Octylamine

Endpoint summary

Key value for chemical safety assessment

Effects on fertility

Link to relevant study records

Reference

Endpoint:

screening for reproductive / developmental toxicity

Remarks:

based on test type (migrated information)

Type of information:

migrated information: read-across from supporting substance (structural analogue or surrogate)

Adequacy of study:

key study

Study period:

2005-10-12 through 2007-07-30

Reliability:

2 (reliable with restrictions)

Rationale for reliability incl. deficiencies:

other: GLP guideline study, but as read-across from supporting substance maximum reliability is 2. Read-across hypothesis: for details please see read-across report in IUCLID section 13.

Reason / purpose for cross-reference:

reference to same study

Qualifier:

according to guideline

Guideline:

OECD Guideline 422 (Combined Repeated Dose Toxicity Study with the Reproduction / Developmental Toxicity Screening Test)

Deviations:

no

GLP compliance:

yes

Limit test:

no

Species:

rat

Strain:

other: Crl:CD (SD) IGS

Sex:

male/female

Route of administration:

oral: gavage

Vehicle:

water

Details on mating procedure:

- M/F ratio per cage: 1:1
- Length of cohabitation: 14 days
- Proof of pregnancy: sperm in vaginal smear; referred to as day 0 of pregnancy
- After successful mating each pregnant female was caged (how): singly

Analytical verification of doses or concentrations:

yes

Duration of treatment / exposure:

Males 47-48 days; females 42-46 days

Frequency of treatment:

daily

Details on study schedule:

- Age at mating of the mated animals in the study: 13 weeks

Remarks:

Doses / Concentrations:
0, 37.5, 75, 100/150 mg/kg bw/day
Basis:
analytical conc.

No. of animals per sex per dose:

12

Control animals:

yes, concurrent vehicle

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (actual dose received)

Sex:

male

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEL

Effect level:

100 mg/kg bw/day (actual dose received)

Sex:

female

Basis for effect level:

other: see 'Remark'

Dose descriptor:

NOAEL

Generation:

F1

Effect level:

100 mg/kg bw/day (actual dose received)

Sex:

male/female

Basis for effect level:

other: no adverse effects on clinical signs; mortality; body weight live birth index; litter size; pup weight; sex ratio; survival index;

Reproductive effects observed:

not specified

Read-across hypothesis: for details please see read-across report in IUCLID section 13.

 

.There was no statistically significant change in any of the dose groups compared to the control group in any of the parameters examined in the parental animals or in the offspring. Detail infromation is contained in the attached document.

Conclusions:

There were no signs of toxicity to reproduction seen in parental animals or offspring in a valid OECD TG 422 oral gavage screening study using rats up to and including 100 mg octylamine hydrochloride/kg bw/day. The NOAEL for reproduction toxicity was therefore 100 mg/kg bw/day.

Executive summary:

Octylamine-HCl was examined for its potential for repeated toxicity, developmental and neurotoxicity in a combined OECD TG 422 study under GLP conditions. The dose levels used (0, 37.5, 75, an 100/150 mg/kg bw/day; oral gavage; 12 rats/sex/dose) were selected based on the results of two range finding studies, one in the range 100-1000 mg/kg bw/day, and one in the range 3-100 mg/kg bw/day. The high dose group was initially dosed at 150 mg/kg bw/day, but this was lowered 100 mg/kg bw/day by test day 14 because two mortalities were seen in this group. Therefore, this dose level is called “100/150 mg/kg bw/day”. It should however be mentioned that subsequent examinations revealed that these mortalities resulted from maldosing and were not related to the test substance.

 

The parameters examined in parental animals (gestation length, reproductive function indices [mating index, fertility index, gestation index, implantation efficiency], and corpora lutea counts] and in the offspring (viability at birth and on post partum day 4, sex ratio, weight at birth and on post partum day 4, clinical signs) were comparable across all groups including the control group. The NOAEL for reproduction toxicity was therefore 100 mg/kg bw/day under the conditions of this study.

Overall, there were no signs of toxicity to reproduction seen in parental rats or offspring in a valid OECD TG 422 oral gavage screening study receiving

octylamine hydrochloride up to and including 100 mg/kg bw/day (DuPont, 2007).

