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Description of key information

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: No analytical certificate (no data on batch number and expiry date of the test substance), no data on GLP and experimental conditions. The very high tested dose enables a reliable conclusion.
Qualifier:
according to guideline
Guideline:
other: Federal Hazardous Substance Act.
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
yes
Species:
rat
Strain:
Sprague-Dawley
Sex:
male/female
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Laboratory Supply Company, Indianapolis, Indiana
- Weight at study initiation: 200 to 275 g
Route of administration:
oral: gavage
Vehicle:
unchanged (no vehicle)
Details on oral exposure:
MAXIMUM DOSE VOLUME APPLIED: 10 mL/kg
Doses:
10 mL/kg
No. of animals per sex per dose:
5 males and 5 females
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: no data
- Necropsy of survivors performed: yes
- Other examinations performed: clinical signs
Preliminary study:
Yes, but results were not indicated.
Sex:
male/female
Dose descriptor:
LD50
Effect level:
> 10 mL/kg bw
Based on:
test mat.
Mortality:
2 males and 1 female were found dead.
Clinical signs:
other: No clinical signs were observed.
Gross pathology:
No gross abnormalities were noted at necrospy.
Interpretation of results:
other: inconclusive
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LD50 was expressed in mL/kg. The volume mass of the substance is 0.96 kg/L (0.96 g/mL). Therefore, when treating rats with 10 mL/kg, rats received 9.6 g/kg of substance, lowest limit of the LD50.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD50
Value:
> 9 600 mg/kg bw
Quality of whole database:
Only one study is available which has been given a reliability rating of 2, despite a number of limitations.

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:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: see 'Remark'
Remarks:
Only 4 instead of 5 tested animals + unknown shaved area surface (cm2) + no mention of application under gauze + no detail on investigations (unknown whether any post-mortem examination done) + number of deaths not indicated = doubtful sensitivity and lack of details. The skin was abraded before treatment. However the moderate skin penetration (see 7.1) and the absence of acute oral toxicity imply an absence of dermal toxicity.
Qualifier:
according to guideline
Guideline:
other: Federal Hazardous Substance Act
GLP compliance:
no
Test type:
fixed dose procedure
Limit test:
no
Species:
rabbit
Strain:
New Zealand White
Sex:
not specified
Details on test animals or test system and environmental conditions:
TEST ANIMALS
- Source: Small Stock Industries, Pea Ridge, Arkansas
- Age at study initiation: young adults
- Weight at study initiation: 2.5 to 3.5 kg
Type of coverage:
not specified
Vehicle:
unchanged (no vehicle)
Details on dermal exposure:
TEST SITE
- Area of exposure: not indicated
- % coverage: not indicated
- Type of wrap if used: rubber dam

REMOVAL OF TEST SUBSTANCE
- Washing (if done): with lukewarm water
- Time after start of exposure: just after removal of the rubber dams

TEST MATERIAL
- Amount(s) applied (volume or weight with unit): 5 mL/kg
Duration of exposure:
24 hours
Doses:
5 mL/kg
No. of animals per sex per dose:
4 animals
Control animals:
no
Details on study design:
- Duration of observation period following administration: 14 days
- Frequency of observations and weighing: not indicated
- Necropsy of survivors performed: not indicated
- Other examinations performed: clinical signs
Preliminary study:
Not indicated
Sex:
not specified
Dose descriptor:
LDLo
Effect level:
> 5 mL/kg bw
Based on:
test mat.
Mortality:
None
Clinical signs:
other: None
Gross pathology:
Not indicated.
Interpretation of results:
other: inconclusive
Remarks:
Criteria used for interpretation of results: EU
Conclusions:
The LDLo of the test substance after skin exposure during 24 hours is > 5 mL/kg. According to the volume mass of the test substance (0.96 kg/L), the LDLo of the test substance under the experimental conditions of the study is > 4.8 g/kg.
Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
LD0
Value:
> 4 800 mg/kg bw
Quality of whole database:
Only one study is available which has been given a reliability rating of 2, despite a number of limitations.

Additional information

Animal data suggest a total absence of toxicity by oral and dermal routes. Data from the inhalative route are not reliable.

However, there are reports of effects in workers including dizziness, headaches. Organic nitrates have vasodilatation properties that could account for such effects. There is also a problem of habituation to their effects, followed by possible effects upon cessation of exposure.

Justification for classification or non-classification

As a worst-case, Xn, R20/21/22 and Acute tox 4 are proposed based on human data (corresponding dose-levels unknown).