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Administrative data

Description of key information

Based on the study results, the acute oral LD50 of the test substance was determined to be 5000 mg/kg bw.

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:
experimental study
Adequacy of study:
key study
Study period:
From Oct 20, 1988 to Nov 30, 1988
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Charles river portage,Michigen, USA
- Age at study initiation: 4-6 weeks
- Weight at study initiation: 116-152 g
- Fasting period before study: Overnight
- Housing: Individually; metal cages with wire mesh floors
- Diet (e.g. ad libitum): Standard laboratory rodent diet(ad libitum)
- Water (e.g. ad libitum): Domestic quality portable water(ad libitum)
- Acclimation period: 14 d
ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22⁰ C
- Humidity (%): 53%
- Air changes (per hr): Approx 15
- Photoperiod (hrs dark / hrs light): 12 h
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
VEHICLE
Test substance was administered as supplied by the sponsor

MAXIMUM DOSE VOLUME APPLIED: 4.5 mL/kg bw (specific gravity 1.1)
- Rationale for the selection of the starting dose: Preliminary study
Doses:
5000 mg/kg bw (4.54 mL/kg bw)
No. of animals per sex per dose:
5/sex/dose
Control animals:
no
Details on study design:
Five males and five females were treated at 5000 mg/kg bw using syringe and plastic catheter (8 choke). Animals were observed after 5 h on day 1 and in subsequent days the animals were observed once in the morning and again at the end of the experiment. Observation period was 14 d.

- Frequency of observations and weighing: Clinical observations done soon after dosing and remainder of Day 1. For the subsequent days observations were done in the morning and at the end of the experimental day.

- Necropsy of survivors performed: Yes along with macroscopic examinations of thoracic, abdominal and cranial cavities. Marcoscopic appearance of abnormal organs was also recorded.

- Other examinations performed: Body weights of each rat was examined at Days 1, 8 and 15 or at death.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
No mortality at 5000 mg/kg bw
Clinical signs:
Pilo-erection in all rats within 5 min after dosing which remained for 1 d followed by increased salivation during 1st 2 h after treatment. No other clinical signs were observed and recovery was complete by Day 3.
Body weight:
Slightly low body weight gains during the 1st week (for majority of female rats) and anticipated gain between Day 8 and 15 in all rats.
Other findings:
Terminal autopsy was normal.
Interpretation of results:
other: CLP criteria not met
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Under the test condition, the acute lethal oral dose of di-TMPTTA was > 5,000 mg/kg bw.
Executive summary:

A study was conducted to assess the acute oral toxicity of di-TMPTTA according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. Five males and five females were administered a single oral dose of 5,000 mg/kg bw by gavage. Animals were observed for 14 d. On Day 1, pilo-erection was seen within 5 min of dosing along with increased salivation during 2 h after treatment. Low body weight gain during the first week of the study was recorded but all rats achieved anticipated weight gains between Days 8 and 15. No other clinical signs were observed and recovery, judged by appearance and behaviour, was complete by Day 3. Under the test conditions, the acute lethal oral dose of the test substance was > 5,000 mg/kg bw (Liggett 1989).

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
From 28 July, 1998 to 14 Aug, 1998
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
no
Species:
rat
Strain:
other: CD rats of Sprague-Dawley origin (Hsd:Sprague-Dawley(CD))
Sex:
male/female
Details on test animals and environmental conditions:
Animals chosen for this study were selected from a stock supply of healthy male and female CD rat of Sprague-Dawley origin (Hsd:Sprague-Dawley(CD)) obtained from Harlan U.K. Ltd., Bicester, Oxon, England. They were in the weight range of 125 to 152 g and approx 5-7 weeks of age prior to dosing (Day 1). All the rats were acclimatised to the experimental environment for a minimum period of 15 d prior to the start of the study. Rats were allocated without conscious bias to cages within the treatment groups. They were housed in groups of 5 rats of the same sex in metal cages (RS biotech sub-dividable rodent cages polished stainless steel (20 cm high x 39 cm wide x 39 cm long). The cages were suspended in the mobile stainless steel racks in room 6 of building R14.

