Octanoic acid, compound with dicyclohexylamine (1:1)

Endpoint summary

Description of key information

In aqueous systems Octanoic acid, compound with dicyclohexylamine (1:1) is hydrolytically very unstable so that in aqueous solution a rapid decomposition to the educts can be observed. The substance will rapidly dissociate to octanoic acid and dicyclohexylamine. Therefore Octanoic acid, compound with dicyclohexylamine (1:1) is not stable at “standard” testing conditions representative for human and environmental exposure. Hence, it is fully justified to apply the read-across methodology by use of the respective data from the breakdown/decomposition products to describe the toxicological behaviour of the substance.

Repeated dose toxicity data for octanoic acid:

Subchronic oral toxicity: NOAEL >= 7000 mg/kg bw

Chronic oral toxicity: NOAEL >= 8000 mg/kg bw

Repeated dose toxicity data for dicyclohexylamine:

subacute oral toxicity: NOAEL 20 mg/kg bw

The NOAEL of 20 mg/kg bw for dicyclohexylamine is used as key value for chemical safety assessment. Since the substance to be registered is Octanoic acid, compound with N-cyclohexylcyclohexanamine (1:1) which will dissociate to 1 mol octanoic acid and 1 mol dicyclohexylamine, the NOAEL of dicyclohexylamine is calculated for the entire substance considering the molar mass of 325.5 g/mol (55.7% dicyclohexylamine).

Therefore the NOAEL for Octanoic acid, compound with dicyclohexylamine (1:1) is 35.9 mg/kg bw.

Key value for chemical safety assessment

Repeated dose toxicity: via oral route - systemic effects

Link to relevant study records

Reference

Endpoint:

short-term repeated dose toxicity: oral

Type of information:

experimental study

Adequacy of study:

key study

Study period:

1998

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

comparable to guideline study with acceptable restrictions

Qualifier:

equivalent or similar to guideline

Guideline:

OECD Guideline 407 (Repeated Dose 28-Day Oral Toxicity Study in Rodents)

Deviations:

not specified

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

Crj: CD(SD)

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

corn oil

Analytical verification of doses or concentrations:

not specified

Duration of treatment / exposure:

28 days

Frequency of treatment:

once daily

Dose / conc.:

20 mg/kg bw/day (nominal)

Dose / conc.:

70 mg/kg bw/day (nominal)

Dose / conc.:

200 mg/kg bw/day (nominal)

No. of animals per sex per dose:

Males, 13; females, 13: 0, 200 mg/kg bw
Males, 5, females, 5: 20, 70 mg/kg bw

Control animals:

yes, concurrent vehicle

Clinical signs:

effects observed, treatment-related

Description (incidence and severity):

signs of intoxication such as salivation and convulsion at 70 and 200 mg/kg bw

Mortality:

mortality observed, treatment-related

Description (incidence):

8/13 rats given 200 mg/kg bw. both sexes

Body weight and weight changes:

effects observed, treatment-related

Description (incidence and severity):

significantly decreased in rats of both sexes given 200 mg/kg bw/day

Food consumption and compound intake (if feeding study):

effects observed, treatment-related

Description (incidence and severity):

significantly decreased in rats of both sexes given 200 mg/kg bw/day

Food efficiency:

not examined

Water consumption and compound intake (if drinking water study):

not examined

Ophthalmological findings:

not examined

Haematological findings:

effects observed, treatment-related

Description (incidence and severity):

Numbers of WBCs in females given 200 mg/kg bw/day were increased at the end of the administration period.

Clinical biochemistry findings:

effects observed, treatment-related

Description (incidence and severity):

In the blood chemical analysis at the end of the administration period, inorganic phosphorus and calcium concentrations were elevated in rats of both sexes given 200 mg/kg bw/day.

Urinalysis findings:

not specified

Behaviour (functional findings):

not specified

Immunological findings:

not specified

Organ weight findings including organ / body weight ratios:

effects observed, treatment-related

Description (incidence and severity):

200 mg/kg bw: weights of adrenal glands were elevated in animals of both sexes
70, 200 mg/kg bw: weights of ovaries were significantly decreased in female rats

Gross pathological findings:

no effects observed

Neuropathological findings:

not specified

Histopathological findings: non-neoplastic:

no effects observed

Histopathological findings: neoplastic:

no effects observed

Other effects:

not specified

Key result

Dose descriptor:

NOAEL

Effect level:

20 mg/kg bw/day (nominal)

Based on:

test mat.

Sex:

male/female

Basis for effect level:

body weight and weight gain

clinical signs

gross pathology

haematology

mortality

organ weights and organ / body weight ratios

urinalysis

Key result

Critical effects observed:

not specified

Conclusions:

The NOEL for the 28-day repeat dose oral toxicity test of dicyclohexylamine in rats is considered to be 20 mg/kg/day for both sexes.

Executive summary:

Repeated dose toxicity of DCHA following oral application was tested in male and female CD rats for 28-days.

Animals received 0, 20, 70, and 200 mg/kg bw/day dissolved in corn oil by gavage. Control rats and the high dosed rats were kept for a 14-day recovery period.

Eight out of 13 rats died in both sexes given 200 mg/kg of dicyclohexylamine. Myocardial degeneration was observed in 1 dead male. In the other dead animals, no histological changes were found to explain the cause of death. Several signs, such as salivation, convulsion etc. which suggested certain neural effects were observed in the animals of both sexes given 70 mg/kg and more. These signs disappeared during the recovery period. Responses due to sympathetic stimulation caused by dicyclohexylamine was supposed to be one of the causes of death. Body weight and food consumption were significantly decreased in the animals of both sexes given 200 mg/kg. The lower body weight continued to the end of the recovery period, but food consumption had recovered by the end of the test. Numbers of WBCs in females given 200 mg/kg were increased at the end of the administration period. In the blood chemical analysis at the end of the administration period, inorganic phosphorus and calcium concentrations were elevated in the animals of both sexes given 200 mg/kg, suggesting that the dicyclohexylamine treatment had influenced phosphorus/calcium metabolism. The weights of the adrenal glands were elevated in the animals of both sexes given 200 mg/kg and the weights of ovaries were decreased in the animals given 70 mg/kg or more compared with those in the control group. The NOEL for the 28-day repeat dose oral toxicity test of dicyclohexylamine in rats is considered to be 20 mg/kg/day for both sexes.

Endpoint conclusion

Endpoint conclusion:

adverse effect observed

Dose descriptor:

NOAEL

35.9 mg/kg bw/day

Study duration:

subacute

Species:

rat

Organ:

adrenal glands

blood

ovary

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

Justification for classification or non-classification

No specific target organ can be identified based on the available data in experimental animals. Therefore specific target organ toxicity to humans is not likely.

No classification for specific target organ toxicity is required.