Registration Dossier

Administrative data

Description of key information

Acute oral toxicity: 

Acute oral toxicity dose (LD50) for target chemical test chemical was considered based on experimental study conducted on rats. The LD50 value was considered to be >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, test chemical cannot be classified for acute oral toxicity.

Acute Inhalation toxicity:

The acute Inhalation toxicity dose (LC50) for test chemical was considered based on experimental study conducted on rats. The LC50 value was considered to be >200 mg/L (>200000 mg/m3). The study concluded that the LC50 value is >5 mg/L, for acute inhalation toxicity. Thus, comparing this value with the criteria of CLP regulation, test chemical cannot be classified for acute inhalation toxicity.

Acute Dermal toxicity:

The acute dermal toxicity dose (LD50) for target chemical was considered based on experimental study conducted on rabbits, the value was considered to be >2000 mg/kg bw, for acute dermal toxicity. Thus, comparing this value with the criteria of CLP regulation, test chemical cannot be classified for acute dermal toxicity.

Key value for chemical safety assessment

Acute toxicity: via oral route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 1 and from experimental study report.

Acute toxicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
200 000 mg/m³
Quality of whole database:
Data is Klimisch 2 and from publication.

Acute toxicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
2 000 mg/kg bw
Quality of whole database:
Data is Klimisch 2 and from publication.

Additional information

Acute oral toxicity:

In different experimental studies, test chemical has been investigated for acute oral toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats and mice for test chemical. The studies are summarized as below –

Acute oral toxicity study of test chemical was performed on rats as per OECD No. 423. Six female Wistar rats were selected for acute oral toxcity. Rats were fasted for 16 to 18 hours, prior to dosing (water was given ad libitum). After test item administration, feed was withheld for a further 4 hours. The time interval between dosing was determined by the onset, duration and severity of toxic signs Three rats of group G1 were dosed with starting dose of 2000 mg/kg body weight and the animals showed no mortality post dosing, so another three rats of the same group were dosed with 2000 mg/kg weight and no mortality was observed. At 2000mg/kg, all the six animals were observed with normal clinical sign till day 14 . No mortality was observed througout the experimentation period. Mean body weight of animals treated with 2000mg/kg body weight was observed with gain on day 7 and 14, as compared to day 0 .No external and internal gross pathological examination were seen in all the six animals treated with 2000 mg/kg body weight during terminal sacrifice Under the conditions of this; acute oral toxicity study of test chemical in female rats is as given below: The acute oral LD50 value of test chemical was >2000 mg/kg body weight. Thus by considering the CLP criteria for acute toxicity rating for the chemicals, it infers that test chemical does not exhibit acute oral toxicity i.e it is acutely non toxic to animals.

The above experimental study is supported with the study conducted on rats and mentioned in peer-reviewed journals, authoritative databases and secondary sources for the target chemical. The acute oral toxicity study was conducted in rats at the dose concentration of 5000 mg/kg bw. No mortality was observed at 5000 mg/kg bw. Hence, LD50 value was considered to be >5000 mg/kg bw, when rats were treated with test chemical via oral route.

 

These studies are supported with the study mentioned in peer-reviewed journals, authoritative databases and secondary source and conducted in rats for the target chemical. The acute oral toxicity study was conducted in albino rats at the dose concentration range from 50 to 10000 mg/kg bw. The given test chemical was dissolved as 25% suspension in corn oil and administered via oral route. Animals were observed for mortality and clinical signs for 14 days. The LD50 value was estimated by Hagan; Litchfield and Wilcoxon. No mortality was observed at 10000 mg/kg bw. All animals appeared normal during 14 days. Hence, LD50 value was considered to be >10000 mg/kg bw, when albino rats were treated with test chemical via oral route.

 

All these studies are further supported with the study mentioned in authoritative database and secondary source and conducted on mice for the target chemical. The study was conducted at the dose concentration of 10000 mg/kg bw. No mortality was observed at 10000 mg/kg bw. Hence, LD50 value was considered to be >10000 mg/kg bw, when mice were treated with test chemical via oral route.

 

Thus, based on the above summarised studies on test chemical, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, test chemical cannot be classified for acute oral toxicity.

 

Acute Inhalation Toxicity:

 

In an experimental study, test chemical has been investigated for acute inhalation toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rats for test chemical along with the study available for the structurally and functionally similar read across substance. The studies are summarized as below –

 

The experimental study mentioned in peer-reviewed journals, authoritative database and secondary source for the target chemical was conducted to determine acute inhalation toxicity dose. The study was conducted in 10 rats at the dose concentration of 200 mg/L (200000 mg/m3) for 1 hour exposure. 1 out of 10 rats died within the 14 day-observation period. Therefore, LC50 value was considered to be>200 mg/L (>200000 mg/m3), when 10 rats were treated with test chemical by inhalation route for 1 hour exposure.