A standard laboratory rodent diet (Special Diet Services RM1(E) SQC expanded pellet) and drinking water were provided ad libitum. Access to food only was prevented overnight prior to and approx 4 h after dosing. Each batch of diet used for the study was analyzed for certain nutrients, possible contaminants and micro-organisms. Results of routine physical and chemical examination of drinking water, as conducted by the supplier are made available to Huntingdon Life Sciences Ltd. at regular intervals throughout the year. Animal room environmental controls were set to maintain temperature within the range 22 ± 3°C (actual 21 to 26°C) and relative humidity 30-70% (actual 39 to 58%). These environmental parameters were recorded continously using a 7 d recorder. Lighting was controlled by means of a time switch to provide 12 h of artificial light (0700 – 1900 GMT) in each 24 h period. Each animal was identified by cage number and ear punching.
Route of administration:
oral: gavage
Vehicle:
not specified
Details on oral exposure:
The test substance was administered as supplied at a volume of 4.452 mL/kg bw. The observation and characterization of the homogeneity, stability and purity of the test substance was not undertaken as part of this study and remains the responsibility of the Sponsor.
Doses:
Preliminary study: 3200 mg/kg bw
Main study: 5000 mg/kg bw
No. of animals per sex per dose:
Preliminary study: 2 rats (1 male and female)
Main study: 5/sex/dose
Control animals:
no
Details on study design:
Preliminary study: 2 rats (one male and one female) received a single oral gavage dose of the test substance at a dose level of 3200 mg/kg bw using a syringe and plastic catheter or cannula. This was conducted to help define the toxic potential of the test substance and aid in selection of a suitable dosage for the main study.
Main study:
As results at this dosage indicated the acute lethal oral dose of the test substance to be greater than 3200 mg/kg bw, in compliance with the guidelines, a further group of 10 rats (five males and five females) was similarly dosed at 5000 mg/kg bw to complete the study. The day of dosing was designated Day 1. Cages of rats were checked at least twice daily for any mortalities. For clinical signs animals were observed soon after dosing and at frequent intervals for the remainder of Day 1. On subsequent days, animals were observed once in the morning and again at the end of the experimental day (with the exception of Day 15 - morning only). The nature and severity of the clinical signs and time were recorded at each observation. All animals were observed for 7 to 14 d after dosing. The bw of each rat was recorded on 1 (prior to dosing), 8 and 15 d. Individual weekly bodyweight changes and group mean bw were calculated. All animals were killed on Day 15 by carbon dioxide asphyxiation. All animals were subjected to a macroscopic examination which consisted of opening the thoracic and abdominal cavities. The macroscopic appearance of all examined organs was recorded.
Key result
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Based on:
test mat.
Mortality:
There were no deaths following a single oral gavage dose of the test substance in the preliminary or the main study at a dose level of either 3200 or 5000 mg/kg bw.
Clinical signs:
Preliminary study: Clinical signs of reaction to treatment comprised of abnormal piloerection, soft to liquid feces and increased salivation (in male rat only).

Main study: Clinical signs of reaction to treatment comprised of abnormal piloerection in all the animals within 7 minutes and persisted during the study. Also, soft to liquid feces and increased salivation in botht he sexes. Recovery of rats, as judged by external appearance and behaviour, was complete in males by Day 5 and in females by Day 4..
Body weight:
All animals were considered to have achieved satisfactory bw gains throughout the preliminary and the main studies.
Gross pathology:
No abnormalities were revealed at the macroscopic examination at study termination on Day 15 in the preliminary and the main studies.
Interpretation of results:
other: CLP criteria not met
Conclusions:
Under the conditions of the study, the acute oral lethal dose of the test substance to rats was found to be greater than 5,000 mg/kg bw.
Executive summary:

A study was performed to assess the acute oral toxicity of di-TMPTTA to the rat according to OECD Guideline 401 and EU Method B.1, in compliance with GLP. In a preliminary test, 2 rats (one male and one female) received a single oral gavage dose of the test substance at a dose level of 3,200 mg/kg bw. As results at this dosage indicated the acute lethal oral dose of the test substance to be greater than 3,200 mg/kg bw, a further group of 10 fasted rats (five males and five females) was similarly dosed at 5,000 mg/kg bw in the main study. No abnormalities were revealed at macroscopic examination on Day 15. Under the conditions of the study, the acute lethal oral dose to rats was > 5,000 mg/kg bw (McRae 1998).

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
5 000 mg/kg bw
Quality of whole database:
The information requirements for this tonnage band is sufficiently met with the available data.

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

A study was conducted to assess the acute oral toxicity of the test substance according to OECD Guideline 401 and EU Method B.1. Five males and five females were administered a single oral dose of 5,000 mg/kg bw by gavage. Animals were observed for 14 d. On Day 1, pilo-erection was seen within 5 min of dosing along with increased salivation during 2 h after treatment. Low body weight gain during the first week of the study was recorded but all rats achieved anticipated weight gains between Days 8 and 15. No other clinical signs were observed and recovery, judged by appearance and behaviour, was complete by Day 3. Under the test conditions, the acute lethal oral dose of the test substance was > 5,000 mg/kg bw(Liggett 1989).

A further study was performed to assess the acute oral toxicity of the test substance to the rat according to OECD Guideline 401 and EU Method B.1. In a preliminary test, 2 rats (one male and one female) received a single oral gavage dose of the test substance at a dose level of 3,200 mg/kg bw. As results at this dosage indicated the acute lethal oral dose of the test substance to be greater than 3,200 mg/kg bw, a further group of 10 fasted rats (five males and five females) was similarly dosed at 5,000 mg/kg bw in the main study. No abnormalities were revealed at macroscopic examination on Day 15. Under the conditions of the study, the acute lethal oral dose to rats was > 5,000 mg/kg bw(McRae 1998).

Inhalation

The test substance has low vapour pressure so that normal processing and use conditions will not generate inhalation exposure. Furthermore, there are no spray applications of the substance. Acute inhalation exposure is therefore not expected to pose an issue for human health and no further testing is required for this endpoint, in accordance with Annex VIII, Section 8.5, Column 2 of the REACH legislation.

Dermal

The acute dermal toxicity testing is not needed as the substance does not meet the criteria for classification for acute toxicity and STOT SE for the oral route. This is also supported by the absence of any systemic effects in thein vivoskin sensitisation study available with the test substance. Moreover, given the physico-chemical properties of the test substance, the dermal LD50 value is less likely (due to lower absorption potential of dermal route) to be lower than oral LD50 or the oral doses showing clinical signs. Hence, testing via dermal route will less likely result in any additional hazard identification and testing is therefore considered unnecessary.

Justification for classification or non-classification

Based on the LD50 values obtained in acute oral toxicity studies conducted with the test substance, the substance is not considered to require classification for acute effects according to CLP (EC 1272/2008) criteria.