Diethyl carbonate

Carcinogenicity

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 or test system 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

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.

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).