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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
11 April 2016 - 28 June 2016
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2016
Report date:
2016

Materials and methods

Test guideline
Qualifier:
according to guideline
Guideline:
OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)
Version / remarks:
17 December 2001
Deviations:
no
GLP compliance:
yes
Test type:
acute toxic class method
Limit test:
yes

Test material

Constituent 1
Reference substance name:
1-Propanol, 2-methyl-, reaction products with 1,5-diisocyanatopentane
Cas Number:
1357171-37-9
Molecular formula:
not applicable (a generic formula cannot be provided for this UVCB substance)
IUPAC Name:
1-Propanol, 2-methyl-, reaction products with 1,5-diisocyanatopentane
Test material form:
liquid
Details on test material:
- Physical appearance: colourless or light yellow liquid
- Storage conditions: at room temperature, in air-tight containers filled with nitrogen and protected from light
Specific details on test material used for the study:
The test item was used as it was received from the sponsor. Since 1 mL of the test item weighed 1.20 g, the conversion factor (weight/volume) was set at 0.83.

Test animals

Species:
rat
Strain:
other: Crl:CD
Sex:
female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Atsugi Breeding Center, Charles River Laboratories Japan, Inc.
- Age at study initiation: 8 weeks
- Weight at study initiation: 210-222 g
- Fasting period before study: overnight (approx. 18 hours)
- Housing: in groups of 3 animals in plastic cages with bedding.
- Diet: CR-LPF pelleted diet, ad libitum
- Water: tap water, ad libitum
- Acclimation period: 1 week

ENVIRONMENTAL CONDITIONS (set to maintain)
- Temperature (°C): 23 ±3 (actual: 23-25°C)
- Humidity (%): 50 ±20 (actual: 44-47%)
- Air changes (per hr): 10-15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 25 April 2016 To: 11 May 2016

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 1.66 mL/kg bw

CLASS METHOD
- Rationale for the selection of the starting dose: it was expected that the acute oral toxicity of the test item was low and therefore the starting dose level was set at 2000 mg/kg bw.
Doses:
2000 mg/kg bw
No. of animals per sex per dose:
3 for the first dose step and 3 for the second dose step (females only)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
* clinical observations: 5 minutes, 15 minutes, 30 minutes, 1 hour, 2 hours, 4 hours and 6 hours after administration and once daily thereafter for 14 days.
* body weight: day 0 (pre-administration), 1, 3, 7 and 14.
- Necropsy of survivors performed: yes
- Other: external appearance and organs/tissues in the cranial, thoracic and abdominal cavities were examined macroscopically.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 2 000 mg/kg bw
Based on:
test mat.
Mortality:
No deaths occurred in any animal in the first and the second dosing step.
Clinical signs:
No abnormal clinical signs in any animal in the first or second dosing step were observed.
Body weight:
There were no abnormal body weight changes in any animal in the first or second dosing step during the observation period.
Gross pathology:
There were no abnormal findings in external appearance or in organs/tissues in the cranial, thoracic or abdominal cavities in any animal in the first or second dosing step.

Applicant's summary and conclusion

Interpretation of results:
GHS criteria not met
Conclusions:
In an acute oral toxicity study performed in accordance with OECD guideline 423, the LD50 for acute toxicity of D-370N in rats exceeded 2000 mg/kg bw. Based on these results, the test item is not classified according to GHS.
Executive summary:

An acute oral toxicity study was performed according to OECD guideline 423 and GLP principles to assess the toxic potential of D-370N in female Wistar rats. The test item was applied as such by oral gavage in a stepwise manner, starting with a first dosing step of 2000 mg/kg bw. Based on the results of the first dosing step, a second dosing step was performed with a test item concentration of 2000 mg/kg to confirm the results of the first dosing step. Test groups for both dosing steps consisted of 3 female rats of approximately 8 weeks of age. Mortality, clinical signs and body weights were recorded for 14 days after administration. After the observation period, all animals were sacrificed and pathological examination was performed.

No mortality occurred and no abnormal clinical signs were observed in any of the animals in any of the dosing steps. Body weight changes were considered normal. There were no abnormal pathological findings. The LD50 was determined to exceed the highest dose tested (LD50 >2000 mg/kg bw). Based on these results, D-370N is not classified for oral toxicity according to GHS.