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Description of key information

Reliable information on repeated dose toxicity shows a NOAEL of 2500 mg/kg bw/day.  Due to explosive properties of the substance, no further testing could be conducted.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Referenceopen allclose all

Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 weeks
Reliability:
2 (reliable with restrictions)
Qualifier:
according to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
not specified
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:3100 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:6200 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:12500 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:25000 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:50000 ppmBasis:nominal in diet
No. of animals per sex per dose:
10 males and 10 females
Control animals:
yes
Observations and examinations performed and frequency:
Cage side observations: No dataDermal irritation: No dermal study Body weight: Yes, female rats receiving diets containing 5000 or 10 000 ppm weighted 6-7% less than controlsFood consumption and compound intake: No dataFood efficiency: No dataWater consumption and compound intake (if drinking water study): No dataOphthalmoscopic examination: No dataHaematology: No effectsClinical chemistry: No effectsNeurobehavioural examination: No effects
Sacrifice and pathology:
Gross pathology: No effectsHistopathology: An adenoma of the Zymbal gland was observed in 1/10 high-dose female rats
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Female rats receiving diets containing 5000 or 10 000 ppm weighted 6-7% less than controls
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Low increase of adenoma of the Zymbal gland
Dose descriptor:
NOAEL
Effect level:
<= 50 000 mg/kg diet
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
Dose descriptor:
NOAEL
Effect level:
> 12 500 - <= 25 000 mg/kg diet
Based on:
test mat.
Sex:
female
Basis for effect level:
body weight and weight gain
Critical effects observed:
not specified
Conclusions:
Effects on the animals cannot be attributed to the ingestion of PETN.
Endpoint:
chronic toxicity: oral
Remarks:
combined repeated dose and carcinogenicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 years
Reliability:
2 (reliable with restrictions)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 453 (Combined Chronic Toxicity / Carcinogenicity Studies)
GLP compliance:
not specified
Species:
rat
Strain:
Fischer 344
Sex:
male/female
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
2 years
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:0 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:6200 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:12500 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:25000 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:50000 ppmBasis:nominal in diet
No. of animals per sex per dose:
50
Control animals:
yes
Details on study design:
50 male rats were fed with diets containing 0, 25,000, or 50,000 ppm PETNfor 103 weeks. 50 female rats were fed with diets containing 0, 6,200, or 12,500 ppm PETN for 103 weeks.
Observations and examinations performed and frequency:
Cage side observations: No data. Dermal irritation: No dermal study. Body weight: Yes, Male rats receiving diets containing 10 000 ppm weighted 2-5% less than controls male rats. Food consumption and compound intake: Male rats consumed 240-490 mg/ kg day. Food efficiency: No data. Water consumption and compound intake (if drinking water study): No data. Ophthalmoscopic examination: No data. Haematology: No effects. Clinical chemistry: No effects. Neurobehavioural examination: No effects
Sacrifice and pathology:
Mortality: survival, control 22/50, low dose 29/50, high dose 29/50Histopathology: carcinomas of the Zymbal gland
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Yes, Male rats receiving diets containing 10 000 ppm weighted 2-5% less than controls male rats
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Male rats consumed 240-490 mg/ kg day.
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
effects observed, treatment-related
Description (incidence and severity):
carcinomas of the Zymbal gland
Dose descriptor:
NOAEL
Effect level:
> 1 200 - < 2 500 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
body weight and weight gain
Dose descriptor:
NOAEL
Effect level:
> 400 - < 830 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
body weight and weight gain
Critical effects observed:
not specified
Conclusions:
Effects on the animals cannot be attributed to the ingestion of PETN.
Endpoint:
sub-chronic toxicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
13 weeks
Reliability:
2 (reliable with restrictions)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
not specified
Species:
other: mice
Strain:
B6C3F1
Sex:
male/female
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
13 weeks
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:3100 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:6200 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:12500 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:25000 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:50000 ppmBasis:nominal in diet
No. of animals per sex per dose:
10
Control animals:
yes
