Registration Dossier

Administrative data

Description of key information

The acute toxicity of the substance is is low, the substance seems to be slowly absorbed by all routes and metabolized efficiently by epoxide hydrolases. The acute oral toxicity in rats (LD50) is greater 5000 mg/kg body weight, the acute dermal toxicity in rabbits is >3000 mg/kg body weight, and the acute inhalation toxicity in rats (LC50)was measured to be  >30 mg/m3 air (highest valour concentration to be achieved technically). 
At all routes of exposure no signs of toxicity were recorded. Only during the oral test with a dose of 10'000 mg/kg body weight 1/2 animals died without any adverse effects observed during necropsy.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1982
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP, but according to guideline OECD 401
Reason / purpose:
reference to same study
Qualifier:
according to
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
GLP compliance:
no
Test type:
other: limit test
Limit test:
yes
Species:
mouse
Strain:
other: Tif:MAG (SPF)
Sex:
male/female
Details on test animals and environmental conditions:
4-5 week old mice, the mice were kept in groups of 2, in Macrolon cages type 2, with standarized soft wood bedding.
The animal room was air conditioned at 22 +/-3 °C, a relative humidity of 55 +/- 15%, a 12-hour light/dark cycle, and approximately 15 air changes per hour. Mouse standard food and water was supplied ad libitum.
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Details on oral exposure:
-rior to dosing the animals were fasted over night.
Doses:
males and females were exposed to 5000 mg/kg body weight (single application)
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
Observation for mortality was on every day, mortality was checked daily, and body weight was determined on days 1, 7, 14, and at death
Statistics:
LD50 calculated including 95% confidence limits by the logit method (J. Berkson, J. Am. Stat. Ass. 39, 357 - 365 (1944)
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 5 000 mg/kg bw
Mortality:
1/5 male mice died after 24 hours, no female mouse died at all (0/5)
Clinical signs:
sedation, dyspnoera, ruffeld fur, curved body position were the only symptoms observed, they disappeared on day 11 completely.
Body weight:
Body weight gain was normal in males and females.
Gross pathology:
no gross pathological findings were recorded.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The oral LD50 in mice is > 5000 mg/kg body weight with only one dead male mouse.
Executive summary:

The oral LD50 in mice is > 5000 mg/kg body weight with only one dead male mouse.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
5 000 mg/kg bw

Acute toxicity: via inhalation route

Link to relevant study records
Reference
Endpoint:
acute toxicity: inhalation
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1973
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Non-GLP study performed without analytical measurements.
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
Vapour generated by an air-stream was passed through a inhalation chamber in which rats were exposed (whole body exposure) to the vapour stream for 4 hours. Observation was for 14 days post exposure.
GLP compliance:
no
Test type:
fixed concentration procedure
Limit test:
yes
Species:
rat
Strain:
other: Charles River albino rats
Sex:
male/female
Details on test animals and environmental conditions:
Younf male and female rats (average weight 209 gm) were checked for health before entering the test. Animals were housed individually , and food and water was supplied ad libitum.
Route of administration:
inhalation: vapour
Type of inhalation exposure:
whole body
Vehicle:
other: unchanged (no vehicle)
Details on inhalation exposure:
Exposure was in a 70l plexiglass chamber in which all rats were exposed by whole-body-exposure.
Cold air (-40°C) was passed through the test substance at a flow rate of 4.9 l/min, at a pressure of 29.92 inches of Hg at 25°C.
The average nominal vspour conc. was 30 mg/m3 air . This was the highest technically achievable concentration.
Analytical verification of test atmosphere concentrations:
yes
Duration of exposure:
>= 4 h
Concentrations:
30 mg/m3 air (average)
No. of animals per sex per dose:
5 ales and 5 females
Control animals:
yes
Statistics:
no statistics was applied
Sex:
male/female
Dose descriptor:
LC50
Effect level:
> 30 mg/m³ air (nominal)
Exp. duration:
4 h
Remarks on result:
other: whole body exposure
Mortality:
no mortality occurred during the exposure and during the 14-day observation period.
Clinical signs:
no substance-related clinical signs were recorded.
Body weight:
body weight development was equal to that of the air control group.
Gross pathology:
Compared to the control group, a slight discoloration of the liver of all treated animals was observed.
Other findings:
none
Interpretation of results:
relatively harmless
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
under the conditions of the test (30 mg/ MY720 per m3 air, for 4 hours) no signs of toxicity were recorded during the 14-day observation period.
The concentration used was the highest technically achievable concentration with this compound.
The LC50 is > 30 mg/m3 air as no mortality occurred and no adverse effects were noted.
Executive summary:

under the conditions of the test (30 mg/ MY720 per m3 air, for 4 hours) no signs of toxicity were recorded during the 14-day observation period. The concentration used was the highest technically achievable concentration with this compound. The LC50 is > 30 mg/m3 air as no mortality occurred and no adverse effects were noted.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LC50
30 mg/m³

