Use of this information is subject to copyright laws and may require the permission of the owner of the information, as described in the ECHA Legal Notice.
EC number: 824-801-7 | CAS number: 1093628-27-3
The study was designed to investigate the systemic toxicity and potential adverse effects of the test item on reproduction (including offspring development), to evaluate some endocrine disruptor relevant endpoints and is designed to be compatible with the requirements of the OECD Guidelines for Testing of Chemicals No. 422 “Combined Repeated Dose Toxicity Study with the Reproduction/ Developmental Toxicity Screening Test” (adopted 29 July 2016).
This study was also designed to be compatible with Commission Regulation (EC) No 440/2008 of 30 May 2008 laying down test methods pursuant to Regulation (EC) No 1907/2006 of the European Parliament and of the Council on the Registration, Evaluation, Authorisation and Restriction of Chemicals (REACH).
The test item was administered by gavage to three groups, each of twelve male and twelve female Wistar Han™:RccHan™:WIST strain rats, for approximately 6 weeks (males) and up to eight weeks (females) (including a two week pre-pairing phase, pairing, gestation and early lactation for females), at dose levels of 40, 100 and 250 mg/kg bw/day of Active Ingredient (A.I.) (incorporating a correction factor for 59.7% purity). A control group of twelve males and twelve females was dosed with vehicle alone (Polyethylene glycol 400).
Clinical signs, behavioral assessments, body weight change and food and water consumption were monitored during the study.
Pairing of animals within each dose group was undertaken on a one male: one female basis within each treatment group on Day 15 of the study, with females subsequently being allowed to litter and rear their offspring to Day 13 of lactation.
During the lactation phase, daily clinical observations were performed on all surviving offspring, together with litter size and offspring weights and assessment of ano-genital distance and visible nipple count (male offspring only).
Extensive functional observations were performed on five selected males from each dose group after the completion of the pairing phase, and for five selected parental females from each dose group on Day 12 post partum. Hematology and blood chemistry were evaluated prior to termination on five selected males and females from each dose group. Additionally, blood samples were taken at termination from all adult animals and from one male and one female offspring per litter (where possible) on Days 4 and 13 post partum, for thyroid hormone analysis; samples from all adult males and Day 13 offspring were analyzed for Thyroxine (T4).
Vaginal smears were performed for all females from the day after arrival (enabling the exclusion of females not showing appropriate estrous cycling from dosing) and for all treated females including controls through pre-pairing, pairing and up to confirmation of mating.
Vaginal smears were also performed in the morning on the day of termination for all treated females.
Adult males were terminated on Day 44 or 45, followed by the termination of all females and all surviving offspring on Day 14 and 13 post partum, respectively. Any female which did not produce a pregnancy was terminated around the same time as littering females. All animals were subjected to a gross necropsy examination and histopathological evaluation of selected tissues was performed.
There were no unscheduled deaths on the study.
Instances of increased salivation and/or noisy respiration were observed during the course of the study in animals of either sex treated with 250 or 100 mg/kg bw/day A.I.
No toxicologically significant effects were evident in animals treated with 40 mg/kg bw/day A.I.
There were no treatment-related changes in the behavioural parameters.
Functional Performance Tests
There were no treatment related changes in functional performance.
Sensory Reactivity Assessments
There were no inter-group differences in sensory reactivity scores.
Males treated with 250 mg/kg bw/day A.I. showed a reduction in body weight gain during Weeks 1, 2 and 5. Consequently overall body weight gain for these males was lower than controls. Females treated with 250 mg/kg bw/day A.I. showed a reduction in body weight gain during Week 1. Recovery was evident thereafter.
No such effects were detected in animals of either sex treated with 100 or 40 mg/kg bw/day A.I.
