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Toxicological information

Acute Toxicity: oral

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Administrative data

Endpoint:
acute toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
18 February 2009 - 13 May 2009
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
guideline study

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2009
Report Date:
2009

Materials and methods

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

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
other: liquid
Details on test material:
- Name of test material (as cited in study report): 1,4-Bis(isocyanatmethyl)cyclohexane
- Substance type: organic
- Physical state: Liquid (at room temperature)
- Storage condition of test material: Room temperature (19-23°C), under nitrogen atmosphere

Test animals

Species:
rat
Strain:
Sprague-Dawley
Sex:
female
Details on test animals and environmental conditions:
TEST ANIMALS
- Source: Atsugi Breeding Center, Charles River laboratories Japan, Inc.
- Age at study initiation: 8 or 9 weeks
- Weight at study initiation: 198 - 208g
- Fasting period before study: yes, o/n (appr. 16 hours)
- Housing: one or two (individually after grouping) in bracket-type metallic wire-mesh cages
- Diet: ad libitum, pelleted diet CRF-1 (Oriental Yeast, Co., ltd.), except for appr. 16 hours before and 4 hours after test substance application
- Water: tap water, ad libitum
- Acclimation period: at least one week

ENVIRONMENTAL CONDITIONS
- Temperature (°C): 21-23
- Humidity (%): 51-59
- Air changes (per hr): 10 to 15
- Photoperiod (hrs dark / hrs light): 12/12

IN-LIFE DATES: From: 18 February 2009 To: 13 May 2009

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Details on oral exposure:
VEHICLE
- Concentration in vehicle: 30 mg/mL and 200 mg/mL
- Amount of vehicle (if gavage): 10 mL/ kg bw
- Lot no.: V8N8411 (Nacalai Tesque, Inc.)

MAXIMUM DOSE VOLUME APPLIED: 10 mL/ kg bw
Doses:
300 and 2000 mg/kg bw (applied in a step-wise manner).
No. of animals per sex per dose:
3 (2000 mg/kg bw); 6 (300 mg/ kg bw)
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing:
Clinical signs were observed frequently for 6 hours after administration (immediately after to 5 minutes, 15 minutes and 30 minutes, and 1, 2, 4 and 6 hours after administration) and once every day for 14 days;
All animals were weighed on the day of administration, and on days 1,3, 7 and 14 (or at the time when found dead (if applicable)).
- Necropsy of survivors performed: yes (gross macroscopy)
Statistics:
Approximate LD50 value was estimated based on the deaths occurrence during the 14-day period after administration. For body weight, mean with standard deviation was calculated for each measurement day of each dose step. Body weight gain during the observation period was calculated from the body weight on day 0 and day 14 after administration, and mean with standard deviation calculated in the same manner.

Results and discussion

Effect levels
Key result
Sex:
female
Dose descriptor:
LD50
Effect level:
> 300 - < 2 000 mg/kg bw
Based on:
test mat.
Mortality:
Two animals died on the second day after dosing at 2000 mg/ kg bw. No other mortality occurred.
Clinical signs:
At 2000 mg/ kg bw, decrease in spontaneous movement was noted on day 1. For the surviving animals, this resolved after 3 days.
At 300 mg/ kg bw, no clinical signs were noted.
Body weight:
At 2000 mg/kg bw, weight decrease was noted in all animals. The surviving animal showed body weight decrease until day 3 after administration, but showed largely regular body weight gain thereafter. The body weight gain in animals dosed at 300 mg/kg bw was slightly low on the day following administration, but the rats showed largely regular body weight development thereafter.
Gross pathology:
No abnormalities in external appearance or in organs/ tissues in the cephalic, thoracic or abdominal regions were noted.

Applicant's summary and conclusion

Interpretation of results:
Category 4 based on GHS criteria
Conclusions:
In an acute oral toxicity test, the oral LD50 of 1,4-H6XDI was found to be > 300 mg/kg bw and < 2000 mg/kg bw.
Executive summary:

An acute oral toxicity test was performed according to OECD guideline 423 and GLP principles. Three female rats were exposed to 2000 mg 1,4 -H6XDI/ kg bw, which resulted in mortality of two rats on day 2. Decrease in spontaneous movement on day 1 was the only clinical sign observed in this group. The surviving animals showed decreased body weight, but regained body weight from day 4. Two groups of 3 females were exposed to 300 mg/kg bw in a step-wise manner. No mortality occurred, no clinical signs were noted. Slight depression in body weight gain was noted on the first day after administration, but this was resolved the next day. No abnormalities in external appearance or in organs/ tissues in the cephalic, thoracic or abdominal regions were noted. Based on these results, the oral LD50 of 1,4-H6XDI was found to be > 300 mg/kg bw and therefore 1,4 -H6XDI is classified cat. 4 for acute oral toxicity according to Regulation EC 1272/2008.