Acute toxicity: via dermal route

Link to relevant study records
Reference
Endpoint:
acute toxicity: dermal
Type of information:
migrated information: read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
key study
Study period:
1974
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No GLP, no Guideline , but method similar to what has been later written down in to the guidelines.
Reason / purpose:
reference to same study
Qualifier:
no guideline followed
Principles of method if other than guideline:
The rabbits were shaved on the back and 48 hours later substance was applied to the shaved area and wrapped semi-occlusively for 24 hours, then skin reactions were scored over a period of 14 days.
GLP compliance:
no
Test type:
standard acute method
Species:
rabbit
Strain:
New Zealand White
Sex:
male/female
Details on test animals and environmental conditions:
All rabbits kept for seven days in quarantene before introducing to the test. Animals were housed individually, in suspended wire-mesh cages, food and water was supplied ad libitum.
Type of coverage:
semiocclusive
Vehicle:
other: methal ethyl ketone
Details on dermal exposure:
rabbits were shaved on the back 48 hours before treatment, substance was dissolved in methyl ethyl ketone, and applied to the backs of the animals (30% of the animals body surface), the substance was then covered with a plastic sheet and fixed with a bandage to the animal. Animals were fixed a plastic collar to avoid licking on the sites. Substance remained 24 hours on the site, then the sites were washed and animals were observed daily for skin reactions and mortality.
Duration of exposure:
24 hours
Doses:
0, 1000, 3000 mg/kg bw
No. of animals per sex per dose:
2 male & 2 female rabbits per dose
Control animals:
yes, concurrent vehicle
Details on study design:
Initial and final body weights were measured, and at necropsy after 14 says a full observation of the entire organs was made, and organs were fixed in formalin for potential furhter investigations.
Statistics:
No statistical analysis was performed on the results
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 3 000 mg/kg bw
Mortality:
No mortality occurred during the 14 day observation period.
Clinical signs:
Ataxia and hyporeactivity were observed in all animals 1 hour post treatment, but disappeared within 24 hours. MY 720 was slightly irritant to the skin, while the solvebt caused only marginal skin reactions (irritation).
Body weight:
There were no body weight changes observed over the entire observation period.
Gross pathology:
No gross pathological changes were recorded during necropsy.
Other findings:
Histopathological examination of liver and kidney did not reveal any changes in the treated animals.
Interpretation of results:
practically nontoxic
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Dermal treatment of rabbits with 1000 and 3000 mg/kg body weight for 24 hours did not cause any mortality or other sings of toxicity apart from slight irritation on the application sites.
The LD50 (dermal, in rabbits) is > 3000 mg/kg bw
Executive summary:

Dermal treatment of rabbits with 1000 and 3000 mg/kg body weight for 24 hours did not cause any mortality or other sings of toxicity apart from slight irritation on the application sites. The LD50 (dermal, in rabbits) is > 3000 mg/kg bw

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
3 000 mg/kg bw

Additional information

The substance has been evaluated by using a read-across. The justification is given in a statement in Section 13. The substance is of low acute toxicity by all three routes of exposure, oral, dermal and inhalation. Several acute oral and dermal toxicity studies in rats and rabbits show a similar result: up to 3000 mg/kg body weight no specific signs of toxicity were recorded, and no death occurred. Only at 10'000 mg/kg body weight 1/2 rats died most likely due to test substance effects. The only acute inhalation study was performed with a single dose of 30 mg/m3 air; the dose was chosen as it is the highest technically achievable vapour concentration. TGMDA is of low vapour pressure, and thus, higher dose levels are technically impossible, and to test as droplet aerosols (liquid) would give a completely different exposure scenario. Nevertheless, under the experimental conditions of 30 mg/kg body weight (whole body exposure) the animals showed no sings of toxicity, indicating that 30 mg/m3 air is far below the NOEC .

Justification for classification or non-classification

Based on the oral and dermal LD50 determined, no classification is required.

Concering the acute inhalation toxicity, the situation is slightly more complex. The dose of 30 mg/m3 air is far below the dose which would not require classification and labelling. However, due to the fact that this technically the highest achievable concentration in air of the substance (due to low vapour pressure and due to tha fact that no solid inhalable dust aerosol is possible , no higher concentrations could be tested. Using a droplet-aerosol would have caused a situation of no inhalation but oral uptake as these droplet would have been absorbed in the nasal cavity and transported to the upper part of the intestinal tract.