Observations and examinations performed and frequency:
Cage side observations: No dataDermal irritation: No dermal study Body weight: No effectsFood consumption and compound intake: No dataFood efficiency: No dataWater consumption and compound intake (if drinking water study): No dataOphthalmoscopic examination: No dataHaematology: No effectsClinical chemistry: No effectsNeurobehavioural examination: No effects
Sacrifice and pathology:
Gross pathology: No effectsHistopathology: An adenoma of the Zymbal gland was observed in 1/10 high-dose female mice
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
not specified
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
effects observed, treatment-related
Description (incidence and severity):
Low increase of adenoma of the Zymbal gland
Dose descriptor:
NOAEL
Effect level:
<= 25 000 mg/kg diet
Based on:
test mat.
Sex:
male/female
Basis for effect level:
body weight and weight gain
Critical effects observed:
not specified
Conclusions:
Effects on the animals cannot be attributed to the ingestion of PETN.
Endpoint:
sub-chronic toxicity: oral
Remarks:
combined repeated dose and carcinogenicity
Type of information:
experimental study
Adequacy of study:
key study
Study period:
2 years
Reliability:
2 (reliable with restrictions)
Qualifier:
equivalent or similar to guideline
Guideline:
OECD Guideline 408 (Repeated Dose 90-Day Oral Toxicity Study in Rodents)
GLP compliance:
not specified
Species:
other: mice
Strain:
B6C3F1
Sex:
male/female
Route of administration:
oral: drinking water
Vehicle:
water
Analytical verification of doses or concentrations:
not specified
Duration of treatment / exposure:
2 years
Frequency of treatment:
daily
Remarks:
Doses / Concentrations:0 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:25000 ppmBasis:nominal in diet
Remarks:
Doses / Concentrations:50000 ppmBasis:nominal in diet
No. of animals per sex per dose:
50
Control animals:
yes
Details on study design:
The average amount of PETN consumed per day was approximately 4,000 or 8,100 mglkg for low dose or high dose male mice and 5,100 or 9,700 mg/kg for low dose or high dose female mice.
Observations and examinations performed and frequency:
Cage side observations: No dataDermal irritation: No dermal study Body weight: No effectsFood consumption and compound intake: Male mice consumed 810-1620 mg/ kg day; female mice consumed 1020-1936 mg/kg dayClinical chemistry: No clinical effects
Sacrifice and pathology:
Moratality: Survival of dosed male mice was greater than that of controls [survival: controls 26/49 (one animal was mis-sexed), low dose 38/50, high dose 38/50]; survival of female mice did not differ among groups (38/50, 30/50, 38/50).Histopathology: No effects
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
no effects observed
Food consumption and compound intake (if feeding study):
effects observed, treatment-related
Description (incidence and severity):
Male mice consumed 810-1620 mg/ kg day; female mice consumed 1020-1936 mg/kg day
Food efficiency:
not specified
Water consumption and compound intake (if drinking water study):
not specified
Ophthalmological findings:
not specified
Haematological findings:
no effects observed
Clinical biochemistry findings:
no effects observed
Urinalysis findings:
not specified
Behaviour (functional findings):
no effects observed
Organ weight findings including organ / body weight ratios:
no effects observed
Gross pathological findings:
no effects observed
Histopathological findings: non-neoplastic:
no effects observed
Histopathological findings: neoplastic:
no effects observed
Dose descriptor:
NOAEL
Effect level:
> 4 000 - < 8 100 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Effects on the animals cannot be attributed to the ingestion of PETN
Dose descriptor:
NOAEL
Effect level:
> 5 100 - < 9 700 mg/kg bw/day (nominal)
Based on:
test mat.
Sex:
female
Basis for effect level:
body weight and weight gain
Critical effects observed:
not specified
Conclusions:
Effects on the animals cannot be attributed to the ingestion of PETN.
Endpoint conclusion
Dose descriptor:
NOAEL
2 500 mg/kg bw/day
Study duration:
chronic
Species:
rat

Repeated dose toxicity: inhalation - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: inhalation - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - systemic effects

Endpoint conclusion
Endpoint conclusion:
no study available

Repeated dose toxicity: dermal - local effects

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

PETN was found to be nontoxic to both rats and mice in a 13/14-week studies. No effects such as increase in methemoglobin were observed. As no evidence of toxicity of pentaerythritol tetranitrate in the 2- or 13-week studies was found, a 2 -year study on rats and mice was carried out using the maximum dietary concentrations recommended for chronic studies. Survival of treated male rats and male mice was higher than that of controls. No effects directly attributable to the ingestion of pentaerythritol tetranitrate were found.


Repeated dose toxicity: via oral route - systemic effects (target organ) cardiovascular / hematological: heart; cardiovascular / hematological: thymus; digestive: liver; neurologic: brain (multiple sections); respiratory: lung; urogenital: kidneys

Justification for classification or non-classification

No classification is proposed based on results obtained from the studies.