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Toxicological information

Repeated dose toxicity: oral

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Administrative data

Endpoint:
short-term repeated dose toxicity: oral
Type of information:
experimental study
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Cross-reference
Reason / purpose:
read-across: supporting information
Reference
Endpoint:
short-term repeated dose toxicity: oral
Type of information:
read-across from supporting substance (structural analogue or surrogate)
Adequacy of study:
weight of evidence
Reliability:
1 (reliable without restriction)
Rationale for reliability incl. deficiencies:
test procedure in accordance with generally accepted scientific standards and described in sufficient detail
Justification for type of information:
A discussion and report on the read across strategy is given as an attachment in IUCLID Section 13.
Reason / purpose:
read-across source
Qualifier:
no guideline available
Version / remarks:
A 14-Day Study of Hexyl Cinnamic Aldehyde by Oral (Gavage) in Rats
Principles of method if other than guideline:
A range finding 14-day oral gavage study on HCA
GLP compliance:
yes (incl. certificate)
Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female
Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
yes
Frequency of treatment:
once daily via gavage for 14 consecutive days
Remarks:
Doses / Concentrations:
0,100,250,500,1000mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle
Key result
Dose descriptor:
NOEL
Effect level:
100 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Based on effects (not adverse) observed at the 250 mg/Kg/day dose
Key result
Dose descriptor:
NOEL
Effect level:
250 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Based on effects (not adverse) observed at the 500 mg/Kg/day dose
Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Based on mortality and adverse effects observed at the 1000 mg/Kg/day dose
Critical effects observed:
not specified
Conclusions:
In this 14-day repeat-dose study, hexyl cinnamic aldehyde was administered orally by gavage to 5 rats/sex/dosage at 0 (Vehicle), 100, 250, 500 and 1000 mg/kg/day. Several rats died or were euthanized after two or three days of treatment at 1000 mg/kg/day, and dosage administration in this dosage group was subsequently discontinued. Clinical signs attributed to hexyl cinnamic aldehyde were primarily observed at 1000 mg/kg/day, and a few observations of excess salivation occurred in males and females at 500 mg/kg/day. At 1000 mg/kg/day, net losses in body weight were observed in both sexes during the first three days of dosage administration, with transient reductions in body weight gain occurring at 250 and/or 500 mg/kg/day during the same period. Corresponding reductions in feed consumption occurred in male and female rats given 1000 mg/kg/day ofhexyl cinnamic aldehyde during the first three days ofthe study. Gross pathological observation revealed irritation of the gastric mucosa in male and female rats that died or were euthanized early in the 1000 mg/kg/day dosage group. Microscopic examination revealed test substance-related changes in the kidneys and in the stomach at 1000 mg/kg/day. No gross pathological or microscopic changes attributable to treatment with hexyl cinnamic aldehyde were observed at dosages up to 500 mg/kg/day.

In the conditions of this test hexyl cinnamic aldehyde has an NOAEL 14d oral of 500 mg/kg/bw/day

Data source

Reference
Reference Type:
study report
Title:
Unnamed
Year:
2004

Materials and methods

Test guideline
Qualifier:
no guideline available
Version / remarks:
A 14-Day Study of Hexyl Cinnamic Aldehyde by Oral (Gavage) in Rats
Principles of method if other than guideline:
A range finding 14-day oral gavage study on HCA
GLP compliance:
yes (incl. certificate)

Test material

Reference
Name:
Unnamed
Type:
Constituent
Test material form:
liquid

Test animals

Species:
rat
Strain:
Crj: CD(SD)
Sex:
male/female

Administration / exposure

Route of administration:
oral: gavage
Vehicle:
corn oil
Analytical verification of doses or concentrations:
yes
Frequency of treatment:
once daily via gavage for 14 consecutive days
Doses / concentrations
Remarks:
Doses / Concentrations:
0,100,250,500,1000mg/kg/day
Basis:
actual ingested
No. of animals per sex per dose:
5
Control animals:
yes, concurrent vehicle

Results and discussion

Effect levels

open allclose all
Key result
Dose descriptor:
NOEL
Effect level:
100 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
female
Basis for effect level:
other: Based on effects (not adverse) observed at the 250 mg/Kg/day dose
Key result
Dose descriptor:
NOEL
Effect level:
250 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male
Basis for effect level:
other: Based on effects (not adverse) observed at the 500 mg/Kg/day dose
Key result
Dose descriptor:
NOAEL
Effect level:
500 mg/kg bw/day (actual dose received)
Based on:
test mat.
Sex:
male/female
Basis for effect level:
other: Based on mortality and adverse effects observed at the 1000 mg/Kg/day dose

Target system / organ toxicity

Critical effects observed:
not specified

Applicant's summary and conclusion

Conclusions:
In this 14-day repeat-dose study, hexyl cinnamic aldehyde was administered orally by gavage to 5 rats/sex/dosage at 0 (Vehicle), 100, 250, 500 and 1000 mg/kg/day. Several rats died or were euthanized after two or three days of treatment at 1000 mg/kg/day, and dosage administration in this dosage group was subsequently discontinued. Clinical signs attributed to hexyl cinnamic aldehyde were primarily observed at 1000 mg/kg/day, and a few observations of excess salivation occurred in males and females at 500 mg/kg/day. At 1000 mg/kg/day, net losses in body weight were observed in both sexes during the first three days of dosage administration, with transient reductions in body weight gain occurring at 250 and/or 500 mg/kg/day during the same period. Corresponding reductions in feed consumption occurred in male and female rats given 1000 mg/kg/day ofhexyl cinnamic aldehyde during the first three days ofthe study. Gross pathological observation revealed irritation of the gastric mucosa in male and female rats that died or were euthanized early in the 1000 mg/kg/day dosage group. Microscopic examination revealed test substance-related changes in the kidneys and in the stomach at 1000 mg/kg/day. No gross pathological or microscopic changes attributable to treatment with hexyl cinnamic aldehyde were observed at dosages up to 500 mg/kg/day.

In the conditions of this test hexyl cinnamic aldehyde has an NOAEL 14d oral of 500 mg/kg/bw/day