Registration Dossier

Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
12 July to 4 August 1993
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: Proprietary GLP guideline-compliant study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
1993
Report Date:
1993

Materials and methods

Test guidelineopen allclose all
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Qualifier:
according to
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
GLP compliance:
yes (incl. certificate)
Test type:
standard acute method
Limit test:
yes

Test material

Reference
Name:
Unnamed
Type:
Constituent
Details on test material:
TMPDE. The trade name of the substance was NEOALLYL T-20, lot no. 30341, received on 7 June 1993. The substance was a mixture of Trimethylolpropane Diallyl Ether (87.4%), Trimethylolpropane Monoallyl Ether (6.9%), and Trimethyolpropane Triallyl Ether (5.7%). The purity was given as 100%. The substance was described as a colourless liquid, and was stored in a metal canister at 4°C in the dark.
The specific gravity of the test substance was determined at the test facility for dose calculation, and found to be 0.956.

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals and environmental conditions:
The animals were male and female Sprague-Dawley rats, supplied by Charles River (UK) Ltd., Kent. At the start of the main study the males weighed 150-169 g, and the females 140-170 g, and were approximately 5-8 weeks old. The animals were acclimatised for at least 5 days. Individuals were identified by indellible ink markings on the tail. Group selection was random.
The animals were housed in groups of five by sex in solid-floor polypropylene cages with sawdust bedding. With the exception of an overnight fast immediately before dosing and for approximately 2 hours after dosing, free access to mains drinking water and food (Rat and Mouse Expanded Diet No. 1, SDS Ltd., UK) was allowed throughout the study.
The animal room was maintained at a temperature of 19-23°C and relative humidity of 48-66%. The rate of air exchange was approximately 15 changes per hour and the lighting was controlled by a time switch to give 12 hours light and 12 hours darkness.

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
All animals were dosed once by gavage using a metal canula attached to a graduated syringe. The volume administered to each animal was calculated according to its fasted bodyweight at the tine of dosing. The dose volume was 2.10 ml/kg, and the specific gravity of the test substabce was 0.956.
Doses:
2000 mg/kg
No. of animals per sex per dose:
5 rats/sex/dose (main study).
Control animals:
no
Details on study design:
A range finding study with 1 male and 1 female rat was conducted. A single dose of 2000 mg/kg (dose volume 2.10 ml/kg) was adminsitered via gavage. The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing then once daily thereafter for 5 days. Individual bodyweights were recorded on the day of dosing to allow calculation of individual treatment volumes. No necropsies were performed.

In the main study, individual bodyweights were recorded prior to dosing on Day 0 and on Days 7 and 14. The animals were observed for deaths or overt signs of toxicity 30 minutes, 1, 2 and 4 hours after dosing then once daily thereafter for 14 days. At the end of the 14 day observation period the animals were killed annd subjected to gross pathological examination, consisting of an external examination and opening of the abdominal and thoracic cavities. THe appearance of any macropscopic abnormalities was recorded. No tissues were retained.
Statistics:
Statistical evaluation was not required.

Results and discussion

Preliminary study:
There were no deaths, common signs of systemic toxicity noted were ataxia, hunched posture, lethargy, decreased respiratory rate and laboured respiration with an isolated incident of piloerection. The main study proceeded with a dose of 2000 mg/kg.
Effect levels
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred during the study.
Clinical signs:
Signs of systemic toxicity noted were ataxia, hunched posture, lethargy, decreased respiratory rate and laboured respiration. Animals recovered one or two days after dosing.
Body weight:
All animals showed expected bodyweight gain during the study.
Gross pathology:
No abnormalities were noted at necropsy.
Other findings:
No other findings were reported.

Any other information on results incl. tables

The acute oral LD50 of the test substance was found to be greater than 2000 mg/kg bw.

Applicant's summary and conclusion

Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The acute oral LD50 was found to be greater than 2000 mg/kg bw.
Executive summary:

The acute oral toxicity of TMPDE (NEOALLYL T-20) was determined in male and female Sprague-Dawley rats, according to OECD method 404. Following a range-finding study, a group of five male and five female fasted rats were given a single oral dose of undiluted test substance at a dose level of 2000 mg/kg bw. The rats were observed for 14 days then killed for gross pathological examination.

No deaths occurred during the study. Common signs of toxicity noted were ataxia, hunched posture, lethargy, decreased respiratory rate and laboured respiration. Animals recovered one or two days after dosing. Bodyweight gain was normal throughout the study, and no abnormalities were noted at necropsy.

The acute oral LD50of TMPDE in the rat was found to be greater than 2000 mg/kg bw. No symbol and risk phrase are required according to EEC labelling regulations.