1-Heptanol, 2-propyl-, 1,1'-carbonate

Endpoint summary

Description of key information

The test item was tested in a repeated-dose 28 -day toxicity study according to OECD guideline no. 407. The oral administration of test item via diet over a period of 4 weeks revealed pathological findings in male Wistar rats at a concentration of 15000 ppm. Therefore, under the conditions of the present study the no observed adverse effect level (NOAEL) was 415 mg/kg bw/d (5000 ppm) in male and 1351 mg/kg bw/d (15000 ppm) in female Wistar rats.
Furthermore, the test item was tested in a repeated-dose 90 -day toxicity study according to OECD guideline no. 408. The oral administration of test item via diet over a period of 13 weeks revealed pathological findings in male Wistar rats at a concentration of 1000 mg/kg. Therefore, under the conditions of the present study the no observed adverse effect level (NOAEL) was 356 mg/kg bw/d  in male and 1166 mg/kg bw/d in female Wistar rats.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Endpoint conclusion

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

356 mg/kg bw/day

Study duration:

subchronic

Species:

rat

Quality of whole database:

OECD guideline was followed.
GLP study

Additional information

The test item was tested in a repeated-dose 28 -day toxicity study according to OECD guideline no. 407 and EU method B.7. The test item was administered via the diet to groups of 5 male and 5 female Wistar rats at concentration levels of 0 ppm (maintenance diet served as vehicle control; test group 0), 1500 ppm (test group 1), 5000 ppm (test group 2) and 15000 ppm (test group 3) over a period of 4 weeks. Food consumption and body weight were determined weekly. The animals were examined for signs of toxicity or mortality at least once a day. Detailed clinical examinations in an open field were conducted prior to the start of the administration period and weekly thereafter. Clinicochemical and hematological examinations as well as urinalyses were performed towards the end of the administration period. After the administration period all rats were sacrificed and assessed by gross pathology, followed by histopathological examinations. The following test substance-related, relevant findings were noted: No treatment-related, adverse findings were observed in test group 3: 15000 ppm (1306 mg/kg bw/d in males and 1351 mg/kg bw/d in females. Minimal proximal tubular cell hypertrophy in the kidney of in 4 of 5 male animals accompanied by increased organ weight

(120% absolute and 118% relative). No treatment-related, adverse findings were observed in test group 2: 5000 ppm (415 mg/kg bw/d in males and 456 mg/kg bw/d in females). No treatment-related, adverse findings were observed in test group 1: 1500 ppm (125 mg/kg bw/d in males and 127 mg/kg bw/d in females.

The oral administration of test item via diet over a period of 4 weeks revealed pathological findings in male Wistar rats at a concentration of 15000 ppm. Therefore, under the conditions of the present study the no observed adverse effect level (NOAEL) was 415 mg/kg bw/d (5000 ppm) in male and 1351 mg/kg bw/d (15000 ppm) in female Wistar rats.

Dipropylheptylcarbonate (was administered via the diet to groups of 10 male and 10 female Wistar rats over a period 3 months. For the first 2 weeks concentrations in the diet of 0 (vehicle control; test group 0), 1500 (test group 1), 5000 (test group 2) and 15000 ppm (test group 3) were prepared and administered to the animals. After the first 2 weeks until the end of the study period the concentrations in the diet were adjusted to obtain target dose levels of 0 (vehicle control; test group 0), 100 (test group 1), 300 (test group 2) and 1000 mg/kg body weight/day (test group 3).

Food consumption and body weights were determined weekly. The animals were examined for signs of toxicity or mortality at least once a day. Moreover, detailed clinical examinations in an open field were conducted prior to the start of the administration period and weekly thereafter. Ophthalmological examinations were performed before the beginning and at the end of the administration period. For at least 3 weeks an estrous cycle determination was performed. Beside this, a functional observational battery (FOB) as well as measurement of motor activity (MA) were carried out at the end of the administration period. Clinicochemical and hematological examinations as well as urinalyses were performed

towards the end of the administration period. After the administration period all animals were sacrificed and assessed by gross pathology, followed by histopathological examinations.

The following test substance-related, adverse findings were noted:

Test group 3: target dose of 1000 mg/kg bw/d

(achieved doses: about 1141 mg/kg bw/d in males; about 1166 mg/kg bw/d in females)

Clinical Examinations

• No treatment-related, adverse findings were observed.

Clinical Pathology

• Decreased total protein and globulin levels in males

• Decreased sodium and increased potassium levels in males

Pathology

• No treatment-related, adverse findings were observed.

Test group 2: target dose of 300 mg/kg bw/d

(achieved doses: about 356 mg/kg bw/d in males; about 355 mg/kg bw/d in females)

Clinical Examinations, Clinical Pathology and Pathology

• No treatment-related, adverse findings were observed.

Test group 1: target dose of 100 mg/kg bw/d

(achieved dose about 114 mg/kg bw/d in males; about 115 mg/kg bw/d in females)

Clinical Examinations, Clinical Pathology and Pathology

• No treatment-related, adverse findings were observed.

In conclusion, the oral administration of Dipropylheptylcarbonate (Cetiol P5) via diet over a period of 3 months revealed findings with regard to clinical pathology in male Wistar rats at a target dose level of 1000 mg/kg bw/d (achieved dose about 1141 mg/kg bw/d). Therefore, under the conditions of the present study the no observed adverse effect level (NOAEL) was 356 mg/kg bw/d in male and 1166 mg/kg bw/d in female Wistar rats.

Justification for selection of repeated dose toxicity via oral route - systemic effects endpoint:
one key study