Octylamine

Toxicity to reproduction

Administrative data

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.

Cross-reference

Reason / purpose for cross-reference:

reference to same study

Data source

Reference

Reference 1

Reference Type:

study report

Title:

Unnamed

Year:

2007

Report date:

2007

Reference 2

Reference Type:

other: TSCA 8(e)

Title:

Unnamed

Year:

2005

Report date:

2005

Materials and methods

Test guideline

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

Test material

Test material information

Constituent 1

Reference substance name:

Octylammonium chloride

EC Number:

205-574-8

EC Name:

Octylammonium chloride

Constituent 2

Reference substance name:

octyl ammoniumchloride

IUPAC Name:

octyl ammoniumchloride

Details on test material:

- Name of test material (as cited in study report): octylamin hydrochloride
- Analytical purity: 99.9%
- further details: cf. Robust Study Summary contained in section 7.5.1

Test animals

Species:

rat

Strain:

other: Crl:CD (SD) IGS

Sex:

male/female

Administration / exposure

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

Doses / concentrations

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

Results and discussion

Results: P0 (first parental generation)

Effect levels (P0)

1

Dose descriptor:

NOAEL

Effect level:

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

Sex:

male

Basis for effect level:

other: see 'Remark'

2

Dose descriptor:

NOAEL

Effect level:

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

Sex:

female

Basis for effect level:

other: see 'Remark'

Results: F1 generation

Effect levels (F1)

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;

Overall reproductive toxicity

Reproductive effects observed:

not specified

Any other information on results incl. tables

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.

Applicant's summary and conclusion

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).