Registration Dossier

Administrative data

Description of key information

oral

Read- across: key, rat, OECD 429 (Class method), GLP, LD50 > 2000 mg/kg bw (Caruso 2018)

Read-across: supporting, rat OECD 401 (standard acute method), GLP, LD50 > 2000 mg/kg bw (Müller 1998)

dermal

Read- across: key, rat, OECD 402 (standard acute method), GLP, LD50 > 2000 mg/kg bw (Müller 1999)

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:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
assessment report
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality occurred in the 6 animals following dosing at 2000 mg/kg.
Clinical signs:
No signs of toxicity were observed in the 6 animals following dosing at 2000 mg/kg.
Body weight:
Changes in body weight observed during the study were within the expected range for this strain and age of animals.
Gross pathology:
No abnormalities were seen at necropsy examination performed on all animals dosed at 2000mg/kg (Groups 2 and 4) at the end of the observation period.
Interpretation of results:
GHS criteria not met
Conclusions:
These results indicate that the test item did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the acute toxicity estimate (ATE) to be greater than 2000 mg/kg body weight.
Executive summary:

The acute toxicity of TP1740 was investigated following OECD 429 (Class method) and GLP. A single oral administration to the Sprague Dawley rat was followed by a 14-day observation period. A first group of 3 female animals was initially dosed at 2000 mg/kg (Step 1). No mortality occurred and no clinical signs were observed. A second group of 3 female animals was then dosed at the same dose level (Step 2). No death occurred and no clinical signs were noted. Body weight changes recorded during the study were within the expected range for this strain and age of animals. No abnormalities were seen at necropsy examination performed at the end of the observation period on animals of both groups. These results indicate that the test item did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the acute toxicity estimate (ATE) to be greater than 2000 mg/kg body weight. The source substance has the identical organic molecular moieties as the target substance. Therefore, the acute toxicity of the target substance is expected to be similar to the source substance.

Endpoint:
acute toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
supporting study
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
assessment report
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Male: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Signs of toxicity related to dose levels: On the day of administration of the test article a slight apathy was observed in all animals and a slight squatting position was shortly observed in one male and in two female animals. None of the animals showed further alterations of their general state of well-being and behaviour.
Body weight:
The body weight gain was not affected.
Gross pathology:
No macroscopic pathological findings in the animals.

Other findings:
none
Interpretation of results:
GHS criteria not met
Conclusions:
The test item is neither a toxic nor a harmful substance according to this acute oral toxicity study.
Executive summary:

Acute oral toxicity of the test item was tested in male and female Charles River Wistar rats following OECD Guideline 401 and GLP. The test article was administered at a single dose of 2000 mg/kg body weight by gavage. Animals were examined for mortality, clinical signs, body weight gain and pathological alterations of organs at the end of a 14-day observation period. None of the animals died during the course of investigation. On the day of administration of the test article a slight apathy was observed in all animalsand a slight squatting position was shortly observed in one male and in two female animals. No pathological findings were observed at necropsy. The body weight gain was not affected.

The LD50 is > 2000 mg/kg body weight .

The source substance contains the major organic moieties of the target substance. Therefore, this study shows that no acute oral toxicity can be attributed to the organic moieties of the target substance.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Since two GLP and OECD guideline compliant studies are available with adequate source substance, the quality of the database is high.

