male: 2250 mg/kg bw; LD50 female: 1680 mg/kg bw (not used for classification as the documentation was insufficient for assessment)

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008.
Conclusions:
Several acute oral toxicity studies are available for the source substance CAS 1760-24-3 which all show LD50 > 2000 mg/kg bw. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in acute oral toxicity potential.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1) from a source substance with similar structure and intrinsic properties. Read-across is justified based on common functional group and similarities in physico-chemical and toxicological properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Reason / purpose:
read-across source
Duration of exposure:
h
No. of animals per sex per dose:
Five
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 1.49 - < 2.44 mg/L air (analytical)
Based on:
test mat.
Exp. duration:
4 h
Remarks on result:
other: CAS 1760-24-3, Dow Corning Corporation, 2000
Interpretation of results:
other: CLP/EU GHS criteria are met, Category 4 classification is required according to Regulations (EC) No 1272/2008.
Conclusions:
An acute inhalation (aerosol) study conducted to EPA OPPTS 870.1300, which is comparable to OECD 403, and to GLP (reliability score 1) is available with the source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3). A LC50 between 1.49 - 2.44 mg/L was derived. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in acute inhalation toxicity potential.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1) from a source substance with similar structure and intrinsic properties. Read-across is justified based on common functional group and similarities in physico-chemical and toxicological properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

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)
Remarks:
Summary of available data used for the endpoint assessment of the target substance
Adequacy of study:
key study
Justification for type of information:
Please refer to the attached justification below and the overall justification for grouping of substances attached in IUCLID Section 13.
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Reason / purpose:
read-across source
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Remarks on result:
other: CAS 1760-24-3, Dow Corning Corporation, 2000

Further supporting studies are available for the source substance CAS 1760-24-3:

Hazelton France, 1992: LD50 male/female > 2009 mg/kg bw

Mellon Institute, 1975: LD50 male = 16000 mg/kg bw

Mellon Institute, 1966: LD50 male > 16000 mg/kg bw

Interpretation of results:
other: CLP/EU GHS criteria are not met, no classification required according to Regulations (EC) No 1272/2008.
Conclusions:
An acute dermal toxicity study conducted to EPA OPPTS 870.1200 (Acute Dermal Toxicity) and to GLP (reliability score 1) is available with the source substance N-(3-(trimethoxysilyl)propyl)ethylenediamine. The LD50 was at least 2000 mg/kg bw in rabbits as no deaths occurred at the highest dose of 2000 mg/kg bw. There were no clinical signs, macroscopic findings, or significant effects on bodyweight. The only findings were irritation at the application site. Three further supporting studies are available which support the key study. As explained in the analogue justification, it is considered that the target and the source substances are unlikely to lead to differences in acute dermal toxicity potential.
Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Quality of whole database:
The available information comprises an adequate and reliable study (Klimisch score 1) from a source substance with similar structure and intrinsic properties. Read-across is justified based on common functional group and similarities in physico-chemical and toxicological properties (refer to endpoint discussion for further details). The selected study is thus sufficient to fulfil the standard information requirements set out in Annex VIII, 8.5, in accordance with Annex XI, 1.5, of Regulation (EC) No 1907/2006.

Additional information

No data on acute oral, inhalation, or dermal toxicity is available for 1,2-ethanediamine, N-{3-(trimethoxysilyl)propyl}-,N-{(ethenylphenyl)methyl}derivate,hydrochlorides (CAS 171869-89-9). The registration substance contains 40% silane and 60% methanol. Hence, to address the acute toxicity hazard of methanol, the harmonised EU classifications for methanol was adopted for CAS 171869-89-9. On the other hand, the acute toxicity hazard of the silane 1,2-ethanediamine, N-{3-(trimethoxysilyl)propyl}-,N-{(ethenylphenyl)methyl}derivate,hydrochlorides was addressed based on the available data from the source substance, N-(3-(trimethoxysilyl)propyl)ethylenediamine (CAS 1760-24-3). In accordance with Regulation (EC) No. 1907/2006 Annex XI, 1.5 “Grouping of substances and read across” and following the Read across assessment framework (RAAF, ECHA 2017) read across from an analogue substance has been applied to support the human health hazard assessment of 1,2-ethanediamine, N-{3-(trimethoxysilyl)propyl}-,N-{(ethenylphenyl)methyl}derivate,hydrochlorides (CAS 171869-89-9). Details on read across justifications can be found in the attached justification in the respective target entry and in the overall justification for grouping of substances attached in IUCLID Section 13.