Effect on fertility: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

reliable guideline study with RA substance octylamine-HCl

Effect on fertility: via inhalation route

Endpoint conclusion:

no study available

Effect on fertility: via dermal route

Endpoint conclusion:

no study available

Additional information

Octylamine-HCl was examined for its potential for repeated toxicity, developmental and neurotoxicity in a combined OECD TG 422 study under GLP conditions. The dose levels used (0, 37.5, 75, an 100/150 mg/kg bw/day; oral gavage; 12 rats/sex/dose) were selected based on the results of two range finding studies, one in the range 100-1000 mg/kg bw/day, and one in the range 3-100 mg/kg bw/day. The high dose group was initially dosed at 150 mg/kg bw/day, but this was lowered 100 mg/kg bw/day by test day 14 because two mortalities were seen in this group. Therefore, this dose level is called “100/150 mg/kg bw/day”. It should however be mentioned that subsequent examinations revealed that these mortalities resulted from maldosing and were not related to the test substance.

 

The parameters examined in parental animals (gestation length, reproductive function indices [mating index, fertility index, gestation index, implantation efficiency], and corpora lutea counts] and in the offspring (viability at birth and on post partum day 4, sex ratio, weight at birth and on post partum day 4, clinical signs) were comparable across all groups including the control group. The NOAEL for reproduction toxicity was therefore 100 mg/kg bw/day under the conditions of this study.

Overall, there were no signs of toxicity to reproduction seen in parental rats or offspring in a valid OECD TG 422 oral gavage screening study receiving

octylamine hydrochloride up to and including 100 mg/kg bw/day (DuPont, 2007).

Short description of key information:
No toxicity to reproduction was seen in parental rats or offspring in a valid OECD TG 422 oral gavage GLP screening study receiving
octylamine hydrochloride up to and including 100 mg/kg bw/day (DuPont, 2007).

Justification for selection of Effect on fertility via oral route:
only study available

Effects on developmental toxicity

Description of key information

No toxicity to reproduction was seen in parental rats or offspring in a valid OECD TG 422 oral gavage GLP screening study receiving
octylamine hydrochloride up to and including 100 mg/kg bw/day (DuPont, 2007).

Effect on developmental toxicity: via oral route

Endpoint conclusion:

no adverse effect observed

Dose descriptor:

NOAEL

100 mg/kg bw/day

Study duration:

subacute

Species:

rat

Quality of whole database:

reliable guideline study with RA substance octylamine-HCl

Effect on developmental toxicity: via inhalation route

Endpoint conclusion:

no study available

Effect on developmental toxicity: via dermal route

Endpoint conclusion:

no study available

Additional information

Octylamine-HCl was examined for its potential for repeated toxicity, developmental and neurotoxicity in a combined OECD TG 422 study under GLP conditions. The dose levels used (0, 37.5, 75, an 100/150 mg/kg bw/day; oral gavage; 12 rats/sex/dose) were selected based on the results of two range finding studies, one in the range 100-1000 mg/kg bw/day, and one in the range 3-100 mg/kg bw/day. The high dose group was initially dosed at 150 mg/kg bw/day, but this was lowered 100 mg/kg bw/day by test day 14 because two mortalities were seen in this group. Therefore, this dose level is called “100/150 mg/kg bw/day”. It should however be mentioned that subsequent examinations revealed that these mortalities resulted from maldosing and were not related to the test substance.

 

The parameters examined in parental animals (gestation length, reproductive function indices [mating index, fertility index, gestation index, implantation efficiency], and corpora lutea counts] and in the offspring (viability at birth and on post partum day 4, sex ratio, weight at birth and on post partum day 4, clinical signs) were comparable across all groups including the control group. The NOAEL for reproduction toxicity was therefore 100 mg/kg bw/day under the conditions of this study.

Overall, there were no signs of toxicity to reproduction seen in parental rats or offspring in a valid OECD TG 422 oral gavage screening study receiving

octylamine hydrochloride up to and including 100 mg/kg bw/day (DuPont, 2007).

Justification for selection of Effect on developmental toxicity: via oral route:
only study available

Justification for classification or non-classification

A reproductive and developmental NOAEL of 100 mg/kg bw/day (highest dose tested), determined in a combined repeated dose toxicity study with a reproduction/developmental toxicity screening test (OECD test guideline 422), indicates that no classification is required under Regulation (EC) No 1272/2008. There is no evidence of n-octylamine hydrochloride inducing adverse effects on parental fertility or development of offspring.