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:
weight of evidence
Reason / purpose for cross-reference:
read-across source
Reason / purpose for cross-reference:
assessment report
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Mortality:
No animal died during the course of investigation.
Male: > 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Female: > 2000 mg/kg bw; Number of animals: 5; Number of deaths: 0
Clinical signs:
Clinical observations: No clinical signs were observed during the cours of investigation.
Body weight:
The body weight gain of the male and female animals was in the range of the historical control data in the test facility.
Gross pathology:
There were no macroscopic pathological findings in the animals.
Other findings:
The skin of the application area was not altered.
Interpretation of results:
GHS criteria not met
Conclusions:
The test item is neither a toxic nor a harmful substance according to this acute dermal toxicity study.
Executive summary:

Acute dermal toxicity of the test item was tested according to OECD Guideline 402 and GLP in five female and five male Cooles River Wistar rats. The test article was applied at a single dose of 2000 mg/kg bw to a shaved dorsal area of the trunk of the animals and was then covered with a gauze patch which was held in contact with the skin with an occlusive dressing. Exposure was for 24 hours. The area to which it was applied was then washed with water. Animals were examined for mortality, clinical signs, alterations of the application area, body weight gain and pathological alterations of organs at the end of a 14-day observation period. None of the animals died during the course of the investigation. Clinical signs, skin alterations on the application area or pathological findings at necropsy were not observed. The body weight gain was not affected.

The dermal LD50in the rat is > 2000 mg/kg b.w.

The source substance contains the major organic moieties of the target substance. Therefore, the results of this study show that the organic moieties of the target substance are not acut dermal toxic.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw
Quality of whole database:
Since an GLP and OECD guideline compliant study is available with adequate source substance, the quality of the database is high.

Additional information

oral

In the key study the acute toxicity of the source substance was investigated following OECD 423 (Class method) and GLP. A single oral administration to the Sprague Dawley rat was followed by a 14-day observation period. A first group of 3 female animals was initially dosed at 2000 mg/kg (Step 1). No mortality occurred and no clinical signs were observed. A second group of 3 female animals was then dosed at the same dose level (Step 2). No death occurred and no clinical signs were noted. Body weight changes recorded during the study were within the expected range for this strain and age of animals. No abnormalities were seen at necropsy examination performed at the end of the observation period on animals of both groups. These results indicate that the test item did not induce toxic effects in the rat following oral administration of a single dose at a level of 2000 mg/kg. The lack of mortality demonstrates the acute toxicity estimate (ATE) to be greater than 2000 mg/kg body weight. The source substance has the identical organic molecular moieties as the target substance. In addition, as the target substance, it contains zinc ion. Therefore, the acute toxicity of the target substance is expected to be similar to the source substance.

This result is supported by a study result of the other source substance. The acute oral toxicity was tested in male and female Charles River Wistar rats following OECD Guideline 401 and GLP. The test article was administered at a single dose of 2000 mg/kg body weight by gavage. Animals were examined for mortality, clinical signs, body weight gain and pathological alterations of organs at the end of a 14-day observation period. None of the animals died during the course of investigation. On the day of administration of the test article a slight apathy was observed in all animals and a slight squatting position was shortly observed in one male and in two female animals. No pathological findings were observed at necropsy. The body weight gain was not affected. The LD50 is > 2000 mg/kg body weight . The source substance contains the major organic moieties of the target substance. Therefore, this study shows that no acute oral toxicity can be attributed to the organic moieties of the target substance.

dermal

Acute dermal toxicity of the test item was tested according to OECD Guideline 402 and GLP in five female and five male Cooles River Wistar rats. The test article was applied at a single dose of 2000 mg/kg bw to a shaved dorsal area of the trunk of the animals and was then covered with a gauze patch which was held in contact with the skin with an occlusive dressing. Exposure was for 24 hours. The area to which it was applied was then washed with water. Animals were examined for mortality, clinical signs, alterations of the application area, body weight gain and pathological alterations of organs at the end of a 14-day observation period. None of the animals died during the course of the investigation. Clinical signs, skin alterations on the application area or pathological findings at necropsy were not observed. The body weight gain was not affected.

The dermal LD50in the rat is > 2000 mg/kg bw. The source substance contains the major organic moieties of the target substance. Therefore, the results of this study show that the organic moieties of the target substance are not acute dermal toxic.

Justification for classification or non-classification

Based on the results for the source substances the target substance is not classified according to Regulation (EC) No 1272/2008.