Acute Oral

An LD50 value of 2295 mg/kg bw in rats is reported in the key acute oral study with the structural analogue substance (CAS 1760 -24 -3), conducted according to EPA OPPTS 870.1100 (Acute Oral Toxicity) and to GLP (Dow Corning Corporation, 2001). Deaths occurred at 3000 and 5000 mg/kg bw but in no other groups (500 and 1200 mg/kg bw). Overt toxicity including hunched posture, waddling or unsteady gait, pallid extremities, abnormal respiration or lethargy occurred at 1200 mg/kg bw and above. All animals that died had congestive changes in the majority of organs and tissues.

Three other rat gavage studies conducted according to an appropriate test protocol, with or without GLP (reliability 1 or 2), provide LD50 values in excess of that of the key study (Mellon Institute 1966 and 1975; Wacker, 1992). A more limited study cited in the SIAR of 2003, for which it has not been possible to obtain the primary source (reliability 4), gives LD50 values in male and female rats of 2.3 and 1.7 mL/kg bw, respectively (Tejin, undated). These latter values would not give cause to cast doubt on the validity of a classification based on the key and supporting studies.

  

Acute Inhalation

Five rats of each sex and dose were exposed to the structural analogue (CAS 1760 -24 -3) in a whole body exposure chamber for 4 h at concentrations (aerosols) of 0.515, 1.06, 1.49, 2.44 and 5.75 mg/L. The animals were observed for 14 days after administration. The LC50 was calculated to be > 1.49 - < 2.44 mg/L air. Eight out of ten animals (5 male, 3 female) died at a concentration of 2.44 mg/L during the observation period. Nine out of 10 animals (5 male, 4 female) died during the observation period when exposed to the highest concentration of 5.75 mg/l. The predominant clinical signs detected during exposure were exaggerated breathing and partially closed eyes in all test groups as well as reduced motor activity in exposure groups 0.515 to 2.44 mg/L. Clinical signs recorded during the observation period were irregular noisy and/or exaggerated breathing in all groups as well as partially closed eyes in all treated groups, except the 0.515 mg/L group. Ataxia was observed in the two female rats from the 2.44 mg/l group that survived. A dose-related reduction in body weight gain over the observation period was observed in animals from 0.515 to 1.49 mg/L. Gross pathology revealed severely congested lungs in all deceased animals, which is considered to be associated with the cause of death. Pale raised lungs were also observed in the lungs of a proportion of surviving rats of both sexes in all other groups exposed to the test aerosol. Food consumption by the test groups was lower compared to the control group during the observation period.

 

Acute Dermal

An LD50 in rabbits greater that 2000 mg/kg bw was identified in the key acute dermal toxicity study with the structural analogue substance (CAS 1760 -24 -3), conducted according to EPA OPPTS 870.1200 (Acute Dermal Toxicity) and to GLP (Dow Corning Corporation, 2000b). At this limit dose there were no deaths, clinical signs of concern, macroscopic findings or significant effects on bodyweight. The only findings were irritation at the application site.

A further limit study conducted in the rat to a standard guideline and GLP, reliability 1, reported the LD50 as >2009 mg/kg bw (Hazelton France, 1992). Two studiesin the rabbit, one sufficiently documented but without GLP and reliability 2 (Mellon Institute, 1975) and one identified only as a brief report and therefore reliability 4 (Mellon Institute, 1966) reported LD50 values in excess of that of the key study.

Justification for classification or non-classification

The available experimental data with a structural analogue on acute oral and dermal toxicitydo not meet the criteria for classification according to Regulation (EC) No. 1272/2008 (CLP) and are therefore conclusive but not sufficient for classification. For acute inhalation toxicity with a structural analogue available data meet the criteria for classification according to Regulation (EC) 1272/2008, and is therefore classified as acute toxic Category 4 (H332). However, due to the constituent methanol not present in the tested material but relevant for substance identity, classification and labelling as acute toxic Category 4 (H302) and Category 3 (311, 331) as well as for STOT SE 1 (oral, dermal, inhalation; H370) of the substance according to Regulation (EC) No. 1272/2008 is warranted due to the presence of the constituent = 60%.