Hexamethylene diisocyanate, oligomers, reaction products with 3-methoxypropylamine

Endpoint summary

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

Study period:

From November 05, 2002 to November 21, 2002

Reliability:

1 (reliable without restriction)

Rationale for reliability incl. deficiencies:

guideline study

Qualifier:

according to guideline

Guideline:

OECD Guideline 423 (Acute Oral toxicity - Acute Toxic Class Method)

Deviations:

no

Qualifier:

according to guideline

Guideline:

EU Method B.1 tris (Acute Oral Toxicity - Acute Toxic Class Method)

Deviations:

no

Guideline:

EPA OPPTS 870.1100 (Acute Oral Toxicity)

Deviations:

no

GLP compliance:

yes

Test type:

acute toxic class method

Limit test:

no

Specific details on test material used for the study:

CAS No.: 162492-07-1; Batch No.: lab; Purity: unknown by the sponsor, treated as 100 % pure; Appearance: white to off-white solid

Species:

rat

Strain:

Wistar

Remarks:

Crl:(WI) BR

Sex:

male/female

Details on test animals or test system and environmental conditions:

Species: Rat, Wistar strain Crl:(WI) BR (outbred, SPF-Quality),
Source: Charles River Deutschland, Sulzfeld, Germany,
Age and body weight: young adult animals (approx. 8 weeks old) were selected, body weight variation did not exceed +/- 20 % of the sex mean,
Identification: Earmark,
Conditions: acontrolled environment was maintained in the room with optimal conditions considered as being approximately 15 air changes per hour, a temperature of 21±3 °C, a relative humidity of 30-70 % and 12 hours artificial fluorescent light and 12 hours dark per day,
Accommodation: group housing of 3 animals per sex per cage in labelled Macrolon cages (type IV; height 18 cm) containing purified sawdust as bedding material (SAWI, Jelu Werk, Germany),
Acclimatization period: at least 5 days before start of treatment under laboratory conditions,
Diet: free access to standard pelleted laboratory animal diet (from Altromin (code VRF 1), Germany,
Water: free access to tap-water.

Route of administration:

oral: gavage

Vehicle:

propylene glycol

Remarks:

specitic gravily: 1.036

Details on oral exposure:

The formulations (w/w) were prepared within 4 hours prior to dosing. Homogeneity was accomplished to a visually acceptable level. Adjustment was made tor specific gravity of the vehicle.

Doses:

2000 mg/kg bw (10 mi/kg) bw

No. of animals per sex per dose:

3

Control animals:

no

Details on study design:

A health inspection was performed prior to commencement of treatment, to ensure that the animals were in a good state of health.
Fasting: food was withheld overnight (for a maximum of 20 hours) prior to dosing until approximately 3-4 hours after administration of the test substance,
Frequency: single dosage, on day 1,
Dose level (volume): 2000 mg/kg (10 mi/kg) body weight,
Mortality/viability: twice daily,
Body weights: days 1 (pre-administration), 8 and 15,
Clinical signs: At periodic intervals on the day of dosing (day 1) and once daily thereafter, until day 15. The symptoms were graded according to fixed scales and the time of onset, degree and duration were recorded:
Maximum grade 4: grading slight (1) to very severe (4)
Maximum grade 3: grading slight (1) to severe (3)
Maximum grade 1: presence is scored (1)
Necropsy: At the end of the observation period, all animals were sacrificed by asphyxlation using an oxygen/carbon dioxide procedure and subjected to necropsy.

Statistics:

No statistical analysis was performed.

Key result

Sex:

male/female

Dose descriptor:

LD50

Effect level:

> 2 000 mg/kg bw

Based on:

test mat.

Mortality:

No mortality occurred.

Clinical signs:

Salivation was shown by one male and uncoordinated movements were displayed by all females on day 1. No further clinical signs were noted.

Body weight:

The body weight gain shown by the animals over the study period was considered to be similar to that expected of normal untreated animals of the same age and strain.

Gross pathology:

One female showed dark red hard nodules on the left kidney and an enlarged spleen. No further abnormalities were found at macroscopic examination of the animals.

Interpretation of results:

GHS criteria not met

Conclusions:

Under the study conditions, the LD50 in Wistar rats was considered to be >2000 mg/kg bw.

Executive summary:

A study was conducted to determine the toxicity of the test substance when administered as a single oral dose to Wistar rats according to OECD Guideline 423 (Acute Toxic Class (ATC)) method, EU Method B.1 tris and OPPTS Guideline 870.1100, in compliance with GLP. The substance was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg bw. Animals were subjected to 10 daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Salivation was shown by one male and uncoordinated movements were displayed by all females on Day 1. No further clinical signs were noted. The body weight gain of the animals over the study period was considered to be normal. One female showed dark red hard nodules on the left kidney and an enlarged spleen. No further abnormalities were found at macroscopic examination. Under the study conditions, the LD50 in Wistar rats was considered to be >2000 mg/kg bw (van Huygevoort, 2003).

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

LD50

Value:

2 000 mg/kg bw

Acute toxicity: via inhalation route

Endpoint conclusion

Endpoint conclusion:

no study available

Acute toxicity: via dermal route

Endpoint conclusion

Endpoint conclusion:

no study available

Additional information

A study was conducted to determine the toxicity of the test substance when administered as a single oral dose to Wistar rats according to OECD Guideline 423 (Acute Toxic Class (ATC)) method, EU Method B.1 tris and OPPTS Guideline 870.1100, in compliance with GLP. The substance was administered by oral gavage to three Wistar rats of each sex at 2000 mg/kg bw. Animals were subjected to 10 daily observations and weekly determination of body weight. Macroscopic examination was performed after terminal sacrifice (Day 15). No mortality occurred. Salivation was shown by one male and uncoordinated movements were displayed by all females on Day 1. No further clinical signs were noted. The body weight gain of the animals over the study period was considered to be normal. One female showed dark red hard nodules on the left kidney and an enlarged spleen. No further abnormalities were found at macroscopic examination. Under the study conditions, the LD50 in Wistar rats was considered to be >2000 mg/kg bw (van Huygevoort, 2003).

Justification for classification or non-classification

Based on the results of an acute oral toxicity study, the test substance does not need to be classified according to CLP (EC 1272/2008) criteria.