A slight reduction in food consumption was evident in males treated with 250 mg/kg bw/day A.I. throughout the treatment period. Minor fluctuations in food conversion efficiency were evident in animals of either sex treated with 250 mg/kg bw/day A.I., which generally followed the reductions in body weight gains seen in these animals. No such effect on food consumption was evident in females treated with 100 mg/kg bw/day A.I. or in animals of either sex treated with 100 or 40 mg/kg bw/day A.I. Food conversion efficiency for either sex treated with 100 or 40 mg/kg bw/day A.I. was comparable to controls.
Daily visual assessment of water consumption did not reveal any significant intergroup differences.
There was no effect of treatment with the test item at any dose level on the nature of estrous cycle with most females showing regular cycles over the pre-pairing phase of the study. There were also no intergroup differences in the stage of estrus on the day of necropsy.
There was no effect of treatment on mating performance. With the exception of one animal, all animals mated within four days of pairing.
There were no treatment-related effects in conception rates for test item treated animals in relation to controls.
There were no differences in gestation lengths in animals receiving the test item when compared with controls.
Offspring Litter Size, Sex Ratio and Viability
There were no adverse effects of treatment with the test item on the mean number of implantations, post-implantation loss, litter size, sex ratio and subsequent offspring survival to Day 13 of age at 40, 100 or 250 mg/kg bw/day A.I.
Offspring Growth and Development
There was no detrimental effect of treatment with the test item indicated by offspring body weight or body weight gain and litter weights, ano-genital distance on Day 1 post partum or visible nipple count in male offspring on Day 13 post partum at 40, 100 and 250 mg/kg bw/day A.I.
The clinical signs and necropsy findings apparent for offspring on the study were typical for the age observed. Neither the incidence nor distribution of these observations indicated any adverse effect of maternal treatment on offspring development at 40, 100 and 250 mg/kg bw/day A.I.
There were no toxicologically significant effects detected in the hematological parameters examined.
There were no toxicologically significant effects detected in the blood chemical parameters examined.
No toxicologically significant effects were detected in animals of either sex treated with 40, 100 and 250 mg/kg bw/day A.I.
No toxicologically significant effects were detected in the organ weights measured in animals of either sex treated with 40, 100 and 250 mg/kg bw/day A.I.
There were no treatment-related microscopic abnormalities detected.
Thyroid Hormone Analysis
An evaluation of Thyroxine (T4) in adult males and male/female offspring (Day 13 of age) did not identify any treatment-related findings.
The oral administration of Benzenesulfonic acid, mono-C10-13-alkyl derivs., compds. with N1,N1-dimethyl-1,3-propanediamine (ACAR 16001) to rats by gavage, at dose levels of 40, 100 and 250 mg/kg bw/day A.I., resulted in males treated with 250 mg/kg bw/day A.I. showing a lower overall body weight gain and food consumption in relation to controls (in relation to controls, body weights were 4% lower compared to controls) and the
corresponding females during the first week of treatment also showed reduced body weight gains. There were no histopathological findings related to treatment at any dose level and the effect on body weight development was considered to be non-adverse. The ‘No Observed Adverse Effect Level’ (NOAEL) for systemic toxicity was therefore considered to be 250 mg/kg bw/day A.I.
The ‘No Observed Adverse Effect Level’ (NOAEL) for reproductive toxicity was considered to be 250 mg/kg bw/day A.I.
Information on Registered Substances comes from registration dossiers which have been assigned a registration number. The assignment of a registration number does however not guarantee that the information in the dossier is correct or that the dossier is compliant with Regulation (EC) No 1907/2006 (the REACH Regulation). This information has not been reviewed or verified by the Agency or any other authority. The content is subject to change without prior notice.Reproduction or further distribution of this information may be subject to copyright protection. Use of the information without obtaining the permission from the owner(s) of the respective information might violate the rights of the owner.
Welcome to the ECHA website. This site is not fully supported in Internet Explorer 7 (and earlier versions). Please upgrade your Internet Explorer to a newer version.
Close Do not show this message again