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Toxicological information

Carcinogenicity

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Description of key information

Key value for chemical safety assessment

Carcinogenicity: via oral route

Link to relevant study records
Reference
Endpoint:
carcinogenicity: oral
Type of information:
experimental study
Adequacy of study:
key study
Study period:
1966
Reliability:
2 (reliable with restrictions)
Rationale for reliability incl. deficiencies:
other: Study well documented, acceptable for assessment. However, the number of animals in study or the limited examined endpoints do fulfil recent standards.
Qualifier:
no guideline followed
Principles of method if other than guideline:
Groups of 30 m and 30 f rats were dosed for up to 100 weeks via drinking water.
Two additional groups dosed with 0 or 0.015% via drinking water and consisting of 40 males and 40 females each were included for reproduction studies.
GLP compliance:
no
Species:
rat
Strain:
Wistar
Sex:
male/female
Details on test animals and environmental conditions:
Weight at study initiation: 145-160 g
Housing: individually caging
Diet: ad libitum
Water: ad libitum

ENVIRONMENTAL CONDITIONS
Temperature (°C): 26-28
Route of administration:
oral: drinking water
Vehicle:
water
Details on exposure:
Drinking water solutions were prepared daily
Concentration in vehicle: 0, 0.015, 0.075 or 0.3 % (w/v)
Analytical verification of doses or concentrations:
no
Duration of treatment / exposure:
up to 100 weeks
Frequency of treatment:
continuously via drinking water
Post exposure period:
none
Remarks:
Doses / Concentrations:
0, 0.015, 0.075 or 0.3 % (w/v) (ca. 0, 15, 75 or 300 mg/kg bw)
Basis:

No. of animals per sex per dose:
30 m / 30 f
Control animals:
yes, concurrent vehicle
Details on study design:
not further specified
Positive control:
none
Observations and examinations performed and frequency:
CAGE SIDE OBSERVATIONS / CLINICAL OBSERVATIONS: Yes (not further specified)
BODY WEIGHT: Yes (until week 13 every 2 weeks and every 4 weeks thereafter)
HAEMATOLOGY: Yes (in weeks 16, 32 and 55)
URINALYSIS: Yes (in weeks 38 and 85)
Sacrifice and pathology:
Interim sacrifices in some animals of each group were done in week 32 and at this time point and also at termination endocrine glands were weighed and the heart, lungs, liver, spleen, kidneys, bladder, stomach, gut, thyroid gland, adrenal glands, ovaries, testes and pituitary gland were examined histopathologically.
Statistics:
not further specified
Clinical signs:
no effects observed
Mortality:
no mortality observed
Body weight and weight changes:
effects observed, treatment-related
Description (incidence and severity):
Dose-dependent increased body weight gain compared with controls, especially in males
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 examined
Haematological findings:
no effects observed
Clinical biochemistry findings:
not examined
Urinalysis findings:
no effects observed
Behaviour (functional findings):
not examined
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:
300 mg/kg bw/day (nominal)
Sex:
male/female
Remarks on result:
other: Effect type: carcinogenicity (migrated information)
Conclusions:
In a well-documented, but older study (lower number of animals in study and limited examined endpoints), the dosing with up to 300 mg/kg bw via drinking water for up to 100 weeks gave no indications for a carcinogenic effect of diethyl carbonate in rats.
Executive summary:

In a well-documented, but older study (lower number of animals in study and limited examined endpoints), the dosing with up to 300 mg/kg bw via drinking water for up to 100 weeks gave no indications for a carcinogenic effect of diethyl carbonate in rats. The dosing also caused no clear substance related signs of toxicity.

Endpoint conclusion
Endpoint conclusion:
no adverse effect observed
Dose descriptor:
NOAEL
300 mg/kg bw/day
Study duration:
chronic
Species:
rat

Carcinogenicity: via inhalation route

Endpoint conclusion
Endpoint conclusion:
no study available

Carcinogenicity: via dermal route

Endpoint conclusion
Endpoint conclusion:
no study available

Additional information

In a well-documented, but older study (lower number of animals in study and limited examined endpoints), the dosing with up to 300 mg/kg bw via drinking water for up to 100 weeks gave no indications for a carcinogenic effect of diethyl carbonate in rats. The dosing also caused no clear substance related signs of toxicity.

In another study, mice were dosed via drinking water with 0 - 1000 ppm for 83 weeks. The treatment had no adverse effects on mortality, body weight gain or the incidence of histopathological findings, including tumours. Although there were isolated differences between treated and control mice in haematological parameters and in liver weights of female mice, these were not considered to be treatment related. Therefore, the NOAEL was 1000 ppm (ca. 140 mg/kg bw/d).

Justification for classification or non-classification

Based on the negative results obtained in two long-term studies with oral dosing in rats and mice, no classification according to EU and GHS criteria is required.