Registration Dossier

Diss Factsheets

Administrative data

Description of key information

The acute toxicity of MATMD was tested for the oral and dermal route, while for the inhalatory route no studies are available.

Key value for chemical safety assessment

Acute toxicity: via oral route

Link to relevant study records
Reference
Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in compliance with GLP and according to the OECD guideline 401 (acute oral toxicity).
Qualifier:
according to guideline
Guideline:
OECD Guideline 401 (Acute Oral Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.1 (Acute Toxicity (Oral))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: males 9-10 weeks, females 11-12 weeks (at start of treatment)
- Weight at study initiation: males 175-224 g, females 162-194 g
- Fasting period before study: 15 to 22 hours (food was again presented approximately one hour after dosing)
- Housing: 5 animals/cage
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12/12
Route of administration:
oral: gavage
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL
Doses:
200 mg/kg b.w., 800 mg/kg b.w., 2000 mg/kg b.w.
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Observations:
Mortality / Viability: Four times during test day 1, and daily during days 2 - 15.
Body Weights: Test days 1 (pre-administration), 8 and 15.
Clinical Signs: Each animal was examined for changes in appearance and behavior four times during day 1, and daily during days 2-15. All
abnormalities were recorded. The animals were checked for the clinical signs.


Sex:
male
Dose descriptor:
LD50
Effect level:
1 319.39 mg/kg bw
Based on:
test mat.
Sex:
female
Dose descriptor:
LD50
Effect level:
908.3 mg/kg bw
Based on:
test mat.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
ca. 1 106 mg/kg bw
Based on:
test mat.
95% CL:
> 682.22 - < 2 170.79
Mortality:
at 200 mg/kg: no mortality
at 800 mg/kg: 2 males (days 1 and 2) and 1 female (day 1)
at 2000 mg/kg: 3 males (2 on day 1 and 1 on day 2) and 5 females (2 on day 1 and 3 on day 2)
Clinical signs:
other: The following systemic signs were observed: 200 mg/kg: males/females - no clinical signs noted. 800 mg/kg: males/females - sedated, ruffled fur. males - hunched posture. females - la
Gross pathology:
Necropsies were performed by experienced prosectors. All animals were necropsied.
All animals surviving to the end of the observation period were killed by intraperitoneal injection of sodium pentobarbitone.
At 200 mg/kg: dark red dicoloration of lungs in 1 male and pale discoloration of lungs in 1 female
At 800 mg/kg: dark red dicoloration of lungs in each 1 male and female
At 2000 mg/kg: dark red dicoloration of lungs in 3 males, dard red discoloration of jejunum, duodenum, ileum and caecum in 1 male as well as dar or light red discoloration of lungs in each 2 females and reddish discoloration of duodenum and jejunum in 1 female
Interpretation of results:
Toxicity Category IV
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
Based on these observations, the LOGIT-ESTIMATION for the acute oral toxicity of MATMD in rats of both sexes observed for a period of 15 days is:
1106.12 mg/kg
Executive summary:

For rats of both sexes the Logit-Estimation rersulted in an LD50 of 1106.12 mg/kg.

Endpoint conclusion
Endpoint conclusion:
adverse effect observed
Dose descriptor:
LD50
Value:
1 106 mg/kg bw

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:
experimental study
Adequacy of study:
key study
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
other: The study was conducted in compliance with GLP and according to the OECD guideline 402 (acute dermal toxicity).
Qualifier:
according to guideline
Guideline:
OECD Guideline 402 (Acute Dermal Toxicity)
Deviations:
no
Qualifier:
according to guideline
Guideline:
EU Method B.3 (Acute Toxicity (Dermal))
Deviations:
no
GLP compliance:
yes
Test type:
standard acute method
Limit test:
yes
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Age at study initiation: males 10 weeks, females 12 weeks (at start of treatment)
- Weight at study initiation: males 243 - 264 g, females 194 - 216 g
- Housing: individually
- Diet: ad libitum
- Water: ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 22°C +/- 3°C
- Humidity (%): 40-70%
- Photoperiod (hrs dark / hrs light): 12/12
Type of coverage:
semiocclusive
Vehicle:
polyethylene glycol
Remarks:
PEG 400
Details on dermal exposure:
Approximately 24 hours before treatment, the backs of the animals were shaved with an electric clipper, exposing an area of approximately 10% of
the total body surface.
On test day 1 the test article was applied evenly on the skin with a syringe and covered with a semi-occlusive dressing. The dressing was wrapped
around the abdomen and fixed with an elastic adhesive bandage.
Twenty-four hours after the application, the dressing was removed. The treated skin was washed with lukewarm tap water and dried with disposable
paper towels.
Duration of exposure:
24 hours
Doses:
2000 mg/kg
No. of animals per sex per dose:
5
Control animals:
no
Details on study design:
Observations:
Mortality I Viability: Four times during test day 1, and daily during days 2 - 15
Body Weights: Test days 1 (pre-administration), 8 and 15.
Clinical Signs: Each animal had an examination for changes in appearance and behavior four times during day 1, and daily during days 2-15. All
abnormalities were recorded.
Due to the 24 hour semi-occlusive treatment, the local findings were observed starting with day 2 of test.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
At 2000 mg/kg: no mortality, no further dose levels were tested
Clinical signs:
other: The following local symptoms were observed on the back of the animals: 2000 mg/kg: males/females - general erythema, scales. The rats had recovered from erythema after 7 (males) and 14 (females) observation days. Scales were observed in both sexes until d
Gross pathology:
At 2000 mg/kg: In each 1 female dar red or pale discoloration of lungs was noted.
Interpretation of results:
not classified
Remarks:
Migrated information Criteria used for interpretation of results: EU
Conclusions:
The toxicity of MATMD was estimated to be greater than 2000 mg/kg.
Executive summary:

The toxicity of MATMD was estimated to be greater than 2000 mg/kg.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
2 000 mg/kg bw

Additional information

MATMD was tested in an acute oral toxicity study with male and female Wistar rats according to OECD guideline 401 with GLP compliance. From this study a LD50 value of ca. 1106 mg/kg bw was derived for male and female rats.

MATMD was tested in an acute dermal toxicity study with male and female Wistar rats according to OECD guideline 402 with GLP compliance. From this study a LD50 value of > 2000 mg/kg bw was derived.

Justification for classification or non-classification