 

The above experimental study is supported with the data available for the structurally and functionally similar read across chemical. The acute Inhalation toxicity study was conducted by using test material in groups of 10 rats at a single 6-h exposure of vapors (26 ppm) under dynamic conditions, followed by a 24-h holding period, was reported. Necropsies were performed on the animals at the end of the holding period. Local irritation due to the alcohol vapor was slight and involved the mucous membranes of the eyes, nose, throat, and respiratory passages. There were no signs of systemic toxicity and no deaths were reported. Therefore, LC50 was considered to be >26 mg/L, when groups of 10 rats were treated with given test chemical via inhalation by vapor.

In another study Acute inhalation toxicity study was conducted by using test chemical in group of 10 Wistar rats at the concentration of 12 ppm for 6 hours of exposure. The exposures were at atmospheres nearly saturated with vapors of the alcohol. The generators were fritted-disk glass bubblers containing a measured amount of alcohol through which all air entering the chamber was passed.Observations were made for mortality, signs of toxic effect, and body weight changes.Gross necropsies were performed on the animals that died and at the end of the holding period.Dose reported is calculated from sample loss and airflow. No deaths were seen in the 6 hour vapor inhalation studies.Signs of systemic toxicity were not pronounced and consisted primarily of central nervous system depression. Local irritation was observed to a very less extent in all the test animals. This irritation involved the mucous membranes of the eyes, nose, throat, and respiratory passages and was manifest as blinking, lacrimation, preening, nasal discharge, salivation, gasping, and chewing movements. Therefore, the acute inhalation toxicity dose (LC50) was considered to be >12 ppm (>12000 mg/m3), when rats were exposed with test chemical via inhalation route for 6 hours.

 

Thus, based on the above summarized studies on test chemical and it’s structurally and functionally similar read across substance, it can be concluded that LC50 value is >5 mg/L. Thus, comparing this value with the criteria of CLP regulation, test chemical cannot be classified for acute inhalation toxicity.

 

Acute Dermal Toxicity:

 

In an experimental study test chemical has been investigated for acute dermal toxicity to a greater or lesser extent. Often are the studies based on in-vivo experiments in rodents, i.e. most commonly in rabbits for test chemical along with the studies available for structurally and functionally similar read across chemicals. The studies are summarized as below -

 

The experimental study mentioned in peer-reviewed journals, authoritative databases and secondary sources for the target chemical was designed to determine acute dermal toxicity dose. The acute dermal toxicity study of was conducted in 10 rabbits at the dose concentration of 2000 mg/kg bw by dermal application in eye shadow form. No mortality was observed at 2000 mg/kg bw. Hence, LD50 value was considered to be >2000 mg/kg bw, when 10 rabbits were treated with test chemical by dermal application in eye shadow form.

 

The above experimental study is supported with the data available for structurally and functionally similar read across chemical and mentioned in study report. The study was designed and conducted to determine the acute dermal toxicity profile of test chemical in Sprague Dawley rats. The test item was applied to shorn skin of 5 male and 5 female animals at 2000 mg/kg body weight. Administration of the test item at 2000 mg/kg did not result in any skin reaction at the site of application during the study period of 14 days. Administration of the test item did not result in any signs of toxicity and mortality during the study period of 14 days. Animals exhibited normal body weight gain through the study period of 14 days. Gross pathological examination did not reveal any abnormalities attributable to the treatment. It was concluded that the acute dermal median lethal dose (LD50) of test chemical, when administered to male and female Sprague Dawley rats was found to be >2000 mg/kg body weight. Thus, according to CLP criteria for acute toxicity rating for the chemicals, it infers that given test chemical does not classify as an acute dermal toxicant.  CLP Classification: “Not classified”.

 

These studies are further supported with the data available for structurally and functionally similar read across chemical. The acute dermal toxicity study was conducted by using test chemical in 8 male and female albino rabbits at dose of 6800 mg/kg and 10200 mg/kg bw. 2 groups of 2 male and 2 female albino rabbits received a 24-hour patch test of a cosmetic cleansing cream containing 3% test chemical. One group received the undiluted product in a dose of 6.8 g/kg; the other, 10.2 g/kg. Animals were observed for mortality and clinical signs for 14 days. No mortality was observed at 10200 mg/kg bw. Abnormal behaviour, adverse body weight changes, or gross alterations were noted during the 14-day observation period. At the end of the 24-hour contact period, definite red, well-defined erythema was observed at the contact site on each animal. The erythema subsided by Day 7. Therefore, LD50 was considered to be >10200 mg/kg bw, when 8 male and female albino rabbits were treated with test chemical by dermal application.

 

Thus, based on the above summarised study on test chemical and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw. Thus, comparing this value with the criteria of CLP regulation, test chemical cannot be classified for acute dermal toxicity.

Justification for classification or non-classification

Based on the above experimental studies on test chemical and it’s structurally and functionally similar read across substances, it can be concluded that LD50 value is >2000 mg/kg bw, for acute oral and dermal toxicity; and LC50 value is >5 mg/L, for acute inhalation toxicity. Thus, comparing these values with the criteria of CLP regulation, test chemical cannot be classified for acute oral, acute dermal and acute inhalation toxicity.